Caroline Helwick

VIENNA – High response rates to pembrolizumab and to intratumoral delivery of plasmid interleukin-12 (IL-12) were observed among patients with advanced Merkel cell carcinoma (MCC), based on studies presented at the 2015 European Cancer Congress.

There is strong rationale for immunotherapy in MCC. For one thing, the Merkel cell polyomavirus, which is expressed in 80% of tumors, serves as a powerful antigen for stimulating an immune response. Secondly, MCC tumors often express the ligand for the programmed death protein (PD-1), creating an opportunity for PD-1 pathway blockade with PD-1 inhibitors such as pembrolizumab, according to the investigators.

Responses in 10 of 14 given pembrolizumab

Dr. Paul Nghiem of the University of Washington in Seattle, led an open-label, single-arm, multicenter phase II trial of pembrolizumab, which is approved for metastatic melanoma and which could become the first systemic therapy for unresectable or metastatic MCC (Abstract 22LBA).

In the study, which opened in January 2015, there are 24 evaluable patients treated with pembrolizumab 2 mg/kg every 3 weeks for up to 2 years. Fourteen had at least one posttreatment scan; 10 of these 14 patients (71%) have responded, 2 had complete responses. One patient had stable disease and three progressed.

“Responses were rapid, and appear more durable than we see with chemotherapy,” Dr. Nghiem said.

The drug was generally well tolerated, with an adverse event profile similar to what has been seen in melanoma. One patient experienced grade 4 myocarditis after one dose and one developed grade 4 transaminase elevation after two doses. Both improved after discontinuing pembrolizumab and starting corticosteroids.

“Strikingly, despite receiving only one or two doses, both patients had profound and ongoing responses to pembrolizumab,” Dr. Nghiem observed.

Many subjects had “profound shrinkage of tumor that has not rebounded,” he noted. “Pembrolizumab looks to be very favorable in terms of durability of response. With chemotherapy, at 90 days half of our patients have gone off treatment.”

The researchers are considering expanding the study population, and may include a chemotherapy-relapsed cohort. They are also analyzing biomarkers, and hope to evaluate response according to virus-positive versus virus-negative status.

©2015 AACR/Todd Buchanan

Dr. Caroline Robert of the Institut Gustave Roussy in Villejuif, France, commented on the findings, first noting the difficulty of treating patients for whom there are no approved therapies. Median overall survival is less than 10 months, she said, and clinicians have lacked clinical trials to enroll patients.

“MCC patients represent a high medical need,” she said. Although the results with pembrolizumab are early, “they are very promising.”

Intratumoral plasmid IL-12

Dr. Shailender Bhatia of the University of Washington in Seattle, described a different immunotherapeutic approach in an MCC population (Abstract 504).

IL-12, which regulates adaptive type-1 immunity, has demonstrated antitumor efficacy in MCC but is associated with severe toxicities when administered systemically. Local IL-12 delivery to the tumor microenvironment “may provide adequate cytokine concentration in the vicinity of tumor antigens, and therefore improve efficacy while sparing systemic toxicity,” he said.

Intratumoral IL-12 plasmid DNA (pIL-12) injection with electroporation (which uses pulsed electricity to open pores in cell membranes) has shown antitumor activity in melanoma, and might also work in MCC, Dr. Bhatia and his colleagues hypothesized. The concept is one of promoting tumor inflammation and thereby a systemic antitumor immune response. This would be reflected, and measured, by increased IL-12 protein expression in the tumor microenvironment, which became this study’s primary endpoint.

“To the best of our knowledge, this study represents the first prospective clinical trial of immunotherapy in advanced MCC,” Dr. Bhatia noted.

Beginning in January 2012, the study enrolled 15 patients with MCC and superficial injectable tumors. Patients received injections of pIL-12 on days 1, 5, and 8; 2 weeks later, on day 22, their lesions were biopsied. The 3-person cohort with localized MCC (stage IIIb) then underwent definitive surgery and/or radiation therapy starting in week 4, while the 12 with distant metastatic disease (stage IV) could receive additional treatment cycles (maximum of 4) at least 6 weeks apart.

The treatment was well tolerated, with most adverse events – primarily pain and local inflammatory reaction – being mild and transient. No patients discontinued because of toxicity.

The primary endpoint, sustained local expression of IL-12 protein on day 22, was observed in 79% of patients. In paired biopsy samples, comparing baseline to day 22 levels, IL-12 protein expression increased by almost 2-fold to more than 3,000-fold.

In addition, enrichment of Merkel cell polyomavirus-specific CD8-positive T cells were found in the tumor infiltrating lymphocytes (TILs) of treated and distant tumors in some patients.

“Additionally, the pIL-12/electroporation treatment led to objective clinical responses in metastatic MCC,” Dr. Bhatia reported.

Among the three patients with locally advanced disease, one had a pathologic complete response and remains free of recurrence more than 6 months later. Another patient has been recurrence free for more than 3 years. The third patient was recurrence free for 9 months before developing progressive disease.

Among the 12 patients with metastatic disease, 3 responded to treatment and 1 achieved stable disease, while 8 (52%) progressed.

The injections led to regression not only of treated lesions, but also of clearly distinct noninjected MCC tumors. The proportion of treated lesions with major (more than 30%) regression was 44%. Among 10 patients with at least one distant lesion, 30% of noninjected distant lesions regressed.

“We believe this approach warrants further exploration in MCC, perhaps in combination with emerging systemic therapies, such as anti-PD-1/PD-L1 agents,” Dr. Bhatia said.

Dr. Nghiem and Dr. Bhatia had no relevant disclosures. In the IL-12 study, some investigators have financial relationships with OncoSec Medical, which manufactures the study drug.

VIENNA – High response rates to pembrolizumab and to intratumoral delivery of plasmid interleukin-12 (IL-12) were observed among patients with advanced Merkel cell carcinoma (MCC), based on studies presented at the 2015 European Cancer Congress.

There is strong rationale for immunotherapy in MCC. For one thing, the Merkel cell polyomavirus, which is expressed in 80% of tumors, serves as a powerful antigen for stimulating an immune response. Secondly, MCC tumors often express the ligand for the programmed death protein (PD-1), creating an opportunity for PD-1 pathway blockade with PD-1 inhibitors such as pembrolizumab, according to the investigators.

Responses in 10 of 14 given pembrolizumab

Dr. Paul Nghiem of the University of Washington in Seattle, led an open-label, single-arm, multicenter phase II trial of pembrolizumab, which is approved for metastatic melanoma and which could become the first systemic therapy for unresectable or metastatic MCC (Abstract 22LBA).

In the study, which opened in January 2015, there are 24 evaluable patients treated with pembrolizumab 2 mg/kg every 3 weeks for up to 2 years. Fourteen had at least one posttreatment scan; 10 of these 14 patients (71%) have responded, 2 had complete responses. One patient had stable disease and three progressed.

“Responses were rapid, and appear more durable than we see with chemotherapy,” Dr. Nghiem said.

The drug was generally well tolerated, with an adverse event profile similar to what has been seen in melanoma. One patient experienced grade 4 myocarditis after one dose and one developed grade 4 transaminase elevation after two doses. Both improved after discontinuing pembrolizumab and starting corticosteroids.

“Strikingly, despite receiving only one or two doses, both patients had profound and ongoing responses to pembrolizumab,” Dr. Nghiem observed.

Many subjects had “profound shrinkage of tumor that has not rebounded,” he noted. “Pembrolizumab looks to be very favorable in terms of durability of response. With chemotherapy, at 90 days half of our patients have gone off treatment.”

The researchers are considering expanding the study population, and may include a chemotherapy-relapsed cohort. They are also analyzing biomarkers, and hope to evaluate response according to virus-positive versus virus-negative status.

©2015 AACR/Todd Buchanan

Dr. Caroline Robert of the Institut Gustave Roussy in Villejuif, France, commented on the findings, first noting the difficulty of treating patients for whom there are no approved therapies. Median overall survival is less than 10 months, she said, and clinicians have lacked clinical trials to enroll patients.

“MCC patients represent a high medical need,” she said. Although the results with pembrolizumab are early, “they are very promising.”

Intratumoral plasmid IL-12

Dr. Shailender Bhatia of the University of Washington in Seattle, described a different immunotherapeutic approach in an MCC population (Abstract 504).

IL-12, which regulates adaptive type-1 immunity, has demonstrated antitumor efficacy in MCC but is associated with severe toxicities when administered systemically. Local IL-12 delivery to the tumor microenvironment “may provide adequate cytokine concentration in the vicinity of tumor antigens, and therefore improve efficacy while sparing systemic toxicity,” he said.

Intratumoral IL-12 plasmid DNA (pIL-12) injection with electroporation (which uses pulsed electricity to open pores in cell membranes) has shown antitumor activity in melanoma, and might also work in MCC, Dr. Bhatia and his colleagues hypothesized. The concept is one of promoting tumor inflammation and thereby a systemic antitumor immune response. This would be reflected, and measured, by increased IL-12 protein expression in the tumor microenvironment, which became this study’s primary endpoint.

“To the best of our knowledge, this study represents the first prospective clinical trial of immunotherapy in advanced MCC,” Dr. Bhatia noted.

Beginning in January 2012, the study enrolled 15 patients with MCC and superficial injectable tumors. Patients received injections of pIL-12 on days 1, 5, and 8; 2 weeks later, on day 22, their lesions were biopsied. The 3-person cohort with localized MCC (stage IIIb) then underwent definitive surgery and/or radiation therapy starting in week 4, while the 12 with distant metastatic disease (stage IV) could receive additional treatment cycles (maximum of 4) at least 6 weeks apart.

The treatment was well tolerated, with most adverse events – primarily pain and local inflammatory reaction – being mild and transient. No patients discontinued because of toxicity.

The primary endpoint, sustained local expression of IL-12 protein on day 22, was observed in 79% of patients. In paired biopsy samples, comparing baseline to day 22 levels, IL-12 protein expression increased by almost 2-fold to more than 3,000-fold.

In addition, enrichment of Merkel cell polyomavirus-specific CD8-positive T cells were found in the tumor infiltrating lymphocytes (TILs) of treated and distant tumors in some patients.

“Additionally, the pIL-12/electroporation treatment led to objective clinical responses in metastatic MCC,” Dr. Bhatia reported.

Among the three patients with locally advanced disease, one had a pathologic complete response and remains free of recurrence more than 6 months later. Another patient has been recurrence free for more than 3 years. The third patient was recurrence free for 9 months before developing progressive disease.

Among the 12 patients with metastatic disease, 3 responded to treatment and 1 achieved stable disease, while 8 (52%) progressed.

The injections led to regression not only of treated lesions, but also of clearly distinct noninjected MCC tumors. The proportion of treated lesions with major (more than 30%) regression was 44%. Among 10 patients with at least one distant lesion, 30% of noninjected distant lesions regressed.

“We believe this approach warrants further exploration in MCC, perhaps in combination with emerging systemic therapies, such as anti-PD-1/PD-L1 agents,” Dr. Bhatia said.

Dr. Nghiem and Dr. Bhatia had no relevant disclosures. In the IL-12 study, some investigators have financial relationships with OncoSec Medical, which manufactures the study drug.

VIENNA – High response rates to pembrolizumab and to intratumoral delivery of plasmid interleukin-12 (IL-12) were observed among patients with advanced Merkel cell carcinoma (MCC), based on studies presented at the 2015 European Cancer Congress.

There is strong rationale for immunotherapy in MCC. For one thing, the Merkel cell polyomavirus, which is expressed in 80% of tumors, serves as a powerful antigen for stimulating an immune response. Secondly, MCC tumors often express the ligand for the programmed death protein (PD-1), creating an opportunity for PD-1 pathway blockade with PD-1 inhibitors such as pembrolizumab, according to the investigators.

Responses in 10 of 14 given pembrolizumab

Dr. Paul Nghiem of the University of Washington in Seattle, led an open-label, single-arm, multicenter phase II trial of pembrolizumab, which is approved for metastatic melanoma and which could become the first systemic therapy for unresectable or metastatic MCC (Abstract 22LBA).

In the study, which opened in January 2015, there are 24 evaluable patients treated with pembrolizumab 2 mg/kg every 3 weeks for up to 2 years. Fourteen had at least one posttreatment scan; 10 of these 14 patients (71%) have responded, 2 had complete responses. One patient had stable disease and three progressed.

“Responses were rapid, and appear more durable than we see with chemotherapy,” Dr. Nghiem said.

The drug was generally well tolerated, with an adverse event profile similar to what has been seen in melanoma. One patient experienced grade 4 myocarditis after one dose and one developed grade 4 transaminase elevation after two doses. Both improved after discontinuing pembrolizumab and starting corticosteroids.

“Strikingly, despite receiving only one or two doses, both patients had profound and ongoing responses to pembrolizumab,” Dr. Nghiem observed.

Many subjects had “profound shrinkage of tumor that has not rebounded,” he noted. “Pembrolizumab looks to be very favorable in terms of durability of response. With chemotherapy, at 90 days half of our patients have gone off treatment.”

The researchers are considering expanding the study population, and may include a chemotherapy-relapsed cohort. They are also analyzing biomarkers, and hope to evaluate response according to virus-positive versus virus-negative status.

©2015 AACR/Todd Buchanan

Dr. Caroline Robert of the Institut Gustave Roussy in Villejuif, France, commented on the findings, first noting the difficulty of treating patients for whom there are no approved therapies. Median overall survival is less than 10 months, she said, and clinicians have lacked clinical trials to enroll patients.

“MCC patients represent a high medical need,” she said. Although the results with pembrolizumab are early, “they are very promising.”

Intratumoral plasmid IL-12

Dr. Shailender Bhatia of the University of Washington in Seattle, described a different immunotherapeutic approach in an MCC population (Abstract 504).

IL-12, which regulates adaptive type-1 immunity, has demonstrated antitumor efficacy in MCC but is associated with severe toxicities when administered systemically. Local IL-12 delivery to the tumor microenvironment “may provide adequate cytokine concentration in the vicinity of tumor antigens, and therefore improve efficacy while sparing systemic toxicity,” he said.

Intratumoral IL-12 plasmid DNA (pIL-12) injection with electroporation (which uses pulsed electricity to open pores in cell membranes) has shown antitumor activity in melanoma, and might also work in MCC, Dr. Bhatia and his colleagues hypothesized. The concept is one of promoting tumor inflammation and thereby a systemic antitumor immune response. This would be reflected, and measured, by increased IL-12 protein expression in the tumor microenvironment, which became this study’s primary endpoint.

“To the best of our knowledge, this study represents the first prospective clinical trial of immunotherapy in advanced MCC,” Dr. Bhatia noted.

Beginning in January 2012, the study enrolled 15 patients with MCC and superficial injectable tumors. Patients received injections of pIL-12 on days 1, 5, and 8; 2 weeks later, on day 22, their lesions were biopsied. The 3-person cohort with localized MCC (stage IIIb) then underwent definitive surgery and/or radiation therapy starting in week 4, while the 12 with distant metastatic disease (stage IV) could receive additional treatment cycles (maximum of 4) at least 6 weeks apart.

The treatment was well tolerated, with most adverse events – primarily pain and local inflammatory reaction – being mild and transient. No patients discontinued because of toxicity.

The primary endpoint, sustained local expression of IL-12 protein on day 22, was observed in 79% of patients. In paired biopsy samples, comparing baseline to day 22 levels, IL-12 protein expression increased by almost 2-fold to more than 3,000-fold.

