Kerri Wachter

Women with HER2-positive metastatic breast cancer have been given a double-edged sword, with the Food and Drug Administration granting approval to pertuzumab on Friday, June 8, as a first-line therapy.*

The addition of pertuzumab (Perjeta), a new HER2 blocker, to a standard chemotherapy combination of trastuzumab (Herceptin) and docetaxel (Taxotere) has been shown to extend progression-free survival in these patients. Overall survival data are not yet available.

Pertuzumab is a humanized monoclonal antibody, manufactured through biotechnology methods by Genentech, a subsidiary of Roche. It also blocks other HER family members, including EGFR, HER3, and HER4, and is believed to complement HER2 inhibition by trastuzumab, also made by Genentech and Roche.

The approval rides largely on the results of the CLEOPATRA (Clinical Evaluation of Pertuzumab and Trastuzumab) trial. Dual HER2 blockade boosted median progression-free survival from 12.4 months in a control group treated with only the standard combination to 18.5 months in a group treated with standard therapy plus-pertuzumab. This is a statistically significant difference that corresponds to a 38% reduction in the risk for progression or death and an increase of 6.1 months in median progression-free survival. These results were published in the New England Journal of Medicine (2012;366:109-19).

For the double-blind phase III trial, 808 patients aged 18 years and older with centrally confirmed HER2-positive metastatic or locally recurrent, unresectable breast cancer were randomized either to a control group that received placebo plus trastuzumab and docetaxel or to the pertuzumab group, which received pertuzumab plus trastuzumab and docetaxel.

Preliminary data from the CLEOPATRA trial were presented at the annual San Antonio Breast Cancer Symposium in early December 2011. For expert commentary on the trial, see our video report.

Supply, Cost Could Be Concerns

In their announcements of pertuzumab approval, Genentech, maker of the drug, and the FDA disclosed that production issues could affect the long-term supply of the drug.

"We expect to meet demand for Perjeta following today\'s FDA approval. We recently identified a cell growth issue that might affect our future supply of the medicine," said Patrick Y. Yang, Ph.D., head, Pharma Global Technical Operations. "We take this very seriously and are working with the FDA to ensure a consistent manufacturing process that maintains drug supply for the people who need it."

With the approval, Genentech has agreed to postmarketing commitments related to the manufacturing process for Perjeta. These include FDA review of data from the next several productions of the medicine.

The FDA limited its approval to drug product that has not been affected by production issues, according to Dr. Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research.

"Given the need for additional treatments for metastatic breast cancer, we made the decision to approve this drug today and not to delay its availability to patients pending resolution of the production issues relating to future supply," she said in the FDA announcement.

"Genentech is currently developing a plan to mitigate the effect on patients of any potential shortage of Perjeta."

An added concern is the high cost of dual HER2 inhibition at a time when oncologists are under pressure to contain costs. According to the New York Times, Genentech is putting the wholesale cost of pertuzumab at $5,900/month, which added to the typical $4,500/month costs of trastuzumab, would drive the cost of 18 months of treatment to $187,000.

Boxed Warning Put on Label

Pertuzumab is indicated in combination with trastuzumab and docetaxel for "patients with HER2-positive metastatic breast cancer who have not received prior anti–HER2 therapy or chemotherapy for metastatic disease."

The FDA announced that pertuzumab would have a boxed warning on its label. This is to alert clinicians and patients to the potential risk of death or severe effects to a fetus. "Pregnancy status must be verified prior to the start of Perjeta treatment," it said; patients should be advised "of these risks and need for effective contraception prior to starting pertuzumab."

According to the agency, the most common side effects observed with use of pertuzumab in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral sensory neuropathy.

Although left ventricular dysfunction was observed, the FDA said the combination of pertuzumab with standard therapy "was not associated with increases in the incidence of symptomatic left ventricular systolic dysfunction or decreases in left ventricular ejection fraction, compared with placebo in combination with trastuzumab and docetaxel.

The FDA recommended that pertuzumab be started at an initial dose of 840 mg administered as a 60-minute IV infusion, followed every 3 weeks, thereafter, by 420 mg administered as a 30- to 60-minute IV infusion. It also recommended that when trastuzumab is used with pertuzumab, trastuzumab should be started at 8 mg/kg administered as a 90-minute IV infusion, followed every 3 weeks by a dose of 6 mg/kg administered IV over 30 to 90 minutes. When docetaxel is given with pertuzumab, the recommended starting docetaxel dose is 75 mg/m² administered as an IV infusion. If well tolerated, docetaxel may be escalated to 100 mg/m² every 3 weeks.

* This story was updated on 11/30/2012.

Women with HER2-positive metastatic breast cancer have been given a double-edged sword, with the Food and Drug Administration granting approval to pertuzumab on Friday, June 8, as a first-line therapy.*

The addition of pertuzumab (Perjeta), a new HER2 blocker, to a standard chemotherapy combination of trastuzumab (Herceptin) and docetaxel (Taxotere) has been shown to extend progression-free survival in these patients. Overall survival data are not yet available.

Pertuzumab is a humanized monoclonal antibody, manufactured through biotechnology methods by Genentech, a subsidiary of Roche. It also blocks other HER family members, including EGFR, HER3, and HER4, and is believed to complement HER2 inhibition by trastuzumab, also made by Genentech and Roche.

The approval rides largely on the results of the CLEOPATRA (Clinical Evaluation of Pertuzumab and Trastuzumab) trial. Dual HER2 blockade boosted median progression-free survival from 12.4 months in a control group treated with only the standard combination to 18.5 months in a group treated with standard therapy plus-pertuzumab. This is a statistically significant difference that corresponds to a 38% reduction in the risk for progression or death and an increase of 6.1 months in median progression-free survival. These results were published in the New England Journal of Medicine (2012;366:109-19).

For the double-blind phase III trial, 808 patients aged 18 years and older with centrally confirmed HER2-positive metastatic or locally recurrent, unresectable breast cancer were randomized either to a control group that received placebo plus trastuzumab and docetaxel or to the pertuzumab group, which received pertuzumab plus trastuzumab and docetaxel.

Preliminary data from the CLEOPATRA trial were presented at the annual San Antonio Breast Cancer Symposium in early December 2011. For expert commentary on the trial, see our video report.

Supply, Cost Could Be Concerns

In their announcements of pertuzumab approval, Genentech, maker of the drug, and the FDA disclosed that production issues could affect the long-term supply of the drug.

"We expect to meet demand for Perjeta following today\'s FDA approval. We recently identified a cell growth issue that might affect our future supply of the medicine," said Patrick Y. Yang, Ph.D., head, Pharma Global Technical Operations. "We take this very seriously and are working with the FDA to ensure a consistent manufacturing process that maintains drug supply for the people who need it."

With the approval, Genentech has agreed to postmarketing commitments related to the manufacturing process for Perjeta. These include FDA review of data from the next several productions of the medicine.

The FDA limited its approval to drug product that has not been affected by production issues, according to Dr. Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research.

"Given the need for additional treatments for metastatic breast cancer, we made the decision to approve this drug today and not to delay its availability to patients pending resolution of the production issues relating to future supply," she said in the FDA announcement.

"Genentech is currently developing a plan to mitigate the effect on patients of any potential shortage of Perjeta."

An added concern is the high cost of dual HER2 inhibition at a time when oncologists are under pressure to contain costs. According to the New York Times, Genentech is putting the wholesale cost of pertuzumab at $5,900/month, which added to the typical $4,500/month costs of trastuzumab, would drive the cost of 18 months of treatment to $187,000.

Boxed Warning Put on Label

Pertuzumab is indicated in combination with trastuzumab and docetaxel for "patients with HER2-positive metastatic breast cancer who have not received prior anti–HER2 therapy or chemotherapy for metastatic disease."

The FDA announced that pertuzumab would have a boxed warning on its label. This is to alert clinicians and patients to the potential risk of death or severe effects to a fetus. "Pregnancy status must be verified prior to the start of Perjeta treatment," it said; patients should be advised "of these risks and need for effective contraception prior to starting pertuzumab."

According to the agency, the most common side effects observed with use of pertuzumab in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral sensory neuropathy.

Although left ventricular dysfunction was observed, the FDA said the combination of pertuzumab with standard therapy "was not associated with increases in the incidence of symptomatic left ventricular systolic dysfunction or decreases in left ventricular ejection fraction, compared with placebo in combination with trastuzumab and docetaxel.

The FDA recommended that pertuzumab be started at an initial dose of 840 mg administered as a 60-minute IV infusion, followed every 3 weeks, thereafter, by 420 mg administered as a 30- to 60-minute IV infusion. It also recommended that when trastuzumab is used with pertuzumab, trastuzumab should be started at 8 mg/kg administered as a 90-minute IV infusion, followed every 3 weeks by a dose of 6 mg/kg administered IV over 30 to 90 minutes. When docetaxel is given with pertuzumab, the recommended starting docetaxel dose is 75 mg/m² administered as an IV infusion. If well tolerated, docetaxel may be escalated to 100 mg/m² every 3 weeks.

* This story was updated on 11/30/2012.

Women with HER2-positive metastatic breast cancer have been given a double-edged sword, with the Food and Drug Administration granting approval to pertuzumab on Friday, June 8, as a first-line therapy.*

The addition of pertuzumab (Perjeta), a new HER2 blocker, to a standard chemotherapy combination of trastuzumab (Herceptin) and docetaxel (Taxotere) has been shown to extend progression-free survival in these patients. Overall survival data are not yet available.

Pertuzumab is a humanized monoclonal antibody, manufactured through biotechnology methods by Genentech, a subsidiary of Roche. It also blocks other HER family members, including EGFR, HER3, and HER4, and is believed to complement HER2 inhibition by trastuzumab, also made by Genentech and Roche.

The approval rides largely on the results of the CLEOPATRA (Clinical Evaluation of Pertuzumab and Trastuzumab) trial. Dual HER2 blockade boosted median progression-free survival from 12.4 months in a control group treated with only the standard combination to 18.5 months in a group treated with standard therapy plus-pertuzumab. This is a statistically significant difference that corresponds to a 38% reduction in the risk for progression or death and an increase of 6.1 months in median progression-free survival. These results were published in the New England Journal of Medicine (2012;366:109-19).

For the double-blind phase III trial, 808 patients aged 18 years and older with centrally confirmed HER2-positive metastatic or locally recurrent, unresectable breast cancer were randomized either to a control group that received placebo plus trastuzumab and docetaxel or to the pertuzumab group, which received pertuzumab plus trastuzumab and docetaxel.

Preliminary data from the CLEOPATRA trial were presented at the annual San Antonio Breast Cancer Symposium in early December 2011. For expert commentary on the trial, see our video report.

Supply, Cost Could Be Concerns

In their announcements of pertuzumab approval, Genentech, maker of the drug, and the FDA disclosed that production issues could affect the long-term supply of the drug.

"We expect to meet demand for Perjeta following today\'s FDA approval. We recently identified a cell growth issue that might affect our future supply of the medicine," said Patrick Y. Yang, Ph.D., head, Pharma Global Technical Operations. "We take this very seriously and are working with the FDA to ensure a consistent manufacturing process that maintains drug supply for the people who need it."

