Kerri Wachter

The recently approved cancer drug crizotinib draws strong responses in children whose cancers have mutations in the gene targeted by the drug, according to early data from a phase I dose-escalating study.

The most dramatic improvements occurred in anaplastic large-cell lymphoma, with complete and durable responses observed in 7 of 8 children with the ALK mutation, which is common in the disease. Crizotinib (Xalkori) also appeared to be active in subsets of children with inflammatory myofibroblastic tumor and neuroblastoma, though the early data were less clear in these cancers.

"Crizotinib appears to have a high degree of activity in children with anaplastic large-cell lymphoma – the majority of whom are driven by the ALK oncogene," lead author Dr. Yael P. Mosse said during a press briefing in advance of the annual meeting of the American Society of Clinical Oncology. She noted that these are phase I results and should be taken with caution.

"Certainly for the eight patients that we enrolled with anaplastic large cell lymphoma – seven of whom have had a complete response and a durable response – I think that this is dramatic activity and has already met the bar for what you would look for in a phase-II trial ... for neuroblastoma there is still a lot of work to be done," said Dr. Mosse of Children’s Hospital of Philadelphia and the University of Pennsylvania.

"The story is really a glimpse at the new paradigm for understanding of cancer and drug development," said ASCO President Dr. Michael Link, comoderator of the press briefing.

"It’s no longer adequate to identify a tumor based on histology organ of origin. It’s now understood that tumors are heterogeneous and it’s key to understand the particular molecular driver," said Dr. Link of Stanford (Calif.) University.

"If you understand the molecular driver of the tumor and pick an appropriate inhibitor – in this case crizotinib for ALK-driven tumors – we have the prospect of seeing dramatic responses."

The ALK (anaplastic lymphoma receptor tyrosine kinase) gene is part of a family of proteins called receptor tyrosine kinases, which transmit signals from the cell surface into the cell via signal transduction. Though the specific function of ALK is unknown, it is thought to act early in development to help regulate the proliferation of nerve cells.

ALK is involved in the formation of several human cancers, including anaplastic large cell lymphoma (ALCL), which typically occurs in childhood. Activating mutations in the ALK gene "are the leading cause for most cases of the hereditary form of neuroblastoma and ... these mutations are also somatically acquired in 14% of patients with the aggressive form of this disease," Dr. Mosse said.

Crizotinib, an oral small-molecule inhibitor of ALK, was approved in August 2011 for the treatment of patients with locally-advanced or metastatic non–small cell lung cancer (NSCLC) that is ALK positive based on a diagnostic test approved concurrently by the Food and Drug Administration.

Dr. Mosse and colleagues conducted the phase I study to assess the safety and efficacy of crizotinib in pediatric patients aged 1-21 years with relapsed or refractory cancer. The children received the drug orally, twice daily for 28-day cycles. Based on the results, the recommended phase II dose for children is 280 mg/m² per day. This is roughly twice the recommended phase II dose for adults, according to Dr. Mosse.

Eight patients with anaplastic large-cell lymphoma were enrolled in the current study. All had an ALK translocation and were heavily pretreated. Seven children had a complete response with doses ranging from 165 mg/m² per day to 280 mg/m² per day. They remain on the drug, with no progression observed for as long as 18 months.

Investigators also enrolled seven patients with inflammatory myofibroblastic tumor – all had an ALK translocation. Of these, one had a minor response and remains on the drug after 2 years. One patient had a partial response and remains on the drug after 10 cycles. It is too early to determine response for five patients.

Lastly, the researchers enrolled 35 patients with neuroblastoma; 27 were evaluable. Eight of these patients had known ALK mutations. Two of these patients have germline mutations. One of these patients had a complete response to therapy and remains on treatment (more than 6 months). The second patient with a germline mutation had a minor response and continues treatment (more than 15 months). A third patient with a somatic ALK mutation has had stable disease for more than eight cycles.

There were 19 neuroblastoma patients who had unknown ALK status. One patient had a complete response and remains on treatment (more than 24 cycles). Six patients have had prolonged stable disease and remain on treatment (7-29 cycles).

Overall, the drug was "exceedingly well tolerated," Dr. Mosse said. "Most of the toxicities were extremely low-grade and did not affect overall quality of life. At the highest dose level that we tested, we saw irritation of the liver enzymes that were reversible."

The study was sponsored by the Children’s Oncology Group with collaboration from the National Cancer Institute. Dr. Mosse reported receiving research funding from Pfizer, which makes Xalkori.

The recently approved cancer drug crizotinib draws strong responses in children whose cancers have mutations in the gene targeted by the drug, according to early data from a phase I dose-escalating study.

The most dramatic improvements occurred in anaplastic large-cell lymphoma, with complete and durable responses observed in 7 of 8 children with the ALK mutation, which is common in the disease. Crizotinib (Xalkori) also appeared to be active in subsets of children with inflammatory myofibroblastic tumor and neuroblastoma, though the early data were less clear in these cancers.

"Crizotinib appears to have a high degree of activity in children with anaplastic large-cell lymphoma – the majority of whom are driven by the ALK oncogene," lead author Dr. Yael P. Mosse said during a press briefing in advance of the annual meeting of the American Society of Clinical Oncology. She noted that these are phase I results and should be taken with caution.

"Certainly for the eight patients that we enrolled with anaplastic large cell lymphoma – seven of whom have had a complete response and a durable response – I think that this is dramatic activity and has already met the bar for what you would look for in a phase-II trial ... for neuroblastoma there is still a lot of work to be done," said Dr. Mosse of Children’s Hospital of Philadelphia and the University of Pennsylvania.

"The story is really a glimpse at the new paradigm for understanding of cancer and drug development," said ASCO President Dr. Michael Link, comoderator of the press briefing.

"It’s no longer adequate to identify a tumor based on histology organ of origin. It’s now understood that tumors are heterogeneous and it’s key to understand the particular molecular driver," said Dr. Link of Stanford (Calif.) University.

"If you understand the molecular driver of the tumor and pick an appropriate inhibitor – in this case crizotinib for ALK-driven tumors – we have the prospect of seeing dramatic responses."

The ALK (anaplastic lymphoma receptor tyrosine kinase) gene is part of a family of proteins called receptor tyrosine kinases, which transmit signals from the cell surface into the cell via signal transduction. Though the specific function of ALK is unknown, it is thought to act early in development to help regulate the proliferation of nerve cells.

ALK is involved in the formation of several human cancers, including anaplastic large cell lymphoma (ALCL), which typically occurs in childhood. Activating mutations in the ALK gene "are the leading cause for most cases of the hereditary form of neuroblastoma and ... these mutations are also somatically acquired in 14% of patients with the aggressive form of this disease," Dr. Mosse said.

Crizotinib, an oral small-molecule inhibitor of ALK, was approved in August 2011 for the treatment of patients with locally-advanced or metastatic non–small cell lung cancer (NSCLC) that is ALK positive based on a diagnostic test approved concurrently by the Food and Drug Administration.

Dr. Mosse and colleagues conducted the phase I study to assess the safety and efficacy of crizotinib in pediatric patients aged 1-21 years with relapsed or refractory cancer. The children received the drug orally, twice daily for 28-day cycles. Based on the results, the recommended phase II dose for children is 280 mg/m² per day. This is roughly twice the recommended phase II dose for adults, according to Dr. Mosse.

Eight patients with anaplastic large-cell lymphoma were enrolled in the current study. All had an ALK translocation and were heavily pretreated. Seven children had a complete response with doses ranging from 165 mg/m² per day to 280 mg/m² per day. They remain on the drug, with no progression observed for as long as 18 months.

Investigators also enrolled seven patients with inflammatory myofibroblastic tumor – all had an ALK translocation. Of these, one had a minor response and remains on the drug after 2 years. One patient had a partial response and remains on the drug after 10 cycles. It is too early to determine response for five patients.

Lastly, the researchers enrolled 35 patients with neuroblastoma; 27 were evaluable. Eight of these patients had known ALK mutations. Two of these patients have germline mutations. One of these patients had a complete response to therapy and remains on treatment (more than 6 months). The second patient with a germline mutation had a minor response and continues treatment (more than 15 months). A third patient with a somatic ALK mutation has had stable disease for more than eight cycles.

There were 19 neuroblastoma patients who had unknown ALK status. One patient had a complete response and remains on treatment (more than 24 cycles). Six patients have had prolonged stable disease and remain on treatment (7-29 cycles).

Overall, the drug was "exceedingly well tolerated," Dr. Mosse said. "Most of the toxicities were extremely low-grade and did not affect overall quality of life. At the highest dose level that we tested, we saw irritation of the liver enzymes that were reversible."

The study was sponsored by the Children’s Oncology Group with collaboration from the National Cancer Institute. Dr. Mosse reported receiving research funding from Pfizer, which makes Xalkori.

The recently approved cancer drug crizotinib draws strong responses in children whose cancers have mutations in the gene targeted by the drug, according to early data from a phase I dose-escalating study.

The most dramatic improvements occurred in anaplastic large-cell lymphoma, with complete and durable responses observed in 7 of 8 children with the ALK mutation, which is common in the disease. Crizotinib (Xalkori) also appeared to be active in subsets of children with inflammatory myofibroblastic tumor and neuroblastoma, though the early data were less clear in these cancers.

"Crizotinib appears to have a high degree of activity in children with anaplastic large-cell lymphoma – the majority of whom are driven by the ALK oncogene," lead author Dr. Yael P. Mosse said during a press briefing in advance of the annual meeting of the American Society of Clinical Oncology. She noted that these are phase I results and should be taken with caution.

"Certainly for the eight patients that we enrolled with anaplastic large cell lymphoma – seven of whom have had a complete response and a durable response – I think that this is dramatic activity and has already met the bar for what you would look for in a phase-II trial ... for neuroblastoma there is still a lot of work to be done," said Dr. Mosse of Children’s Hospital of Philadelphia and the University of Pennsylvania.

"The story is really a glimpse at the new paradigm for understanding of cancer and drug development," said ASCO President Dr. Michael Link, comoderator of the press briefing.

"It’s no longer adequate to identify a tumor based on histology organ of origin. It’s now understood that tumors are heterogeneous and it’s key to understand the particular molecular driver," said Dr. Link of Stanford (Calif.) University.

"If you understand the molecular driver of the tumor and pick an appropriate inhibitor – in this case crizotinib for ALK-driven tumors – we have the prospect of seeing dramatic responses."

The ALK (anaplastic lymphoma receptor tyrosine kinase) gene is part of a family of proteins called receptor tyrosine kinases, which transmit signals from the cell surface into the cell via signal transduction. Though the specific function of ALK is unknown, it is thought to act early in development to help regulate the proliferation of nerve cells.

ALK is involved in the formation of several human cancers, including anaplastic large cell lymphoma (ALCL), which typically occurs in childhood. Activating mutations in the ALK gene "are the leading cause for most cases of the hereditary form of neuroblastoma and ... these mutations are also somatically acquired in 14% of patients with the aggressive form of this disease," Dr. Mosse said.

Crizotinib, an oral small-molecule inhibitor of ALK, was approved in August 2011 for the treatment of patients with locally-advanced or metastatic non–small cell lung cancer (NSCLC) that is ALK positive based on a diagnostic test approved concurrently by the Food and Drug Administration.