In addition, enrichment of Merkel cell polyomavirus-specific CD8-positive T cells were found in the tumor infiltrating lymphocytes (TILs) of treated and distant tumors in some patients.

“Additionally, the pIL-12/electroporation treatment led to objective clinical responses in metastatic MCC,” Dr. Bhatia reported.

Among the three patients with locally advanced disease, one had a pathologic complete response and remains free of recurrence more than 6 months later. Another patient has been recurrence free for more than 3 years. The third patient was recurrence free for 9 months before developing progressive disease.

Among the 12 patients with metastatic disease, 3 responded to treatment and 1 achieved stable disease, while 8 (52%) progressed.

The injections led to regression not only of treated lesions, but also of clearly distinct noninjected MCC tumors. The proportion of treated lesions with major (more than 30%) regression was 44%. Among 10 patients with at least one distant lesion, 30% of noninjected distant lesions regressed.

“We believe this approach warrants further exploration in MCC, perhaps in combination with emerging systemic therapies, such as anti-PD-1/PD-L1 agents,” Dr. Bhatia said.

Dr. Nghiem and Dr. Bhatia had no relevant disclosures. In the IL-12 study, some investigators have financial relationships with OncoSec Medical, which manufactures the study drug.

NEW ORLEANS – Because of problems inherent in the "expert medical testimony" system for medical liability cases, some form of extrajudicial oversight is probably needed, according to Dr. Steve Waxman.

Dr. Waxman, a urologist and a lawyer who is an expert in medicolegal issues, spoke at the annual conference of the American College of Legal Medicine.

Medical experts play a crucial role in determining causation, whether a physician has met the standard of care, and whether a case should move forward. While they used to be given great deference by the court and enjoyed near-immunity, problems with expert testimony are now being acknowledged, Dr. Waxman said.

These include, in particular, the varying levels of expertise and the questionable impartiality of some medical experts and the fact that scientific support for testimony is often lacking. "Their opinions on causation are not always supported by facts," he observed. And while expert witnesses should see themselves as "educators," they often become "advocates," depending upon who is paying their fee, he said, noting they could be swayed by financial gain.

"There is a big difference in level 1 evidence and expert opinion, but to a jury those distinguishing characteristics are not so clear, especially when presented by a smooth-talking expert witness," he continued.

Medical experts should determine the standard of care based on several factors: scientific basis, method and testability; peer-reviewed literature; clinical practice guidelines; and majority or respected minority opinion. The standard of care upon which a physician defendant is judged "should not just be personal opinion or experience," he emphasized.

Such concerns raise the question of whether "extrajudicial oversight" is necessary. "If a judge, jury, or attorney cannot recognize and therefore challenge false or misleading testimony, can it or should it be challenged outside of the courtroom?" Dr. Waxman asked.

A Need for Extrajudicial Review of Experts?

There are Federal Rules of Evidence that give trial judges oversight of expert witness testimony, although the court is not inclined to impose punitive measures against experts who testify falsely, according to Dr. Waxman. "The view of the medical community is that the judicial oversight of medical expert testimony is incomplete," he said.

Extrajudicial oversight, therefore, has been advocated by a number of entities, including medical specialty organizations, state medical boards, and national and state medical associations. A number have instituted some means of peer review, evaluating medical experts with regard to ethics and bylaws violations, unprofessional behavior, and the "practice of medicine."

Some of the medical specialty organizations providing extrajudicial oversight include the American Association of Neurological Surgeons (Professional Conduct Committee and Procedural Guidelines), Society of Thoracic Surgeons (Expert Registry), American Academy of Emergency Medicine (Remarkable Testimony), and the American Urological Association (Judicial and Ethics Committee). The Society of Hospital Medicine does not have a policy statement on the issue.

The American Urological Association, of which Dr. Waxman is a member, lays out qualifications that must be met by medical. Members pay their dues and sign an affirmation statement agreeing to the guidelines. Members who violate this agreement can be disciplined.

But such extrajudicial oversight is not welcomed by the plaintiff bar, he said. The American Association for Justice maintains that cross-examination should uncover the truth; that peer-review programs may be "facially neutral," but their real purpose is suspect; that the threat of extrajudicial review will reduce the pool of available medical experts for plaintiffs; and that medical associations have a conflict of interest in participating (they want to protect their members).

Emerging Alternatives

Some specialty societies are developing their own expert registries, which are aimed at improving the availability of qualified medical expert witnesses for the plaintiff, to raise the bar for testimony, and to weed out frivolous suits and encourage settlement of meritorious suits. "The defense bar likes this idea, but the plaintiff bar is not very interested," Dr. Waxman said. "They have a stable of experts whose responses are predictable. If they use the registry, they may not like the answers they get. This is not a case of ‘if you build it, they will come,’ in terms of the plaintiff bar."

Physician panels are another emerging alternative and are in place in Indiana and Louisiana. These panels review all cases to determine merit, but plaintiff attorneys can proceed in spite of the outcome.

Dr. Waxman concluded that "the current system is working, most of the time," and that problematic medical experts are being weeded out of the system, though there is room for improvement. Peer oversight is "probably appropriate and necessary," he maintained, "because it usually takes a physician to spot a physician giving false or misleading testimony."

"Because of the esoteric nature of many specialties, judges and juries are not able to spot irresponsible, misleading, or even fraudulent testimony. Physicians are best suited to review the quality of medical expert testimony, but the current judicial system does not adequately allow for a critical objective review of this form of testimony," he said.

"My view is that physician panels or physician review of medical expert testimony, early on in the litigation process, is preferable to extrajudicial review by medical societies, associations, or boards after the fact. If there is a three-to-zero decision by the panel, and the plaintiff still wants to bring in the expert, this expert is on notice that he or she has three of their own who disagree. The expert better be able to back the testimony up with science."

American Urological Association Qualifications for Expert Witness Testimony

• Active in the practice of clinical urology with a current valid and unrestricted license at the time of the alleged occurrence.

• Current certification in urology from the American Board of Urology.

• At least 5 years of clinical practice after satisfactorily completing residency/fellowship training.

• Expertise with texts, journals, guidelines, and other sources of information that establish the applicable standard of care at the time of the alleged occurrence.

• Perform a complete and thorough review of all available medical and legal information, including other medical depositions, before rendering any opinion regarding the case.

• Identify personal opinions as such, particularly where these deviate from other urologic viewpoints.

• Proficiency and experience in the area of clinical practice that is the subject of the case.

• Willingness to serve for either defendant or plaintiff in a fair and impartial manner; refusal to be manipulated by an attorney into becoming an advocate or partisan for one side.

• Willingness to declare and document the particulars related to the expert witness practice, inclusive of the number of cases for the defense or plaintiff, percentage of time spent in expert witness testimony, fees and compensation; refusal to accept contingency fees.

• Willingness to sign the AUA Expert Witness Affirmation Statement.

NEW ORLEANS – Because of problems inherent in the "expert medical testimony" system for medical liability cases, some form of extrajudicial oversight is probably needed, according to Dr. Steve Waxman.

Dr. Waxman, a urologist and a lawyer who is an expert in medicolegal issues, spoke at the annual conference of the American College of Legal Medicine.

Medical experts play a crucial role in determining causation, whether a physician has met the standard of care, and whether a case should move forward. While they used to be given great deference by the court and enjoyed near-immunity, problems with expert testimony are now being acknowledged, Dr. Waxman said.

These include, in particular, the varying levels of expertise and the questionable impartiality of some medical experts and the fact that scientific support for testimony is often lacking. "Their opinions on causation are not always supported by facts," he observed. And while expert witnesses should see themselves as "educators," they often become "advocates," depending upon who is paying their fee, he said, noting they could be swayed by financial gain.

"There is a big difference in level 1 evidence and expert opinion, but to a jury those distinguishing characteristics are not so clear, especially when presented by a smooth-talking expert witness," he continued.

Medical experts should determine the standard of care based on several factors: scientific basis, method and testability; peer-reviewed literature; clinical practice guidelines; and majority or respected minority opinion. The standard of care upon which a physician defendant is judged "should not just be personal opinion or experience," he emphasized.

Such concerns raise the question of whether "extrajudicial oversight" is necessary. "If a judge, jury, or attorney cannot recognize and therefore challenge false or misleading testimony, can it or should it be challenged outside of the courtroom?" Dr. Waxman asked.

A Need for Extrajudicial Review of Experts?

There are Federal Rules of Evidence that give trial judges oversight of expert witness testimony, although the court is not inclined to impose punitive measures against experts who testify falsely, according to Dr. Waxman. "The view of the medical community is that the judicial oversight of medical expert testimony is incomplete," he said.

Extrajudicial oversight, therefore, has been advocated by a number of entities, including medical specialty organizations, state medical boards, and national and state medical associations. A number have instituted some means of peer review, evaluating medical experts with regard to ethics and bylaws violations, unprofessional behavior, and the "practice of medicine."

Some of the medical specialty organizations providing extrajudicial oversight include the American Association of Neurological Surgeons (Professional Conduct Committee and Procedural Guidelines), Society of Thoracic Surgeons (Expert Registry), American Academy of Emergency Medicine (Remarkable Testimony), and the American Urological Association (Judicial and Ethics Committee). The Society of Hospital Medicine does not have a policy statement on the issue.

The American Urological Association, of which Dr. Waxman is a member, lays out qualifications that must be met by medical. Members pay their dues and sign an affirmation statement agreeing to the guidelines. Members who violate this agreement can be disciplined.

But such extrajudicial oversight is not welcomed by the plaintiff bar, he said. The American Association for Justice maintains that cross-examination should uncover the truth; that peer-review programs may be "facially neutral," but their real purpose is suspect; that the threat of extrajudicial review will reduce the pool of available medical experts for plaintiffs; and that medical associations have a conflict of interest in participating (they want to protect their members).

Emerging Alternatives

Some specialty societies are developing their own expert registries, which are aimed at improving the availability of qualified medical expert witnesses for the plaintiff, to raise the bar for testimony, and to weed out frivolous suits and encourage settlement of meritorious suits. "The defense bar likes this idea, but the plaintiff bar is not very interested," Dr. Waxman said. "They have a stable of experts whose responses are predictable. If they use the registry, they may not like the answers they get. This is not a case of ‘if you build it, they will come,’ in terms of the plaintiff bar."

Physician panels are another emerging alternative and are in place in Indiana and Louisiana. These panels review all cases to determine merit, but plaintiff attorneys can proceed in spite of the outcome.

Dr. Waxman concluded that "the current system is working, most of the time," and that problematic medical experts are being weeded out of the system, though there is room for improvement. Peer oversight is "probably appropriate and necessary," he maintained, "because it usually takes a physician to spot a physician giving false or misleading testimony."

"Because of the esoteric nature of many specialties, judges and juries are not able to spot irresponsible, misleading, or even fraudulent testimony. Physicians are best suited to review the quality of medical expert testimony, but the current judicial system does not adequately allow for a critical objective review of this form of testimony," he said.

"My view is that physician panels or physician review of medical expert testimony, early on in the litigation process, is preferable to extrajudicial review by medical societies, associations, or boards after the fact. If there is a three-to-zero decision by the panel, and the plaintiff still wants to bring in the expert, this expert is on notice that he or she has three of their own who disagree. The expert better be able to back the testimony up with science."

American Urological Association Qualifications for Expert Witness Testimony

• Active in the practice of clinical urology with a current valid and unrestricted license at the time of the alleged occurrence.

• Current certification in urology from the American Board of Urology.

• At least 5 years of clinical practice after satisfactorily completing residency/fellowship training.

• Expertise with texts, journals, guidelines, and other sources of information that establish the applicable standard of care at the time of the alleged occurrence.

• Perform a complete and thorough review of all available medical and legal information, including other medical depositions, before rendering any opinion regarding the case.

• Identify personal opinions as such, particularly where these deviate from other urologic viewpoints.

• Proficiency and experience in the area of clinical practice that is the subject of the case.

• Willingness to serve for either defendant or plaintiff in a fair and impartial manner; refusal to be manipulated by an attorney into becoming an advocate or partisan for one side.

• Willingness to declare and document the particulars related to the expert witness practice, inclusive of the number of cases for the defense or plaintiff, percentage of time spent in expert witness testimony, fees and compensation; refusal to accept contingency fees.

• Willingness to sign the AUA Expert Witness Affirmation Statement.

NEW ORLEANS – Because of problems inherent in the "expert medical testimony" system for medical liability cases, some form of extrajudicial oversight is probably needed, according to Dr. Steve Waxman.

Dr. Waxman, a urologist and a lawyer who is an expert in medicolegal issues, spoke at the annual conference of the American College of Legal Medicine.

Medical experts play a crucial role in determining causation, whether a physician has met the standard of care, and whether a case should move forward. While they used to be given great deference by the court and enjoyed near-immunity, problems with expert testimony are now being acknowledged, Dr. Waxman said.

These include, in particular, the varying levels of expertise and the questionable impartiality of some medical experts and the fact that scientific support for testimony is often lacking. "Their opinions on causation are not always supported by facts," he observed. And while expert witnesses should see themselves as "educators," they often become "advocates," depending upon who is paying their fee, he said, noting they could be swayed by financial gain.

"There is a big difference in level 1 evidence and expert opinion, but to a jury those distinguishing characteristics are not so clear, especially when presented by a smooth-talking expert witness," he continued.

Medical experts should determine the standard of care based on several factors: scientific basis, method and testability; peer-reviewed literature; clinical practice guidelines; and majority or respected minority opinion. The standard of care upon which a physician defendant is judged "should not just be personal opinion or experience," he emphasized.

Such concerns raise the question of whether "extrajudicial oversight" is necessary. "If a judge, jury, or attorney cannot recognize and therefore challenge false or misleading testimony, can it or should it be challenged outside of the courtroom?" Dr. Waxman asked.

A Need for Extrajudicial Review of Experts?

There are Federal Rules of Evidence that give trial judges oversight of expert witness testimony, although the court is not inclined to impose punitive measures against experts who testify falsely, according to Dr. Waxman. "The view of the medical community is that the judicial oversight of medical expert testimony is incomplete," he said.

Extrajudicial oversight, therefore, has been advocated by a number of entities, including medical specialty organizations, state medical boards, and national and state medical associations. A number have instituted some means of peer review, evaluating medical experts with regard to ethics and bylaws violations, unprofessional behavior, and the "practice of medicine."

Some of the medical specialty organizations providing extrajudicial oversight include the American Association of Neurological Surgeons (Professional Conduct Committee and Procedural Guidelines), Society of Thoracic Surgeons (Expert Registry), American Academy of Emergency Medicine (Remarkable Testimony), and the American Urological Association (Judicial and Ethics Committee). The Society of Hospital Medicine does not have a policy statement on the issue.

The American Urological Association, of which Dr. Waxman is a member, lays out qualifications that must be met by medical. Members pay their dues and sign an affirmation statement agreeing to the guidelines. Members who violate this agreement can be disciplined.

But such extrajudicial oversight is not welcomed by the plaintiff bar, he said. The American Association for Justice maintains that cross-examination should uncover the truth; that peer-review programs may be "facially neutral," but their real purpose is suspect; that the threat of extrajudicial review will reduce the pool of available medical experts for plaintiffs; and that medical associations have a conflict of interest in participating (they want to protect their members).

Emerging Alternatives

Some specialty societies are developing their own expert registries, which are aimed at improving the availability of qualified medical expert witnesses for the plaintiff, to raise the bar for testimony, and to weed out frivolous suits and encourage settlement of meritorious suits. "The defense bar likes this idea, but the plaintiff bar is not very interested," Dr. Waxman said. "They have a stable of experts whose responses are predictable. If they use the registry, they may not like the answers they get. This is not a case of ‘if you build it, they will come,’ in terms of the plaintiff bar."