With the approval, Genentech has agreed to postmarketing commitments related to the manufacturing process for Perjeta. These include FDA review of data from the next several productions of the medicine.

The FDA limited its approval to drug product that has not been affected by production issues, according to Dr. Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research.

"Given the need for additional treatments for metastatic breast cancer, we made the decision to approve this drug today and not to delay its availability to patients pending resolution of the production issues relating to future supply," she said in the FDA announcement.

"Genentech is currently developing a plan to mitigate the effect on patients of any potential shortage of Perjeta."

An added concern is the high cost of dual HER2 inhibition at a time when oncologists are under pressure to contain costs. According to the New York Times, Genentech is putting the wholesale cost of pertuzumab at $5,900/month, which added to the typical $4,500/month costs of trastuzumab, would drive the cost of 18 months of treatment to $187,000.

Boxed Warning Put on Label

Pertuzumab is indicated in combination with trastuzumab and docetaxel for "patients with HER2-positive metastatic breast cancer who have not received prior anti–HER2 therapy or chemotherapy for metastatic disease."

The FDA announced that pertuzumab would have a boxed warning on its label. This is to alert clinicians and patients to the potential risk of death or severe effects to a fetus. "Pregnancy status must be verified prior to the start of Perjeta treatment," it said; patients should be advised "of these risks and need for effective contraception prior to starting pertuzumab."

According to the agency, the most common side effects observed with use of pertuzumab in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral sensory neuropathy.

Although left ventricular dysfunction was observed, the FDA said the combination of pertuzumab with standard therapy "was not associated with increases in the incidence of symptomatic left ventricular systolic dysfunction or decreases in left ventricular ejection fraction, compared with placebo in combination with trastuzumab and docetaxel.

The FDA recommended that pertuzumab be started at an initial dose of 840 mg administered as a 60-minute IV infusion, followed every 3 weeks, thereafter, by 420 mg administered as a 30- to 60-minute IV infusion. It also recommended that when trastuzumab is used with pertuzumab, trastuzumab should be started at 8 mg/kg administered as a 90-minute IV infusion, followed every 3 weeks by a dose of 6 mg/kg administered IV over 30 to 90 minutes. When docetaxel is given with pertuzumab, the recommended starting docetaxel dose is 75 mg/m² administered as an IV infusion. If well tolerated, docetaxel may be escalated to 100 mg/m² every 3 weeks.

* This story was updated on 11/30/2012.

SAN FRANCISCO – Regional recurrence is rare in breast cancer patients with a negative sentinel lymph node biopsy and does not appear to be associated with reduced overall survival, based on the latest results of a clinical trial including more than 5,500 patients.

"Regional recurrences were very low and remained so over the follow-up period," Dr. Kelly K. Hunt said at the annual meeting of the American Surgical Association. The 3-year cumulative incidence rate for regional recurrence was 0.003, and the rate at 5 years was 0.005. In comparison, the 3-year and 5-year rates for local recurrence were 0.013 and 0.024, respectively; the 3-year and 5-year rates for distant recurrence were 0.017 and 0.028, respectively.

Sentinel lymph node (SLN) dissection has been shown to improve staging, compared with axillary lymph node dissection (ALND) alone, and reduced morbidity and improved quality of life have been associated with SLN dissection. Thus, SLN dissection has replaced ALND in clinical practice for staging of regional lymph nodes in women with clinically node-negative, early-stage breast cancer. However, studies have shown false-negative rates ranging from 5% to 17%, noted Dr. Hunt of the department of surgical oncology at the MD Anderson Cancer Center in Houston.

She and her fellow researchers analyzed data from the American College of Surgeons Oncology Group (ACOSOG) Z0010 trial, a prospective multicenter trial designed to evaluate the prognostic implications of SLN and bone marrow micrometastases in women with early-stage breast cancer.

Eligible patients had biopsy-proven T1 or T2 breast cancer with clinically negative lymph nodes and were candidates for lumpectomy and whole breast irradiation. A total of 5,539 patients were enrolled from 126 participating sites. A total of 5,200 patients were fully evaluable, and a sentinel node was identified in 5,119.

Of those, 3,904 patients had negative lymph nodes based on standard H&E staining. Of the patients with negative SLNs on H&E staining, there were 3,326 who had sufficient samples for immunohistochemical staining for cytokeratin. Ten percent of these patients had positive nodes on immunohistochemistry (IHC).

In outcomes published last year, women with H&E positive sentinel nodes had decreased survival compared with those with H&E negative sentinel nodes (JAMA 2011;306:385-93 [doi:10.1001/jama.2011.1034]).

Patients were largely postmenopausal women with ductal breast cancers. They had mostly T1 tumors, many of which were hormone receptor–positive, low to intermediate grade. The majority of patients (98%) had breast-conserving surgery, and 68% patients received hormonal therapy as part of adjuvant treatment. Most patients (92%) finished adjuvant radiation, and almost half (44%) also received systemic chemotherapy. The median follow-up was 8.4 years. There were 127 local failures, 20 regional recurrences, and 134 distant recurrences. There were 317 deaths.

"Within this small group of locoregional recurrences, we did look at the differences in the patients who had IHC-positive vs. IHC-negative sentinel nodes and we did not see any difference between those two groups," Dr. Hunt said. As a result, they combined the two groups for subsequent analyses. "We did not see a difference in recurrence rates based on IHC status, despite the fact that we would suspect that some of these patients have residual disease in the axilla based on published false-negative rates from multicenter trials."

They also examined clinical factors, pathologic factors, and treatment factors that may have affected local and regional recurrences on univariable and multivariable analyses. In both models, younger age and negative hormone receptor status predicted both a greater rate of local failures and locoregional recurrences. With respect to distant recurrence, the important factors were increasing tumor size, the presence of lymphovascular invasion, and higher tumor grade.

Older age, larger tumor size, higher tumor grade, and the presence of a local recurrence predicted reduced overall survival. The hazard rate for local recurrence alone on multivariable analysis was 6.73 (P less than .0001).

"This study reassures anyone practicing in this field ... that those early clinical judgments we all made that drove early adoption of sentinel lymph node axillary staging and early, occasionally angst-ridden decisions to forgo axillary dissection in patients with early-stage breast cancer and minimal axillary nodal disease ... that those choices were correct," said invited discussant Dr. Barbara L. Bass, the John F. and Carolyn Bookout Distinguished Endowed Chair in the department of surgery at the Methodist Hospital in Houston and a professor of surgery at Cornell University in New York.

The regional recurrence rates are particularly interesting, she noted. "It practically makes you think that the axilla – our current bedrock for decision making and staging – is in fact a hostile soil for tumor cells, compared to the breast and distant sites." She asked why the axilla was practically immune from recurrence. "Clearly, those lymph nodes in that space were still there, but tumor does not go or grow there."

Dr. Hunt said earlier studies have suggested that some nodal disease is not clinically relevant and requires no treatment. However, with SLN surgery, "the more that we look, the more we find these micrometastases, and the bias is to treat them."

With improved adjuvant therapy, "we are eradicating disease with those treatments. We know that from neoadjuvant trials as well," Dr. Hunt added. In trials at MD Anderson, after chemotherapy 25% of patients who had fine-needle biopsy at initial diagnosis have complete eradication of disease in the nodes, she said.

"Now that we understand more about the subtypes, we see that in HER-2 positive disease, we’re eradicating about 75% of the disease in regional nodes with targeted therapies." Systemic therapy has gotten better, but it also appears that there are metastases that are not clinically or biologically relevant.

Because the first site of failure is generally the only site recorded, the researchers also performed a competing risk regression model to account for patients with local, regional, and distant recurrences. Evaluating competing risks demonstrated that hormone receptor–negative disease and lack of systemic chemotherapy are associated with increased risk of local recurrence. Older age, higher tumor size, greater tumor grade, and local recurrence predicted decreased survival.

Dr. Bass observed that currently, staging is based largely on the features of the primary tumor – gene assessments, tumor markers, and so on. In light of this, she wondered how long will it will be necessary to surgically stage the clinically negative axilla in patients with early-stage disease who are treated with breast-conserving therapy.

"Do the results of this trial mean that it might be possible to forgo sentinel lymph node staging of the axilla in some patients?" she asked.

That question remains to be answered, according to Dr. Hunt. Planning is underway for a trial in early-stage breast cancer to compare SLN surgery with no treatment of the axilla. "This is based on the fact that we know that different biologic subtypes have very different local and regional recurrence patterns." So, for example, in women with HER-2 positive or triple-negative disease, the systemic treatment regimen is clear with or without nodal involvement.

The researchers reported that they have no relevant conflicts of interest.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

SAN FRANCISCO – Regional recurrence is rare in breast cancer patients with a negative sentinel lymph node biopsy and does not appear to be associated with reduced overall survival, based on the latest results of a clinical trial including more than 5,500 patients.

"Regional recurrences were very low and remained so over the follow-up period," Dr. Kelly K. Hunt said at the annual meeting of the American Surgical Association. The 3-year cumulative incidence rate for regional recurrence was 0.003, and the rate at 5 years was 0.005. In comparison, the 3-year and 5-year rates for local recurrence were 0.013 and 0.024, respectively; the 3-year and 5-year rates for distant recurrence were 0.017 and 0.028, respectively.

Sentinel lymph node (SLN) dissection has been shown to improve staging, compared with axillary lymph node dissection (ALND) alone, and reduced morbidity and improved quality of life have been associated with SLN dissection. Thus, SLN dissection has replaced ALND in clinical practice for staging of regional lymph nodes in women with clinically node-negative, early-stage breast cancer. However, studies have shown false-negative rates ranging from 5% to 17%, noted Dr. Hunt of the department of surgical oncology at the MD Anderson Cancer Center in Houston.

She and her fellow researchers analyzed data from the American College of Surgeons Oncology Group (ACOSOG) Z0010 trial, a prospective multicenter trial designed to evaluate the prognostic implications of SLN and bone marrow micrometastases in women with early-stage breast cancer.

Eligible patients had biopsy-proven T1 or T2 breast cancer with clinically negative lymph nodes and were candidates for lumpectomy and whole breast irradiation. A total of 5,539 patients were enrolled from 126 participating sites. A total of 5,200 patients were fully evaluable, and a sentinel node was identified in 5,119.

Of those, 3,904 patients had negative lymph nodes based on standard H&E staining. Of the patients with negative SLNs on H&E staining, there were 3,326 who had sufficient samples for immunohistochemical staining for cytokeratin. Ten percent of these patients had positive nodes on immunohistochemistry (IHC).

In outcomes published last year, women with H&E positive sentinel nodes had decreased survival compared with those with H&E negative sentinel nodes (JAMA 2011;306:385-93 [doi:10.1001/jama.2011.1034]).

Patients were largely postmenopausal women with ductal breast cancers. They had mostly T1 tumors, many of which were hormone receptor–positive, low to intermediate grade. The majority of patients (98%) had breast-conserving surgery, and 68% patients received hormonal therapy as part of adjuvant treatment. Most patients (92%) finished adjuvant radiation, and almost half (44%) also received systemic chemotherapy. The median follow-up was 8.4 years. There were 127 local failures, 20 regional recurrences, and 134 distant recurrences. There were 317 deaths.