Dr. Mosse and colleagues conducted the phase I study to assess the safety and efficacy of crizotinib in pediatric patients aged 1-21 years with relapsed or refractory cancer. The children received the drug orally, twice daily for 28-day cycles. Based on the results, the recommended phase II dose for children is 280 mg/m² per day. This is roughly twice the recommended phase II dose for adults, according to Dr. Mosse.

Eight patients with anaplastic large-cell lymphoma were enrolled in the current study. All had an ALK translocation and were heavily pretreated. Seven children had a complete response with doses ranging from 165 mg/m² per day to 280 mg/m² per day. They remain on the drug, with no progression observed for as long as 18 months.

Investigators also enrolled seven patients with inflammatory myofibroblastic tumor – all had an ALK translocation. Of these, one had a minor response and remains on the drug after 2 years. One patient had a partial response and remains on the drug after 10 cycles. It is too early to determine response for five patients.

Lastly, the researchers enrolled 35 patients with neuroblastoma; 27 were evaluable. Eight of these patients had known ALK mutations. Two of these patients have germline mutations. One of these patients had a complete response to therapy and remains on treatment (more than 6 months). The second patient with a germline mutation had a minor response and continues treatment (more than 15 months). A third patient with a somatic ALK mutation has had stable disease for more than eight cycles.

There were 19 neuroblastoma patients who had unknown ALK status. One patient had a complete response and remains on treatment (more than 24 cycles). Six patients have had prolonged stable disease and remain on treatment (7-29 cycles).

Overall, the drug was "exceedingly well tolerated," Dr. Mosse said. "Most of the toxicities were extremely low-grade and did not affect overall quality of life. At the highest dose level that we tested, we saw irritation of the liver enzymes that were reversible."

The study was sponsored by the Children’s Oncology Group with collaboration from the National Cancer Institute. Dr. Mosse reported receiving research funding from Pfizer, which makes Xalkori.

BALTIMORE – Robotic procedures compare favorably with vaginal apical prolapse repair in elderly women, for whom pelvic organ prolapse repair is the most common gynecologic procedure.

In a retrospective study of 136 patients, estimated blood loss and need for postoperative transfusion were significantly lower in the robotic surgery group. Estimated blood loss was 91 mL in the robotic surgery group, compared with 172 mL in the vaginal surgery group. No patients needed postoperative transfusion in the robotic group, compared with 10 patients in the vaginal group, reported Dr. Barbara L. Robinson at the annual meeting of the Society of Gynecologic Surgeons.

"We demonstrate low rates of perioperative morbidity in elderly women undergoing both robotic and vaginal reconstructive procedures for apical prolapse repair."

Total operative and total anesthesia times were significantly lower in the vaginal surgery group. Total operative time was 139 minutes for the vaginal surgery group, compared with 201 minutes in the robotic surgery group; total anesthesia time was 168 and 237 minutes in the vaginal and robotic groups, respectively.

"We demonstrate low rates of perioperative morbidity in elderly women undergoing both robotic and vaginal reconstructive procedures for apical prolapse repair," said Dr. Robinson of the department of obstetrics and gynecology, University of North Carolina at Chapel Hill.

The researchers conducted a chart review of women aged 65 years and older who underwent robotic or vaginal apical support surgery (including colpocleisis) between March 2006 and April 2011. Patients were excluded if they had undergone a primary abdominal or laparoscopic apical support procedure for malignancy.

Preoperative risks were assessed using the American Society of Anesthesiologists (ASA) physical classification system and the Charlson Comorbidity Index (CCI). The CCI predicts 10-year mortality risk based on age and comorbidities. The ASA physical classification system is used to assess patient fitness prior to surgery. The researchers sought to determine if these measures of preoperative risk can predict risk in this population, and to characterize complications during apical support procedures using the Dindo classification of surgical complications. The Dindo system is used to grade and define perioperative complications. This system has five grades; a greater grade is associated with more severe complications. Cases were reviewed for surgical complications up to 12 months after surgery, and a Dindo grade was assigned accordingly.

Dr. Robinson and her colleagues identified a total of 136 patients – 70 had robotic surgery and 66 had vaginal surgery. The average age was 72 years, although patients in the vaginal surgery group were significantly older (74 vs. 70 years). The two groups did not significantly differ by body mass index, parity, or smoking status. The average apical prolapse stage was significantly lower in women who had vaginal surgery compared with robotic surgery – 1.6 vs. 2.1.

In the robotic surgery group, sacrocolpopexy was the most common procedure. In the vaginal group, uterine sacral ligament suspension and colpocleisis were the two most common procedures. Length of hospital stay was significantly longer for the vaginal surgery group than the robotic group – 2.2 vs. 2.0 days, respectively.

The most common preoperative comorbidities were hypertension, coronary artery disease, and diabetes. These morbidities were not significantly different between the two groups. However, history of a myocardial infarction was significantly lower in patients who had robotic surgery than in the vaginal surgery group (9% vs. 21%), as was the presence of dementia (0% vs. 9%).

"The [overall] study population was generally healthy, with a low mean CCI of 0.97. However, the vaginal surgery group had more severe comorbidities than the robotic surgery group based on the CCI," said Dr. Robinson. In contrast, based on ASA class, comorbidity was similar for the two groups. The most commonly assigned ASA classes were 2 and 3. No patients were assigned as class 5 or 6.

There were no significant differences in overall intraoperative complications, including cystotomy, trocar injury to the bladder, ureteral injury, bowel injury, or intraoperative transfusion. However, there were significantly fewer urinary tract infections – 6% vs. 18% – in the robotic surgery group following the procedure, she said at the meeting, which was jointly sponsored by the American College of Surgeons.

Overall, the majority of procedures – both robotic (67%) and vaginal (56%) – were associated with no complications based on Dindo class, she said. No patients were classified as grade IV or V. The Dindo classification was similar between the two groups.

"Neither the ASA or CCI correlated significantly with the Dindo grade," he said. Given the lack of correlation with the Dindo classification, ASA and CCI may have limited utility in elderly women undergoing pelvic floor reconstruction.

The authors reported that they had no relevant financial disclosures.

BALTIMORE – Robotic procedures compare favorably with vaginal apical prolapse repair in elderly women, for whom pelvic organ prolapse repair is the most common gynecologic procedure.

In a retrospective study of 136 patients, estimated blood loss and need for postoperative transfusion were significantly lower in the robotic surgery group. Estimated blood loss was 91 mL in the robotic surgery group, compared with 172 mL in the vaginal surgery group. No patients needed postoperative transfusion in the robotic group, compared with 10 patients in the vaginal group, reported Dr. Barbara L. Robinson at the annual meeting of the Society of Gynecologic Surgeons.

"We demonstrate low rates of perioperative morbidity in elderly women undergoing both robotic and vaginal reconstructive procedures for apical prolapse repair."

Total operative and total anesthesia times were significantly lower in the vaginal surgery group. Total operative time was 139 minutes for the vaginal surgery group, compared with 201 minutes in the robotic surgery group; total anesthesia time was 168 and 237 minutes in the vaginal and robotic groups, respectively.

"We demonstrate low rates of perioperative morbidity in elderly women undergoing both robotic and vaginal reconstructive procedures for apical prolapse repair," said Dr. Robinson of the department of obstetrics and gynecology, University of North Carolina at Chapel Hill.

The researchers conducted a chart review of women aged 65 years and older who underwent robotic or vaginal apical support surgery (including colpocleisis) between March 2006 and April 2011. Patients were excluded if they had undergone a primary abdominal or laparoscopic apical support procedure for malignancy.

Preoperative risks were assessed using the American Society of Anesthesiologists (ASA) physical classification system and the Charlson Comorbidity Index (CCI). The CCI predicts 10-year mortality risk based on age and comorbidities. The ASA physical classification system is used to assess patient fitness prior to surgery. The researchers sought to determine if these measures of preoperative risk can predict risk in this population, and to characterize complications during apical support procedures using the Dindo classification of surgical complications. The Dindo system is used to grade and define perioperative complications. This system has five grades; a greater grade is associated with more severe complications. Cases were reviewed for surgical complications up to 12 months after surgery, and a Dindo grade was assigned accordingly.

Dr. Robinson and her colleagues identified a total of 136 patients – 70 had robotic surgery and 66 had vaginal surgery. The average age was 72 years, although patients in the vaginal surgery group were significantly older (74 vs. 70 years). The two groups did not significantly differ by body mass index, parity, or smoking status. The average apical prolapse stage was significantly lower in women who had vaginal surgery compared with robotic surgery – 1.6 vs. 2.1.

In the robotic surgery group, sacrocolpopexy was the most common procedure. In the vaginal group, uterine sacral ligament suspension and colpocleisis were the two most common procedures. Length of hospital stay was significantly longer for the vaginal surgery group than the robotic group – 2.2 vs. 2.0 days, respectively.

The most common preoperative comorbidities were hypertension, coronary artery disease, and diabetes. These morbidities were not significantly different between the two groups. However, history of a myocardial infarction was significantly lower in patients who had robotic surgery than in the vaginal surgery group (9% vs. 21%), as was the presence of dementia (0% vs. 9%).

"The [overall] study population was generally healthy, with a low mean CCI of 0.97. However, the vaginal surgery group had more severe comorbidities than the robotic surgery group based on the CCI," said Dr. Robinson. In contrast, based on ASA class, comorbidity was similar for the two groups. The most commonly assigned ASA classes were 2 and 3. No patients were assigned as class 5 or 6.

There were no significant differences in overall intraoperative complications, including cystotomy, trocar injury to the bladder, ureteral injury, bowel injury, or intraoperative transfusion. However, there were significantly fewer urinary tract infections – 6% vs. 18% – in the robotic surgery group following the procedure, she said at the meeting, which was jointly sponsored by the American College of Surgeons.

Overall, the majority of procedures – both robotic (67%) and vaginal (56%) – were associated with no complications based on Dindo class, she said. No patients were classified as grade IV or V. The Dindo classification was similar between the two groups.

"Neither the ASA or CCI correlated significantly with the Dindo grade," he said. Given the lack of correlation with the Dindo classification, ASA and CCI may have limited utility in elderly women undergoing pelvic floor reconstruction.

The authors reported that they had no relevant financial disclosures.

BALTIMORE – Robotic procedures compare favorably with vaginal apical prolapse repair in elderly women, for whom pelvic organ prolapse repair is the most common gynecologic procedure.

In a retrospective study of 136 patients, estimated blood loss and need for postoperative transfusion were significantly lower in the robotic surgery group. Estimated blood loss was 91 mL in the robotic surgery group, compared with 172 mL in the vaginal surgery group. No patients needed postoperative transfusion in the robotic group, compared with 10 patients in the vaginal group, reported Dr. Barbara L. Robinson at the annual meeting of the Society of Gynecologic Surgeons.

"We demonstrate low rates of perioperative morbidity in elderly women undergoing both robotic and vaginal reconstructive procedures for apical prolapse repair."

Total operative and total anesthesia times were significantly lower in the vaginal surgery group. Total operative time was 139 minutes for the vaginal surgery group, compared with 201 minutes in the robotic surgery group; total anesthesia time was 168 and 237 minutes in the vaginal and robotic groups, respectively.

"We demonstrate low rates of perioperative morbidity in elderly women undergoing both robotic and vaginal reconstructive procedures for apical prolapse repair," said Dr. Robinson of the department of obstetrics and gynecology, University of North Carolina at Chapel Hill.

The researchers conducted a chart review of women aged 65 years and older who underwent robotic or vaginal apical support surgery (including colpocleisis) between March 2006 and April 2011. Patients were excluded if they had undergone a primary abdominal or laparoscopic apical support procedure for malignancy.