Physician panels are another emerging alternative and are in place in Indiana and Louisiana. These panels review all cases to determine merit, but plaintiff attorneys can proceed in spite of the outcome.

Dr. Waxman concluded that "the current system is working, most of the time," and that problematic medical experts are being weeded out of the system, though there is room for improvement. Peer oversight is "probably appropriate and necessary," he maintained, "because it usually takes a physician to spot a physician giving false or misleading testimony."

"Because of the esoteric nature of many specialties, judges and juries are not able to spot irresponsible, misleading, or even fraudulent testimony. Physicians are best suited to review the quality of medical expert testimony, but the current judicial system does not adequately allow for a critical objective review of this form of testimony," he said.

"My view is that physician panels or physician review of medical expert testimony, early on in the litigation process, is preferable to extrajudicial review by medical societies, associations, or boards after the fact. If there is a three-to-zero decision by the panel, and the plaintiff still wants to bring in the expert, this expert is on notice that he or she has three of their own who disagree. The expert better be able to back the testimony up with science."

American Urological Association Qualifications for Expert Witness Testimony

• Active in the practice of clinical urology with a current valid and unrestricted license at the time of the alleged occurrence.

• Current certification in urology from the American Board of Urology.

• At least 5 years of clinical practice after satisfactorily completing residency/fellowship training.

• Expertise with texts, journals, guidelines, and other sources of information that establish the applicable standard of care at the time of the alleged occurrence.

• Perform a complete and thorough review of all available medical and legal information, including other medical depositions, before rendering any opinion regarding the case.

• Identify personal opinions as such, particularly where these deviate from other urologic viewpoints.

• Proficiency and experience in the area of clinical practice that is the subject of the case.

• Willingness to serve for either defendant or plaintiff in a fair and impartial manner; refusal to be manipulated by an attorney into becoming an advocate or partisan for one side.

• Willingness to declare and document the particulars related to the expert witness practice, inclusive of the number of cases for the defense or plaintiff, percentage of time spent in expert witness testimony, fees and compensation; refusal to accept contingency fees.

• Willingness to sign the AUA Expert Witness Affirmation Statement.

CHICAGO – A newly developed assessment tool can identify child and parent coping behaviors, and ultimately could be used to guide real-time behavioral and medical interventions to make the perioperative experience less traumatic for children.

Research on the novel assessment tool called the Perioperative Adult Child Behavioral Interaction Scale (PACBIS) earned a "Best Clinical Abstract" award at the annual meeting of the American Society of Anesthesiologists.

"Behavioral factors during pediatric surgery significantly contribute to postoperative outcomes, including delayed hospital discharge and poor parental satisfaction. While the existing real-time scales identify preoperative anxiety, they are limited because they don’t assess children’s coping efforts or parent behaviors," said Dr. Nancy Hagerman of Cincinnati Children’s Hospital Medical Center.

With PACBIS, if the child is anxious and the parent is exhibiting distress-promoting behavior during induction, an anesthesiologist can distract the child and engage the parents in the process of distraction and nonprocedural talk. If the child has excessive anxiety before anesthesia, child life specialists can explain to the child and parents what to expect during induction, offer sedation, or teach parents how to promote coping behaviors by engaging their child in nonprocedural discussions and distractions during induction of anesthesia.

PACBIS uses a scale of 1-5, with 1 being the lowest, to rate child coping and distress as well as parent and staff promotion of coping and distress (Anesth. Analg. 2009;108:822-6).

The study correlated PACBIS results with postoperative and postdischarge maladaptive behaviors by prospectively assessing 405 children, aged 3-12 years, undergoing tonsillectomies and adenoidectomies and their parents before surgery, during induction of anesthesia, upon emergence, and in the pediatric acute care unit with removal of the parenteral intravenous lines.

The researchers assessed for coping, distress, and anxiety behaviors using the PACBIS, the modified Yale Preoperative Anxiety Scale (mYPAS), and the Induction Compliance Checklist (ICC). They correlated findings on the PACBIS with postoperative pain and behavioral outcomes using the Pediatric Anesthesia Emergence Delirium (PAED) scores, the Post-discharge Parental Pain Measurements (PPPM), and Post-Hospitalization Behavior Questionnaire (PHBQ) on day 1 and day 7 (or later) after surgery (Anesthesiology 2004;100:1138-45).

"The PACBIS strongly predicted postoperative and postdischarge maladaptive behaviors and postoperative pain in children" undergoing tonsillectomy or adenoidectomy, Dr. Hagerman said. The PACBIS had strong concurrent validity with existing scales in assessing perioperative behaviors at all phases, perhaps most importantly during induction of anesthesia.

The PACBIS measures of child and parent coping and distress correlated well with those of the PAED, PPPM, and PHBQ. A 2-unit increase in PACBIS child distress measure during induction correlated with a 6-point increase in the PAED. As the PACBIS child coping measure improved 2 units (mild = 0; extreme = 2), there was a 45% reduction in the odds of the child having severe pain as measured by the PPPM on postoperative days 1-2. A preoperative child distress increase of 2 units was associated with a 4.6-fold increase in the odds of having severe pain as measured by the PPPM on postoperative days 7-8.

Higher PACBIS child distress during induction was associated with increased separation anxiety, sleep disturbances, aggression, and withdrawal (P less than .01). Higher parent distress on the PACBIS during induction was associated with increased separation anxiety and sleep disturbances (P less than .01).

Higher parent coping on the PACBIS during induction was associated with less withdrawal (P less than .01) and fewer eating disturbances (P less than .05).

The parents’ scores are very important, Dr. Hagerman emphasized, in keeping children calm during the surgical experience. "Parents who cope well and provide distracting nonprocedural talk help their child reduce distress and emergence delirium, postoperative pain, and new-onset maladaptive behaviors," she said, adding that members of the surgical team are also influential in achieving optimal perioperative behavioral outcomes.

Dr. Hagerman said she had no relevant conflicts of interest.

CHICAGO – A newly developed assessment tool can identify child and parent coping behaviors, and ultimately could be used to guide real-time behavioral and medical interventions to make the perioperative experience less traumatic for children.

Research on the novel assessment tool called the Perioperative Adult Child Behavioral Interaction Scale (PACBIS) earned a "Best Clinical Abstract" award at the annual meeting of the American Society of Anesthesiologists.

"Behavioral factors during pediatric surgery significantly contribute to postoperative outcomes, including delayed hospital discharge and poor parental satisfaction. While the existing real-time scales identify preoperative anxiety, they are limited because they don’t assess children’s coping efforts or parent behaviors," said Dr. Nancy Hagerman of Cincinnati Children’s Hospital Medical Center.

With PACBIS, if the child is anxious and the parent is exhibiting distress-promoting behavior during induction, an anesthesiologist can distract the child and engage the parents in the process of distraction and nonprocedural talk. If the child has excessive anxiety before anesthesia, child life specialists can explain to the child and parents what to expect during induction, offer sedation, or teach parents how to promote coping behaviors by engaging their child in nonprocedural discussions and distractions during induction of anesthesia.

PACBIS uses a scale of 1-5, with 1 being the lowest, to rate child coping and distress as well as parent and staff promotion of coping and distress (Anesth. Analg. 2009;108:822-6).

The study correlated PACBIS results with postoperative and postdischarge maladaptive behaviors by prospectively assessing 405 children, aged 3-12 years, undergoing tonsillectomies and adenoidectomies and their parents before surgery, during induction of anesthesia, upon emergence, and in the pediatric acute care unit with removal of the parenteral intravenous lines.

The researchers assessed for coping, distress, and anxiety behaviors using the PACBIS, the modified Yale Preoperative Anxiety Scale (mYPAS), and the Induction Compliance Checklist (ICC). They correlated findings on the PACBIS with postoperative pain and behavioral outcomes using the Pediatric Anesthesia Emergence Delirium (PAED) scores, the Post-discharge Parental Pain Measurements (PPPM), and Post-Hospitalization Behavior Questionnaire (PHBQ) on day 1 and day 7 (or later) after surgery (Anesthesiology 2004;100:1138-45).

"The PACBIS strongly predicted postoperative and postdischarge maladaptive behaviors and postoperative pain in children" undergoing tonsillectomy or adenoidectomy, Dr. Hagerman said. The PACBIS had strong concurrent validity with existing scales in assessing perioperative behaviors at all phases, perhaps most importantly during induction of anesthesia.

The PACBIS measures of child and parent coping and distress correlated well with those of the PAED, PPPM, and PHBQ. A 2-unit increase in PACBIS child distress measure during induction correlated with a 6-point increase in the PAED. As the PACBIS child coping measure improved 2 units (mild = 0; extreme = 2), there was a 45% reduction in the odds of the child having severe pain as measured by the PPPM on postoperative days 1-2. A preoperative child distress increase of 2 units was associated with a 4.6-fold increase in the odds of having severe pain as measured by the PPPM on postoperative days 7-8.

Higher PACBIS child distress during induction was associated with increased separation anxiety, sleep disturbances, aggression, and withdrawal (P less than .01). Higher parent distress on the PACBIS during induction was associated with increased separation anxiety and sleep disturbances (P less than .01).

Higher parent coping on the PACBIS during induction was associated with less withdrawal (P less than .01) and fewer eating disturbances (P less than .05).

The parents’ scores are very important, Dr. Hagerman emphasized, in keeping children calm during the surgical experience. "Parents who cope well and provide distracting nonprocedural talk help their child reduce distress and emergence delirium, postoperative pain, and new-onset maladaptive behaviors," she said, adding that members of the surgical team are also influential in achieving optimal perioperative behavioral outcomes.

Dr. Hagerman said she had no relevant conflicts of interest.

CHICAGO – A newly developed assessment tool can identify child and parent coping behaviors, and ultimately could be used to guide real-time behavioral and medical interventions to make the perioperative experience less traumatic for children.

Research on the novel assessment tool called the Perioperative Adult Child Behavioral Interaction Scale (PACBIS) earned a "Best Clinical Abstract" award at the annual meeting of the American Society of Anesthesiologists.

"Behavioral factors during pediatric surgery significantly contribute to postoperative outcomes, including delayed hospital discharge and poor parental satisfaction. While the existing real-time scales identify preoperative anxiety, they are limited because they don’t assess children’s coping efforts or parent behaviors," said Dr. Nancy Hagerman of Cincinnati Children’s Hospital Medical Center.

With PACBIS, if the child is anxious and the parent is exhibiting distress-promoting behavior during induction, an anesthesiologist can distract the child and engage the parents in the process of distraction and nonprocedural talk. If the child has excessive anxiety before anesthesia, child life specialists can explain to the child and parents what to expect during induction, offer sedation, or teach parents how to promote coping behaviors by engaging their child in nonprocedural discussions and distractions during induction of anesthesia.

PACBIS uses a scale of 1-5, with 1 being the lowest, to rate child coping and distress as well as parent and staff promotion of coping and distress (Anesth. Analg. 2009;108:822-6).

The study correlated PACBIS results with postoperative and postdischarge maladaptive behaviors by prospectively assessing 405 children, aged 3-12 years, undergoing tonsillectomies and adenoidectomies and their parents before surgery, during induction of anesthesia, upon emergence, and in the pediatric acute care unit with removal of the parenteral intravenous lines.

The researchers assessed for coping, distress, and anxiety behaviors using the PACBIS, the modified Yale Preoperative Anxiety Scale (mYPAS), and the Induction Compliance Checklist (ICC). They correlated findings on the PACBIS with postoperative pain and behavioral outcomes using the Pediatric Anesthesia Emergence Delirium (PAED) scores, the Post-discharge Parental Pain Measurements (PPPM), and Post-Hospitalization Behavior Questionnaire (PHBQ) on day 1 and day 7 (or later) after surgery (Anesthesiology 2004;100:1138-45).

"The PACBIS strongly predicted postoperative and postdischarge maladaptive behaviors and postoperative pain in children" undergoing tonsillectomy or adenoidectomy, Dr. Hagerman said. The PACBIS had strong concurrent validity with existing scales in assessing perioperative behaviors at all phases, perhaps most importantly during induction of anesthesia.

The PACBIS measures of child and parent coping and distress correlated well with those of the PAED, PPPM, and PHBQ. A 2-unit increase in PACBIS child distress measure during induction correlated with a 6-point increase in the PAED. As the PACBIS child coping measure improved 2 units (mild = 0; extreme = 2), there was a 45% reduction in the odds of the child having severe pain as measured by the PPPM on postoperative days 1-2. A preoperative child distress increase of 2 units was associated with a 4.6-fold increase in the odds of having severe pain as measured by the PPPM on postoperative days 7-8.

Higher PACBIS child distress during induction was associated with increased separation anxiety, sleep disturbances, aggression, and withdrawal (P less than .01). Higher parent distress on the PACBIS during induction was associated with increased separation anxiety and sleep disturbances (P less than .01).

Higher parent coping on the PACBIS during induction was associated with less withdrawal (P less than .01) and fewer eating disturbances (P less than .05).

The parents’ scores are very important, Dr. Hagerman emphasized, in keeping children calm during the surgical experience. "Parents who cope well and provide distracting nonprocedural talk help their child reduce distress and emergence delirium, postoperative pain, and new-onset maladaptive behaviors," she said, adding that members of the surgical team are also influential in achieving optimal perioperative behavioral outcomes.

Dr. Hagerman said she had no relevant conflicts of interest.

SAN FRANCISCO – Surgical consultation is appropriate for all patients aged 80 years or older with primary hyperparathyroidism, the majority of whom will have a single adenoma, according to researchers from the University of Pennsylvania, Philadelphia, who evaluated safety and outcomes in the very elderly.

"General anesthesia for bilateral exploration can be performed safely in these older patients, and morbidity from parathyroidectomy is very low," said Dr. Parth Kishore Shah, a surgery resident who presented the study at the annual clinical congress of the American College of Surgeons.

Primary hyperparathyroidism is increasingly found to have a significant impact on quality of life in patients aged 80 years and older. The advantages of parathyroidectomy for primary hyperparathyroidism (pHPT) are well established, and include decreased risk of renal stones as well as improvements in constitutional symptoms, bone mineral density, and overall health-related quality of life.

The current indications for surgery include presence of symptoms, or, in asymptomatic patients, one of the following: age younger than 50 years; serum calcium 1 mg/dL above the upper limit of normal; 24-hour urinary calcium excretion less than 400 mg/24 hr; 30% reduction in creatinine clearance; diagnosis of osteoporosis; or difficulty in accomplishing medical surveillance.

"Patients aged 80 years and older, though, are often excluded from surgical management of pHPT because of their age, unappreciated symptoms, presence of comorbidities, and/or suspected high anesthesia and surgical risk," said Dr. Shah.

Large Database Analyzed

From a prospective database of 2,050 patients undergoing parathyroidectomy in 1997-2010, the investigators identified 61 patients aged 80 years or older and collected data on their preoperative clinical presentation, biochemical studies, intraoperative findings, and final pathology results.

Most patients (90%) were women, and the median age was 83 years. Presenting symptoms – including fatigue, mental impairment, depression, and bone pain – were observed in 48 patients (79%). All patients had evidence of osteoporosis, and comorbidities were also common, especially hypertension (69%).

The median preoperative calcium level was 11 mg/dL, and the median serum intact PTH level was 126 pg/mL. Two-thirds of patients had a positive preoperative localization.