"Within this small group of locoregional recurrences, we did look at the differences in the patients who had IHC-positive vs. IHC-negative sentinel nodes and we did not see any difference between those two groups," Dr. Hunt said. As a result, they combined the two groups for subsequent analyses. "We did not see a difference in recurrence rates based on IHC status, despite the fact that we would suspect that some of these patients have residual disease in the axilla based on published false-negative rates from multicenter trials."

They also examined clinical factors, pathologic factors, and treatment factors that may have affected local and regional recurrences on univariable and multivariable analyses. In both models, younger age and negative hormone receptor status predicted both a greater rate of local failures and locoregional recurrences. With respect to distant recurrence, the important factors were increasing tumor size, the presence of lymphovascular invasion, and higher tumor grade.

Older age, larger tumor size, higher tumor grade, and the presence of a local recurrence predicted reduced overall survival. The hazard rate for local recurrence alone on multivariable analysis was 6.73 (P less than .0001).

"This study reassures anyone practicing in this field ... that those early clinical judgments we all made that drove early adoption of sentinel lymph node axillary staging and early, occasionally angst-ridden decisions to forgo axillary dissection in patients with early-stage breast cancer and minimal axillary nodal disease ... that those choices were correct," said invited discussant Dr. Barbara L. Bass, the John F. and Carolyn Bookout Distinguished Endowed Chair in the department of surgery at the Methodist Hospital in Houston and a professor of surgery at Cornell University in New York.

The regional recurrence rates are particularly interesting, she noted. "It practically makes you think that the axilla – our current bedrock for decision making and staging – is in fact a hostile soil for tumor cells, compared to the breast and distant sites." She asked why the axilla was practically immune from recurrence. "Clearly, those lymph nodes in that space were still there, but tumor does not go or grow there."

Dr. Hunt said earlier studies have suggested that some nodal disease is not clinically relevant and requires no treatment. However, with SLN surgery, "the more that we look, the more we find these micrometastases, and the bias is to treat them."

With improved adjuvant therapy, "we are eradicating disease with those treatments. We know that from neoadjuvant trials as well," Dr. Hunt added. In trials at MD Anderson, after chemotherapy 25% of patients who had fine-needle biopsy at initial diagnosis have complete eradication of disease in the nodes, she said.

"Now that we understand more about the subtypes, we see that in HER-2 positive disease, we’re eradicating about 75% of the disease in regional nodes with targeted therapies." Systemic therapy has gotten better, but it also appears that there are metastases that are not clinically or biologically relevant.

Because the first site of failure is generally the only site recorded, the researchers also performed a competing risk regression model to account for patients with local, regional, and distant recurrences. Evaluating competing risks demonstrated that hormone receptor–negative disease and lack of systemic chemotherapy are associated with increased risk of local recurrence. Older age, higher tumor size, greater tumor grade, and local recurrence predicted decreased survival.

Dr. Bass observed that currently, staging is based largely on the features of the primary tumor – gene assessments, tumor markers, and so on. In light of this, she wondered how long will it will be necessary to surgically stage the clinically negative axilla in patients with early-stage disease who are treated with breast-conserving therapy.

"Do the results of this trial mean that it might be possible to forgo sentinel lymph node staging of the axilla in some patients?" she asked.

That question remains to be answered, according to Dr. Hunt. Planning is underway for a trial in early-stage breast cancer to compare SLN surgery with no treatment of the axilla. "This is based on the fact that we know that different biologic subtypes have very different local and regional recurrence patterns." So, for example, in women with HER-2 positive or triple-negative disease, the systemic treatment regimen is clear with or without nodal involvement.

The researchers reported that they have no relevant conflicts of interest.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

SAN FRANCISCO – Regional recurrence is rare in breast cancer patients with a negative sentinel lymph node biopsy and does not appear to be associated with reduced overall survival, based on the latest results of a clinical trial including more than 5,500 patients.

"Regional recurrences were very low and remained so over the follow-up period," Dr. Kelly K. Hunt said at the annual meeting of the American Surgical Association. The 3-year cumulative incidence rate for regional recurrence was 0.003, and the rate at 5 years was 0.005. In comparison, the 3-year and 5-year rates for local recurrence were 0.013 and 0.024, respectively; the 3-year and 5-year rates for distant recurrence were 0.017 and 0.028, respectively.

Sentinel lymph node (SLN) dissection has been shown to improve staging, compared with axillary lymph node dissection (ALND) alone, and reduced morbidity and improved quality of life have been associated with SLN dissection. Thus, SLN dissection has replaced ALND in clinical practice for staging of regional lymph nodes in women with clinically node-negative, early-stage breast cancer. However, studies have shown false-negative rates ranging from 5% to 17%, noted Dr. Hunt of the department of surgical oncology at the MD Anderson Cancer Center in Houston.

She and her fellow researchers analyzed data from the American College of Surgeons Oncology Group (ACOSOG) Z0010 trial, a prospective multicenter trial designed to evaluate the prognostic implications of SLN and bone marrow micrometastases in women with early-stage breast cancer.

Eligible patients had biopsy-proven T1 or T2 breast cancer with clinically negative lymph nodes and were candidates for lumpectomy and whole breast irradiation. A total of 5,539 patients were enrolled from 126 participating sites. A total of 5,200 patients were fully evaluable, and a sentinel node was identified in 5,119.

Of those, 3,904 patients had negative lymph nodes based on standard H&E staining. Of the patients with negative SLNs on H&E staining, there were 3,326 who had sufficient samples for immunohistochemical staining for cytokeratin. Ten percent of these patients had positive nodes on immunohistochemistry (IHC).

In outcomes published last year, women with H&E positive sentinel nodes had decreased survival compared with those with H&E negative sentinel nodes (JAMA 2011;306:385-93 [doi:10.1001/jama.2011.1034]).

Patients were largely postmenopausal women with ductal breast cancers. They had mostly T1 tumors, many of which were hormone receptor–positive, low to intermediate grade. The majority of patients (98%) had breast-conserving surgery, and 68% patients received hormonal therapy as part of adjuvant treatment. Most patients (92%) finished adjuvant radiation, and almost half (44%) also received systemic chemotherapy. The median follow-up was 8.4 years. There were 127 local failures, 20 regional recurrences, and 134 distant recurrences. There were 317 deaths.

"Within this small group of locoregional recurrences, we did look at the differences in the patients who had IHC-positive vs. IHC-negative sentinel nodes and we did not see any difference between those two groups," Dr. Hunt said. As a result, they combined the two groups for subsequent analyses. "We did not see a difference in recurrence rates based on IHC status, despite the fact that we would suspect that some of these patients have residual disease in the axilla based on published false-negative rates from multicenter trials."

They also examined clinical factors, pathologic factors, and treatment factors that may have affected local and regional recurrences on univariable and multivariable analyses. In both models, younger age and negative hormone receptor status predicted both a greater rate of local failures and locoregional recurrences. With respect to distant recurrence, the important factors were increasing tumor size, the presence of lymphovascular invasion, and higher tumor grade.

Older age, larger tumor size, higher tumor grade, and the presence of a local recurrence predicted reduced overall survival. The hazard rate for local recurrence alone on multivariable analysis was 6.73 (P less than .0001).

"This study reassures anyone practicing in this field ... that those early clinical judgments we all made that drove early adoption of sentinel lymph node axillary staging and early, occasionally angst-ridden decisions to forgo axillary dissection in patients with early-stage breast cancer and minimal axillary nodal disease ... that those choices were correct," said invited discussant Dr. Barbara L. Bass, the John F. and Carolyn Bookout Distinguished Endowed Chair in the department of surgery at the Methodist Hospital in Houston and a professor of surgery at Cornell University in New York.

The regional recurrence rates are particularly interesting, she noted. "It practically makes you think that the axilla – our current bedrock for decision making and staging – is in fact a hostile soil for tumor cells, compared to the breast and distant sites." She asked why the axilla was practically immune from recurrence. "Clearly, those lymph nodes in that space were still there, but tumor does not go or grow there."

Dr. Hunt said earlier studies have suggested that some nodal disease is not clinically relevant and requires no treatment. However, with SLN surgery, "the more that we look, the more we find these micrometastases, and the bias is to treat them."

With improved adjuvant therapy, "we are eradicating disease with those treatments. We know that from neoadjuvant trials as well," Dr. Hunt added. In trials at MD Anderson, after chemotherapy 25% of patients who had fine-needle biopsy at initial diagnosis have complete eradication of disease in the nodes, she said.

"Now that we understand more about the subtypes, we see that in HER-2 positive disease, we’re eradicating about 75% of the disease in regional nodes with targeted therapies." Systemic therapy has gotten better, but it also appears that there are metastases that are not clinically or biologically relevant.

Because the first site of failure is generally the only site recorded, the researchers also performed a competing risk regression model to account for patients with local, regional, and distant recurrences. Evaluating competing risks demonstrated that hormone receptor–negative disease and lack of systemic chemotherapy are associated with increased risk of local recurrence. Older age, higher tumor size, greater tumor grade, and local recurrence predicted decreased survival.

Dr. Bass observed that currently, staging is based largely on the features of the primary tumor – gene assessments, tumor markers, and so on. In light of this, she wondered how long will it will be necessary to surgically stage the clinically negative axilla in patients with early-stage disease who are treated with breast-conserving therapy.

"Do the results of this trial mean that it might be possible to forgo sentinel lymph node staging of the axilla in some patients?" she asked.

That question remains to be answered, according to Dr. Hunt. Planning is underway for a trial in early-stage breast cancer to compare SLN surgery with no treatment of the axilla. "This is based on the fact that we know that different biologic subtypes have very different local and regional recurrence patterns." So, for example, in women with HER-2 positive or triple-negative disease, the systemic treatment regimen is clear with or without nodal involvement.

The researchers reported that they have no relevant conflicts of interest.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

SAN FRANCISCO – The introduction of endovascular aneurysm repair, or EVAR, has improved outcomes for the repair of intact and ruptured aortic abdominal aneurysms, particularly among those aged 80 years and older, based on a review of more than 400,000 Medicare beneficiaries.

Among patients in this age group, there was an increase in the number of intact abdominal aortic aneurysm (AAA) repairs, coupled with declines in rupture deaths. In those younger than 75 years, intact repair rates decreased about 10%. Those aged 75-79 years had an increase of about 10%. However, those aged 80 years and older had a more dramatic increase of more than 50%. In addition, operative mortality for intact repair has decreased over time for all age groups, although the decline becomes greater with increasing age.

"The greatest benefit [of EVAR] has been seen in those over 80, who had the largest increase in intact repair rates, the largest decline in intact repair mortality, and the largest decline in rupture deaths," Dr. Marc L. Schermerhorn said at the annual meeting of the American Surgical Association.

The researchers used a 100% sample of Medicare data between 1995 and 2008. They identified patients with intact AAAs undergoing repair – by either EVAR or open surgical repair – as well as patients with ruptured AAAs (with and without repair). They determined the 30-day or in-hospital mortality, then standardized the rates (per 100,000 beneficiaries), adjusting for changes in age, sex, and population size over time.

They identified 338,278 intact repairs and 69,653 ruptures (with 47,524 repairs). EVAR use rapidly increased after Food and Drug Administration approval of the procedure in 1999; as of 2008, EVAR was used for 77% of all intact aneurysm repairs.