Preoperative risks were assessed using the American Society of Anesthesiologists (ASA) physical classification system and the Charlson Comorbidity Index (CCI). The CCI predicts 10-year mortality risk based on age and comorbidities. The ASA physical classification system is used to assess patient fitness prior to surgery. The researchers sought to determine if these measures of preoperative risk can predict risk in this population, and to characterize complications during apical support procedures using the Dindo classification of surgical complications. The Dindo system is used to grade and define perioperative complications. This system has five grades; a greater grade is associated with more severe complications. Cases were reviewed for surgical complications up to 12 months after surgery, and a Dindo grade was assigned accordingly.

Dr. Robinson and her colleagues identified a total of 136 patients – 70 had robotic surgery and 66 had vaginal surgery. The average age was 72 years, although patients in the vaginal surgery group were significantly older (74 vs. 70 years). The two groups did not significantly differ by body mass index, parity, or smoking status. The average apical prolapse stage was significantly lower in women who had vaginal surgery compared with robotic surgery – 1.6 vs. 2.1.

In the robotic surgery group, sacrocolpopexy was the most common procedure. In the vaginal group, uterine sacral ligament suspension and colpocleisis were the two most common procedures. Length of hospital stay was significantly longer for the vaginal surgery group than the robotic group – 2.2 vs. 2.0 days, respectively.

The most common preoperative comorbidities were hypertension, coronary artery disease, and diabetes. These morbidities were not significantly different between the two groups. However, history of a myocardial infarction was significantly lower in patients who had robotic surgery than in the vaginal surgery group (9% vs. 21%), as was the presence of dementia (0% vs. 9%).

"The [overall] study population was generally healthy, with a low mean CCI of 0.97. However, the vaginal surgery group had more severe comorbidities than the robotic surgery group based on the CCI," said Dr. Robinson. In contrast, based on ASA class, comorbidity was similar for the two groups. The most commonly assigned ASA classes were 2 and 3. No patients were assigned as class 5 or 6.

There were no significant differences in overall intraoperative complications, including cystotomy, trocar injury to the bladder, ureteral injury, bowel injury, or intraoperative transfusion. However, there were significantly fewer urinary tract infections – 6% vs. 18% – in the robotic surgery group following the procedure, she said at the meeting, which was jointly sponsored by the American College of Surgeons.

Overall, the majority of procedures – both robotic (67%) and vaginal (56%) – were associated with no complications based on Dindo class, she said. No patients were classified as grade IV or V. The Dindo classification was similar between the two groups.

"Neither the ASA or CCI correlated significantly with the Dindo grade," he said. Given the lack of correlation with the Dindo classification, ASA and CCI may have limited utility in elderly women undergoing pelvic floor reconstruction.

The authors reported that they had no relevant financial disclosures.

The antipsychotic olanzapine trounced standard therapy for breakthrough chemotherapy-induced nausea and vomiting in a clinical trial that could change the way some cancer patients are treated.

In the double-blind phase III study, 30 (71%) of 42 patients, who received olanzapine (Zyprexa) had no emesis, compared with 12 (32%) of 38 patients who received metoclopramide (P less than .01) during a 72-hour observation period after highly emetic chemotherapy.

In addition, 28 (67%) patients on olanzapine had no nausea, compared with 9 (24%) of those patients on metoclopramide (P less than .01), said Dr. Rudolph M. Navari, who presented the study during a press briefing in advance of the annual meeting of American Society of Clinical Oncology, June 1-5, in Chicago. Dr. Navari is the director of the Harper Cancer Institute at Indiana University in South Bend.

ASCO president-elect Dr. Sandra M. Swain, medical director of the Cancer Institute at Washington Hospital Center, called the findings "a great step forward for quality of life for our patients.

"This is a huge advance," said Dr. Swain, a breast cancer expert, who comoderated the teleconference. "We’ve come a long way to really treat and cure these patients ... these side effects can be intolerable to patients. Sometimes patients will opt out of curative treatment, and we certainly don’t want that, when we know we’ve made advances."

The researchers included chemotherapy-naive patients who received highly emetogenic chemotherapy: more than 70 mg/m² cisplatin, or more than 50 mg/m² doxorubicin and more than 600 mg/m² cyclophosphamide.

Patients who developed breakthrough emesis or nausea despite guideline-directed prophylaxis were randomized to receive olanzapine or metoclopramide. Pre-chemotherapy prophylaxis included intravenous dexamethasone (12 mg), intravenous palonosetron (0.25 mg), and intravenous fosaprepitant (150 mg); post-chemotherapy prophylaxis was daily oral dexamethasone (8 mg, days 2-4).

Patients received 10 mg oral olanzapine for 3 days or 10 mg oral metoclopramide three times daily for 3 days. Patients were monitored for emesis and nausea for the 72 hours after the initiation of therapy. In addition, nausea was measured by patients on a visual analog scale (0-10), with 0 being no nausea and 10 being maximal nausea.

Patients in the two groups were similar for age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, and diagnosis (5 bladder cancers, 40 breast cancers, 8 lymphomas, and 27 lung cancers).

"Both olanzapine and metoclopramide were well tolerated with no grade 3 or 4 toxicities," said Dr. Navari. No central nervous system toxicities were observed in either group.

Olanzapine is indicated for treatment of psychosis and is associated with weight gain, but the side effect should not be a problem for cancer patients.

"The side effect of weight gain occurs in patients, who receive the drug for 3 to 6 to 9 months," Dr. Ravari noted. "So using it for a short period of 3-4 days once a month – we did not see that in the current study, nor did we see that in previous studies."

Dr. Navari had previously reported that patients receiving highly emetogenic chemotherapy were about twice as likely not to experience any delayed nausea with an olanzapine regimen compared with a standard aprepitant (Emend) regimen (68% vs. 37%) in a phase III clinical trial. The two regimens worked similarly well for preventing acute nausea and for preventing both acute and delayed vomiting, that study found (Support. Oncol. 2011;9:188-95).

ASCO presented a preview of some meeting highlights with many of the abstracts being posted online as of 6 p.m. EST at www.asco.org.

The authors reported that they have nothing to disclose.

The antipsychotic olanzapine trounced standard therapy for breakthrough chemotherapy-induced nausea and vomiting in a clinical trial that could change the way some cancer patients are treated.

In the double-blind phase III study, 30 (71%) of 42 patients, who received olanzapine (Zyprexa) had no emesis, compared with 12 (32%) of 38 patients who received metoclopramide (P less than .01) during a 72-hour observation period after highly emetic chemotherapy.

In addition, 28 (67%) patients on olanzapine had no nausea, compared with 9 (24%) of those patients on metoclopramide (P less than .01), said Dr. Rudolph M. Navari, who presented the study during a press briefing in advance of the annual meeting of American Society of Clinical Oncology, June 1-5, in Chicago. Dr. Navari is the director of the Harper Cancer Institute at Indiana University in South Bend.

ASCO president-elect Dr. Sandra M. Swain, medical director of the Cancer Institute at Washington Hospital Center, called the findings "a great step forward for quality of life for our patients.

"This is a huge advance," said Dr. Swain, a breast cancer expert, who comoderated the teleconference. "We’ve come a long way to really treat and cure these patients ... these side effects can be intolerable to patients. Sometimes patients will opt out of curative treatment, and we certainly don’t want that, when we know we’ve made advances."

The researchers included chemotherapy-naive patients who received highly emetogenic chemotherapy: more than 70 mg/m² cisplatin, or more than 50 mg/m² doxorubicin and more than 600 mg/m² cyclophosphamide.

Patients who developed breakthrough emesis or nausea despite guideline-directed prophylaxis were randomized to receive olanzapine or metoclopramide. Pre-chemotherapy prophylaxis included intravenous dexamethasone (12 mg), intravenous palonosetron (0.25 mg), and intravenous fosaprepitant (150 mg); post-chemotherapy prophylaxis was daily oral dexamethasone (8 mg, days 2-4).

Patients received 10 mg oral olanzapine for 3 days or 10 mg oral metoclopramide three times daily for 3 days. Patients were monitored for emesis and nausea for the 72 hours after the initiation of therapy. In addition, nausea was measured by patients on a visual analog scale (0-10), with 0 being no nausea and 10 being maximal nausea.

Patients in the two groups were similar for age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, and diagnosis (5 bladder cancers, 40 breast cancers, 8 lymphomas, and 27 lung cancers).

"Both olanzapine and metoclopramide were well tolerated with no grade 3 or 4 toxicities," said Dr. Navari. No central nervous system toxicities were observed in either group.

Olanzapine is indicated for treatment of psychosis and is associated with weight gain, but the side effect should not be a problem for cancer patients.

"The side effect of weight gain occurs in patients, who receive the drug for 3 to 6 to 9 months," Dr. Ravari noted. "So using it for a short period of 3-4 days once a month – we did not see that in the current study, nor did we see that in previous studies."

Dr. Navari had previously reported that patients receiving highly emetogenic chemotherapy were about twice as likely not to experience any delayed nausea with an olanzapine regimen compared with a standard aprepitant (Emend) regimen (68% vs. 37%) in a phase III clinical trial. The two regimens worked similarly well for preventing acute nausea and for preventing both acute and delayed vomiting, that study found (Support. Oncol. 2011;9:188-95).

ASCO presented a preview of some meeting highlights with many of the abstracts being posted online as of 6 p.m. EST at www.asco.org.

The authors reported that they have nothing to disclose.

The antipsychotic olanzapine trounced standard therapy for breakthrough chemotherapy-induced nausea and vomiting in a clinical trial that could change the way some cancer patients are treated.

In the double-blind phase III study, 30 (71%) of 42 patients, who received olanzapine (Zyprexa) had no emesis, compared with 12 (32%) of 38 patients who received metoclopramide (P less than .01) during a 72-hour observation period after highly emetic chemotherapy.

In addition, 28 (67%) patients on olanzapine had no nausea, compared with 9 (24%) of those patients on metoclopramide (P less than .01), said Dr. Rudolph M. Navari, who presented the study during a press briefing in advance of the annual meeting of American Society of Clinical Oncology, June 1-5, in Chicago. Dr. Navari is the director of the Harper Cancer Institute at Indiana University in South Bend.

ASCO president-elect Dr. Sandra M. Swain, medical director of the Cancer Institute at Washington Hospital Center, called the findings "a great step forward for quality of life for our patients.

"This is a huge advance," said Dr. Swain, a breast cancer expert, who comoderated the teleconference. "We’ve come a long way to really treat and cure these patients ... these side effects can be intolerable to patients. Sometimes patients will opt out of curative treatment, and we certainly don’t want that, when we know we’ve made advances."

The researchers included chemotherapy-naive patients who received highly emetogenic chemotherapy: more than 70 mg/m² cisplatin, or more than 50 mg/m² doxorubicin and more than 600 mg/m² cyclophosphamide.

Patients who developed breakthrough emesis or nausea despite guideline-directed prophylaxis were randomized to receive olanzapine or metoclopramide. Pre-chemotherapy prophylaxis included intravenous dexamethasone (12 mg), intravenous palonosetron (0.25 mg), and intravenous fosaprepitant (150 mg); post-chemotherapy prophylaxis was daily oral dexamethasone (8 mg, days 2-4).