In all, 13 patients (21%) were asymptomatic, and they met guidelines for parathyroidectomy in the following proportions: serum calcium level at least 1 mg/dL greater than normal (46%), 30% reduction in creatinine clearance (69%), and T score greater than –2.5 on DXA (dual-energy x-ray absorptiometry) scan to assess bone health (62%). More than half of the patients met more than one of the criteria, and 91% of the asymptomatic group had successful preoperative localization, Dr. Shah reported.

Operative Details and Pathology Results

General anesthesia was administered to 78%, whereas 19% had local anesthesia. Local was converted to general anesthesia in the remaining 3%. The method of parathyroidectomy was bilateral exploration in 49%, minimally invasive parathyroidectomy (MIP) in 41%, and MIP converted to bilateral in 10%. The median operative time was 86 minutes.

Intraoperative PTH (IOPTH) monitoring was done in 95% of patients, who had a mean IOPTH drop of 80%. A drop greater than 50% was observed in 95% of patients. "IOPTH monitoring can be used effectively in this group," Dr. Shah noted.

On final pathology review, 75% had a single adenoma, 17% had double adenomas, and 8% had four-gland hyperplasia. Presence of ectopic glands was noted in 7% of patients.

Procedure Found Safe

There were no postoperative deaths, and only four patients (6.6%) had complications, which were pneumothorax, stroke, aspiration, and reintubation for respiratory insufficiency. Complications were not related to any baseline or operative characteristics. Most patients (86%) were discharged in less than 24 hours.

"The morbidity from parathyroidectomy in this age group is very low and is comparable to that seen in patients younger than 80, although there appears to be a predilection for respiratory complications," Dr. Shah said.

Compared with a cohort of 122 patients younger than 80 years, the older patients were more likely to present with more than one symptom (62% vs. 37%; P = .001) and were more likely to have more than one comorbidity (46% vs. 30%; P = .05). The rates of general anesthesia and bilateral neck exploration were almost the same for the two age groups, as was the incidence of complications, except that there were more respiratory problems in the elderly.

"Our findings corroborate prior studies that report parathyroidectomy in patients aged 80 and older for pHPT can be safely performed, with little disruption to daily life," Dr. Shah concluded. "We believe that symptomatic patients with hypercalcemia in this age group should be strongly considered for surgery."

Dr. Shah reported no conflicts of interest.

SAN FRANCISCO – Surgical consultation is appropriate for all patients aged 80 years or older with primary hyperparathyroidism, the majority of whom will have a single adenoma, according to researchers from the University of Pennsylvania, Philadelphia, who evaluated safety and outcomes in the very elderly.

"General anesthesia for bilateral exploration can be performed safely in these older patients, and morbidity from parathyroidectomy is very low," said Dr. Parth Kishore Shah, a surgery resident who presented the study at the annual clinical congress of the American College of Surgeons.

Primary hyperparathyroidism is increasingly found to have a significant impact on quality of life in patients aged 80 years and older. The advantages of parathyroidectomy for primary hyperparathyroidism (pHPT) are well established, and include decreased risk of renal stones as well as improvements in constitutional symptoms, bone mineral density, and overall health-related quality of life.

The current indications for surgery include presence of symptoms, or, in asymptomatic patients, one of the following: age younger than 50 years; serum calcium 1 mg/dL above the upper limit of normal; 24-hour urinary calcium excretion less than 400 mg/24 hr; 30% reduction in creatinine clearance; diagnosis of osteoporosis; or difficulty in accomplishing medical surveillance.

"Patients aged 80 years and older, though, are often excluded from surgical management of pHPT because of their age, unappreciated symptoms, presence of comorbidities, and/or suspected high anesthesia and surgical risk," said Dr. Shah.

Large Database Analyzed

From a prospective database of 2,050 patients undergoing parathyroidectomy in 1997-2010, the investigators identified 61 patients aged 80 years or older and collected data on their preoperative clinical presentation, biochemical studies, intraoperative findings, and final pathology results.

Most patients (90%) were women, and the median age was 83 years. Presenting symptoms – including fatigue, mental impairment, depression, and bone pain – were observed in 48 patients (79%). All patients had evidence of osteoporosis, and comorbidities were also common, especially hypertension (69%).

The median preoperative calcium level was 11 mg/dL, and the median serum intact PTH level was 126 pg/mL. Two-thirds of patients had a positive preoperative localization.

In all, 13 patients (21%) were asymptomatic, and they met guidelines for parathyroidectomy in the following proportions: serum calcium level at least 1 mg/dL greater than normal (46%), 30% reduction in creatinine clearance (69%), and T score greater than –2.5 on DXA (dual-energy x-ray absorptiometry) scan to assess bone health (62%). More than half of the patients met more than one of the criteria, and 91% of the asymptomatic group had successful preoperative localization, Dr. Shah reported.

Operative Details and Pathology Results

General anesthesia was administered to 78%, whereas 19% had local anesthesia. Local was converted to general anesthesia in the remaining 3%. The method of parathyroidectomy was bilateral exploration in 49%, minimally invasive parathyroidectomy (MIP) in 41%, and MIP converted to bilateral in 10%. The median operative time was 86 minutes.

Intraoperative PTH (IOPTH) monitoring was done in 95% of patients, who had a mean IOPTH drop of 80%. A drop greater than 50% was observed in 95% of patients. "IOPTH monitoring can be used effectively in this group," Dr. Shah noted.

On final pathology review, 75% had a single adenoma, 17% had double adenomas, and 8% had four-gland hyperplasia. Presence of ectopic glands was noted in 7% of patients.

Procedure Found Safe

There were no postoperative deaths, and only four patients (6.6%) had complications, which were pneumothorax, stroke, aspiration, and reintubation for respiratory insufficiency. Complications were not related to any baseline or operative characteristics. Most patients (86%) were discharged in less than 24 hours.

"The morbidity from parathyroidectomy in this age group is very low and is comparable to that seen in patients younger than 80, although there appears to be a predilection for respiratory complications," Dr. Shah said.

Compared with a cohort of 122 patients younger than 80 years, the older patients were more likely to present with more than one symptom (62% vs. 37%; P = .001) and were more likely to have more than one comorbidity (46% vs. 30%; P = .05). The rates of general anesthesia and bilateral neck exploration were almost the same for the two age groups, as was the incidence of complications, except that there were more respiratory problems in the elderly.

"Our findings corroborate prior studies that report parathyroidectomy in patients aged 80 and older for pHPT can be safely performed, with little disruption to daily life," Dr. Shah concluded. "We believe that symptomatic patients with hypercalcemia in this age group should be strongly considered for surgery."

Dr. Shah reported no conflicts of interest.

SAN FRANCISCO – Surgical consultation is appropriate for all patients aged 80 years or older with primary hyperparathyroidism, the majority of whom will have a single adenoma, according to researchers from the University of Pennsylvania, Philadelphia, who evaluated safety and outcomes in the very elderly.

"General anesthesia for bilateral exploration can be performed safely in these older patients, and morbidity from parathyroidectomy is very low," said Dr. Parth Kishore Shah, a surgery resident who presented the study at the annual clinical congress of the American College of Surgeons.

Primary hyperparathyroidism is increasingly found to have a significant impact on quality of life in patients aged 80 years and older. The advantages of parathyroidectomy for primary hyperparathyroidism (pHPT) are well established, and include decreased risk of renal stones as well as improvements in constitutional symptoms, bone mineral density, and overall health-related quality of life.

The current indications for surgery include presence of symptoms, or, in asymptomatic patients, one of the following: age younger than 50 years; serum calcium 1 mg/dL above the upper limit of normal; 24-hour urinary calcium excretion less than 400 mg/24 hr; 30% reduction in creatinine clearance; diagnosis of osteoporosis; or difficulty in accomplishing medical surveillance.

"Patients aged 80 years and older, though, are often excluded from surgical management of pHPT because of their age, unappreciated symptoms, presence of comorbidities, and/or suspected high anesthesia and surgical risk," said Dr. Shah.

Large Database Analyzed

From a prospective database of 2,050 patients undergoing parathyroidectomy in 1997-2010, the investigators identified 61 patients aged 80 years or older and collected data on their preoperative clinical presentation, biochemical studies, intraoperative findings, and final pathology results.

Most patients (90%) were women, and the median age was 83 years. Presenting symptoms – including fatigue, mental impairment, depression, and bone pain – were observed in 48 patients (79%). All patients had evidence of osteoporosis, and comorbidities were also common, especially hypertension (69%).

The median preoperative calcium level was 11 mg/dL, and the median serum intact PTH level was 126 pg/mL. Two-thirds of patients had a positive preoperative localization.

In all, 13 patients (21%) were asymptomatic, and they met guidelines for parathyroidectomy in the following proportions: serum calcium level at least 1 mg/dL greater than normal (46%), 30% reduction in creatinine clearance (69%), and T score greater than –2.5 on DXA (dual-energy x-ray absorptiometry) scan to assess bone health (62%). More than half of the patients met more than one of the criteria, and 91% of the asymptomatic group had successful preoperative localization, Dr. Shah reported.

Operative Details and Pathology Results

General anesthesia was administered to 78%, whereas 19% had local anesthesia. Local was converted to general anesthesia in the remaining 3%. The method of parathyroidectomy was bilateral exploration in 49%, minimally invasive parathyroidectomy (MIP) in 41%, and MIP converted to bilateral in 10%. The median operative time was 86 minutes.

Intraoperative PTH (IOPTH) monitoring was done in 95% of patients, who had a mean IOPTH drop of 80%. A drop greater than 50% was observed in 95% of patients. "IOPTH monitoring can be used effectively in this group," Dr. Shah noted.

On final pathology review, 75% had a single adenoma, 17% had double adenomas, and 8% had four-gland hyperplasia. Presence of ectopic glands was noted in 7% of patients.

Procedure Found Safe

There were no postoperative deaths, and only four patients (6.6%) had complications, which were pneumothorax, stroke, aspiration, and reintubation for respiratory insufficiency. Complications were not related to any baseline or operative characteristics. Most patients (86%) were discharged in less than 24 hours.

"The morbidity from parathyroidectomy in this age group is very low and is comparable to that seen in patients younger than 80, although there appears to be a predilection for respiratory complications," Dr. Shah said.

Compared with a cohort of 122 patients younger than 80 years, the older patients were more likely to present with more than one symptom (62% vs. 37%; P = .001) and were more likely to have more than one comorbidity (46% vs. 30%; P = .05). The rates of general anesthesia and bilateral neck exploration were almost the same for the two age groups, as was the incidence of complications, except that there were more respiratory problems in the elderly.

"Our findings corroborate prior studies that report parathyroidectomy in patients aged 80 and older for pHPT can be safely performed, with little disruption to daily life," Dr. Shah concluded. "We believe that symptomatic patients with hypercalcemia in this age group should be strongly considered for surgery."

Dr. Shah reported no conflicts of interest.

CHICAGO – More than 40% of patients who presented to a tertiary pain center with axial spine pain met the criteria for fibromyalgia. These patients may represent a subset of the spine pain population who will be unresponsive to standard interventions.

The presence of fibromyalgia may undermine the effectiveness of opioids, according to the investigators.

"Our group is very interested in the concept of centralized pain and in trying to better differentiate patients based on phenotype at the point of care. Many patients seek care for axial spine pain, and the outcomes are mixed," Dr. Chad M. Brummett noted at the annual meeting of the American Society of Anesthesiologists.

"Fibromyalgia-positive patients were different in all phenotypic measures of pain, mood, and function assessed."

"We are interested in applying what has been learned about fibromyalgia to the spine community. The field has been writing about personalized care for 20 years, but we still tend to give all patients the same drugs. Our aim is to provide physicians with information that will guide therapy," said Dr. Brummett, director of adult pain research at the University of Michigan Back and Pain Center in Ann Arbor.

He noted that failure rates for facet interventions for the treatment of axial spine pain have ranged from 39% to 47%, and persistent pain is common. There is a growing appreciation in the pain community of a subset of patients with altered central pain processing leading to widespread body pain, such as fibromyalgia, who may require a different treatment approach, he said.

The observational cohort study included 256 new patients categorized as having axial spine pain; of the 244 who completed the American College of Rheumatology fibromyalgia survey, 101 patients (41.4%) met the ACR fibromyalgia criteria.

"We saw profound phenotypic differences between the two groups," Dr. Brummett noted, although he acknowledged that as a tertiary care facility his group is "bound to see a more failed population."

"Some would argue whether this means they have fibromyalgia or not, and that is not clear, but certainly this is a different group," he emphasized.

Dr. Brummett and colleagues observed significant differences in pain, function, mood, and anxiety in the fibromyalgia-positive pain population, compared with patients who did not meet the ACR criteria for fibromyalgia. For example, among the 101 patients with fibromyalgia, the mean pain intensity score on the Brief Pain Inventory was 7.05, while it was 6.10 in those without fibromyalgia. Scores for both depression and anxiety were higher for those with fibromyalgia than those without (mean depression and anxiety scores on the Hospital Anxiety and Depression Scale were 11.33 and 11.38, respectively, for those with fibromyalgia and 7.47 and 6.81, respectively, for those without). Likewise, the mean Patient Reported Outcomes Measurement Information System score for physical function was 27.96 for those with fibromyalgia and 32.24 for those without.

"Fibromyalgia-positive patients were different in all phenotypic measures of pain, mood, and function assessed," reported Dr. Brummett, who along with his colleagues was awarded for having the "Best Clinical Abstract" at the meeting.

The investigators also asked the patients questions about the efficacy of previous interventions. Current use of opioid medications was reported by 60.4% of fibromyalgia-positive patients and 43.4% of fibromyalgia-negative patients (P = .012). Although not significant, fibromyalgia-positive patients taking opioids reported lower efficacy. Epidural interventions were common in both groups, at 37.6% and 43.8%, respectively, but fibromyalgia-positive patients rated the epidurals as being less effective (P = .036).

"We are not saying that patients meeting fibromyalgia criteria, if they have clear-cut radiculopathy, should not have steroid injections. But there may be a difference in response to these interventions," he explained.

"I don’t think our ability to predict response to treatment is very good, even with diagnostic algorithms laid out to us," he added. "Our data should help us better define the most appropriate treatments for these patients."

There were significantly more women in the fibromyalgia-positive group than there were in the fibromyalgia-negative group (64% vs. 50%). This was the only demographic characteristic that was significantly different between the two groups.

Fibromyalgia patients are known to have alterations of central pain processing and may respond differently to interventions and medications. "If patients understand that they may have only a 50/50 chance of responding to a standard intervention for spine pain, they may rethink it," he suggested.

He maintained that future studies of pain medications and interventions should include a measure of central sensitization, such as the fibromyalgia survey. "It is our belief that these are different patients, but we don’t yet have enough objective data to guide treatment. We have to understand our patient population better," Dr. Brummett concluded.

Dr. John Dombrowski, director of the Washington (D.C.) Pain Center and head of the American Society of Anesthesiologists communications committee, commented that the percentage of concurrent fibromyalgia in the study seems high, "but since this is a tertiary setting they are probably seeing the worst of the worse patients."

"While this may be a selected population, the results are still interesting," he said. "Obviously, this subset of patients has issues. They have a predilection for more central pain, and many will need multimodal therapy. Pain patients are challenging, and fibromyalgia makes them even more challenging. This study underlines the fact that we cannot rely on interventional treatments alone."

Dr. Brummett said that he had no relevant disclosures.

CHICAGO – More than 40% of patients who presented to a tertiary pain center with axial spine pain met the criteria for fibromyalgia. These patients may represent a subset of the spine pain population who will be unresponsive to standard interventions.