"There was a more delayed response but an increase nonetheless in the use of EVAR for ruptured aneurysms, to the point where [in 2008] 31% of all ruptured aneurysms are treated with EVAR," said Dr. Schermerhorn. During this time period, the average age of those undergoing repair increased from 73.7 to 75.5 years.

Operative mortality during open intact repair remained steady, at roughly 5%. EVAR mortality dropped from about 2% in 1995 to 1.4% in 2008. The total operative mortality for intact repair (open and EVAR) fell from roughly 5% to 2.4%, despite the fact that there were more repairs in 2008 and the average age of these patients increased.

"As we increase our utilization of EVAR, this is driving down the total mortality of intact aneurysm repair, so that it’s half of what it was at the beginning of that time period," said Dr. Schermerhorn, chief of vascular and endovascular surgery at Beth Israel Deaconess Medical Center in Boston.

The researchers also found that the annual number of ruptures decreased from 6,535 in 1995 to 3,298 in 2008. The greatest decrease in ruptures (repaired or not) was seen in older patients – those 75 years and older – but there was also a decline among patients younger than 75 years. The mortality with open rupture repair remained largely unchanged during the time period (approximately 45%). However, EVAR rupture repair declined from about 45% to 28%. The rate of all rupture repairs also has decreased from about 45% to 36%.

"Rather than suggesting that we’re simply taking the hemodynamically stable patients for EVAR, the best evidence to say that there’s actually a true reduction in mortality is the fact that for the first time in 3 decades, the overall mortality for ruptured aneurysm repair is now well below 40%," Dr. Schermerhorn said. The mortality for all ruptures (repaired or not) has gone down the most dramatically in those aged 80 years and older, although there were declines in the other age groups as well.

Invited discussant Dr. Philip B. Paty noted that reduced rates of intact aneurysm repair and rupture in patients aged 65-74 years may be attributed to a change in the natural history or a decline in the incidence of aneurysms.

"Did you evaluate the age-specific incidence of comorbidities or medical risk over the period of study to see if we are, in fact, dealing with different patient populations? Alternatively, is it possible that repair in recent years was deferred until a larger sac size was present?" he asked.

"We did look at comorbidities over time, and there have been increases in all of the various comorbidities that you would typically associate with aortic aneurysm patients. Coronary artery disease, peripheral arterial disease, hypertension, and [heart failure] all increased. We did not have access to data about rates of cigarette smoking or medication," Dr. Schermerhorn said.

Other studies have shown that the rate of smoking has gone down with time and the use of statins has gone up. There may be better control of hypertension as well. "We think that it’s possible that for those reasons, there may be a decreasing incidence of aortic aneurysm in the United States." Data from the United Kingdom, Sweden, and Australia suggest that there may be a decline in those countries, he added.

Dr. Paty, vice chair of clinical research in the department of surgery at Memorial Sloan-Kettering Cancer Center in New York, also questioned whether the data reflect a change in practice to observing smaller aneurysms, delaying repair.

This may be the case, according to Dr. Schermerhorn. "Are we deferring aneurysms? I would agree completely." Studies have shown "that it’s safe for us to wait until the aneurysms are up in the 5.5-cm range. So I think that a lot of that redistribution of those [younger than 75 years to those just older than 75] may represent that. That should, however, decrease the rate of aneurysm repair that we do, and some patients will die of competitive causes during that observation period. So that should not be reflected in the increased rate of repair that we detected." In addition, the increased use of advanced abdominal imaging has led to the identification of more aneurysms.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

The authors reported that they have no relevant conflicts of interest.

SAN FRANCISCO – The introduction of endovascular aneurysm repair, or EVAR, has improved outcomes for the repair of intact and ruptured aortic abdominal aneurysms, particularly among those aged 80 years and older, based on a review of more than 400,000 Medicare beneficiaries.

Among patients in this age group, there was an increase in the number of intact abdominal aortic aneurysm (AAA) repairs, coupled with declines in rupture deaths. In those younger than 75 years, intact repair rates decreased about 10%. Those aged 75-79 years had an increase of about 10%. However, those aged 80 years and older had a more dramatic increase of more than 50%. In addition, operative mortality for intact repair has decreased over time for all age groups, although the decline becomes greater with increasing age.

"The greatest benefit [of EVAR] has been seen in those over 80, who had the largest increase in intact repair rates, the largest decline in intact repair mortality, and the largest decline in rupture deaths," Dr. Marc L. Schermerhorn said at the annual meeting of the American Surgical Association.

The researchers used a 100% sample of Medicare data between 1995 and 2008. They identified patients with intact AAAs undergoing repair – by either EVAR or open surgical repair – as well as patients with ruptured AAAs (with and without repair). They determined the 30-day or in-hospital mortality, then standardized the rates (per 100,000 beneficiaries), adjusting for changes in age, sex, and population size over time.

They identified 338,278 intact repairs and 69,653 ruptures (with 47,524 repairs). EVAR use rapidly increased after Food and Drug Administration approval of the procedure in 1999; as of 2008, EVAR was used for 77% of all intact aneurysm repairs.

"There was a more delayed response but an increase nonetheless in the use of EVAR for ruptured aneurysms, to the point where [in 2008] 31% of all ruptured aneurysms are treated with EVAR," said Dr. Schermerhorn. During this time period, the average age of those undergoing repair increased from 73.7 to 75.5 years.

Operative mortality during open intact repair remained steady, at roughly 5%. EVAR mortality dropped from about 2% in 1995 to 1.4% in 2008. The total operative mortality for intact repair (open and EVAR) fell from roughly 5% to 2.4%, despite the fact that there were more repairs in 2008 and the average age of these patients increased.

"As we increase our utilization of EVAR, this is driving down the total mortality of intact aneurysm repair, so that it’s half of what it was at the beginning of that time period," said Dr. Schermerhorn, chief of vascular and endovascular surgery at Beth Israel Deaconess Medical Center in Boston.

The researchers also found that the annual number of ruptures decreased from 6,535 in 1995 to 3,298 in 2008. The greatest decrease in ruptures (repaired or not) was seen in older patients – those 75 years and older – but there was also a decline among patients younger than 75 years. The mortality with open rupture repair remained largely unchanged during the time period (approximately 45%). However, EVAR rupture repair declined from about 45% to 28%. The rate of all rupture repairs also has decreased from about 45% to 36%.

"Rather than suggesting that we’re simply taking the hemodynamically stable patients for EVAR, the best evidence to say that there’s actually a true reduction in mortality is the fact that for the first time in 3 decades, the overall mortality for ruptured aneurysm repair is now well below 40%," Dr. Schermerhorn said. The mortality for all ruptures (repaired or not) has gone down the most dramatically in those aged 80 years and older, although there were declines in the other age groups as well.

Invited discussant Dr. Philip B. Paty noted that reduced rates of intact aneurysm repair and rupture in patients aged 65-74 years may be attributed to a change in the natural history or a decline in the incidence of aneurysms.

"Did you evaluate the age-specific incidence of comorbidities or medical risk over the period of study to see if we are, in fact, dealing with different patient populations? Alternatively, is it possible that repair in recent years was deferred until a larger sac size was present?" he asked.

"We did look at comorbidities over time, and there have been increases in all of the various comorbidities that you would typically associate with aortic aneurysm patients. Coronary artery disease, peripheral arterial disease, hypertension, and [heart failure] all increased. We did not have access to data about rates of cigarette smoking or medication," Dr. Schermerhorn said.

Other studies have shown that the rate of smoking has gone down with time and the use of statins has gone up. There may be better control of hypertension as well. "We think that it’s possible that for those reasons, there may be a decreasing incidence of aortic aneurysm in the United States." Data from the United Kingdom, Sweden, and Australia suggest that there may be a decline in those countries, he added.

Dr. Paty, vice chair of clinical research in the department of surgery at Memorial Sloan-Kettering Cancer Center in New York, also questioned whether the data reflect a change in practice to observing smaller aneurysms, delaying repair.

This may be the case, according to Dr. Schermerhorn. "Are we deferring aneurysms? I would agree completely." Studies have shown "that it’s safe for us to wait until the aneurysms are up in the 5.5-cm range. So I think that a lot of that redistribution of those [younger than 75 years to those just older than 75] may represent that. That should, however, decrease the rate of aneurysm repair that we do, and some patients will die of competitive causes during that observation period. So that should not be reflected in the increased rate of repair that we detected." In addition, the increased use of advanced abdominal imaging has led to the identification of more aneurysms.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

The authors reported that they have no relevant conflicts of interest.

SAN FRANCISCO – The introduction of endovascular aneurysm repair, or EVAR, has improved outcomes for the repair of intact and ruptured aortic abdominal aneurysms, particularly among those aged 80 years and older, based on a review of more than 400,000 Medicare beneficiaries.

Among patients in this age group, there was an increase in the number of intact abdominal aortic aneurysm (AAA) repairs, coupled with declines in rupture deaths. In those younger than 75 years, intact repair rates decreased about 10%. Those aged 75-79 years had an increase of about 10%. However, those aged 80 years and older had a more dramatic increase of more than 50%. In addition, operative mortality for intact repair has decreased over time for all age groups, although the decline becomes greater with increasing age.

"The greatest benefit [of EVAR] has been seen in those over 80, who had the largest increase in intact repair rates, the largest decline in intact repair mortality, and the largest decline in rupture deaths," Dr. Marc L. Schermerhorn said at the annual meeting of the American Surgical Association.

The researchers used a 100% sample of Medicare data between 1995 and 2008. They identified patients with intact AAAs undergoing repair – by either EVAR or open surgical repair – as well as patients with ruptured AAAs (with and without repair). They determined the 30-day or in-hospital mortality, then standardized the rates (per 100,000 beneficiaries), adjusting for changes in age, sex, and population size over time.

They identified 338,278 intact repairs and 69,653 ruptures (with 47,524 repairs). EVAR use rapidly increased after Food and Drug Administration approval of the procedure in 1999; as of 2008, EVAR was used for 77% of all intact aneurysm repairs.

"There was a more delayed response but an increase nonetheless in the use of EVAR for ruptured aneurysms, to the point where [in 2008] 31% of all ruptured aneurysms are treated with EVAR," said Dr. Schermerhorn. During this time period, the average age of those undergoing repair increased from 73.7 to 75.5 years.

Operative mortality during open intact repair remained steady, at roughly 5%. EVAR mortality dropped from about 2% in 1995 to 1.4% in 2008. The total operative mortality for intact repair (open and EVAR) fell from roughly 5% to 2.4%, despite the fact that there were more repairs in 2008 and the average age of these patients increased.

"As we increase our utilization of EVAR, this is driving down the total mortality of intact aneurysm repair, so that it’s half of what it was at the beginning of that time period," said Dr. Schermerhorn, chief of vascular and endovascular surgery at Beth Israel Deaconess Medical Center in Boston.

The researchers also found that the annual number of ruptures decreased from 6,535 in 1995 to 3,298 in 2008. The greatest decrease in ruptures (repaired or not) was seen in older patients – those 75 years and older – but there was also a decline among patients younger than 75 years. The mortality with open rupture repair remained largely unchanged during the time period (approximately 45%). However, EVAR rupture repair declined from about 45% to 28%. The rate of all rupture repairs also has decreased from about 45% to 36%.