Patients received 10 mg oral olanzapine for 3 days or 10 mg oral metoclopramide three times daily for 3 days. Patients were monitored for emesis and nausea for the 72 hours after the initiation of therapy. In addition, nausea was measured by patients on a visual analog scale (0-10), with 0 being no nausea and 10 being maximal nausea.

Patients in the two groups were similar for age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, and diagnosis (5 bladder cancers, 40 breast cancers, 8 lymphomas, and 27 lung cancers).

"Both olanzapine and metoclopramide were well tolerated with no grade 3 or 4 toxicities," said Dr. Navari. No central nervous system toxicities were observed in either group.

Olanzapine is indicated for treatment of psychosis and is associated with weight gain, but the side effect should not be a problem for cancer patients.

"The side effect of weight gain occurs in patients, who receive the drug for 3 to 6 to 9 months," Dr. Ravari noted. "So using it for a short period of 3-4 days once a month – we did not see that in the current study, nor did we see that in previous studies."

Dr. Navari had previously reported that patients receiving highly emetogenic chemotherapy were about twice as likely not to experience any delayed nausea with an olanzapine regimen compared with a standard aprepitant (Emend) regimen (68% vs. 37%) in a phase III clinical trial. The two regimens worked similarly well for preventing acute nausea and for preventing both acute and delayed vomiting, that study found (Support. Oncol. 2011;9:188-95).

ASCO presented a preview of some meeting highlights with many of the abstracts being posted online as of 6 p.m. EST at www.asco.org.

The authors reported that they have nothing to disclose.

BALTIMORE – Gastrointestinal complication rates from laparoscopic sacrocolpopexy are low, although a significant portion of these complications require readmissions and reoperations, based on the results of a retrospective analysis of 390 patients.

Functional GI complications occurred in 1.8% of patients, and bowel injury occurred in 1.3% of patients. Of the seven patients with functional GI complications, four were related to the ileus/small-bowel obstruction and three had nausea and vomiting. Of the five bowel injuries, three were small-bowel injuries and two were rectal injuries, Dr. William B. Warner reported at the annual meeting of the Society of Gynecologic Surgeons.

The researchers conducted a retrospective cohort study of patients at Inova Fairfax Hospital in Falls Church, Va., who underwent a laparoscopic sacrocolpopexy between January 2006 and August 2010. They collected demographic information, operative details, and data on intraoperative and postoperative complications.

The study included 390 patients who had a mean age of 59 years, a mean body mass index of 27, and a median follow-up of 6 months. The mean hospital stay was 1.7 days, with 93% leaving on postoperative days 1 (44%) or 2 (49%). Almost three-quarters (72%) of patients had a concurrent hysterectomy.

The researchers divided GI complications into two groups: functional complications (nausea/emesis, ileus and small-bowel obstruction) and bowel injury (injury to either the small bowel or rectum). A complication was considered to be functional if it involved prolonged admission (greater than 48 hours), readmission, or reoperation.

There were seven functional GI complications, four of which involved ileus/small-bowel obstruction (four readmissions and one reoperation), and three cases of nausea and vomiting (two that required prolonged stay and one that required readmission). There were also five cases of bowel injury (1.3%), three of which involved the small bowel (one that was recognized and repaired intraoperatively, and two that were unrecognized, resulting in reoperation and lengthy readmission), and two rectal injuries (one that was repaired intraoperatively and one rectovaginal fistula).

"We attempted to find risk factors for the most common complications," said Dr. Warner, who is an urogynecology fellow at the Walter Reed National Military Medical Center in Bethesda, Md.

They found that all patients with functional GI complications had prior abdominal surgery. "This association with prior abdominal surgery was statistically significant. Interestingly, bowel injury was not associated with prior abdominal surgery," he said at the meeting, which was jointly sponsored by the American College of Surgeons. Neither functional GI complications nor bowel injury was associated with age, body mass index, estimated blood loss, or operating room time.

Most patients used oral sodium for bowel preparation. Only polypropylene mesh was used, and the peritoneum was closed over the mesh in almost all cases. Patients were given a clear liquid diet immediately after surgery and were started on regular food the following morning. The aim was to discharge patients on the first postoperative day.

The authors reported that they have no relevant financial disclosures.

BALTIMORE – Gastrointestinal complication rates from laparoscopic sacrocolpopexy are low, although a significant portion of these complications require readmissions and reoperations, based on the results of a retrospective analysis of 390 patients.

Functional GI complications occurred in 1.8% of patients, and bowel injury occurred in 1.3% of patients. Of the seven patients with functional GI complications, four were related to the ileus/small-bowel obstruction and three had nausea and vomiting. Of the five bowel injuries, three were small-bowel injuries and two were rectal injuries, Dr. William B. Warner reported at the annual meeting of the Society of Gynecologic Surgeons.

The researchers conducted a retrospective cohort study of patients at Inova Fairfax Hospital in Falls Church, Va., who underwent a laparoscopic sacrocolpopexy between January 2006 and August 2010. They collected demographic information, operative details, and data on intraoperative and postoperative complications.

The study included 390 patients who had a mean age of 59 years, a mean body mass index of 27, and a median follow-up of 6 months. The mean hospital stay was 1.7 days, with 93% leaving on postoperative days 1 (44%) or 2 (49%). Almost three-quarters (72%) of patients had a concurrent hysterectomy.

The researchers divided GI complications into two groups: functional complications (nausea/emesis, ileus and small-bowel obstruction) and bowel injury (injury to either the small bowel or rectum). A complication was considered to be functional if it involved prolonged admission (greater than 48 hours), readmission, or reoperation.

There were seven functional GI complications, four of which involved ileus/small-bowel obstruction (four readmissions and one reoperation), and three cases of nausea and vomiting (two that required prolonged stay and one that required readmission). There were also five cases of bowel injury (1.3%), three of which involved the small bowel (one that was recognized and repaired intraoperatively, and two that were unrecognized, resulting in reoperation and lengthy readmission), and two rectal injuries (one that was repaired intraoperatively and one rectovaginal fistula).

"We attempted to find risk factors for the most common complications," said Dr. Warner, who is an urogynecology fellow at the Walter Reed National Military Medical Center in Bethesda, Md.

They found that all patients with functional GI complications had prior abdominal surgery. "This association with prior abdominal surgery was statistically significant. Interestingly, bowel injury was not associated with prior abdominal surgery," he said at the meeting, which was jointly sponsored by the American College of Surgeons. Neither functional GI complications nor bowel injury was associated with age, body mass index, estimated blood loss, or operating room time.

Most patients used oral sodium for bowel preparation. Only polypropylene mesh was used, and the peritoneum was closed over the mesh in almost all cases. Patients were given a clear liquid diet immediately after surgery and were started on regular food the following morning. The aim was to discharge patients on the first postoperative day.

The authors reported that they have no relevant financial disclosures.

BALTIMORE – Gastrointestinal complication rates from laparoscopic sacrocolpopexy are low, although a significant portion of these complications require readmissions and reoperations, based on the results of a retrospective analysis of 390 patients.

Functional GI complications occurred in 1.8% of patients, and bowel injury occurred in 1.3% of patients. Of the seven patients with functional GI complications, four were related to the ileus/small-bowel obstruction and three had nausea and vomiting. Of the five bowel injuries, three were small-bowel injuries and two were rectal injuries, Dr. William B. Warner reported at the annual meeting of the Society of Gynecologic Surgeons.

The researchers conducted a retrospective cohort study of patients at Inova Fairfax Hospital in Falls Church, Va., who underwent a laparoscopic sacrocolpopexy between January 2006 and August 2010. They collected demographic information, operative details, and data on intraoperative and postoperative complications.

The study included 390 patients who had a mean age of 59 years, a mean body mass index of 27, and a median follow-up of 6 months. The mean hospital stay was 1.7 days, with 93% leaving on postoperative days 1 (44%) or 2 (49%). Almost three-quarters (72%) of patients had a concurrent hysterectomy.

The researchers divided GI complications into two groups: functional complications (nausea/emesis, ileus and small-bowel obstruction) and bowel injury (injury to either the small bowel or rectum). A complication was considered to be functional if it involved prolonged admission (greater than 48 hours), readmission, or reoperation.

There were seven functional GI complications, four of which involved ileus/small-bowel obstruction (four readmissions and one reoperation), and three cases of nausea and vomiting (two that required prolonged stay and one that required readmission). There were also five cases of bowel injury (1.3%), three of which involved the small bowel (one that was recognized and repaired intraoperatively, and two that were unrecognized, resulting in reoperation and lengthy readmission), and two rectal injuries (one that was repaired intraoperatively and one rectovaginal fistula).

"We attempted to find risk factors for the most common complications," said Dr. Warner, who is an urogynecology fellow at the Walter Reed National Military Medical Center in Bethesda, Md.

They found that all patients with functional GI complications had prior abdominal surgery. "This association with prior abdominal surgery was statistically significant. Interestingly, bowel injury was not associated with prior abdominal surgery," he said at the meeting, which was jointly sponsored by the American College of Surgeons. Neither functional GI complications nor bowel injury was associated with age, body mass index, estimated blood loss, or operating room time.

Most patients used oral sodium for bowel preparation. Only polypropylene mesh was used, and the peritoneum was closed over the mesh in almost all cases. Patients were given a clear liquid diet immediately after surgery and were started on regular food the following morning. The aim was to discharge patients on the first postoperative day.

The authors reported that they have no relevant financial disclosures.

BALTIMORE – Concomitant hysterectomy increases the risk of mesh extrusion in pelvic reconstructive surgery by more than fivefold, according to the results of a retrospective case-control study of women undergoing abdominal sacral colpopexy or vaginal mesh procedures.

"This is a very timely and important research topic, especially given the recent [Food and Drug Administration] advisory," said Dr. Nazanin Ehsani, who presented the results at the annual meeting of the Society of Gynecologic Surgeons.

In 2008 and again in 2011, the FDA issued warnings about the use of transvaginal mesh. The 2011 warning was issued to inform health care professionals that serious complications associated with surgical mesh for transvaginal repair of pelvic organ prolapse (POP) are not rare. The agency also noted that it is not clear that transvaginal repair with mesh is more effective than traditional non-mesh repair in all patients with POP, and it may expose patients to greater risk.

On multivariate analysis, concomitant hysterectomy was associated with an increased risk of mesh extrusion compared with no hysterectomy (odds ratio, 5.97; P = .003). Previous hysterectomy showed a trend toward increased risk of mesh extrusion compared with no hysterectomy (OR, 2.63; P = .06). In addition, concomitant hysterectomy was significantly associated with increased risk of mesh extrusion compared with previous hysterectomy (OR, 2.27; P =.03), Dr. Ehsani said at the meeting, which was jointly sponsored by the American College of Surgeons.

The researchers conducted a case-control study of women who underwent an abdominal sacral colpopexy (ASC) or vaginal mesh procedure (VMP) and developed mesh extrusion. Cases were matched with controls in a ratio of 1:3 by procedure data and type. Cases and controls were identified using diagnosis and procedure codes. Cases and control patients underwent the procedures between January 2006 and December 2009. The researchers collected information on age, race, type of procedure, estrogen status, hysterectomy status, type of vaginal incision, comorbidities, and smoking history.

They identified 84 case patients – 43 who underwent an ASC and 41 who underwent a VMP – and 314 controls. The mean age of the entire patient population was 62 years, with a median body mass index of 27.1 kg/m². The median time to the diagnosis of mesh extrusion was 16 weeks. Patients with ASCs were significantly younger than women in the other groups; patients in the ASC and control groups were significantly less likely to be smokers.