The presence of fibromyalgia may undermine the effectiveness of opioids, according to the investigators.

"Our group is very interested in the concept of centralized pain and in trying to better differentiate patients based on phenotype at the point of care. Many patients seek care for axial spine pain, and the outcomes are mixed," Dr. Chad M. Brummett noted at the annual meeting of the American Society of Anesthesiologists.

"Fibromyalgia-positive patients were different in all phenotypic measures of pain, mood, and function assessed."

"We are interested in applying what has been learned about fibromyalgia to the spine community. The field has been writing about personalized care for 20 years, but we still tend to give all patients the same drugs. Our aim is to provide physicians with information that will guide therapy," said Dr. Brummett, director of adult pain research at the University of Michigan Back and Pain Center in Ann Arbor.

He noted that failure rates for facet interventions for the treatment of axial spine pain have ranged from 39% to 47%, and persistent pain is common. There is a growing appreciation in the pain community of a subset of patients with altered central pain processing leading to widespread body pain, such as fibromyalgia, who may require a different treatment approach, he said.

The observational cohort study included 256 new patients categorized as having axial spine pain; of the 244 who completed the American College of Rheumatology fibromyalgia survey, 101 patients (41.4%) met the ACR fibromyalgia criteria.

"We saw profound phenotypic differences between the two groups," Dr. Brummett noted, although he acknowledged that as a tertiary care facility his group is "bound to see a more failed population."

"Some would argue whether this means they have fibromyalgia or not, and that is not clear, but certainly this is a different group," he emphasized.

Dr. Brummett and colleagues observed significant differences in pain, function, mood, and anxiety in the fibromyalgia-positive pain population, compared with patients who did not meet the ACR criteria for fibromyalgia. For example, among the 101 patients with fibromyalgia, the mean pain intensity score on the Brief Pain Inventory was 7.05, while it was 6.10 in those without fibromyalgia. Scores for both depression and anxiety were higher for those with fibromyalgia than those without (mean depression and anxiety scores on the Hospital Anxiety and Depression Scale were 11.33 and 11.38, respectively, for those with fibromyalgia and 7.47 and 6.81, respectively, for those without). Likewise, the mean Patient Reported Outcomes Measurement Information System score for physical function was 27.96 for those with fibromyalgia and 32.24 for those without.

"Fibromyalgia-positive patients were different in all phenotypic measures of pain, mood, and function assessed," reported Dr. Brummett, who along with his colleagues was awarded for having the "Best Clinical Abstract" at the meeting.

The investigators also asked the patients questions about the efficacy of previous interventions. Current use of opioid medications was reported by 60.4% of fibromyalgia-positive patients and 43.4% of fibromyalgia-negative patients (P = .012). Although not significant, fibromyalgia-positive patients taking opioids reported lower efficacy. Epidural interventions were common in both groups, at 37.6% and 43.8%, respectively, but fibromyalgia-positive patients rated the epidurals as being less effective (P = .036).

"We are not saying that patients meeting fibromyalgia criteria, if they have clear-cut radiculopathy, should not have steroid injections. But there may be a difference in response to these interventions," he explained.

"I don’t think our ability to predict response to treatment is very good, even with diagnostic algorithms laid out to us," he added. "Our data should help us better define the most appropriate treatments for these patients."

There were significantly more women in the fibromyalgia-positive group than there were in the fibromyalgia-negative group (64% vs. 50%). This was the only demographic characteristic that was significantly different between the two groups.

Fibromyalgia patients are known to have alterations of central pain processing and may respond differently to interventions and medications. "If patients understand that they may have only a 50/50 chance of responding to a standard intervention for spine pain, they may rethink it," he suggested.

He maintained that future studies of pain medications and interventions should include a measure of central sensitization, such as the fibromyalgia survey. "It is our belief that these are different patients, but we don’t yet have enough objective data to guide treatment. We have to understand our patient population better," Dr. Brummett concluded.

Dr. John Dombrowski, director of the Washington (D.C.) Pain Center and head of the American Society of Anesthesiologists communications committee, commented that the percentage of concurrent fibromyalgia in the study seems high, "but since this is a tertiary setting they are probably seeing the worst of the worse patients."

"While this may be a selected population, the results are still interesting," he said. "Obviously, this subset of patients has issues. They have a predilection for more central pain, and many will need multimodal therapy. Pain patients are challenging, and fibromyalgia makes them even more challenging. This study underlines the fact that we cannot rely on interventional treatments alone."

Dr. Brummett said that he had no relevant disclosures.

CHICAGO – More than 40% of patients who presented to a tertiary pain center with axial spine pain met the criteria for fibromyalgia. These patients may represent a subset of the spine pain population who will be unresponsive to standard interventions.

The presence of fibromyalgia may undermine the effectiveness of opioids, according to the investigators.

"Our group is very interested in the concept of centralized pain and in trying to better differentiate patients based on phenotype at the point of care. Many patients seek care for axial spine pain, and the outcomes are mixed," Dr. Chad M. Brummett noted at the annual meeting of the American Society of Anesthesiologists.

"Fibromyalgia-positive patients were different in all phenotypic measures of pain, mood, and function assessed."

"We are interested in applying what has been learned about fibromyalgia to the spine community. The field has been writing about personalized care for 20 years, but we still tend to give all patients the same drugs. Our aim is to provide physicians with information that will guide therapy," said Dr. Brummett, director of adult pain research at the University of Michigan Back and Pain Center in Ann Arbor.

He noted that failure rates for facet interventions for the treatment of axial spine pain have ranged from 39% to 47%, and persistent pain is common. There is a growing appreciation in the pain community of a subset of patients with altered central pain processing leading to widespread body pain, such as fibromyalgia, who may require a different treatment approach, he said.

The observational cohort study included 256 new patients categorized as having axial spine pain; of the 244 who completed the American College of Rheumatology fibromyalgia survey, 101 patients (41.4%) met the ACR fibromyalgia criteria.

"We saw profound phenotypic differences between the two groups," Dr. Brummett noted, although he acknowledged that as a tertiary care facility his group is "bound to see a more failed population."

"Some would argue whether this means they have fibromyalgia or not, and that is not clear, but certainly this is a different group," he emphasized.

Dr. Brummett and colleagues observed significant differences in pain, function, mood, and anxiety in the fibromyalgia-positive pain population, compared with patients who did not meet the ACR criteria for fibromyalgia. For example, among the 101 patients with fibromyalgia, the mean pain intensity score on the Brief Pain Inventory was 7.05, while it was 6.10 in those without fibromyalgia. Scores for both depression and anxiety were higher for those with fibromyalgia than those without (mean depression and anxiety scores on the Hospital Anxiety and Depression Scale were 11.33 and 11.38, respectively, for those with fibromyalgia and 7.47 and 6.81, respectively, for those without). Likewise, the mean Patient Reported Outcomes Measurement Information System score for physical function was 27.96 for those with fibromyalgia and 32.24 for those without.

"Fibromyalgia-positive patients were different in all phenotypic measures of pain, mood, and function assessed," reported Dr. Brummett, who along with his colleagues was awarded for having the "Best Clinical Abstract" at the meeting.

The investigators also asked the patients questions about the efficacy of previous interventions. Current use of opioid medications was reported by 60.4% of fibromyalgia-positive patients and 43.4% of fibromyalgia-negative patients (P = .012). Although not significant, fibromyalgia-positive patients taking opioids reported lower efficacy. Epidural interventions were common in both groups, at 37.6% and 43.8%, respectively, but fibromyalgia-positive patients rated the epidurals as being less effective (P = .036).

"We are not saying that patients meeting fibromyalgia criteria, if they have clear-cut radiculopathy, should not have steroid injections. But there may be a difference in response to these interventions," he explained.

"I don’t think our ability to predict response to treatment is very good, even with diagnostic algorithms laid out to us," he added. "Our data should help us better define the most appropriate treatments for these patients."

There were significantly more women in the fibromyalgia-positive group than there were in the fibromyalgia-negative group (64% vs. 50%). This was the only demographic characteristic that was significantly different between the two groups.

Fibromyalgia patients are known to have alterations of central pain processing and may respond differently to interventions and medications. "If patients understand that they may have only a 50/50 chance of responding to a standard intervention for spine pain, they may rethink it," he suggested.

He maintained that future studies of pain medications and interventions should include a measure of central sensitization, such as the fibromyalgia survey. "It is our belief that these are different patients, but we don’t yet have enough objective data to guide treatment. We have to understand our patient population better," Dr. Brummett concluded.

Dr. John Dombrowski, director of the Washington (D.C.) Pain Center and head of the American Society of Anesthesiologists communications committee, commented that the percentage of concurrent fibromyalgia in the study seems high, "but since this is a tertiary setting they are probably seeing the worst of the worse patients."

"While this may be a selected population, the results are still interesting," he said. "Obviously, this subset of patients has issues. They have a predilection for more central pain, and many will need multimodal therapy. Pain patients are challenging, and fibromyalgia makes them even more challenging. This study underlines the fact that we cannot rely on interventional treatments alone."

Dr. Brummett said that he had no relevant disclosures.

SAN FRANCISCO – Thyroid cancer recurs in almost 40% of elderly patients, and while recurrence is accompanied by an increased mortality risk, this seems to be confined to the subset of patients with papillary thyroid cancer, according to researchers from Penn State Milton S. Hershey Medical Center in Hershey, Pa.

"Elderly patients with follicular disease and recurrence did not have a significantly different risk of death compared to patients without recurrences," said lead author Melissa M. Boltz, D.O., who presented the findings at the annual clinical congress of the American College of Surgeons.

About half of patients who develop recurrent disease will die from this, but little is known about the risk of recurrence. "We questioned whether the implications could be different for the elderly population," she said.

The researchers focused on recurrent well-differentiated thyroid cancer (WDTC) in patients aged 65 years or older and assessed its impact on 1-year and 5-year survival, controlling for patient-, disease-, and treatment-related variables.

From the SEER (Surveillance Epidemiology and End Results), Medicare-linked database, they identified 2,883 patients with primary WDTC treated between 1995 and 2007. They documented recurrence through billing codes, evidence of I-131 treatment, thyroid imaging, or the performance of additional thyroid procedures beyond 6 months of diagnosis.

Of these, 1,126 patients (39%) developed recurrent disease, and the recurrent group was not demographically different from the group of patients without recurrence. The majority recurred within the first 2 years of initial treatment, after which the probability of developing recurrence was never more than 45% over 10 years, Dr. Boltz said.

Risk factors associated with recurrence included older age, advanced stage, lack of surgical treatment, and regional disease, she reported.

Regional disease was present in 44% of the recurrent group, vs. only 24% of the nonrecurrent group, and thyroidectomy was performed on 33% vs. 60%, respectively.

At 10 years, of the total thyroid cancer population, 662 (23%) died of some form of cancer with thyroid cancer as the cause of death in 273 (41%).

"In the 1-year landmark analysis, patients with recurrence had a higher risk for cancer-specific mortality within 10 years, versus those without recurrence, and the trend was similar at the 5-year landmark," Dr. Boltz noted.

By histology, patients who recurred with papillary thyroid cancer were significantly more likely to die of thyroid cancer as compared to papillary thyroid cancer patients not experiencing recurrence. Papillary patients who were older, had regional or distant disease, and who did not undergo surgery were also at increased risk for cancer-specific death.

The hazard ratios for thyroid cancer death for papillary thyroid cancer patients were as follows:

• Recurrence: HR, 1.96 (P less than .001).

• Age, 5-year increases: HR, 1.46 (P less than .001).

• Regional disease: HR, 4.90 (P less than .001).

• Distant disease: HR, 16.97 (P less than .001).

• No surgery: HR, 7.98 (P less than .001).

• Treatment other than surgery: HR, 3.47 (P less than 0.001).

In contrast, patients with follicular thyroid cancer had an increase in cancer-specific mortality only in relation to the presence of distant disease (HR, 17.78; P less than 0.001). Older age was also associated with an increase in cancer-specific mortality (HR, 1.24; P = 0.04), but disease recurrence was not (HR 0.58; P = 0.16).

"Unlike papillary cancer, follicular cancer recurrence did not contribute to cancer-specific mortality. The only risks were related to older age and advanced stage," Dr. Boltz reported.

Dr. Boltz cautioned that this study pertained to elderly Medicare patients, and the results should not be generalized to a younger population, in which thyroid cancer is more prevalent.

Dr. Boltz reported no relevant conflicts of interest.

SAN FRANCISCO – Thyroid cancer recurs in almost 40% of elderly patients, and while recurrence is accompanied by an increased mortality risk, this seems to be confined to the subset of patients with papillary thyroid cancer, according to researchers from Penn State Milton S. Hershey Medical Center in Hershey, Pa.

"Elderly patients with follicular disease and recurrence did not have a significantly different risk of death compared to patients without recurrences," said lead author Melissa M. Boltz, D.O., who presented the findings at the annual clinical congress of the American College of Surgeons.

About half of patients who develop recurrent disease will die from this, but little is known about the risk of recurrence. "We questioned whether the implications could be different for the elderly population," she said.

The researchers focused on recurrent well-differentiated thyroid cancer (WDTC) in patients aged 65 years or older and assessed its impact on 1-year and 5-year survival, controlling for patient-, disease-, and treatment-related variables.

From the SEER (Surveillance Epidemiology and End Results), Medicare-linked database, they identified 2,883 patients with primary WDTC treated between 1995 and 2007. They documented recurrence through billing codes, evidence of I-131 treatment, thyroid imaging, or the performance of additional thyroid procedures beyond 6 months of diagnosis.

Of these, 1,126 patients (39%) developed recurrent disease, and the recurrent group was not demographically different from the group of patients without recurrence. The majority recurred within the first 2 years of initial treatment, after which the probability of developing recurrence was never more than 45% over 10 years, Dr. Boltz said.

Risk factors associated with recurrence included older age, advanced stage, lack of surgical treatment, and regional disease, she reported.

Regional disease was present in 44% of the recurrent group, vs. only 24% of the nonrecurrent group, and thyroidectomy was performed on 33% vs. 60%, respectively.

At 10 years, of the total thyroid cancer population, 662 (23%) died of some form of cancer with thyroid cancer as the cause of death in 273 (41%).

"In the 1-year landmark analysis, patients with recurrence had a higher risk for cancer-specific mortality within 10 years, versus those without recurrence, and the trend was similar at the 5-year landmark," Dr. Boltz noted.

By histology, patients who recurred with papillary thyroid cancer were significantly more likely to die of thyroid cancer as compared to papillary thyroid cancer patients not experiencing recurrence. Papillary patients who were older, had regional or distant disease, and who did not undergo surgery were also at increased risk for cancer-specific death.

The hazard ratios for thyroid cancer death for papillary thyroid cancer patients were as follows:

• Recurrence: HR, 1.96 (P less than .001).

• Age, 5-year increases: HR, 1.46 (P less than .001).

• Regional disease: HR, 4.90 (P less than .001).

• Distant disease: HR, 16.97 (P less than .001).

• No surgery: HR, 7.98 (P less than .001).

• Treatment other than surgery: HR, 3.47 (P less than 0.001).

In contrast, patients with follicular thyroid cancer had an increase in cancer-specific mortality only in relation to the presence of distant disease (HR, 17.78; P less than 0.001). Older age was also associated with an increase in cancer-specific mortality (HR, 1.24; P = 0.04), but disease recurrence was not (HR 0.58; P = 0.16).