"Rather than suggesting that we’re simply taking the hemodynamically stable patients for EVAR, the best evidence to say that there’s actually a true reduction in mortality is the fact that for the first time in 3 decades, the overall mortality for ruptured aneurysm repair is now well below 40%," Dr. Schermerhorn said. The mortality for all ruptures (repaired or not) has gone down the most dramatically in those aged 80 years and older, although there were declines in the other age groups as well.

Invited discussant Dr. Philip B. Paty noted that reduced rates of intact aneurysm repair and rupture in patients aged 65-74 years may be attributed to a change in the natural history or a decline in the incidence of aneurysms.

"Did you evaluate the age-specific incidence of comorbidities or medical risk over the period of study to see if we are, in fact, dealing with different patient populations? Alternatively, is it possible that repair in recent years was deferred until a larger sac size was present?" he asked.

"We did look at comorbidities over time, and there have been increases in all of the various comorbidities that you would typically associate with aortic aneurysm patients. Coronary artery disease, peripheral arterial disease, hypertension, and [heart failure] all increased. We did not have access to data about rates of cigarette smoking or medication," Dr. Schermerhorn said.

Other studies have shown that the rate of smoking has gone down with time and the use of statins has gone up. There may be better control of hypertension as well. "We think that it’s possible that for those reasons, there may be a decreasing incidence of aortic aneurysm in the United States." Data from the United Kingdom, Sweden, and Australia suggest that there may be a decline in those countries, he added.

Dr. Paty, vice chair of clinical research in the department of surgery at Memorial Sloan-Kettering Cancer Center in New York, also questioned whether the data reflect a change in practice to observing smaller aneurysms, delaying repair.

This may be the case, according to Dr. Schermerhorn. "Are we deferring aneurysms? I would agree completely." Studies have shown "that it’s safe for us to wait until the aneurysms are up in the 5.5-cm range. So I think that a lot of that redistribution of those [younger than 75 years to those just older than 75] may represent that. That should, however, decrease the rate of aneurysm repair that we do, and some patients will die of competitive causes during that observation period. So that should not be reflected in the increased rate of repair that we detected." In addition, the increased use of advanced abdominal imaging has led to the identification of more aneurysms.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

The authors reported that they have no relevant conflicts of interest.

SAN FRANCISCO – Laparoscopic duodenal switch should be considered a revisional procedure rather than a primary procedure for morbidly obese patients unable to lose enough weight with other bariatric procedures, a retrospective database review indicates.

"I see a role for laparoscopic DS [duodenal switch], for example, following a failed laparoscopic sleeve ... in patients who have a high BMI ... . If they lose all of their weight or at least [reach] a reasonable weight, that’s fine. If they can’t lose the weight, then adding laparoscopic DS in patients who have lost some weight becomes an easier operation," said Dr. Namir Katkhouda, director of the bariatric surgery program at the Keck School of Medicine of the University of Southern California in Los Angeles.

Data from a review of open DS cases for morbid obesity between 1993 and 2011 at the Keck Medical Center showed that the DS procedure is associated with a high ongoing morbidity, Dr. Katkhouda said at the annual meeting of the American Surgical Association. Complications such as strictures and reflux could be linked, and the open approach was responsible for a high rate of hernias. Therefore, DS should not be routinely recommended as a primary procedure for morbid obesity, he noted.

"With the continued scrutiny for the safety of bariatric surgery, I agree with the authors that the DS is an operation that should only be performed in selected high-volume centers and on patients with severe concomitant medical metabolic disease who are willing to return for follow-up" to assess complications, said invited discussant Dr. Ninh T. Nguyen, chief of the gastrointestinal surgery at the University of California in Irvine.

Dr. Katkhouda and his colleagues performed a retrospective study of a prospective bariatric surgery database and electronic medical records. They included all patients who had a DS procedure for morbid obesity between 1993 and 2011. Follow-up data included all hospital readmissions and standardized telephone questionnaires. Mortality was assessed by using the Social Security death index database.

Among the 1,162 patients they identified, the median age was 42 years and most patients (80%) were women. Their median BMI was 51 kg/m². Median follow-up was 115 months. Common comorbidities included hypertension, pulmonary disease, diabetes, hyperlipidemia, and cardiac disease. Most patients had one to five comorbidities.

The overall readmission rate was 52%. The mean number of readmissions in patients with complications was 2.4. The median length of stay was 6 days for patients with complications vs. 5 days for those without complications, a significant difference. Overall, 40% of patients had reoperations and 14% had two or more reoperations.

The overall complication rate was 58% and the median time to complication was 19 months. Among patients with complications, the reoperation rate was 68%. For patients with fistula, leak, DS failure, dehiscence, small bowel obstruction, or hernia, the reoperation rate was greater than 50%.

Gastroesophageal reflux disease occurred in 64 patients – half de novo and half persistent. Among patients with GERD, the reoperative rate with conversion to Roux-en-Y gastric bypass was 39%. The rate of small bowel obstruction was 7%; the reoperation rate in this group was 74%. Severe malabsorption occurred in 11% of patients. Of these, 29% had hypoalbuminemia, 21% were iron deficient, and 21% had hypocalcemia. An additional 29% had other types of malabsorption. Overall, 42% of patients with malabsorption required reoperation.

On univariate analysis, coronary artery disease, pulmonary disease, dyslipidemia, and degenerative joint disease were identified as risk factors for complications. The presence of more than two comorbidities and age were also risk factors for complications. On multivariate analysis, patients with degenerative joint disease had a fivefold increased risk of complications. Patients with dyslipidemia had a 42% greater risk of complications; African Americans had an 87% greater risk.

The overall mortality was 7%. The median age at death was 51 years. Perioperative mortality was 0.9%; three patients had fatal cardiac events, one had pulmonary embolism, two had respiratory failure, and four had multiorgan failure.

On univariate analysis, gender, race, coronary artery disease, hypertension, age, and BMI were significant predictors of mortality. On multivariate analysis, only age and African American race were significant predictors.

Limitations of the study include the fact that it is a single-center, observational study, and results were not compared with those of another method such as gastric bypass, Dr. Katkhouda said, noting that outcomes could be different in a multicenter study.

Dr. Nguyen said that duodenal switch is not a common bariatric procedure; it accounts for less than 1% of all bariatric procedures performed in the United States. "The perioperative mortality at 0.9% in this series is fourfold higher than that of contemporary data for banded, bypass, or sleeve," he said.

Attributing the high reoperation rate in this series primarily to the use of an open approach, he suggested that outcomes could potentially be improved with a laparoscopic approach.

The authors reported that they have no financial disclosures relevant to the study. However, Dr. Katkhouda is a consultant for Karl Storz, W.L. Gore & Associates Inc., Baxter, and C. R. Bard Inc.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

SAN FRANCISCO – Laparoscopic duodenal switch should be considered a revisional procedure rather than a primary procedure for morbidly obese patients unable to lose enough weight with other bariatric procedures, a retrospective database review indicates.

"I see a role for laparoscopic DS [duodenal switch], for example, following a failed laparoscopic sleeve ... in patients who have a high BMI ... . If they lose all of their weight or at least [reach] a reasonable weight, that’s fine. If they can’t lose the weight, then adding laparoscopic DS in patients who have lost some weight becomes an easier operation," said Dr. Namir Katkhouda, director of the bariatric surgery program at the Keck School of Medicine of the University of Southern California in Los Angeles.

Data from a review of open DS cases for morbid obesity between 1993 and 2011 at the Keck Medical Center showed that the DS procedure is associated with a high ongoing morbidity, Dr. Katkhouda said at the annual meeting of the American Surgical Association. Complications such as strictures and reflux could be linked, and the open approach was responsible for a high rate of hernias. Therefore, DS should not be routinely recommended as a primary procedure for morbid obesity, he noted.

"With the continued scrutiny for the safety of bariatric surgery, I agree with the authors that the DS is an operation that should only be performed in selected high-volume centers and on patients with severe concomitant medical metabolic disease who are willing to return for follow-up" to assess complications, said invited discussant Dr. Ninh T. Nguyen, chief of the gastrointestinal surgery at the University of California in Irvine.

Dr. Katkhouda and his colleagues performed a retrospective study of a prospective bariatric surgery database and electronic medical records. They included all patients who had a DS procedure for morbid obesity between 1993 and 2011. Follow-up data included all hospital readmissions and standardized telephone questionnaires. Mortality was assessed by using the Social Security death index database.

Among the 1,162 patients they identified, the median age was 42 years and most patients (80%) were women. Their median BMI was 51 kg/m². Median follow-up was 115 months. Common comorbidities included hypertension, pulmonary disease, diabetes, hyperlipidemia, and cardiac disease. Most patients had one to five comorbidities.

The overall readmission rate was 52%. The mean number of readmissions in patients with complications was 2.4. The median length of stay was 6 days for patients with complications vs. 5 days for those without complications, a significant difference. Overall, 40% of patients had reoperations and 14% had two or more reoperations.

The overall complication rate was 58% and the median time to complication was 19 months. Among patients with complications, the reoperation rate was 68%. For patients with fistula, leak, DS failure, dehiscence, small bowel obstruction, or hernia, the reoperation rate was greater than 50%.

Gastroesophageal reflux disease occurred in 64 patients – half de novo and half persistent. Among patients with GERD, the reoperative rate with conversion to Roux-en-Y gastric bypass was 39%. The rate of small bowel obstruction was 7%; the reoperation rate in this group was 74%. Severe malabsorption occurred in 11% of patients. Of these, 29% had hypoalbuminemia, 21% were iron deficient, and 21% had hypocalcemia. An additional 29% had other types of malabsorption. Overall, 42% of patients with malabsorption required reoperation.

On univariate analysis, coronary artery disease, pulmonary disease, dyslipidemia, and degenerative joint disease were identified as risk factors for complications. The presence of more than two comorbidities and age were also risk factors for complications. On multivariate analysis, patients with degenerative joint disease had a fivefold increased risk of complications. Patients with dyslipidemia had a 42% greater risk of complications; African Americans had an 87% greater risk.

The overall mortality was 7%. The median age at death was 51 years. Perioperative mortality was 0.9%; three patients had fatal cardiac events, one had pulmonary embolism, two had respiratory failure, and four had multiorgan failure.

On univariate analysis, gender, race, coronary artery disease, hypertension, age, and BMI were significant predictors of mortality. On multivariate analysis, only age and African American race were significant predictors.

Limitations of the study include the fact that it is a single-center, observational study, and results were not compared with those of another method such as gastric bypass, Dr. Katkhouda said, noting that outcomes could be different in a multicenter study.

Dr. Nguyen said that duodenal switch is not a common bariatric procedure; it accounts for less than 1% of all bariatric procedures performed in the United States. "The perioperative mortality at 0.9% in this series is fourfold higher than that of contemporary data for banded, bypass, or sleeve," he said.

Attributing the high reoperation rate in this series primarily to the use of an open approach, he suggested that outcomes could potentially be improved with a laparoscopic approach.