Mesh extrusion occurred most commonly in the anterior compartment (44%) in women who had a VMP, followed by the apical compartment (34%) and the posterior compartment (22%). Among women who had an ASC, extrusion occurred most commonly in the posterior compartment (63%), and occurred in the anterior compartment in 7% and in the apical compartment in 7%. Compartment status was unknown for 23% of women who had an ASC.

Concomitant hysterectomy is a significant risk factor for mesh extrusion in pelvic reconstructive surgery. "If a hysterectomy is indicated at the time of prolapse surgery, different approaches should be considered. When performing an abdominal sacral colpopexy, surgeons may want to consider a supracervical approach. This must be weighed against the risks of cervical preservation, including future cervical pathology and bleeding, as well as patient desires," said Dr. Ehsani of the department of obstetrics and gynecology at St. Luke’s Hospital in Bethlehem, Pa. "In the case of vaginal mesh procedure, surgeons may want to consider making separate vaginal incisions for mesh placement – that do not connect the vaginal cuff incision."

Dr. Ehsani reported that she is a consultant for American Medical Systems. Two of her coauthors are also consultants for American Medical Systems and Ethicon.

BALTIMORE – Concomitant hysterectomy increases the risk of mesh extrusion in pelvic reconstructive surgery by more than fivefold, according to the results of a retrospective case-control study of women undergoing abdominal sacral colpopexy or vaginal mesh procedures.

"This is a very timely and important research topic, especially given the recent [Food and Drug Administration] advisory," said Dr. Nazanin Ehsani, who presented the results at the annual meeting of the Society of Gynecologic Surgeons.

In 2008 and again in 2011, the FDA issued warnings about the use of transvaginal mesh. The 2011 warning was issued to inform health care professionals that serious complications associated with surgical mesh for transvaginal repair of pelvic organ prolapse (POP) are not rare. The agency also noted that it is not clear that transvaginal repair with mesh is more effective than traditional non-mesh repair in all patients with POP, and it may expose patients to greater risk.

On multivariate analysis, concomitant hysterectomy was associated with an increased risk of mesh extrusion compared with no hysterectomy (odds ratio, 5.97; P = .003). Previous hysterectomy showed a trend toward increased risk of mesh extrusion compared with no hysterectomy (OR, 2.63; P = .06). In addition, concomitant hysterectomy was significantly associated with increased risk of mesh extrusion compared with previous hysterectomy (OR, 2.27; P =.03), Dr. Ehsani said at the meeting, which was jointly sponsored by the American College of Surgeons.

The researchers conducted a case-control study of women who underwent an abdominal sacral colpopexy (ASC) or vaginal mesh procedure (VMP) and developed mesh extrusion. Cases were matched with controls in a ratio of 1:3 by procedure data and type. Cases and controls were identified using diagnosis and procedure codes. Cases and control patients underwent the procedures between January 2006 and December 2009. The researchers collected information on age, race, type of procedure, estrogen status, hysterectomy status, type of vaginal incision, comorbidities, and smoking history.

They identified 84 case patients – 43 who underwent an ASC and 41 who underwent a VMP – and 314 controls. The mean age of the entire patient population was 62 years, with a median body mass index of 27.1 kg/m². The median time to the diagnosis of mesh extrusion was 16 weeks. Patients with ASCs were significantly younger than women in the other groups; patients in the ASC and control groups were significantly less likely to be smokers.

Mesh extrusion occurred most commonly in the anterior compartment (44%) in women who had a VMP, followed by the apical compartment (34%) and the posterior compartment (22%). Among women who had an ASC, extrusion occurred most commonly in the posterior compartment (63%), and occurred in the anterior compartment in 7% and in the apical compartment in 7%. Compartment status was unknown for 23% of women who had an ASC.

Concomitant hysterectomy is a significant risk factor for mesh extrusion in pelvic reconstructive surgery. "If a hysterectomy is indicated at the time of prolapse surgery, different approaches should be considered. When performing an abdominal sacral colpopexy, surgeons may want to consider a supracervical approach. This must be weighed against the risks of cervical preservation, including future cervical pathology and bleeding, as well as patient desires," said Dr. Ehsani of the department of obstetrics and gynecology at St. Luke’s Hospital in Bethlehem, Pa. "In the case of vaginal mesh procedure, surgeons may want to consider making separate vaginal incisions for mesh placement – that do not connect the vaginal cuff incision."

Dr. Ehsani reported that she is a consultant for American Medical Systems. Two of her coauthors are also consultants for American Medical Systems and Ethicon.

BALTIMORE – Concomitant hysterectomy increases the risk of mesh extrusion in pelvic reconstructive surgery by more than fivefold, according to the results of a retrospective case-control study of women undergoing abdominal sacral colpopexy or vaginal mesh procedures.

"This is a very timely and important research topic, especially given the recent [Food and Drug Administration] advisory," said Dr. Nazanin Ehsani, who presented the results at the annual meeting of the Society of Gynecologic Surgeons.

In 2008 and again in 2011, the FDA issued warnings about the use of transvaginal mesh. The 2011 warning was issued to inform health care professionals that serious complications associated with surgical mesh for transvaginal repair of pelvic organ prolapse (POP) are not rare. The agency also noted that it is not clear that transvaginal repair with mesh is more effective than traditional non-mesh repair in all patients with POP, and it may expose patients to greater risk.

On multivariate analysis, concomitant hysterectomy was associated with an increased risk of mesh extrusion compared with no hysterectomy (odds ratio, 5.97; P = .003). Previous hysterectomy showed a trend toward increased risk of mesh extrusion compared with no hysterectomy (OR, 2.63; P = .06). In addition, concomitant hysterectomy was significantly associated with increased risk of mesh extrusion compared with previous hysterectomy (OR, 2.27; P =.03), Dr. Ehsani said at the meeting, which was jointly sponsored by the American College of Surgeons.

The researchers conducted a case-control study of women who underwent an abdominal sacral colpopexy (ASC) or vaginal mesh procedure (VMP) and developed mesh extrusion. Cases were matched with controls in a ratio of 1:3 by procedure data and type. Cases and controls were identified using diagnosis and procedure codes. Cases and control patients underwent the procedures between January 2006 and December 2009. The researchers collected information on age, race, type of procedure, estrogen status, hysterectomy status, type of vaginal incision, comorbidities, and smoking history.

They identified 84 case patients – 43 who underwent an ASC and 41 who underwent a VMP – and 314 controls. The mean age of the entire patient population was 62 years, with a median body mass index of 27.1 kg/m². The median time to the diagnosis of mesh extrusion was 16 weeks. Patients with ASCs were significantly younger than women in the other groups; patients in the ASC and control groups were significantly less likely to be smokers.

Mesh extrusion occurred most commonly in the anterior compartment (44%) in women who had a VMP, followed by the apical compartment (34%) and the posterior compartment (22%). Among women who had an ASC, extrusion occurred most commonly in the posterior compartment (63%), and occurred in the anterior compartment in 7% and in the apical compartment in 7%. Compartment status was unknown for 23% of women who had an ASC.

Concomitant hysterectomy is a significant risk factor for mesh extrusion in pelvic reconstructive surgery. "If a hysterectomy is indicated at the time of prolapse surgery, different approaches should be considered. When performing an abdominal sacral colpopexy, surgeons may want to consider a supracervical approach. This must be weighed against the risks of cervical preservation, including future cervical pathology and bleeding, as well as patient desires," said Dr. Ehsani of the department of obstetrics and gynecology at St. Luke’s Hospital in Bethlehem, Pa. "In the case of vaginal mesh procedure, surgeons may want to consider making separate vaginal incisions for mesh placement – that do not connect the vaginal cuff incision."

Dr. Ehsani reported that she is a consultant for American Medical Systems. Two of her coauthors are also consultants for American Medical Systems and Ethicon.

BALTIMORE – Abdominal sacrocolpopexy is associated with a higher rate of peri- and postoperative complications, compared with minimally invasive sacrocolpopexy, based on the results of a review of 831 sacrocolpopexy procedures.

There were significantly more overall intra- and postoperative complications associated with abdominal sacrocolpopexy (ASC) than with minimally invasive sacrocolpopexy (MISC) – 17.2% vs. 10.1% respectively. In particular, there also were significantly more cystotomy complications (4.8% vs. 2.1%) and ileus/small bowel obstruction complications (4.8% vs. 1.8%) in the ASC group, Dr. Patrick A. Nosti reported at the annual meeting of the Society of Gynecologic Surgeons.

Sacrocolpopexy is the preferred surgical treatment for apical prolapse, with a success rate of more than 95%, but there have been a limited number of small prospective and retrospective studies comparing ASC and MISC, said Dr. Nosti, a fellow in the female pelvic medicine and reconstructive surgery fellowship program in the department of obstetrics and gynecology at Washington (D.C.) Hospital Center.

He and his associates conducted a multicenter, retrospective cohort study including cases from January 1999 to December 2010 at four sites. The study was conducted through the Fellows' Pelvic Research Network. The primary outcome was the sum of all intra- and immediate postoperative complications. Secondary outcomes included anatomic success (Pelvic Organ Prolapse Quantification system less than stage II), mesh erosions, estimated blood loss, operative time, and length of hospitalization.

The investigators included 831 sacrocolpopexy procedures; the demographic data was similar between the two groups. The overall mean age was 58 years, mean body mass index was 27.3, and mean parity was three. Of these, 400 patients underwent ASC and 431 underwent MISC. Of the MISC patients, 213 had laparoscopic procedures and 218 had robotic procedures.

There were significantly more anatomical failures (24% vs. 14%), greater estimated blood loss (188 mL vs. 122 mL), longer hospitalization (2.8 vs. 1.2 days), and increased OR time (234 minutes vs. 206) in the ASC group, compared with the MISC group, Dr. Nosti reported.

There were, however, significantly more mesh erosions (3.2% vs. 1%) in the MISC group, compared with the ASC group, he said at the meeting, which was jointly sponsored by the American College of Surgeons.

Mesh erosion was significantly more common after total vs. supracervical hysterectomy (4.2% vs. 0.8% respectively).

In terms of robotic sacrocolpopexy compared with laparoscopic sacrocolpopexy, there was no significant difference in complications (8% vs. 13%). There were fewer failures with robotic procedures than with laparoscopic procedures (6% vs. 19%), despite more advanced preoperative prolapse. In addition, OR time was longer with robotic procedures than with laparoscopic sacrocolpopexy (330 minutes vs. 268 minutes).

The researchers reported that they have no conflicts of interest.

BALTIMORE – Abdominal sacrocolpopexy is associated with a higher rate of peri- and postoperative complications, compared with minimally invasive sacrocolpopexy, based on the results of a review of 831 sacrocolpopexy procedures.

There were significantly more overall intra- and postoperative complications associated with abdominal sacrocolpopexy (ASC) than with minimally invasive sacrocolpopexy (MISC) – 17.2% vs. 10.1% respectively. In particular, there also were significantly more cystotomy complications (4.8% vs. 2.1%) and ileus/small bowel obstruction complications (4.8% vs. 1.8%) in the ASC group, Dr. Patrick A. Nosti reported at the annual meeting of the Society of Gynecologic Surgeons.