"Unlike papillary cancer, follicular cancer recurrence did not contribute to cancer-specific mortality. The only risks were related to older age and advanced stage," Dr. Boltz reported.

Dr. Boltz cautioned that this study pertained to elderly Medicare patients, and the results should not be generalized to a younger population, in which thyroid cancer is more prevalent.

Dr. Boltz reported no relevant conflicts of interest.

SAN FRANCISCO – Thyroid cancer recurs in almost 40% of elderly patients, and while recurrence is accompanied by an increased mortality risk, this seems to be confined to the subset of patients with papillary thyroid cancer, according to researchers from Penn State Milton S. Hershey Medical Center in Hershey, Pa.

"Elderly patients with follicular disease and recurrence did not have a significantly different risk of death compared to patients without recurrences," said lead author Melissa M. Boltz, D.O., who presented the findings at the annual clinical congress of the American College of Surgeons.

About half of patients who develop recurrent disease will die from this, but little is known about the risk of recurrence. "We questioned whether the implications could be different for the elderly population," she said.

The researchers focused on recurrent well-differentiated thyroid cancer (WDTC) in patients aged 65 years or older and assessed its impact on 1-year and 5-year survival, controlling for patient-, disease-, and treatment-related variables.

From the SEER (Surveillance Epidemiology and End Results), Medicare-linked database, they identified 2,883 patients with primary WDTC treated between 1995 and 2007. They documented recurrence through billing codes, evidence of I-131 treatment, thyroid imaging, or the performance of additional thyroid procedures beyond 6 months of diagnosis.

Of these, 1,126 patients (39%) developed recurrent disease, and the recurrent group was not demographically different from the group of patients without recurrence. The majority recurred within the first 2 years of initial treatment, after which the probability of developing recurrence was never more than 45% over 10 years, Dr. Boltz said.

Risk factors associated with recurrence included older age, advanced stage, lack of surgical treatment, and regional disease, she reported.

Regional disease was present in 44% of the recurrent group, vs. only 24% of the nonrecurrent group, and thyroidectomy was performed on 33% vs. 60%, respectively.

At 10 years, of the total thyroid cancer population, 662 (23%) died of some form of cancer with thyroid cancer as the cause of death in 273 (41%).

"In the 1-year landmark analysis, patients with recurrence had a higher risk for cancer-specific mortality within 10 years, versus those without recurrence, and the trend was similar at the 5-year landmark," Dr. Boltz noted.

By histology, patients who recurred with papillary thyroid cancer were significantly more likely to die of thyroid cancer as compared to papillary thyroid cancer patients not experiencing recurrence. Papillary patients who were older, had regional or distant disease, and who did not undergo surgery were also at increased risk for cancer-specific death.

The hazard ratios for thyroid cancer death for papillary thyroid cancer patients were as follows:

• Recurrence: HR, 1.96 (P less than .001).

• Age, 5-year increases: HR, 1.46 (P less than .001).

• Regional disease: HR, 4.90 (P less than .001).

• Distant disease: HR, 16.97 (P less than .001).

• No surgery: HR, 7.98 (P less than .001).

• Treatment other than surgery: HR, 3.47 (P less than 0.001).

In contrast, patients with follicular thyroid cancer had an increase in cancer-specific mortality only in relation to the presence of distant disease (HR, 17.78; P less than 0.001). Older age was also associated with an increase in cancer-specific mortality (HR, 1.24; P = 0.04), but disease recurrence was not (HR 0.58; P = 0.16).

"Unlike papillary cancer, follicular cancer recurrence did not contribute to cancer-specific mortality. The only risks were related to older age and advanced stage," Dr. Boltz reported.

Dr. Boltz cautioned that this study pertained to elderly Medicare patients, and the results should not be generalized to a younger population, in which thyroid cancer is more prevalent.

Dr. Boltz reported no relevant conflicts of interest.

Major Finding: Regular use of PPIs posed fracture risks of 35%-45% when adjusted for age, calcium intake, and body mass index. The fully adjusted hazard ratio was 1.37.

Data Source: A prospective examination of the relationship between chronic PPI use and incident hip fracture among 79,899 postmenopausal women enrolled in the Nurses' Health Study.

Disclosures: Dr. Khalili reported having no conflicts of interest.

CHICAGO – Regular use of proton pump inhibitors is associated with an elevated risk of hip fractures, even after adjusting for important lifestyle risk factors, according to the findings of a prospective evaluation from the Nurses' Health Study.

The association was most striking for women with a history of smoking, observed Dr. Hamed Khalili of Massachusetts General Hospital, Boston.

The Food and Drug Association recently issued an advisory regarding a potential link between PPIs and fractures. While acid-suppressing medications have been hypothesized to increase the risk of osteoporotic fractures, studies examining this association have been inconsistent. These analyses have mostly been based on retrospective studies of small populations that have not controlled for important dietary and lifestyle confounders, and they have ascertained PPI use only at a single time point, Dr. Khalili said.

The current study aimed to be more definitive by prospectively examining the relationship between chronic PPI use and incident hip fracture among 79,899 postmenopausal women enrolled in the Nurses' Health Study, he said.

“We found that longer duration of use was associated with increased risk, and the strongest risk was confined to individuals with a history of smoking. … Our findings support the recent decision of the FDA to revise labeling of PPIs to incorporate concerns about a possible increase in the risk of fractures,” he said at the meeting.

In 1982, participants in the Nurses' Health Study were first asked to report all previous fractures and were queried biennially for new fractures. Among the nearly 80,000 subjects, with 565,786 person-years of follow-up, there were 893 incident hip fractures over 8 years. PPI use was reported by 7% of participants in 2000 and by 19% of participants in 2008.

Regular use of PPIs posed fracture risks of 35%-45% when adjusted for age, calcium intake, and body mass index. The fully adjusted hazard ratio was 1.37, Dr. Khalili reported.

Current smoking status stood out as a significant effect modifier. Women who were current or past smokers and who regularly took a PPI had a 51% increased risk for fracture. In contrast, women who never smoked had only a 6% increased risk, “almost equal to women who never used PPIs,” he noted.

Longer duration of use was significantly associated with greater risk. Compared with never-users, risk in the multivariate analysis was 36% after 2 years of use, 42% after 4 years and 54% when PPIs were used for 6 years or longer, he said.

The investigators adjusted for multiple other risk factors, including physical activity; alcohol intake; total daily calcium and vitamin D intake; history of osteoporosis; and use of hormone replacement therapy, bisphosphonates, and thiazides. “This did not materially alter this association,” he noted.

When PPIs were discontinued, the risks declined. Two or more years after discontinuation, the risk of hip fracture was just 9%-10%, he noted.

“The strengths of our study are that it offers detailed, prospectively collected and validated information on PPI use and other risk factors. We had a high response rate, and the participants are educated health professionals,” he said. “But the study lacks information about PPI use prior to 2000, and it lacks specific information about brand and dose of PPI. It's not clear whether this is generalizable to other populations.”

The study, however, is in line with other reports of an association, and adds weight to the recommendation that clinicians carefully monitor the necessity of postmenopausal women to continue taking PPIs over the long-term, especially those who smoke.

Response from the audience was robust, with one attendee noting, “This is truly excellent work,” and another calling the study “impressive.”

Major Finding: Regular use of PPIs posed fracture risks of 35%-45% when adjusted for age, calcium intake, and body mass index. The fully adjusted hazard ratio was 1.37.

Data Source: A prospective examination of the relationship between chronic PPI use and incident hip fracture among 79,899 postmenopausal women enrolled in the Nurses' Health Study.

Disclosures: Dr. Khalili reported having no conflicts of interest.

CHICAGO – Regular use of proton pump inhibitors is associated with an elevated risk of hip fractures, even after adjusting for important lifestyle risk factors, according to the findings of a prospective evaluation from the Nurses' Health Study.

The association was most striking for women with a history of smoking, observed Dr. Hamed Khalili of Massachusetts General Hospital, Boston.

The Food and Drug Association recently issued an advisory regarding a potential link between PPIs and fractures. While acid-suppressing medications have been hypothesized to increase the risk of osteoporotic fractures, studies examining this association have been inconsistent. These analyses have mostly been based on retrospective studies of small populations that have not controlled for important dietary and lifestyle confounders, and they have ascertained PPI use only at a single time point, Dr. Khalili said.

The current study aimed to be more definitive by prospectively examining the relationship between chronic PPI use and incident hip fracture among 79,899 postmenopausal women enrolled in the Nurses' Health Study, he said.

“We found that longer duration of use was associated with increased risk, and the strongest risk was confined to individuals with a history of smoking. … Our findings support the recent decision of the FDA to revise labeling of PPIs to incorporate concerns about a possible increase in the risk of fractures,” he said at the meeting.

In 1982, participants in the Nurses' Health Study were first asked to report all previous fractures and were queried biennially for new fractures. Among the nearly 80,000 subjects, with 565,786 person-years of follow-up, there were 893 incident hip fractures over 8 years. PPI use was reported by 7% of participants in 2000 and by 19% of participants in 2008.

Regular use of PPIs posed fracture risks of 35%-45% when adjusted for age, calcium intake, and body mass index. The fully adjusted hazard ratio was 1.37, Dr. Khalili reported.

Current smoking status stood out as a significant effect modifier. Women who were current or past smokers and who regularly took a PPI had a 51% increased risk for fracture. In contrast, women who never smoked had only a 6% increased risk, “almost equal to women who never used PPIs,” he noted.

Longer duration of use was significantly associated with greater risk. Compared with never-users, risk in the multivariate analysis was 36% after 2 years of use, 42% after 4 years and 54% when PPIs were used for 6 years or longer, he said.

The investigators adjusted for multiple other risk factors, including physical activity; alcohol intake; total daily calcium and vitamin D intake; history of osteoporosis; and use of hormone replacement therapy, bisphosphonates, and thiazides. “This did not materially alter this association,” he noted.

When PPIs were discontinued, the risks declined. Two or more years after discontinuation, the risk of hip fracture was just 9%-10%, he noted.

“The strengths of our study are that it offers detailed, prospectively collected and validated information on PPI use and other risk factors. We had a high response rate, and the participants are educated health professionals,” he said. “But the study lacks information about PPI use prior to 2000, and it lacks specific information about brand and dose of PPI. It's not clear whether this is generalizable to other populations.”

The study, however, is in line with other reports of an association, and adds weight to the recommendation that clinicians carefully monitor the necessity of postmenopausal women to continue taking PPIs over the long-term, especially those who smoke.

Response from the audience was robust, with one attendee noting, “This is truly excellent work,” and another calling the study “impressive.”

Major Finding: Regular use of PPIs posed fracture risks of 35%-45% when adjusted for age, calcium intake, and body mass index. The fully adjusted hazard ratio was 1.37.

Data Source: A prospective examination of the relationship between chronic PPI use and incident hip fracture among 79,899 postmenopausal women enrolled in the Nurses' Health Study.

Disclosures: Dr. Khalili reported having no conflicts of interest.

CHICAGO – Regular use of proton pump inhibitors is associated with an elevated risk of hip fractures, even after adjusting for important lifestyle risk factors, according to the findings of a prospective evaluation from the Nurses' Health Study.

The association was most striking for women with a history of smoking, observed Dr. Hamed Khalili of Massachusetts General Hospital, Boston.

The Food and Drug Association recently issued an advisory regarding a potential link between PPIs and fractures. While acid-suppressing medications have been hypothesized to increase the risk of osteoporotic fractures, studies examining this association have been inconsistent. These analyses have mostly been based on retrospective studies of small populations that have not controlled for important dietary and lifestyle confounders, and they have ascertained PPI use only at a single time point, Dr. Khalili said.

The current study aimed to be more definitive by prospectively examining the relationship between chronic PPI use and incident hip fracture among 79,899 postmenopausal women enrolled in the Nurses' Health Study, he said.

“We found that longer duration of use was associated with increased risk, and the strongest risk was confined to individuals with a history of smoking. … Our findings support the recent decision of the FDA to revise labeling of PPIs to incorporate concerns about a possible increase in the risk of fractures,” he said at the meeting.

In 1982, participants in the Nurses' Health Study were first asked to report all previous fractures and were queried biennially for new fractures. Among the nearly 80,000 subjects, with 565,786 person-years of follow-up, there were 893 incident hip fractures over 8 years. PPI use was reported by 7% of participants in 2000 and by 19% of participants in 2008.

Regular use of PPIs posed fracture risks of 35%-45% when adjusted for age, calcium intake, and body mass index. The fully adjusted hazard ratio was 1.37, Dr. Khalili reported.

Current smoking status stood out as a significant effect modifier. Women who were current or past smokers and who regularly took a PPI had a 51% increased risk for fracture. In contrast, women who never smoked had only a 6% increased risk, “almost equal to women who never used PPIs,” he noted.

Longer duration of use was significantly associated with greater risk. Compared with never-users, risk in the multivariate analysis was 36% after 2 years of use, 42% after 4 years and 54% when PPIs were used for 6 years or longer, he said.

The investigators adjusted for multiple other risk factors, including physical activity; alcohol intake; total daily calcium and vitamin D intake; history of osteoporosis; and use of hormone replacement therapy, bisphosphonates, and thiazides. “This did not materially alter this association,” he noted.

When PPIs were discontinued, the risks declined. Two or more years after discontinuation, the risk of hip fracture was just 9%-10%, he noted.

“The strengths of our study are that it offers detailed, prospectively collected and validated information on PPI use and other risk factors. We had a high response rate, and the participants are educated health professionals,” he said. “But the study lacks information about PPI use prior to 2000, and it lacks specific information about brand and dose of PPI. It's not clear whether this is generalizable to other populations.”

The study, however, is in line with other reports of an association, and adds weight to the recommendation that clinicians carefully monitor the necessity of postmenopausal women to continue taking PPIs over the long-term, especially those who smoke.

Response from the audience was robust, with one attendee noting, “This is truly excellent work,” and another calling the study “impressive.”

NEW ORLEANS – Treatment with high doses of an angiotensin II receptor blocker or combined treatment with an ARB and a calcium channel blocker provided equal protection against cardiovascular events in elderly hypertensive patients, in a Japanese study presented at the meeting.

There were some differences, however. Greater blood pressure lowering was achieved with the combination, though in diabetic patients cardiovascular outcomes were more likely to be improved with high-dose ARBs, reported Dr. Hisao Ogawa of Kumamoto (Japan) University.

The OSCAR (Olmesartan and Calcium Antagonists Randomized) study enrolled 1,164 high-risk elderly hypertensive patients at 134 centers throughout Japan from 2005 to 2007. Patients had hypertension uncontrolled on standard-dose monotherapy with the ARB olmesartan and had at least one of the following cardiovascular conditions: type 2 diabetes, cardiac disease, vascular disease, renal dysfunction, or cerebrovascular disease.

Patients were randomized to receive either high-dose olmesartan 40 mg/day (n = 578) or a calcium channel blocker (CCB) combined with olmesartan 20 mg/day (n = 586). The primary end point was a composite of fatal and nonfatal cardiovascular events, including coronary artery disease, heart failure, cerebrovascular disease, other arteriosclerotic disease, diabetic complications, and the deterioration of renal function as well as noncardiovascular death.

At 36 months' follow-up, in the intention-to-treat analysis, blood pressure was adequately controlled by both treatment approaches, but the combination reduced blood pressure to significantly lower levels, compared with the ARB. With combination ARB/CCB, mean systolic levels were lower by 2.4 mm Hg, and mean diastolic levels were lower by 1.7 mm Hg, both significant differences.