The authors reported that they have no financial disclosures relevant to the study. However, Dr. Katkhouda is a consultant for Karl Storz, W.L. Gore & Associates Inc., Baxter, and C. R. Bard Inc.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

SAN FRANCISCO – Laparoscopic duodenal switch should be considered a revisional procedure rather than a primary procedure for morbidly obese patients unable to lose enough weight with other bariatric procedures, a retrospective database review indicates.

"I see a role for laparoscopic DS [duodenal switch], for example, following a failed laparoscopic sleeve ... in patients who have a high BMI ... . If they lose all of their weight or at least [reach] a reasonable weight, that’s fine. If they can’t lose the weight, then adding laparoscopic DS in patients who have lost some weight becomes an easier operation," said Dr. Namir Katkhouda, director of the bariatric surgery program at the Keck School of Medicine of the University of Southern California in Los Angeles.

Data from a review of open DS cases for morbid obesity between 1993 and 2011 at the Keck Medical Center showed that the DS procedure is associated with a high ongoing morbidity, Dr. Katkhouda said at the annual meeting of the American Surgical Association. Complications such as strictures and reflux could be linked, and the open approach was responsible for a high rate of hernias. Therefore, DS should not be routinely recommended as a primary procedure for morbid obesity, he noted.

"With the continued scrutiny for the safety of bariatric surgery, I agree with the authors that the DS is an operation that should only be performed in selected high-volume centers and on patients with severe concomitant medical metabolic disease who are willing to return for follow-up" to assess complications, said invited discussant Dr. Ninh T. Nguyen, chief of the gastrointestinal surgery at the University of California in Irvine.

Dr. Katkhouda and his colleagues performed a retrospective study of a prospective bariatric surgery database and electronic medical records. They included all patients who had a DS procedure for morbid obesity between 1993 and 2011. Follow-up data included all hospital readmissions and standardized telephone questionnaires. Mortality was assessed by using the Social Security death index database.

Among the 1,162 patients they identified, the median age was 42 years and most patients (80%) were women. Their median BMI was 51 kg/m². Median follow-up was 115 months. Common comorbidities included hypertension, pulmonary disease, diabetes, hyperlipidemia, and cardiac disease. Most patients had one to five comorbidities.

The overall readmission rate was 52%. The mean number of readmissions in patients with complications was 2.4. The median length of stay was 6 days for patients with complications vs. 5 days for those without complications, a significant difference. Overall, 40% of patients had reoperations and 14% had two or more reoperations.

The overall complication rate was 58% and the median time to complication was 19 months. Among patients with complications, the reoperation rate was 68%. For patients with fistula, leak, DS failure, dehiscence, small bowel obstruction, or hernia, the reoperation rate was greater than 50%.

Gastroesophageal reflux disease occurred in 64 patients – half de novo and half persistent. Among patients with GERD, the reoperative rate with conversion to Roux-en-Y gastric bypass was 39%. The rate of small bowel obstruction was 7%; the reoperation rate in this group was 74%. Severe malabsorption occurred in 11% of patients. Of these, 29% had hypoalbuminemia, 21% were iron deficient, and 21% had hypocalcemia. An additional 29% had other types of malabsorption. Overall, 42% of patients with malabsorption required reoperation.

On univariate analysis, coronary artery disease, pulmonary disease, dyslipidemia, and degenerative joint disease were identified as risk factors for complications. The presence of more than two comorbidities and age were also risk factors for complications. On multivariate analysis, patients with degenerative joint disease had a fivefold increased risk of complications. Patients with dyslipidemia had a 42% greater risk of complications; African Americans had an 87% greater risk.

The overall mortality was 7%. The median age at death was 51 years. Perioperative mortality was 0.9%; three patients had fatal cardiac events, one had pulmonary embolism, two had respiratory failure, and four had multiorgan failure.

On univariate analysis, gender, race, coronary artery disease, hypertension, age, and BMI were significant predictors of mortality. On multivariate analysis, only age and African American race were significant predictors.

Limitations of the study include the fact that it is a single-center, observational study, and results were not compared with those of another method such as gastric bypass, Dr. Katkhouda said, noting that outcomes could be different in a multicenter study.

Dr. Nguyen said that duodenal switch is not a common bariatric procedure; it accounts for less than 1% of all bariatric procedures performed in the United States. "The perioperative mortality at 0.9% in this series is fourfold higher than that of contemporary data for banded, bypass, or sleeve," he said.

Attributing the high reoperation rate in this series primarily to the use of an open approach, he suggested that outcomes could potentially be improved with a laparoscopic approach.

The authors reported that they have no financial disclosures relevant to the study. However, Dr. Katkhouda is a consultant for Karl Storz, W.L. Gore & Associates Inc., Baxter, and C. R. Bard Inc.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

BALTIMORE – Obstetrician/gynecologists frequently use mesh kits for pelvic organ prolapse repair, although a considerable number do not routinely perform cystoscopy after prolapse repair, a survey of 261 physicians has shown.

In the study, almost three-quarters (72%) of the 261 respondents reported using anterior, posterior, or total mesh kits, reported Dr. Maria Estanol, who is a second-year fellow in female pelvic medicine and reconstructive surgery at Good Samaritan Hospital in Cincinnati.

After performing a retropubic midurethral sling, 95% reported performing cystoscopy. However, the numbers declined with other procedures: 82% performed cystoscopy after placing a transobturator midurethral sling; 81%, after placing a retropubic pubovaginal sling; and 74%, after doing a Burch bladder neck suspension. Only 46% reported performing cystoscopy after doing a uterosacral ligament suspension; 29%, after McCall’s culdoplasty; and 34%, after an anterior repair.

These were the findings from a cross-sectional survey of a random sample of 3,225 ob.gyns. The researchers used the American Medical Association’s physician database to identify potential participants. The sample was equally distributed for sex, geographical location of practice, and age group. Subspecialists were excluded. The researchers asked participants to answer a 32-item, Internet-based questionnaire about the management of stress urinary incontinence and pelvic organ prolapse (POP), Dr. Estanol reported at the annual meeting of the Society of Gynecologic Surgeons.

A total of 261 physicians responded (8% response rate). Roughly one-third of participants were between 41 and 60 years of age. The remaining two-thirds were 31-40 years of age or older than 60 years. Almost half (45%) of the physicians had been in practice more than 20 years. About two-thirds were male, and approximately two-thirds were in private practice.

Of the respondents, 54% reported performing urodynamics in their practice, and 57% reported doing residency training in urodynamics. Most (81%) reported performing surgery for stress incontinence. Three-quarters had performed transobturator midurethral sling procedures, 73% had performed retropubic midurethral sling procedures, and 69% had performed Burch bladder neck suspension procedures as treatments for stress urinary incontinence.

Almost all (99%) reported managing POP (surgical or medical), and 88% reported performing surgery for POP. Ninety-three percent reported doing residency surgical training for prolapse.

The meeting was jointly sponsored by the American College of Surgeons.

Dr. Estanol and her associates reported that they had no relevant financial disclosures.

BALTIMORE – Obstetrician/gynecologists frequently use mesh kits for pelvic organ prolapse repair, although a considerable number do not routinely perform cystoscopy after prolapse repair, a survey of 261 physicians has shown.

In the study, almost three-quarters (72%) of the 261 respondents reported using anterior, posterior, or total mesh kits, reported Dr. Maria Estanol, who is a second-year fellow in female pelvic medicine and reconstructive surgery at Good Samaritan Hospital in Cincinnati.

After performing a retropubic midurethral sling, 95% reported performing cystoscopy. However, the numbers declined with other procedures: 82% performed cystoscopy after placing a transobturator midurethral sling; 81%, after placing a retropubic pubovaginal sling; and 74%, after doing a Burch bladder neck suspension. Only 46% reported performing cystoscopy after doing a uterosacral ligament suspension; 29%, after McCall’s culdoplasty; and 34%, after an anterior repair.

These were the findings from a cross-sectional survey of a random sample of 3,225 ob.gyns. The researchers used the American Medical Association’s physician database to identify potential participants. The sample was equally distributed for sex, geographical location of practice, and age group. Subspecialists were excluded. The researchers asked participants to answer a 32-item, Internet-based questionnaire about the management of stress urinary incontinence and pelvic organ prolapse (POP), Dr. Estanol reported at the annual meeting of the Society of Gynecologic Surgeons.

A total of 261 physicians responded (8% response rate). Roughly one-third of participants were between 41 and 60 years of age. The remaining two-thirds were 31-40 years of age or older than 60 years. Almost half (45%) of the physicians had been in practice more than 20 years. About two-thirds were male, and approximately two-thirds were in private practice.

Of the respondents, 54% reported performing urodynamics in their practice, and 57% reported doing residency training in urodynamics. Most (81%) reported performing surgery for stress incontinence. Three-quarters had performed transobturator midurethral sling procedures, 73% had performed retropubic midurethral sling procedures, and 69% had performed Burch bladder neck suspension procedures as treatments for stress urinary incontinence.

Almost all (99%) reported managing POP (surgical or medical), and 88% reported performing surgery for POP. Ninety-three percent reported doing residency surgical training for prolapse.

The meeting was jointly sponsored by the American College of Surgeons.

Dr. Estanol and her associates reported that they had no relevant financial disclosures.

BALTIMORE – Obstetrician/gynecologists frequently use mesh kits for pelvic organ prolapse repair, although a considerable number do not routinely perform cystoscopy after prolapse repair, a survey of 261 physicians has shown.

In the study, almost three-quarters (72%) of the 261 respondents reported using anterior, posterior, or total mesh kits, reported Dr. Maria Estanol, who is a second-year fellow in female pelvic medicine and reconstructive surgery at Good Samaritan Hospital in Cincinnati.

After performing a retropubic midurethral sling, 95% reported performing cystoscopy. However, the numbers declined with other procedures: 82% performed cystoscopy after placing a transobturator midurethral sling; 81%, after placing a retropubic pubovaginal sling; and 74%, after doing a Burch bladder neck suspension. Only 46% reported performing cystoscopy after doing a uterosacral ligament suspension; 29%, after McCall’s culdoplasty; and 34%, after an anterior repair.

These were the findings from a cross-sectional survey of a random sample of 3,225 ob.gyns. The researchers used the American Medical Association’s physician database to identify potential participants. The sample was equally distributed for sex, geographical location of practice, and age group. Subspecialists were excluded. The researchers asked participants to answer a 32-item, Internet-based questionnaire about the management of stress urinary incontinence and pelvic organ prolapse (POP), Dr. Estanol reported at the annual meeting of the Society of Gynecologic Surgeons.

A total of 261 physicians responded (8% response rate). Roughly one-third of participants were between 41 and 60 years of age. The remaining two-thirds were 31-40 years of age or older than 60 years. Almost half (45%) of the physicians had been in practice more than 20 years. About two-thirds were male, and approximately two-thirds were in private practice.

Of the respondents, 54% reported performing urodynamics in their practice, and 57% reported doing residency training in urodynamics. Most (81%) reported performing surgery for stress incontinence. Three-quarters had performed transobturator midurethral sling procedures, 73% had performed retropubic midurethral sling procedures, and 69% had performed Burch bladder neck suspension procedures as treatments for stress urinary incontinence.