Sacrocolpopexy is the preferred surgical treatment for apical prolapse, with a success rate of more than 95%, but there have been a limited number of small prospective and retrospective studies comparing ASC and MISC, said Dr. Nosti, a fellow in the female pelvic medicine and reconstructive surgery fellowship program in the department of obstetrics and gynecology at Washington (D.C.) Hospital Center.

He and his associates conducted a multicenter, retrospective cohort study including cases from January 1999 to December 2010 at four sites. The study was conducted through the Fellows' Pelvic Research Network. The primary outcome was the sum of all intra- and immediate postoperative complications. Secondary outcomes included anatomic success (Pelvic Organ Prolapse Quantification system less than stage II), mesh erosions, estimated blood loss, operative time, and length of hospitalization.

The investigators included 831 sacrocolpopexy procedures; the demographic data was similar between the two groups. The overall mean age was 58 years, mean body mass index was 27.3, and mean parity was three. Of these, 400 patients underwent ASC and 431 underwent MISC. Of the MISC patients, 213 had laparoscopic procedures and 218 had robotic procedures.

There were significantly more anatomical failures (24% vs. 14%), greater estimated blood loss (188 mL vs. 122 mL), longer hospitalization (2.8 vs. 1.2 days), and increased OR time (234 minutes vs. 206) in the ASC group, compared with the MISC group, Dr. Nosti reported.

There were, however, significantly more mesh erosions (3.2% vs. 1%) in the MISC group, compared with the ASC group, he said at the meeting, which was jointly sponsored by the American College of Surgeons.

Mesh erosion was significantly more common after total vs. supracervical hysterectomy (4.2% vs. 0.8% respectively).

In terms of robotic sacrocolpopexy compared with laparoscopic sacrocolpopexy, there was no significant difference in complications (8% vs. 13%). There were fewer failures with robotic procedures than with laparoscopic procedures (6% vs. 19%), despite more advanced preoperative prolapse. In addition, OR time was longer with robotic procedures than with laparoscopic sacrocolpopexy (330 minutes vs. 268 minutes).

The researchers reported that they have no conflicts of interest.

BALTIMORE – Abdominal sacrocolpopexy is associated with a higher rate of peri- and postoperative complications, compared with minimally invasive sacrocolpopexy, based on the results of a review of 831 sacrocolpopexy procedures.

There were significantly more overall intra- and postoperative complications associated with abdominal sacrocolpopexy (ASC) than with minimally invasive sacrocolpopexy (MISC) – 17.2% vs. 10.1% respectively. In particular, there also were significantly more cystotomy complications (4.8% vs. 2.1%) and ileus/small bowel obstruction complications (4.8% vs. 1.8%) in the ASC group, Dr. Patrick A. Nosti reported at the annual meeting of the Society of Gynecologic Surgeons.

Sacrocolpopexy is the preferred surgical treatment for apical prolapse, with a success rate of more than 95%, but there have been a limited number of small prospective and retrospective studies comparing ASC and MISC, said Dr. Nosti, a fellow in the female pelvic medicine and reconstructive surgery fellowship program in the department of obstetrics and gynecology at Washington (D.C.) Hospital Center.

He and his associates conducted a multicenter, retrospective cohort study including cases from January 1999 to December 2010 at four sites. The study was conducted through the Fellows' Pelvic Research Network. The primary outcome was the sum of all intra- and immediate postoperative complications. Secondary outcomes included anatomic success (Pelvic Organ Prolapse Quantification system less than stage II), mesh erosions, estimated blood loss, operative time, and length of hospitalization.

The investigators included 831 sacrocolpopexy procedures; the demographic data was similar between the two groups. The overall mean age was 58 years, mean body mass index was 27.3, and mean parity was three. Of these, 400 patients underwent ASC and 431 underwent MISC. Of the MISC patients, 213 had laparoscopic procedures and 218 had robotic procedures.

There were significantly more anatomical failures (24% vs. 14%), greater estimated blood loss (188 mL vs. 122 mL), longer hospitalization (2.8 vs. 1.2 days), and increased OR time (234 minutes vs. 206) in the ASC group, compared with the MISC group, Dr. Nosti reported.

There were, however, significantly more mesh erosions (3.2% vs. 1%) in the MISC group, compared with the ASC group, he said at the meeting, which was jointly sponsored by the American College of Surgeons.

Mesh erosion was significantly more common after total vs. supracervical hysterectomy (4.2% vs. 0.8% respectively).

In terms of robotic sacrocolpopexy compared with laparoscopic sacrocolpopexy, there was no significant difference in complications (8% vs. 13%). There were fewer failures with robotic procedures than with laparoscopic procedures (6% vs. 19%), despite more advanced preoperative prolapse. In addition, OR time was longer with robotic procedures than with laparoscopic sacrocolpopexy (330 minutes vs. 268 minutes).

The researchers reported that they have no conflicts of interest.

The Food and Drug Administration has identified another batch of counterfeit bevacizumab in the United States, bringing with it concerns for physicians about their legal liability in the complex world of foreign-supplied drugs.

Agency lab tests confirmed that vials of Roche’s Altuzan 400 mg/16mL – a brand of bevacizumab approved in Turkey – contain no active ingredient, the FDA announced early in April. The only bevacizumab brand approved in the United States is Avastin, a product distributed by Roche-owned Genentech.

Subsequently, the agency sent letters to specific physicians in 13 states, who are believed to have purchased medications from foreign or unlicensed suppliers that sold illegal prescription medications. These medical practices "are putting patients at risk of exposure to medications that may be counterfeit, contaminated, improperly stored and transported, ineffective, and dangerous," the agency warned in the letters.

"Even if the identified drugs were not counterfeit, Altuzan is not approved by FDA for use in the United States. ... In virtually all cases, purchasing unapproved prescription drugs from foreign sources violates the Federal Food, Drug, and Cosmetic Act and is illegal," it advised the recipients.

Physicians Could Face Malpractice Suits

This language raises questions about physician liability when drugs are obtained from foreign distributors that have not been approved by the FDA. Not only do concerns about safety come into play, but intellectual property rights do as well, according to Dr. Maxwell Gregg Bloche, who is a physician, a professor of law, and codirector of the Georgetown–Johns Hopkins Joint Program in Law and Public Health.

Dr. Bloche emphasized a distinction between "the vast majority of prescriptions, which are not being supplied in the office" and those such as bevacizumab that are delivered in the context of a medical practice. In the former, the physician – acting as an enforcer of intellectual property law – could be acting against the interests of patients who might suffer terrible health consequences as a result of not being able to afford the drug. "However, when it comes to known counterfeit drugs that could be seriously dangerous, the physician’s role is to safeguard the patient," he said in an interview.

Adding complexity to the situation is an array of FDA-approved foreign suppliers, those foreign companies that knowingly supply dangerous or ineffective drugs, and a third category of suppliers that fall in between.

Outside the United States, there are reputable, high-quality pharmaceutical companies that offer generic drugs at much lower cost, noted Dr. Bloche. However, these companies often do not recognize U.S. patent laws. Only the name-brand drugs are legally available in the United States, until the FDA approves generic versions of those drugs.

"The physician is responsible for making medically sound judgments about risk," he said. If a patient mentions getting a prescribed drug from a foreign source, the physician can indicate that the source produces high-quality, generic versions. The patient may be breaking U.S. laws by doing so; the physician merely offered an opinion.

State malpractice laws come into play once the FDA has identified foreign suppliers that are selling counterfeit drugs – as in this round of counterfeit bevacizumab – and has warned physicians and the public, according to Dr. Bloche. Any physician who is still prescribing and/or using the drug for patients, or who tells the patient that the drug is safe, is then potentially liable.

"I think the medical malpractice law is the one that most physicians are going to be afraid of, which is a state tort law issue, said Dr. Bloche.

In recent months, one oncologist has been prosecuted on charges of distributing and receiving "misbranded and adulterated" prescription drugs in a case brought by the United States Attorney’s Office for the Eastern District of Missouri. Dr. Abid S. Nisar pleaded guilty to one count of "misbranding drugs," according to a government statement. The legal action was part of a larger case involving Neupogen, Herceptin, and Rituxan, but not Avastin, and a distributor known as Ban Dune Marketing Inc. (BDMI).

Buy From a Reputable Distributor

For practicing oncologist Dr. Patrick W. Cobb, "the main way that you know that you’re getting the right thing is to buy it from a reputable distributor. ... When we start looking outside of the large distributors, that’s when you run into problems," said Dr. Cobb, managing partner at Frontier Cancer Center in Billings, Montana, and former president of the Community Oncology Alliance.

When a drug is procured and given directly to a patient by a physician – as is the case with many oncology drugs – "the only safe move is for the physician to follow U.S. law, because then the physician is liable," Dr. Cobb said in an interview.

"When you’re an oncologist administering these kinds of drugs, you just can’t take that chance. You want to make sure that what you give the patient is exactly the drug and exactly the dosage."

In its first fake-bevacizumab warning, the FDA said that 19 U.S. medical practices obtained the counterfeit from Quality Specialty Products (QSP), a foreign supplier also known as Montana Health Care Solutions. QSP products are also distributed by Volunteer Distribution in Gainesboro, Tenn.

The agency specified medications purchased from a foreign distributor named Richards Pharma, also known as Richards Services, Warwick Healthcare Solutions, or Ban Dune Marketing Inc. (BDMI) in its more recent letter alerting oncologists to the second counterfeit.

"Packaging or vials found in the [United States] that claim to be Roche’s Altuzan with lot number B6021 should be considered counterfeit," the agency wrote. The counterfeit version of Altuzan contains "no active ingredient."

Other drugs already obtained from these sources are also suspect, according to the letter. "Many, if not all, of the products sold and distributed through this distributor have not been approved by the FDA," the agency said.

What the FDA Wants Physicians to Do

The FDA advised physicians to stop using these products and to contact the FDA. The products should be retained and securely stored until further notice by the FDA. The agency recommends that physicians take the following actions:

• Report adverse events related to the use of suspect injectable cancer medicines to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

• Verify that a supplier is licensed in a particular state by going to the Drug Integrity and Supply Chain Security section of www.fda.gov for a list of state websites and contacts where this information can be found.

• Report suspected counterfeit products to the FDA Office of Criminal Investigations (OCI) at 800-551-3989, or by e-mail to [email protected].

Dr. Bloche and Dr. Cobb said they have no relevant conflicts of interest.

The Food and Drug Administration has identified another batch of counterfeit bevacizumab in the United States, bringing with it concerns for physicians about their legal liability in the complex world of foreign-supplied drugs.

Agency lab tests confirmed that vials of Roche’s Altuzan 400 mg/16mL – a brand of bevacizumab approved in Turkey – contain no active ingredient, the FDA announced early in April. The only bevacizumab brand approved in the United States is Avastin, a product distributed by Roche-owned Genentech.

Subsequently, the agency sent letters to specific physicians in 13 states, who are believed to have purchased medications from foreign or unlicensed suppliers that sold illegal prescription medications. These medical practices "are putting patients at risk of exposure to medications that may be counterfeit, contaminated, improperly stored and transported, ineffective, and dangerous," the agency warned in the letters.

"Even if the identified drugs were not counterfeit, Altuzan is not approved by FDA for use in the United States. ... In virtually all cases, purchasing unapproved prescription drugs from foreign sources violates the Federal Food, Drug, and Cosmetic Act and is illegal," it advised the recipients.