However, no significant differences were seen between the arms in the composite end point, with 58 events occurring with high-dose ARB treatment and 48 occurring with the combination ARB/CCB. While risk was increased by 31% with the high-dose ARB, the difference was not statistically significant, Dr. Ogawa reported.

Subgroup analyses did reveal differences between the treatments. For patients with preexisting cardiovascular disease, those randomized to the combination therapy had significantly fewer cardiovascular events or deaths than those in the monotherapy group: 34% and 51%, respectively, for a 63% increased risk, he said.

Conversely, in the subgroups of patients with only diabetes and no other evidence of cardiovascular disease, the combination therapy group was at greater risk. Events occurred in 14 patients compared with 7 patients, for a 48% reduced risk with high-dose ARBs, though this was not statistically significant.

“There was a significant treatment-by-subgroup interaction for the primary end points between the patients with and those without cardiovascular disease [only diabetes],” he said. “The OSCAR study suggests that the relative effect of the two therapies depends on the presence of cardiovascular disease or type 2 diabetes.”

The study was funded by the Japan Heart Foundation. Dr. Ogawa has received grant support from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eisai, Kowa, Kyowa Hakko Kirin, Merck, Novartis, Pfizer, Sanofi-Aventis, Schering-Plough, and Takeda.

NEW ORLEANS – Treatment with high doses of an angiotensin II receptor blocker or combined treatment with an ARB and a calcium channel blocker provided equal protection against cardiovascular events in elderly hypertensive patients, in a Japanese study presented at the meeting.

There were some differences, however. Greater blood pressure lowering was achieved with the combination, though in diabetic patients cardiovascular outcomes were more likely to be improved with high-dose ARBs, reported Dr. Hisao Ogawa of Kumamoto (Japan) University.

The OSCAR (Olmesartan and Calcium Antagonists Randomized) study enrolled 1,164 high-risk elderly hypertensive patients at 134 centers throughout Japan from 2005 to 2007. Patients had hypertension uncontrolled on standard-dose monotherapy with the ARB olmesartan and had at least one of the following cardiovascular conditions: type 2 diabetes, cardiac disease, vascular disease, renal dysfunction, or cerebrovascular disease.

Patients were randomized to receive either high-dose olmesartan 40 mg/day (n = 578) or a calcium channel blocker (CCB) combined with olmesartan 20 mg/day (n = 586). The primary end point was a composite of fatal and nonfatal cardiovascular events, including coronary artery disease, heart failure, cerebrovascular disease, other arteriosclerotic disease, diabetic complications, and the deterioration of renal function as well as noncardiovascular death.

At 36 months' follow-up, in the intention-to-treat analysis, blood pressure was adequately controlled by both treatment approaches, but the combination reduced blood pressure to significantly lower levels, compared with the ARB. With combination ARB/CCB, mean systolic levels were lower by 2.4 mm Hg, and mean diastolic levels were lower by 1.7 mm Hg, both significant differences.

However, no significant differences were seen between the arms in the composite end point, with 58 events occurring with high-dose ARB treatment and 48 occurring with the combination ARB/CCB. While risk was increased by 31% with the high-dose ARB, the difference was not statistically significant, Dr. Ogawa reported.

Subgroup analyses did reveal differences between the treatments. For patients with preexisting cardiovascular disease, those randomized to the combination therapy had significantly fewer cardiovascular events or deaths than those in the monotherapy group: 34% and 51%, respectively, for a 63% increased risk, he said.

Conversely, in the subgroups of patients with only diabetes and no other evidence of cardiovascular disease, the combination therapy group was at greater risk. Events occurred in 14 patients compared with 7 patients, for a 48% reduced risk with high-dose ARBs, though this was not statistically significant.

“There was a significant treatment-by-subgroup interaction for the primary end points between the patients with and those without cardiovascular disease [only diabetes],” he said. “The OSCAR study suggests that the relative effect of the two therapies depends on the presence of cardiovascular disease or type 2 diabetes.”

The study was funded by the Japan Heart Foundation. Dr. Ogawa has received grant support from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eisai, Kowa, Kyowa Hakko Kirin, Merck, Novartis, Pfizer, Sanofi-Aventis, Schering-Plough, and Takeda.

NEW ORLEANS – Treatment with high doses of an angiotensin II receptor blocker or combined treatment with an ARB and a calcium channel blocker provided equal protection against cardiovascular events in elderly hypertensive patients, in a Japanese study presented at the meeting.

There were some differences, however. Greater blood pressure lowering was achieved with the combination, though in diabetic patients cardiovascular outcomes were more likely to be improved with high-dose ARBs, reported Dr. Hisao Ogawa of Kumamoto (Japan) University.

The OSCAR (Olmesartan and Calcium Antagonists Randomized) study enrolled 1,164 high-risk elderly hypertensive patients at 134 centers throughout Japan from 2005 to 2007. Patients had hypertension uncontrolled on standard-dose monotherapy with the ARB olmesartan and had at least one of the following cardiovascular conditions: type 2 diabetes, cardiac disease, vascular disease, renal dysfunction, or cerebrovascular disease.

Patients were randomized to receive either high-dose olmesartan 40 mg/day (n = 578) or a calcium channel blocker (CCB) combined with olmesartan 20 mg/day (n = 586). The primary end point was a composite of fatal and nonfatal cardiovascular events, including coronary artery disease, heart failure, cerebrovascular disease, other arteriosclerotic disease, diabetic complications, and the deterioration of renal function as well as noncardiovascular death.

At 36 months' follow-up, in the intention-to-treat analysis, blood pressure was adequately controlled by both treatment approaches, but the combination reduced blood pressure to significantly lower levels, compared with the ARB. With combination ARB/CCB, mean systolic levels were lower by 2.4 mm Hg, and mean diastolic levels were lower by 1.7 mm Hg, both significant differences.

However, no significant differences were seen between the arms in the composite end point, with 58 events occurring with high-dose ARB treatment and 48 occurring with the combination ARB/CCB. While risk was increased by 31% with the high-dose ARB, the difference was not statistically significant, Dr. Ogawa reported.

Subgroup analyses did reveal differences between the treatments. For patients with preexisting cardiovascular disease, those randomized to the combination therapy had significantly fewer cardiovascular events or deaths than those in the monotherapy group: 34% and 51%, respectively, for a 63% increased risk, he said.

Conversely, in the subgroups of patients with only diabetes and no other evidence of cardiovascular disease, the combination therapy group was at greater risk. Events occurred in 14 patients compared with 7 patients, for a 48% reduced risk with high-dose ARBs, though this was not statistically significant.

“There was a significant treatment-by-subgroup interaction for the primary end points between the patients with and those without cardiovascular disease [only diabetes],” he said. “The OSCAR study suggests that the relative effect of the two therapies depends on the presence of cardiovascular disease or type 2 diabetes.”

The study was funded by the Japan Heart Foundation. Dr. Ogawa has received grant support from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eisai, Kowa, Kyowa Hakko Kirin, Merck, Novartis, Pfizer, Sanofi-Aventis, Schering-Plough, and Takeda.

NEW ORLEANS – The durability and safety of treating mitral regurgitation with a percutaneous device as compared with that of surgical repair or replacement persisted at 2 years, based on an updated analysis of the EVEREST II trial results presented at the annual meeting of the American College of Cardiology.

"Our fundamental finding is that outcomes are very stable between 1 and 2 years of follow-up," Dr. Ted Feldman, principal investigator, announced at a press briefing. The 2-year follow-up results show both approaches reduced MR, and meaningful clinical benefits persisted, said Dr. Feldman of the NorthShore University HealthSystem in Evanston, Ill.

Clinical outcome measures at 2 years showed MR grade and left ventricular (LV) volumes remained stable between 1 and 2 years in both groups. The inter-group comparison showed a more favorable reduction in MR and a greater reduction in LV diastolic volume with surgery at 1 and 2 years, and no difference in systolic volume reduction. Also, NYHA functional class was stable between years 1 and 2. "Interestingly, the inter-group comparison showed a more favorable NYHA class outcome at both years with the clip," he reported.

EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) is a prospective, multicenter, randomized controlled phase II trial comparing the safety and efficacy of the MitraClip System with mitral valve surgery in the treatment of MR. The study enrolled 279 patients with 3+ or 4+ MR who were either symptomatic or were asymptomatic with a baseline left ejection fraction of 60%. Approximately half of the patients had New York Heart Association (NYHA) functional class III or IV heart failure.

At the meeting, Dr. Feldman presented two analyses of the 2-year data. The composite primary efficacy endpoint was freedom from death, MV surgery for valve dysfunction (for device patients) or re-operation (for surgery patients), and MR greater than 2+ at 12 months.

In the intention-to-treat analysis, the primary composite endpoint was met at 2 years by 52% of the percutaneous group and by 66% of the surgery group; in the 1-year analysis, these figures were 55% and 73%, respectively.

More patients receiving the clip later underwent MV surgery (22%) compared to the few patients in the surgery arm who required re-operation (3.6%). There was no significant difference in mortality or recurrent MR.

In the second analysis, there was no statistical difference in the effectiveness endpoint between the two arms of the study. "When subsequent surgery within 90 days on device patients is considered a success, we see similarly stable results at 1 and 2 years," he noted.

In this analysis, the primary endpoint was met at 2 years by 63% of the percutaneous group and by 66% of the surgery group. By removing the subsequent need for MV surgery as an end point event, 6.2% of the percutaneous group and 3.6% of the surgery group had MV surgery or re-operation.

There was no difference in the Kaplan-Meier mortality plot for the intention-to-treat analysis at any time point, he stressed. At 1 year, 95% of the patients in each arm were alive; at 2 years, 91% of the surgery arm and 90% of the percutaneous arm were still alive.

Freedom from MV surgery/re-operation, however, favored the surgical arm: 96% versus 78% at 2 years. The "need for surgery in patients in the clip group was almost entirely in the first several months; after 6 months the curves overlapped at 1 and 2 years," he observed. "Importantly, 78% of device patients are free from MV surgery at 2 years." When early failures were excluded, there were no differences in need for MV surgery or reoperation.

At a press conference, Dr. Feldman explained that the two analyses "answer different questions." "The intention-to-treat analysis gives the patient the odds of success with the clip at the end of the year," he said. "It tells them that 78% will be free of the need for surgery at 2 years, and 97% will have NYHA functional class I or II."

The second analysis answers the question, ‘What if I am in the 20% needing surgery?’ It counts the combined strategy of the clip, with surgery as needed.

Dr. Feldman reported consulting and research monies from Abbott Vascular. ☐

NEW ORLEANS – The durability and safety of treating mitral regurgitation with a percutaneous device as compared with that of surgical repair or replacement persisted at 2 years, based on an updated analysis of the EVEREST II trial results presented at the annual meeting of the American College of Cardiology.

"Our fundamental finding is that outcomes are very stable between 1 and 2 years of follow-up," Dr. Ted Feldman, principal investigator, announced at a press briefing. The 2-year follow-up results show both approaches reduced MR, and meaningful clinical benefits persisted, said Dr. Feldman of the NorthShore University HealthSystem in Evanston, Ill.

Clinical outcome measures at 2 years showed MR grade and left ventricular (LV) volumes remained stable between 1 and 2 years in both groups. The inter-group comparison showed a more favorable reduction in MR and a greater reduction in LV diastolic volume with surgery at 1 and 2 years, and no difference in systolic volume reduction. Also, NYHA functional class was stable between years 1 and 2. "Interestingly, the inter-group comparison showed a more favorable NYHA class outcome at both years with the clip," he reported.

EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) is a prospective, multicenter, randomized controlled phase II trial comparing the safety and efficacy of the MitraClip System with mitral valve surgery in the treatment of MR. The study enrolled 279 patients with 3+ or 4+ MR who were either symptomatic or were asymptomatic with a baseline left ejection fraction of 60%. Approximately half of the patients had New York Heart Association (NYHA) functional class III or IV heart failure.

At the meeting, Dr. Feldman presented two analyses of the 2-year data. The composite primary efficacy endpoint was freedom from death, MV surgery for valve dysfunction (for device patients) or re-operation (for surgery patients), and MR greater than 2+ at 12 months.

In the intention-to-treat analysis, the primary composite endpoint was met at 2 years by 52% of the percutaneous group and by 66% of the surgery group; in the 1-year analysis, these figures were 55% and 73%, respectively.

More patients receiving the clip later underwent MV surgery (22%) compared to the few patients in the surgery arm who required re-operation (3.6%). There was no significant difference in mortality or recurrent MR.

In the second analysis, there was no statistical difference in the effectiveness endpoint between the two arms of the study. "When subsequent surgery within 90 days on device patients is considered a success, we see similarly stable results at 1 and 2 years," he noted.

In this analysis, the primary endpoint was met at 2 years by 63% of the percutaneous group and by 66% of the surgery group. By removing the subsequent need for MV surgery as an end point event, 6.2% of the percutaneous group and 3.6% of the surgery group had MV surgery or re-operation.

There was no difference in the Kaplan-Meier mortality plot for the intention-to-treat analysis at any time point, he stressed. At 1 year, 95% of the patients in each arm were alive; at 2 years, 91% of the surgery arm and 90% of the percutaneous arm were still alive.

Freedom from MV surgery/re-operation, however, favored the surgical arm: 96% versus 78% at 2 years. The "need for surgery in patients in the clip group was almost entirely in the first several months; after 6 months the curves overlapped at 1 and 2 years," he observed. "Importantly, 78% of device patients are free from MV surgery at 2 years." When early failures were excluded, there were no differences in need for MV surgery or reoperation.

At a press conference, Dr. Feldman explained that the two analyses "answer different questions." "The intention-to-treat analysis gives the patient the odds of success with the clip at the end of the year," he said. "It tells them that 78% will be free of the need for surgery at 2 years, and 97% will have NYHA functional class I or II."

The second analysis answers the question, ‘What if I am in the 20% needing surgery?’ It counts the combined strategy of the clip, with surgery as needed.

Dr. Feldman reported consulting and research monies from Abbott Vascular. ☐

NEW ORLEANS – The durability and safety of treating mitral regurgitation with a percutaneous device as compared with that of surgical repair or replacement persisted at 2 years, based on an updated analysis of the EVEREST II trial results presented at the annual meeting of the American College of Cardiology.

"Our fundamental finding is that outcomes are very stable between 1 and 2 years of follow-up," Dr. Ted Feldman, principal investigator, announced at a press briefing. The 2-year follow-up results show both approaches reduced MR, and meaningful clinical benefits persisted, said Dr. Feldman of the NorthShore University HealthSystem in Evanston, Ill.

Clinical outcome measures at 2 years showed MR grade and left ventricular (LV) volumes remained stable between 1 and 2 years in both groups. The inter-group comparison showed a more favorable reduction in MR and a greater reduction in LV diastolic volume with surgery at 1 and 2 years, and no difference in systolic volume reduction. Also, NYHA functional class was stable between years 1 and 2. "Interestingly, the inter-group comparison showed a more favorable NYHA class outcome at both years with the clip," he reported.

EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) is a prospective, multicenter, randomized controlled phase II trial comparing the safety and efficacy of the MitraClip System with mitral valve surgery in the treatment of MR. The study enrolled 279 patients with 3+ or 4+ MR who were either symptomatic or were asymptomatic with a baseline left ejection fraction of 60%. Approximately half of the patients had New York Heart Association (NYHA) functional class III or IV heart failure.

At the meeting, Dr. Feldman presented two analyses of the 2-year data. The composite primary efficacy endpoint was freedom from death, MV surgery for valve dysfunction (for device patients) or re-operation (for surgery patients), and MR greater than 2+ at 12 months.