Almost all (99%) reported managing POP (surgical or medical), and 88% reported performing surgery for POP. Ninety-three percent reported doing residency surgical training for prolapse.

The meeting was jointly sponsored by the American College of Surgeons.

Dr. Estanol and her associates reported that they had no relevant financial disclosures.

BALTIMORE – Anal sphincter laceration is significantly associated with anal incontinence 5-10 years after a woman’s first delivery and has significant impact on quality of life, compared with women who had a vaginal delivery without laceration and women who had cesarean section.

The findings come from a secondary analysis of 1,007 women enrolled in a prospective cohort study of pelvic floor outcomes.

However, researchers noted that women who had vaginal delivery without tear had similar anal incontinence symptoms as those seen in women who had cesarean sections.

"This suggests that vaginal delivery – in the absence of sphincter laceration – is not a risk factor for anal incontinence," said Dr. Joan L. Blomquist, an obstetrician at Greater Baltimore Medical Center, who presented the study at the annual meeting of the Society for Gynecologic Surgeons.

Obstetrical anal sphincter laceration is a known risk factor for anal incontinence. In this study, the researchers compared anal incontinence and adverse impact on their quality of life between women who had a vaginal delivery with anal sphincter laceration, compared with woman who had a vaginal delivery without anal sphincter laceration and women who underwent a cesarean procedure.

They performed a secondary analysis of data from the Mothers’ Outcomes After Delivery (MOAD) prospective cohort study of pelvic floor outcomes. For this analysis, the researchers included women whose first delivery was 5-10 years previous. Sphincter laceration was defined as a clinically recognizable third or fourth degree laceration.

Anal incontinence symptoms were assessed using the Epidemiology of Prolapse and Incontinence Questionnaire (EPIQ). The researchers used the published threshold of 22.8 to identify anal incontinence. The impact on quality of life was assessed using the Colorectal-Anal Impact Questionnaire (CRAIQ-7).

Nineteen percent of women who had vaginal delivery and anal sphincter laceration met the criteria for anal incontinence according to the EPIQ. In comparison, among women with vaginal delivery without tear or women who underwent cesarean delivery, only 10% and 9% met the criteria.

They identified 1,007 women – 95 with vaginal delivery with a tear, 353 with vaginal delivery without a tear, and 559 with cesarean delivery. The groups did not differ with regard to race, age at enrollment or age greater than 35 at the first delivery. There were a slightly greater number of multiparous women in the vaginal control group. Women in the cesarean group were more likely to be obese at the time of enrollment.

In terms of bowel symptoms, the researchers asked if the women ever lost gas, liquid stool, or loose well-formed stool beyond their control. There was very little difference between the vaginal delivery without tear group and the cesarean delivery group for all three questions. However, there was a significant difference between cesarean delivery and vaginal delivery with tear.

The researchers also asked women with any bowel symptoms if their symptoms had affected their chores, physical recreation, entertainment, travel, social activities, and feeling frustrated. Again, the numbers were similar for vaginal delivery without tear and cesarean delivery. Women with tears had significantly greater impact on all of the activities.

All of the researchers reported that they have no relevant conflicts of interest to disclose. The study was supported by a National Institutes of Health grant.

BALTIMORE – Anal sphincter laceration is significantly associated with anal incontinence 5-10 years after a woman’s first delivery and has significant impact on quality of life, compared with women who had a vaginal delivery without laceration and women who had cesarean section.

The findings come from a secondary analysis of 1,007 women enrolled in a prospective cohort study of pelvic floor outcomes.

However, researchers noted that women who had vaginal delivery without tear had similar anal incontinence symptoms as those seen in women who had cesarean sections.

"This suggests that vaginal delivery – in the absence of sphincter laceration – is not a risk factor for anal incontinence," said Dr. Joan L. Blomquist, an obstetrician at Greater Baltimore Medical Center, who presented the study at the annual meeting of the Society for Gynecologic Surgeons.

Obstetrical anal sphincter laceration is a known risk factor for anal incontinence. In this study, the researchers compared anal incontinence and adverse impact on their quality of life between women who had a vaginal delivery with anal sphincter laceration, compared with woman who had a vaginal delivery without anal sphincter laceration and women who underwent a cesarean procedure.

They performed a secondary analysis of data from the Mothers’ Outcomes After Delivery (MOAD) prospective cohort study of pelvic floor outcomes. For this analysis, the researchers included women whose first delivery was 5-10 years previous. Sphincter laceration was defined as a clinically recognizable third or fourth degree laceration.

Anal incontinence symptoms were assessed using the Epidemiology of Prolapse and Incontinence Questionnaire (EPIQ). The researchers used the published threshold of 22.8 to identify anal incontinence. The impact on quality of life was assessed using the Colorectal-Anal Impact Questionnaire (CRAIQ-7).

Nineteen percent of women who had vaginal delivery and anal sphincter laceration met the criteria for anal incontinence according to the EPIQ. In comparison, among women with vaginal delivery without tear or women who underwent cesarean delivery, only 10% and 9% met the criteria.

They identified 1,007 women – 95 with vaginal delivery with a tear, 353 with vaginal delivery without a tear, and 559 with cesarean delivery. The groups did not differ with regard to race, age at enrollment or age greater than 35 at the first delivery. There were a slightly greater number of multiparous women in the vaginal control group. Women in the cesarean group were more likely to be obese at the time of enrollment.

In terms of bowel symptoms, the researchers asked if the women ever lost gas, liquid stool, or loose well-formed stool beyond their control. There was very little difference between the vaginal delivery without tear group and the cesarean delivery group for all three questions. However, there was a significant difference between cesarean delivery and vaginal delivery with tear.

The researchers also asked women with any bowel symptoms if their symptoms had affected their chores, physical recreation, entertainment, travel, social activities, and feeling frustrated. Again, the numbers were similar for vaginal delivery without tear and cesarean delivery. Women with tears had significantly greater impact on all of the activities.

All of the researchers reported that they have no relevant conflicts of interest to disclose. The study was supported by a National Institutes of Health grant.

BALTIMORE – Anal sphincter laceration is significantly associated with anal incontinence 5-10 years after a woman’s first delivery and has significant impact on quality of life, compared with women who had a vaginal delivery without laceration and women who had cesarean section.

The findings come from a secondary analysis of 1,007 women enrolled in a prospective cohort study of pelvic floor outcomes.

However, researchers noted that women who had vaginal delivery without tear had similar anal incontinence symptoms as those seen in women who had cesarean sections.

"This suggests that vaginal delivery – in the absence of sphincter laceration – is not a risk factor for anal incontinence," said Dr. Joan L. Blomquist, an obstetrician at Greater Baltimore Medical Center, who presented the study at the annual meeting of the Society for Gynecologic Surgeons.

Obstetrical anal sphincter laceration is a known risk factor for anal incontinence. In this study, the researchers compared anal incontinence and adverse impact on their quality of life between women who had a vaginal delivery with anal sphincter laceration, compared with woman who had a vaginal delivery without anal sphincter laceration and women who underwent a cesarean procedure.

They performed a secondary analysis of data from the Mothers’ Outcomes After Delivery (MOAD) prospective cohort study of pelvic floor outcomes. For this analysis, the researchers included women whose first delivery was 5-10 years previous. Sphincter laceration was defined as a clinically recognizable third or fourth degree laceration.

Anal incontinence symptoms were assessed using the Epidemiology of Prolapse and Incontinence Questionnaire (EPIQ). The researchers used the published threshold of 22.8 to identify anal incontinence. The impact on quality of life was assessed using the Colorectal-Anal Impact Questionnaire (CRAIQ-7).

Nineteen percent of women who had vaginal delivery and anal sphincter laceration met the criteria for anal incontinence according to the EPIQ. In comparison, among women with vaginal delivery without tear or women who underwent cesarean delivery, only 10% and 9% met the criteria.

They identified 1,007 women – 95 with vaginal delivery with a tear, 353 with vaginal delivery without a tear, and 559 with cesarean delivery. The groups did not differ with regard to race, age at enrollment or age greater than 35 at the first delivery. There were a slightly greater number of multiparous women in the vaginal control group. Women in the cesarean group were more likely to be obese at the time of enrollment.

In terms of bowel symptoms, the researchers asked if the women ever lost gas, liquid stool, or loose well-formed stool beyond their control. There was very little difference between the vaginal delivery without tear group and the cesarean delivery group for all three questions. However, there was a significant difference between cesarean delivery and vaginal delivery with tear.

The researchers also asked women with any bowel symptoms if their symptoms had affected their chores, physical recreation, entertainment, travel, social activities, and feeling frustrated. Again, the numbers were similar for vaginal delivery without tear and cesarean delivery. Women with tears had significantly greater impact on all of the activities.

All of the researchers reported that they have no relevant conflicts of interest to disclose. The study was supported by a National Institutes of Health grant.

SAN FRANCISCO – Elderly patients with preexisting Do Not Resuscitate directives appear to be less likely to pursue rescue from complications following emergency surgery than similar patients without such orders, according to an analysis of data from the National Surgical Quality Improvement Program.

When patients with preoperative DNRs were propensity-matched with non-DNR patients, major complication rates were similar – 42% for the DNR group and 41% for the non-DNR group. However, 37% of DNR patients died, compared with 22% of non-DNR patients, Dr. John E. Scarborough reported at the annual meeting of the American Surgical Association. The investigators adjusted for baseline differences in level of illness to create a propensity-matched cohort of 1,053 patients in each group.

"While we called this outcome failure-to-rescue, we believe that term to be misleading. The term implies that rescue from complications is attempted but is unsuccessful. ... We had no reason to believe that the DNR patients in this well-matched cohort were any less capable of being rescued than non-DNR patients," Dr. Scarborough said. "Instead, we believe that the DNR patients in the matched cohort were less likely than non-DNR patients to pursue rescue from complications."

This conclusion is supported by the finding that DNR patients were significantly less likely to undergo reoperation within 30 days of the index procedure (odds ratio, 0.67).

The authors used participant files from the National Surgical Quality Improvement Program (NSQIP) for 2005-2010, involving medical records for 25,558 patients. These patients were at least 65 years old and underwent an emergency operation for one of 10 common surgical diagnoses. The primary predictor variable was preoperative DNR status, which was defined as "an order signed or cosigned by an attending physician in the 30 days prior to surgery ... regardless of whether the DNR order was subsequently rescinded immediately before the index operation." Other predictor variables included patient demographics, chronic comorbid disease burden, acute physical condition at presentation, and complexity of the emergency operation.

Outcome variables included the 30-day postoperative mortality rate and the 30-day major complication rate – organ/space surgical site infection, wound dehiscence, deep vein thrombosis, pulmonary embolism, pneumonia, reintubation, ventilator use longer than 48 hours, cardiac arrest, myocardial infarction, sepsis, shock, coma longer than 24 hours, prosthetic/graft failure, and bleeding. The failure-to-rescue rate was defined as the mortality rate among patients who had one or more major complications.

A total of 1,061 patients had DNR orders, and 24,497 patients did not. The overall 30-day mortality rate for patients with a DNR order was 37% (395/1,061). The overall 30-day morbidity for patients with a DNR was 42% (446/1,061).