Physicians Could Face Malpractice Suits

This language raises questions about physician liability when drugs are obtained from foreign distributors that have not been approved by the FDA. Not only do concerns about safety come into play, but intellectual property rights do as well, according to Dr. Maxwell Gregg Bloche, who is a physician, a professor of law, and codirector of the Georgetown–Johns Hopkins Joint Program in Law and Public Health.

Dr. Bloche emphasized a distinction between "the vast majority of prescriptions, which are not being supplied in the office" and those such as bevacizumab that are delivered in the context of a medical practice. In the former, the physician – acting as an enforcer of intellectual property law – could be acting against the interests of patients who might suffer terrible health consequences as a result of not being able to afford the drug. "However, when it comes to known counterfeit drugs that could be seriously dangerous, the physician’s role is to safeguard the patient," he said in an interview.

Adding complexity to the situation is an array of FDA-approved foreign suppliers, those foreign companies that knowingly supply dangerous or ineffective drugs, and a third category of suppliers that fall in between.

Outside the United States, there are reputable, high-quality pharmaceutical companies that offer generic drugs at much lower cost, noted Dr. Bloche. However, these companies often do not recognize U.S. patent laws. Only the name-brand drugs are legally available in the United States, until the FDA approves generic versions of those drugs.

"The physician is responsible for making medically sound judgments about risk," he said. If a patient mentions getting a prescribed drug from a foreign source, the physician can indicate that the source produces high-quality, generic versions. The patient may be breaking U.S. laws by doing so; the physician merely offered an opinion.

State malpractice laws come into play once the FDA has identified foreign suppliers that are selling counterfeit drugs – as in this round of counterfeit bevacizumab – and has warned physicians and the public, according to Dr. Bloche. Any physician who is still prescribing and/or using the drug for patients, or who tells the patient that the drug is safe, is then potentially liable.

"I think the medical malpractice law is the one that most physicians are going to be afraid of, which is a state tort law issue, said Dr. Bloche.

In recent months, one oncologist has been prosecuted on charges of distributing and receiving "misbranded and adulterated" prescription drugs in a case brought by the United States Attorney’s Office for the Eastern District of Missouri. Dr. Abid S. Nisar pleaded guilty to one count of "misbranding drugs," according to a government statement. The legal action was part of a larger case involving Neupogen, Herceptin, and Rituxan, but not Avastin, and a distributor known as Ban Dune Marketing Inc. (BDMI).

Buy From a Reputable Distributor

For practicing oncologist Dr. Patrick W. Cobb, "the main way that you know that you’re getting the right thing is to buy it from a reputable distributor. ... When we start looking outside of the large distributors, that’s when you run into problems," said Dr. Cobb, managing partner at Frontier Cancer Center in Billings, Montana, and former president of the Community Oncology Alliance.

When a drug is procured and given directly to a patient by a physician – as is the case with many oncology drugs – "the only safe move is for the physician to follow U.S. law, because then the physician is liable," Dr. Cobb said in an interview.

"When you’re an oncologist administering these kinds of drugs, you just can’t take that chance. You want to make sure that what you give the patient is exactly the drug and exactly the dosage."

In its first fake-bevacizumab warning, the FDA said that 19 U.S. medical practices obtained the counterfeit from Quality Specialty Products (QSP), a foreign supplier also known as Montana Health Care Solutions. QSP products are also distributed by Volunteer Distribution in Gainesboro, Tenn.

The agency specified medications purchased from a foreign distributor named Richards Pharma, also known as Richards Services, Warwick Healthcare Solutions, or Ban Dune Marketing Inc. (BDMI) in its more recent letter alerting oncologists to the second counterfeit.

"Packaging or vials found in the [United States] that claim to be Roche’s Altuzan with lot number B6021 should be considered counterfeit," the agency wrote. The counterfeit version of Altuzan contains "no active ingredient."

Other drugs already obtained from these sources are also suspect, according to the letter. "Many, if not all, of the products sold and distributed through this distributor have not been approved by the FDA," the agency said.

What the FDA Wants Physicians to Do

The FDA advised physicians to stop using these products and to contact the FDA. The products should be retained and securely stored until further notice by the FDA. The agency recommends that physicians take the following actions:

• Report adverse events related to the use of suspect injectable cancer medicines to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

• Verify that a supplier is licensed in a particular state by going to the Drug Integrity and Supply Chain Security section of www.fda.gov for a list of state websites and contacts where this information can be found.

• Report suspected counterfeit products to the FDA Office of Criminal Investigations (OCI) at 800-551-3989, or by e-mail to [email protected].

Dr. Bloche and Dr. Cobb said they have no relevant conflicts of interest.

The Food and Drug Administration has identified another batch of counterfeit bevacizumab in the United States, bringing with it concerns for physicians about their legal liability in the complex world of foreign-supplied drugs.

Agency lab tests confirmed that vials of Roche’s Altuzan 400 mg/16mL – a brand of bevacizumab approved in Turkey – contain no active ingredient, the FDA announced early in April. The only bevacizumab brand approved in the United States is Avastin, a product distributed by Roche-owned Genentech.

Subsequently, the agency sent letters to specific physicians in 13 states, who are believed to have purchased medications from foreign or unlicensed suppliers that sold illegal prescription medications. These medical practices "are putting patients at risk of exposure to medications that may be counterfeit, contaminated, improperly stored and transported, ineffective, and dangerous," the agency warned in the letters.

"Even if the identified drugs were not counterfeit, Altuzan is not approved by FDA for use in the United States. ... In virtually all cases, purchasing unapproved prescription drugs from foreign sources violates the Federal Food, Drug, and Cosmetic Act and is illegal," it advised the recipients.

Physicians Could Face Malpractice Suits

This language raises questions about physician liability when drugs are obtained from foreign distributors that have not been approved by the FDA. Not only do concerns about safety come into play, but intellectual property rights do as well, according to Dr. Maxwell Gregg Bloche, who is a physician, a professor of law, and codirector of the Georgetown–Johns Hopkins Joint Program in Law and Public Health.

Dr. Bloche emphasized a distinction between "the vast majority of prescriptions, which are not being supplied in the office" and those such as bevacizumab that are delivered in the context of a medical practice. In the former, the physician – acting as an enforcer of intellectual property law – could be acting against the interests of patients who might suffer terrible health consequences as a result of not being able to afford the drug. "However, when it comes to known counterfeit drugs that could be seriously dangerous, the physician’s role is to safeguard the patient," he said in an interview.

Adding complexity to the situation is an array of FDA-approved foreign suppliers, those foreign companies that knowingly supply dangerous or ineffective drugs, and a third category of suppliers that fall in between.

Outside the United States, there are reputable, high-quality pharmaceutical companies that offer generic drugs at much lower cost, noted Dr. Bloche. However, these companies often do not recognize U.S. patent laws. Only the name-brand drugs are legally available in the United States, until the FDA approves generic versions of those drugs.

"The physician is responsible for making medically sound judgments about risk," he said. If a patient mentions getting a prescribed drug from a foreign source, the physician can indicate that the source produces high-quality, generic versions. The patient may be breaking U.S. laws by doing so; the physician merely offered an opinion.

State malpractice laws come into play once the FDA has identified foreign suppliers that are selling counterfeit drugs – as in this round of counterfeit bevacizumab – and has warned physicians and the public, according to Dr. Bloche. Any physician who is still prescribing and/or using the drug for patients, or who tells the patient that the drug is safe, is then potentially liable.

"I think the medical malpractice law is the one that most physicians are going to be afraid of, which is a state tort law issue, said Dr. Bloche.

In recent months, one oncologist has been prosecuted on charges of distributing and receiving "misbranded and adulterated" prescription drugs in a case brought by the United States Attorney’s Office for the Eastern District of Missouri. Dr. Abid S. Nisar pleaded guilty to one count of "misbranding drugs," according to a government statement. The legal action was part of a larger case involving Neupogen, Herceptin, and Rituxan, but not Avastin, and a distributor known as Ban Dune Marketing Inc. (BDMI).

Buy From a Reputable Distributor

For practicing oncologist Dr. Patrick W. Cobb, "the main way that you know that you’re getting the right thing is to buy it from a reputable distributor. ... When we start looking outside of the large distributors, that’s when you run into problems," said Dr. Cobb, managing partner at Frontier Cancer Center in Billings, Montana, and former president of the Community Oncology Alliance.

When a drug is procured and given directly to a patient by a physician – as is the case with many oncology drugs – "the only safe move is for the physician to follow U.S. law, because then the physician is liable," Dr. Cobb said in an interview.

"When you’re an oncologist administering these kinds of drugs, you just can’t take that chance. You want to make sure that what you give the patient is exactly the drug and exactly the dosage."

In its first fake-bevacizumab warning, the FDA said that 19 U.S. medical practices obtained the counterfeit from Quality Specialty Products (QSP), a foreign supplier also known as Montana Health Care Solutions. QSP products are also distributed by Volunteer Distribution in Gainesboro, Tenn.

The agency specified medications purchased from a foreign distributor named Richards Pharma, also known as Richards Services, Warwick Healthcare Solutions, or Ban Dune Marketing Inc. (BDMI) in its more recent letter alerting oncologists to the second counterfeit.

"Packaging or vials found in the [United States] that claim to be Roche’s Altuzan with lot number B6021 should be considered counterfeit," the agency wrote. The counterfeit version of Altuzan contains "no active ingredient."

Other drugs already obtained from these sources are also suspect, according to the letter. "Many, if not all, of the products sold and distributed through this distributor have not been approved by the FDA," the agency said.

What the FDA Wants Physicians to Do

The FDA advised physicians to stop using these products and to contact the FDA. The products should be retained and securely stored until further notice by the FDA. The agency recommends that physicians take the following actions:

• Report adverse events related to the use of suspect injectable cancer medicines to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

• Verify that a supplier is licensed in a particular state by going to the Drug Integrity and Supply Chain Security section of www.fda.gov for a list of state websites and contacts where this information can be found.

• Report suspected counterfeit products to the FDA Office of Criminal Investigations (OCI) at 800-551-3989, or by e-mail to [email protected].

Dr. Bloche and Dr. Cobb said they have no relevant conflicts of interest.

WASHINGTON – Adolescent males are significantly less likely to receive the human papillomavirus vaccine than females, largely because of the lack of information about the vaccine provided to their parents, based on an analysis of data from a statewide survey.

Researchers found that only 14% of males had initiated HPV vaccination compared with 44% for females, based on answers of 751 parents of adolescents (aged 11-17 years) who completed the 2010 North Carolina Child Health Assessment and Monitoring Program (CHAMP) – a statewide telephone survey.

Photo courtesy: National Cancer Institute

In addition, HPV vaccine uptake in males was correlated with older age, minority race, a lower household income, and other vaccine use in the family. For females, HPV vaccine uptake was associated with older age and public school attendance.

The researchers also assessed parental reasons for not vaccinating their child against HPV. "We found that correlates and concerns related to HPV vaccine initiation varied for boys and girls," the researchers noted in a poster presented at the annual meeting of the American Society for Preventive Oncology. Parents of boys most often cited not getting a recommendation from their health care provider or not knowing that the vaccine was available for boys. Parents of girls most often reported concerns about safety and side effects.

Almost half of parents (48%) reported on a male index child. The mean age of the adolescents was 14 years. Most parents reported on children who were non-Hispanic white (69%) or black (20%). Males and females did not differ in terms of 13 sample characteristics assessed.