In the intention-to-treat analysis, the primary composite endpoint was met at 2 years by 52% of the percutaneous group and by 66% of the surgery group; in the 1-year analysis, these figures were 55% and 73%, respectively.

More patients receiving the clip later underwent MV surgery (22%) compared to the few patients in the surgery arm who required re-operation (3.6%). There was no significant difference in mortality or recurrent MR.

In the second analysis, there was no statistical difference in the effectiveness endpoint between the two arms of the study. "When subsequent surgery within 90 days on device patients is considered a success, we see similarly stable results at 1 and 2 years," he noted.

In this analysis, the primary endpoint was met at 2 years by 63% of the percutaneous group and by 66% of the surgery group. By removing the subsequent need for MV surgery as an end point event, 6.2% of the percutaneous group and 3.6% of the surgery group had MV surgery or re-operation.

There was no difference in the Kaplan-Meier mortality plot for the intention-to-treat analysis at any time point, he stressed. At 1 year, 95% of the patients in each arm were alive; at 2 years, 91% of the surgery arm and 90% of the percutaneous arm were still alive.

Freedom from MV surgery/re-operation, however, favored the surgical arm: 96% versus 78% at 2 years. The "need for surgery in patients in the clip group was almost entirely in the first several months; after 6 months the curves overlapped at 1 and 2 years," he observed. "Importantly, 78% of device patients are free from MV surgery at 2 years." When early failures were excluded, there were no differences in need for MV surgery or reoperation.

At a press conference, Dr. Feldman explained that the two analyses "answer different questions." "The intention-to-treat analysis gives the patient the odds of success with the clip at the end of the year," he said. "It tells them that 78% will be free of the need for surgery at 2 years, and 97% will have NYHA functional class I or II."

The second analysis answers the question, ‘What if I am in the 20% needing surgery?’ It counts the combined strategy of the clip, with surgery as needed.

Dr. Feldman reported consulting and research monies from Abbott Vascular. ☐

CHICAGO – Several modifiable technical factors can influence detection of colorectal adenomas, as can lifestyle factors, based on data from a large study conducted in the United Kingdom.

The findings came from the National Health Service (NHS) Bowel Cancer Screening Program, the largest study to examine the effects of patient and physician factors on adenoma detection during colonoscopy. The colonoscopies in this study were done to follow-up on positive fecal occult blood test (FOBT) results, said Dr. Tom J. Lee of Newcastle (U.K.) University, who presented the data at the annual Digestive Disease Week.

"Many factors affect the chance of an adenoma being detected," he said, "including patient factors, both modifiable and nonmodifiable, and colonoscopy factors, which are usually technical."

The NHS program offers a colonoscopy to any person aged 60-74 years who has a positive FOBT result. "It is a unique opportunity to study the interplay of factors that influence adenoma detection," Dr. Lee said.

From 2006 to 2009, fecal occult blood tests were returned by 2,269,983 persons (mean age 66 years; 60% male), and 2% of these were positive. The total number of colonoscopies (performed by 177 experienced endoscopists at 50 screening centers) was 36,460, of which 31,088 were included in this analysis. Of the patients who underwent colonoscopy, 14,423 (46%) had at least one adenoma.

Data were collected on cecal intubation, rectal retroversion, mean withdrawal time for the endoscopist, quality of bowel prep, use of the antispasmodic hyoscine butylbromide, start time of the procedure, and sedation use. Patient factors included gender, age, smoking and alcohol status, and geographic area.

Adverse lifestyle can negate protection for women

In the multivariate analysis, risk for adenomas was significantly associated with male gender, older age, current or previous smoking, and current alcohol use.

Men were more likely than women to have adenomas, and poor lifestyle habits elevated the risk further beyond that from gender alone. Among patients who did not drink or smoke, 45% of men had one or more adenomas, compared with 32% of women.

In men, this rate rose progressively according to alcohol and smoking status, exceeding 60% for men who reported current smoking and alcohol intake, Dr. Lee said. The same pattern held true for women; those reporting current alcohol intake and cigarette use had a 43% risk of having an adenoma.

All the associations were highly significant for the detection of any adenomas, advanced adenomas, and right-sided adenomas at a P value less than .001.

"Female smokers who drink had a significantly higher risk than men who did not smoke or drink. We found that adverse lifestyle factors can overcome gender protection from adenomas in females," Dr. Lee reported. "This stresses the importance of lifestyle factors in the development of adenomas."

In addition, older age was a significant factor, as was geographic area, even after adjustment for other factors. "There was a significant variation in risk depending on where the procedure was done," he said.

Technical factors linked to detection rate

The technical or procedural factors that were significantly associated with detection of adenomas were cecal intubation, longer withdrawal time, higher-quality bowel preparation, use of an intravenous antispasmodic, earlier procedure start time, and greater colonoscopist experience, Dr. Lee reported.

Similar results were found for the effect of these factors on detection of advanced adenomas and right-sided adenomas.

Procedures in which the cecum was reached had a threefold greater likelihood of detecting adenomas overall (P less than .001), and a more than fivefold greater likelihood in the right colon (P less than .001). A mean withdrawal time for the endoscopist greater than or equal to 10 minutes increased the detection rate by 10% overall and by 28% in the right colon (P less than .001). Bowel prep that was adequate or better was associated with an almost 40% increased chance for detection (P less than .001) and the use of hyoscine was associated with a 30% increase (P less than .001), although it is possible that hyoscine use is "an indicator of a good colonoscopist," Dr. Lee suggested.

The association with the time of day offers "fascinating insight into colonoscopists’ behavior," he added. As the day progressed from 8 a.m. to noon, there was no change in cecal intubation, bowel prep, or withdrawal times, but adenoma detection diminished from nearly 48% to 45%. Adenoma detection rates rose again until 3 p.m., then dropped back to around 45%, creating a "biphasic" pattern, he noted.

"Interestingly, procedures in which rectal retroversion was performed were not associated with increased detection of one or more adenomas and did not increase the detection of rectal adenomas," he added. There was also no association with sedation.

Dr. Lee acknowledged the study’s limitations: it was not a randomized controlled trial, certain risk factors (family history, NSAID use) were not accounted for, and the scoring tools were also not validated, especially for bowel prep quality.

"Our study probably raises more questions than it answers," he acknowledged. Further study of geographical variations, time of day variations, and nontechnical colonoscopy factors should be performed, he suggested. Meanwhile, at least one current recommendation can be emphasized: that colonoscope withdrawal time should be at least 10 minutes, he said.

Dr. Lee had no relevant financial disclosures.

CHICAGO – Several modifiable technical factors can influence detection of colorectal adenomas, as can lifestyle factors, based on data from a large study conducted in the United Kingdom.

The findings came from the National Health Service (NHS) Bowel Cancer Screening Program, the largest study to examine the effects of patient and physician factors on adenoma detection during colonoscopy. The colonoscopies in this study were done to follow-up on positive fecal occult blood test (FOBT) results, said Dr. Tom J. Lee of Newcastle (U.K.) University, who presented the data at the annual Digestive Disease Week.

"Many factors affect the chance of an adenoma being detected," he said, "including patient factors, both modifiable and nonmodifiable, and colonoscopy factors, which are usually technical."

The NHS program offers a colonoscopy to any person aged 60-74 years who has a positive FOBT result. "It is a unique opportunity to study the interplay of factors that influence adenoma detection," Dr. Lee said.

From 2006 to 2009, fecal occult blood tests were returned by 2,269,983 persons (mean age 66 years; 60% male), and 2% of these were positive. The total number of colonoscopies (performed by 177 experienced endoscopists at 50 screening centers) was 36,460, of which 31,088 were included in this analysis. Of the patients who underwent colonoscopy, 14,423 (46%) had at least one adenoma.

Data were collected on cecal intubation, rectal retroversion, mean withdrawal time for the endoscopist, quality of bowel prep, use of the antispasmodic hyoscine butylbromide, start time of the procedure, and sedation use. Patient factors included gender, age, smoking and alcohol status, and geographic area.

Adverse lifestyle can negate protection for women

In the multivariate analysis, risk for adenomas was significantly associated with male gender, older age, current or previous smoking, and current alcohol use.

Men were more likely than women to have adenomas, and poor lifestyle habits elevated the risk further beyond that from gender alone. Among patients who did not drink or smoke, 45% of men had one or more adenomas, compared with 32% of women.

In men, this rate rose progressively according to alcohol and smoking status, exceeding 60% for men who reported current smoking and alcohol intake, Dr. Lee said. The same pattern held true for women; those reporting current alcohol intake and cigarette use had a 43% risk of having an adenoma.

All the associations were highly significant for the detection of any adenomas, advanced adenomas, and right-sided adenomas at a P value less than .001.

"Female smokers who drink had a significantly higher risk than men who did not smoke or drink. We found that adverse lifestyle factors can overcome gender protection from adenomas in females," Dr. Lee reported. "This stresses the importance of lifestyle factors in the development of adenomas."

In addition, older age was a significant factor, as was geographic area, even after adjustment for other factors. "There was a significant variation in risk depending on where the procedure was done," he said.

Technical factors linked to detection rate

The technical or procedural factors that were significantly associated with detection of adenomas were cecal intubation, longer withdrawal time, higher-quality bowel preparation, use of an intravenous antispasmodic, earlier procedure start time, and greater colonoscopist experience, Dr. Lee reported.

Similar results were found for the effect of these factors on detection of advanced adenomas and right-sided adenomas.

Procedures in which the cecum was reached had a threefold greater likelihood of detecting adenomas overall (P less than .001), and a more than fivefold greater likelihood in the right colon (P less than .001). A mean withdrawal time for the endoscopist greater than or equal to 10 minutes increased the detection rate by 10% overall and by 28% in the right colon (P less than .001). Bowel prep that was adequate or better was associated with an almost 40% increased chance for detection (P less than .001) and the use of hyoscine was associated with a 30% increase (P less than .001), although it is possible that hyoscine use is "an indicator of a good colonoscopist," Dr. Lee suggested.

The association with the time of day offers "fascinating insight into colonoscopists’ behavior," he added. As the day progressed from 8 a.m. to noon, there was no change in cecal intubation, bowel prep, or withdrawal times, but adenoma detection diminished from nearly 48% to 45%. Adenoma detection rates rose again until 3 p.m., then dropped back to around 45%, creating a "biphasic" pattern, he noted.

"Interestingly, procedures in which rectal retroversion was performed were not associated with increased detection of one or more adenomas and did not increase the detection of rectal adenomas," he added. There was also no association with sedation.

Dr. Lee acknowledged the study’s limitations: it was not a randomized controlled trial, certain risk factors (family history, NSAID use) were not accounted for, and the scoring tools were also not validated, especially for bowel prep quality.

"Our study probably raises more questions than it answers," he acknowledged. Further study of geographical variations, time of day variations, and nontechnical colonoscopy factors should be performed, he suggested. Meanwhile, at least one current recommendation can be emphasized: that colonoscope withdrawal time should be at least 10 minutes, he said.

Dr. Lee had no relevant financial disclosures.

CHICAGO – Several modifiable technical factors can influence detection of colorectal adenomas, as can lifestyle factors, based on data from a large study conducted in the United Kingdom.

The findings came from the National Health Service (NHS) Bowel Cancer Screening Program, the largest study to examine the effects of patient and physician factors on adenoma detection during colonoscopy. The colonoscopies in this study were done to follow-up on positive fecal occult blood test (FOBT) results, said Dr. Tom J. Lee of Newcastle (U.K.) University, who presented the data at the annual Digestive Disease Week.

"Many factors affect the chance of an adenoma being detected," he said, "including patient factors, both modifiable and nonmodifiable, and colonoscopy factors, which are usually technical."

The NHS program offers a colonoscopy to any person aged 60-74 years who has a positive FOBT result. "It is a unique opportunity to study the interplay of factors that influence adenoma detection," Dr. Lee said.

From 2006 to 2009, fecal occult blood tests were returned by 2,269,983 persons (mean age 66 years; 60% male), and 2% of these were positive. The total number of colonoscopies (performed by 177 experienced endoscopists at 50 screening centers) was 36,460, of which 31,088 were included in this analysis. Of the patients who underwent colonoscopy, 14,423 (46%) had at least one adenoma.

Data were collected on cecal intubation, rectal retroversion, mean withdrawal time for the endoscopist, quality of bowel prep, use of the antispasmodic hyoscine butylbromide, start time of the procedure, and sedation use. Patient factors included gender, age, smoking and alcohol status, and geographic area.

Adverse lifestyle can negate protection for women

In the multivariate analysis, risk for adenomas was significantly associated with male gender, older age, current or previous smoking, and current alcohol use.

Men were more likely than women to have adenomas, and poor lifestyle habits elevated the risk further beyond that from gender alone. Among patients who did not drink or smoke, 45% of men had one or more adenomas, compared with 32% of women.

In men, this rate rose progressively according to alcohol and smoking status, exceeding 60% for men who reported current smoking and alcohol intake, Dr. Lee said. The same pattern held true for women; those reporting current alcohol intake and cigarette use had a 43% risk of having an adenoma.

All the associations were highly significant for the detection of any adenomas, advanced adenomas, and right-sided adenomas at a P value less than .001.

"Female smokers who drink had a significantly higher risk than men who did not smoke or drink. We found that adverse lifestyle factors can overcome gender protection from adenomas in females," Dr. Lee reported. "This stresses the importance of lifestyle factors in the development of adenomas."

In addition, older age was a significant factor, as was geographic area, even after adjustment for other factors. "There was a significant variation in risk depending on where the procedure was done," he said.

Technical factors linked to detection rate

The technical or procedural factors that were significantly associated with detection of adenomas were cecal intubation, longer withdrawal time, higher-quality bowel preparation, use of an intravenous antispasmodic, earlier procedure start time, and greater colonoscopist experience, Dr. Lee reported.

Similar results were found for the effect of these factors on detection of advanced adenomas and right-sided adenomas.

Procedures in which the cecum was reached had a threefold greater likelihood of detecting adenomas overall (P less than .001), and a more than fivefold greater likelihood in the right colon (P less than .001). A mean withdrawal time for the endoscopist greater than or equal to 10 minutes increased the detection rate by 10% overall and by 28% in the right colon (P less than .001). Bowel prep that was adequate or better was associated with an almost 40% increased chance for detection (P less than .001) and the use of hyoscine was associated with a 30% increase (P less than .001), although it is possible that hyoscine use is "an indicator of a good colonoscopist," Dr. Lee suggested.

The association with the time of day offers "fascinating insight into colonoscopists’ behavior," he added. As the day progressed from 8 a.m. to noon, there was no change in cecal intubation, bowel prep, or withdrawal times, but adenoma detection diminished from nearly 48% to 45%. Adenoma detection rates rose again until 3 p.m., then dropped back to around 45%, creating a "biphasic" pattern, he noted.

"Interestingly, procedures in which rectal retroversion was performed were not associated with increased detection of one or more adenomas and did not increase the detection of rectal adenomas," he added. There was also no association with sedation.

Dr. Lee acknowledged the study’s limitations: it was not a randomized controlled trial, certain risk factors (family history, NSAID use) were not accounted for, and the scoring tools were also not validated, especially for bowel prep quality.

"Our study probably raises more questions than it answers," he acknowledged. Further study of geographical variations, time of day variations, and nontechnical colonoscopy factors should be performed, he suggested. Meanwhile, at least one current recommendation can be emphasized: that colonoscope withdrawal time should be at least 10 minutes, he said.

Dr. Lee had no relevant financial disclosures.