Patients with DNR orders were older: 22% were at least 90 years of age, compared with 5% of the non-DNR patients. They were also sicker, with significantly greater rates of non–independent functional status, cognitive dysfunction, known malignancy, congestive heart failure, chronic obstructive pulmonary disease, ASA physical status class 4, preoperative hypoalbuminemia, and septic shock.

"Although the DNR patients were sicker, we did not find any overt evidence that they were treated less aggressively than non-DNR patients in the preoperative period," said Dr. Scarborough, of the department of surgery at Duke University in Durham, N.C. There was no significant difference between DNR and non-DNR patients in terms of preoperative mechanical ventilation (6% vs. 5%, respectively); and DNR patients were significantly more likely to receive a preoperative transfusion.

There was also no indication that DNR patients were treated less aggressively in the operating room. Operative time was significantly longer for DNR patients, and DNR patients underwent procedures at least as complex as, if not more than, procedures for non-DNR patients.

Invited discussant Dr. Ronnie A. Rosenthal asked how these data could be used to improve the way families are counseled before operations involving elderly patients with DNRs. Dr. Rosenthal is surgeon-in-chief at the VA Connecticut Healthcare System in New Haven.

"What we hope this study provides is a more reliable and sturdy resource for surgeons to counsel such patients than merely explaining to them what the average outcomes are," said Dr. Scarborough. He noted that the oncology literature suggests that patients who better understand their prognosis are in a better position to evaluate whether they want to pursue more aggressive treatment or treatments that have a lot of side effects.

Dr. Norman Estes, chair of the surgery department at the University of Illinois in Peoria, questioned how much of a role surgeons should play in advance planning. "I think that sometimes the advance directive creates a self-fulfilling prophecy for the patient."

Dr. Scarborough noted that advance directives need to be signed by the attending physician. "As to whether the surgeon should be more engaged in the conversation, I guess I would say that it depends on the surgeon. This is a very delicate conversation and obviously one that requires a fair amount of time," he said. Other physicians – such as geriatricians and palliative care physicians – are often more skilled at handling these conversations.

However, it is important for surgeons to have a greater understanding of the patient’s intent with regard to DNR directives, he concluded.

The authors reported that they had no financial disclosures.

SAN FRANCISCO – Elderly patients with preexisting Do Not Resuscitate directives appear to be less likely to pursue rescue from complications following emergency surgery than similar patients without such orders, according to an analysis of data from the National Surgical Quality Improvement Program.

When patients with preoperative DNRs were propensity-matched with non-DNR patients, major complication rates were similar – 42% for the DNR group and 41% for the non-DNR group. However, 37% of DNR patients died, compared with 22% of non-DNR patients, Dr. John E. Scarborough reported at the annual meeting of the American Surgical Association. The investigators adjusted for baseline differences in level of illness to create a propensity-matched cohort of 1,053 patients in each group.

"While we called this outcome failure-to-rescue, we believe that term to be misleading. The term implies that rescue from complications is attempted but is unsuccessful. ... We had no reason to believe that the DNR patients in this well-matched cohort were any less capable of being rescued than non-DNR patients," Dr. Scarborough said. "Instead, we believe that the DNR patients in the matched cohort were less likely than non-DNR patients to pursue rescue from complications."

This conclusion is supported by the finding that DNR patients were significantly less likely to undergo reoperation within 30 days of the index procedure (odds ratio, 0.67).

The authors used participant files from the National Surgical Quality Improvement Program (NSQIP) for 2005-2010, involving medical records for 25,558 patients. These patients were at least 65 years old and underwent an emergency operation for one of 10 common surgical diagnoses. The primary predictor variable was preoperative DNR status, which was defined as "an order signed or cosigned by an attending physician in the 30 days prior to surgery ... regardless of whether the DNR order was subsequently rescinded immediately before the index operation." Other predictor variables included patient demographics, chronic comorbid disease burden, acute physical condition at presentation, and complexity of the emergency operation.

Outcome variables included the 30-day postoperative mortality rate and the 30-day major complication rate – organ/space surgical site infection, wound dehiscence, deep vein thrombosis, pulmonary embolism, pneumonia, reintubation, ventilator use longer than 48 hours, cardiac arrest, myocardial infarction, sepsis, shock, coma longer than 24 hours, prosthetic/graft failure, and bleeding. The failure-to-rescue rate was defined as the mortality rate among patients who had one or more major complications.

A total of 1,061 patients had DNR orders, and 24,497 patients did not. The overall 30-day mortality rate for patients with a DNR order was 37% (395/1,061). The overall 30-day morbidity for patients with a DNR was 42% (446/1,061).

Patients with DNR orders were older: 22% were at least 90 years of age, compared with 5% of the non-DNR patients. They were also sicker, with significantly greater rates of non–independent functional status, cognitive dysfunction, known malignancy, congestive heart failure, chronic obstructive pulmonary disease, ASA physical status class 4, preoperative hypoalbuminemia, and septic shock.

"Although the DNR patients were sicker, we did not find any overt evidence that they were treated less aggressively than non-DNR patients in the preoperative period," said Dr. Scarborough, of the department of surgery at Duke University in Durham, N.C. There was no significant difference between DNR and non-DNR patients in terms of preoperative mechanical ventilation (6% vs. 5%, respectively); and DNR patients were significantly more likely to receive a preoperative transfusion.

There was also no indication that DNR patients were treated less aggressively in the operating room. Operative time was significantly longer for DNR patients, and DNR patients underwent procedures at least as complex as, if not more than, procedures for non-DNR patients.

Invited discussant Dr. Ronnie A. Rosenthal asked how these data could be used to improve the way families are counseled before operations involving elderly patients with DNRs. Dr. Rosenthal is surgeon-in-chief at the VA Connecticut Healthcare System in New Haven.

"What we hope this study provides is a more reliable and sturdy resource for surgeons to counsel such patients than merely explaining to them what the average outcomes are," said Dr. Scarborough. He noted that the oncology literature suggests that patients who better understand their prognosis are in a better position to evaluate whether they want to pursue more aggressive treatment or treatments that have a lot of side effects.

Dr. Norman Estes, chair of the surgery department at the University of Illinois in Peoria, questioned how much of a role surgeons should play in advance planning. "I think that sometimes the advance directive creates a self-fulfilling prophecy for the patient."

Dr. Scarborough noted that advance directives need to be signed by the attending physician. "As to whether the surgeon should be more engaged in the conversation, I guess I would say that it depends on the surgeon. This is a very delicate conversation and obviously one that requires a fair amount of time," he said. Other physicians – such as geriatricians and palliative care physicians – are often more skilled at handling these conversations.

However, it is important for surgeons to have a greater understanding of the patient’s intent with regard to DNR directives, he concluded.

The authors reported that they had no financial disclosures.

SAN FRANCISCO – Elderly patients with preexisting Do Not Resuscitate directives appear to be less likely to pursue rescue from complications following emergency surgery than similar patients without such orders, according to an analysis of data from the National Surgical Quality Improvement Program.

When patients with preoperative DNRs were propensity-matched with non-DNR patients, major complication rates were similar – 42% for the DNR group and 41% for the non-DNR group. However, 37% of DNR patients died, compared with 22% of non-DNR patients, Dr. John E. Scarborough reported at the annual meeting of the American Surgical Association. The investigators adjusted for baseline differences in level of illness to create a propensity-matched cohort of 1,053 patients in each group.

"While we called this outcome failure-to-rescue, we believe that term to be misleading. The term implies that rescue from complications is attempted but is unsuccessful. ... We had no reason to believe that the DNR patients in this well-matched cohort were any less capable of being rescued than non-DNR patients," Dr. Scarborough said. "Instead, we believe that the DNR patients in the matched cohort were less likely than non-DNR patients to pursue rescue from complications."

This conclusion is supported by the finding that DNR patients were significantly less likely to undergo reoperation within 30 days of the index procedure (odds ratio, 0.67).

The authors used participant files from the National Surgical Quality Improvement Program (NSQIP) for 2005-2010, involving medical records for 25,558 patients. These patients were at least 65 years old and underwent an emergency operation for one of 10 common surgical diagnoses. The primary predictor variable was preoperative DNR status, which was defined as "an order signed or cosigned by an attending physician in the 30 days prior to surgery ... regardless of whether the DNR order was subsequently rescinded immediately before the index operation." Other predictor variables included patient demographics, chronic comorbid disease burden, acute physical condition at presentation, and complexity of the emergency operation.

Outcome variables included the 30-day postoperative mortality rate and the 30-day major complication rate – organ/space surgical site infection, wound dehiscence, deep vein thrombosis, pulmonary embolism, pneumonia, reintubation, ventilator use longer than 48 hours, cardiac arrest, myocardial infarction, sepsis, shock, coma longer than 24 hours, prosthetic/graft failure, and bleeding. The failure-to-rescue rate was defined as the mortality rate among patients who had one or more major complications.

A total of 1,061 patients had DNR orders, and 24,497 patients did not. The overall 30-day mortality rate for patients with a DNR order was 37% (395/1,061). The overall 30-day morbidity for patients with a DNR was 42% (446/1,061).

Patients with DNR orders were older: 22% were at least 90 years of age, compared with 5% of the non-DNR patients. They were also sicker, with significantly greater rates of non–independent functional status, cognitive dysfunction, known malignancy, congestive heart failure, chronic obstructive pulmonary disease, ASA physical status class 4, preoperative hypoalbuminemia, and septic shock.

"Although the DNR patients were sicker, we did not find any overt evidence that they were treated less aggressively than non-DNR patients in the preoperative period," said Dr. Scarborough, of the department of surgery at Duke University in Durham, N.C. There was no significant difference between DNR and non-DNR patients in terms of preoperative mechanical ventilation (6% vs. 5%, respectively); and DNR patients were significantly more likely to receive a preoperative transfusion.

There was also no indication that DNR patients were treated less aggressively in the operating room. Operative time was significantly longer for DNR patients, and DNR patients underwent procedures at least as complex as, if not more than, procedures for non-DNR patients.

Invited discussant Dr. Ronnie A. Rosenthal asked how these data could be used to improve the way families are counseled before operations involving elderly patients with DNRs. Dr. Rosenthal is surgeon-in-chief at the VA Connecticut Healthcare System in New Haven.

"What we hope this study provides is a more reliable and sturdy resource for surgeons to counsel such patients than merely explaining to them what the average outcomes are," said Dr. Scarborough. He noted that the oncology literature suggests that patients who better understand their prognosis are in a better position to evaluate whether they want to pursue more aggressive treatment or treatments that have a lot of side effects.

Dr. Norman Estes, chair of the surgery department at the University of Illinois in Peoria, questioned how much of a role surgeons should play in advance planning. "I think that sometimes the advance directive creates a self-fulfilling prophecy for the patient."

Dr. Scarborough noted that advance directives need to be signed by the attending physician. "As to whether the surgeon should be more engaged in the conversation, I guess I would say that it depends on the surgeon. This is a very delicate conversation and obviously one that requires a fair amount of time," he said. Other physicians – such as geriatricians and palliative care physicians – are often more skilled at handling these conversations.

However, it is important for surgeons to have a greater understanding of the patient’s intent with regard to DNR directives, he concluded.

The authors reported that they had no financial disclosures.