"Our findings underscore the importance of health care provider recommendation of the HPV vaccine," wrote lead author Melissa B. Gilkey, Ph.D., and her coinvestigators. Dr. Gilkey is a researcher at the Lineberger Comprehensive Cancer Center at the University of North Carolina (UNC) at Chapel Hill.

"The difference in coverage between sons and daughters in our sample is not surprising, as our study was conducted soon after licensure for males," they reported.

It’s hoped that new guidelines on HPV vaccination from the Centers for Disease Control and Prevention are likely to increase boys’ access to the HPV vaccine, as private insurers typically cover the cost of vaccines that are recommended for routine use. "However, the experience with girls suggests that achieving widespread coverage among boys will require a concerted effort," the researchers pointed out. Recommending HPV vaccine alongside other adolescent vaccines is a strategy that may be particularly well suited for addressing the very low levels of uptake among boys."

The study was supported by GlaxoSmithKline, the maker of Cervarix vaccine against HPV types 16 and 18, the cancer control education program at UNC Lineberger, and a National Research Service Award in primary medical care. The investigators did not report whether they had any relevant financial disclosures.

WASHINGTON – Adolescent males are significantly less likely to receive the human papillomavirus vaccine than females, largely because of the lack of information about the vaccine provided to their parents, based on an analysis of data from a statewide survey.

Researchers found that only 14% of males had initiated HPV vaccination compared with 44% for females, based on answers of 751 parents of adolescents (aged 11-17 years) who completed the 2010 North Carolina Child Health Assessment and Monitoring Program (CHAMP) – a statewide telephone survey.

Photo courtesy: National Cancer Institute

In addition, HPV vaccine uptake in males was correlated with older age, minority race, a lower household income, and other vaccine use in the family. For females, HPV vaccine uptake was associated with older age and public school attendance.

The researchers also assessed parental reasons for not vaccinating their child against HPV. "We found that correlates and concerns related to HPV vaccine initiation varied for boys and girls," the researchers noted in a poster presented at the annual meeting of the American Society for Preventive Oncology. Parents of boys most often cited not getting a recommendation from their health care provider or not knowing that the vaccine was available for boys. Parents of girls most often reported concerns about safety and side effects.

Almost half of parents (48%) reported on a male index child. The mean age of the adolescents was 14 years. Most parents reported on children who were non-Hispanic white (69%) or black (20%). Males and females did not differ in terms of 13 sample characteristics assessed.

"Our findings underscore the importance of health care provider recommendation of the HPV vaccine," wrote lead author Melissa B. Gilkey, Ph.D., and her coinvestigators. Dr. Gilkey is a researcher at the Lineberger Comprehensive Cancer Center at the University of North Carolina (UNC) at Chapel Hill.

"The difference in coverage between sons and daughters in our sample is not surprising, as our study was conducted soon after licensure for males," they reported.

It’s hoped that new guidelines on HPV vaccination from the Centers for Disease Control and Prevention are likely to increase boys’ access to the HPV vaccine, as private insurers typically cover the cost of vaccines that are recommended for routine use. "However, the experience with girls suggests that achieving widespread coverage among boys will require a concerted effort," the researchers pointed out. Recommending HPV vaccine alongside other adolescent vaccines is a strategy that may be particularly well suited for addressing the very low levels of uptake among boys."

The study was supported by GlaxoSmithKline, the maker of Cervarix vaccine against HPV types 16 and 18, the cancer control education program at UNC Lineberger, and a National Research Service Award in primary medical care. The investigators did not report whether they had any relevant financial disclosures.

WASHINGTON – Adolescent males are significantly less likely to receive the human papillomavirus vaccine than females, largely because of the lack of information about the vaccine provided to their parents, based on an analysis of data from a statewide survey.

Researchers found that only 14% of males had initiated HPV vaccination compared with 44% for females, based on answers of 751 parents of adolescents (aged 11-17 years) who completed the 2010 North Carolina Child Health Assessment and Monitoring Program (CHAMP) – a statewide telephone survey.

Photo courtesy: National Cancer Institute

In addition, HPV vaccine uptake in males was correlated with older age, minority race, a lower household income, and other vaccine use in the family. For females, HPV vaccine uptake was associated with older age and public school attendance.

The researchers also assessed parental reasons for not vaccinating their child against HPV. "We found that correlates and concerns related to HPV vaccine initiation varied for boys and girls," the researchers noted in a poster presented at the annual meeting of the American Society for Preventive Oncology. Parents of boys most often cited not getting a recommendation from their health care provider or not knowing that the vaccine was available for boys. Parents of girls most often reported concerns about safety and side effects.

Almost half of parents (48%) reported on a male index child. The mean age of the adolescents was 14 years. Most parents reported on children who were non-Hispanic white (69%) or black (20%). Males and females did not differ in terms of 13 sample characteristics assessed.

"Our findings underscore the importance of health care provider recommendation of the HPV vaccine," wrote lead author Melissa B. Gilkey, Ph.D., and her coinvestigators. Dr. Gilkey is a researcher at the Lineberger Comprehensive Cancer Center at the University of North Carolina (UNC) at Chapel Hill.

"The difference in coverage between sons and daughters in our sample is not surprising, as our study was conducted soon after licensure for males," they reported.

It’s hoped that new guidelines on HPV vaccination from the Centers for Disease Control and Prevention are likely to increase boys’ access to the HPV vaccine, as private insurers typically cover the cost of vaccines that are recommended for routine use. "However, the experience with girls suggests that achieving widespread coverage among boys will require a concerted effort," the researchers pointed out. Recommending HPV vaccine alongside other adolescent vaccines is a strategy that may be particularly well suited for addressing the very low levels of uptake among boys."

The study was supported by GlaxoSmithKline, the maker of Cervarix vaccine against HPV types 16 and 18, the cancer control education program at UNC Lineberger, and a National Research Service Award in primary medical care. The investigators did not report whether they had any relevant financial disclosures.

FT. LAUDERDALE, FLA. – Coronary artery bypass graft surgery shows a clear long-term survival advantage in certain high-risk groups over percutaneous coronary intervention, based on results of the largest study of real-world data so far.

The survival advantage for a composite high-risk group – including patients aged 75 years and older, patients with diabetes, those with ejection fractions (EF) less than 50%, and those with a glomerular filtration rate (GFR) less than 60 mL/min per 1.73 m² – was 28% at 4 years, Dr. Fred H. Edwards reported at the annual meeting of the Society of Thoracic Surgeons.

The findings come from the ASCERT (The American College of Cardiology Foundation – The Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies) study, in which researchers compared catheter- and surgery-based procedures using the existing ACC and STS databases, as well as the Centers for Medicare and Medicaid Services 100% denominator file data. The study was designed to identify specific patient characteristics that favor one mode of treatment over the other.

The ACC and the STS both have large registries containing detailed clinical information on millions of procedures. However, the information in these databases extends to only 1 month after the procedure. The researchers linked this short-term clinical information with the administrative data registry from the CMS to provide long-term mortality, rehospitalization, and resource utilization outcomes. The 3- to 5-year outcomes after coronary artery bypass graft (CABG) surgery are being compared with those after percutaneous coronary intervention (PCI) – primarily using drug-eluting coronary stents, from the STS and ACC databases, respectively. In addition to survival, researchers are assessing the need for additional procedures and hospitalizations, new cardiac disease conditions, and the medications being taken at various points in time after the coronary artery procedure.

Patients in this CMS population were at least 65 years of age with two- to three-vessel disease. Patients with either single-vessel disease or left-main disease were excluded.

"[This study has] a population that is actually 10 times greater than the sum total of all patients ever having been enrolled in randomized [revascularization] trials," said Dr. Edwards, who is medical director of cardiothoracic surgery at the University of Florida/Shands Jacksonville,and chairman of the STS National Database.

Data from both the STS and ACC databases were linked to data from the CMS. A propensity score – the probability of having CABG – was calculated for each patient, and clinically important subgroups were identified before the files were linked. The propensity scores and inverse weighting were used to calculate adjusted survival curves. "Then we compared the survival for coronary bypass and percutaneous intervention for groups having very similar characteristics," said Dr. Edwards.

High- and Low-Risk Groups Identified

This analysis included a total of 189,793 patients, of which 103,549 received PCI. Dr. Edwards presented the survival results for high-risk subgroups; the overall results will be presented at the ACC’s Annual Scientific Session in March, he said.

High-risk subgroups include patients who were aged 75 years and older, had diabetes, had EFs less than 50%, and had a GFR less than 60 mL/min per 1.73 m².

For those aged 75 years and older, the mortality risk ratio at 4 years was 0.78 favoring surgery. Correspondingly, the survival advantage in this group for surgery was 22%. For patients with three-vessel disease, the survival advantage at 4 years was 25%. Patients with insulin-dependent diabetes had a 28% survival advantage at 4 years with CABG, compared with PCI. For patients with EFs less than 50%, the survival advantage with surgery was 30% at 4 years.

However, there appears to be a survival advantage with PCI in these groups at up to 1 year of follow-up. "We should keep in mind that in many of these subgroups, the survival with percutaneous intervention is better than surgery in that first 6-10 months after the procedure. The reason for that, of course, is the procedural mortality," Dr. Edwards said.

They also defined a low-risk population (about 20% of the total population). They looked at survival advantages at years 1-4. "I think this is important because it illustrates that surgery really does start to declare its advantage in year 1 to year 2. Then it looks like it begins to plateau off a little bit," he said. "Still, at 4 years for both high-risk and low-risk patients, you’ve got more than a 25% survival advantage for surgery."

He noted that "this is a Medicare population, so we would be on shaky ground if we tried to extrapolate these results to a global population."

He concluded by saying that "the results should improve the quality of care for patients with coronary disease, and it should clarify the indications for intervention in the subgroups that we’ve presented here."

Prediction Models Gleaned From Data

During the same presentation, Dr. David M. Shahian reported on long-term prediction models of death and nonfatal events for both CABG and PCI. "Longer term outcomes are clearly going to be necessary if we’re really going to determine the true comparative effectiveness of these various strategies." he said.

The researchers looked at all isolated CABG patients at STS-participating hospitals who were discharged between the beginning of 2002 and the end of 2007. STS procedural records were linked to CMS claims and denominator files.

The final cohort included 348,341 CABG patients at 917 sites. Follow-up was through 2008 (median follow-up, 4 years). Long-term variables were based on those from short-term CABG models and clinical experience. Separate hazard ratios were estimated for each of these variables for four time intervals: 0-30 days, 31-80 days, 181-730 days, and more than 2 years.

Kaplan-Meier estimated mortality rates for CABG were 3% at 30 days, 6% at 180 days, 8% at 1 year, 11% at 2 years, and 23% at 3 years. Predicted mortality rates were superimposable with observed mortality rates, said Dr. Shahian, who is a cardiothoracic surgeon at Harvard Medical School in Boston. Dr. Shahian is also the chair of the STS Adult Cardiac Surgery Database and the STS Quality Measurement Task Force.

"We did observe the obesity paradox here. It’s the frail, almost cachectic individuals, who do the worst, while the more obese individuals tend to do better over time," he said.

The impact of some predictors changed over time. For example, patients with an acute MI have an increased initial mortality risk, which becomes generally insignificant over 1-2 years. In addition, early reoperation, shock, and emergency status have high up-front risks that decrease over time. However, preoperative atrial fibrillation progressively increases risk over time, he said.

"Among hospital survivors, higher ejection fraction and higher [body mass index] are protective at all time periods. A past history of stroke ... [and] chronic lung-disease immunosuppression have a persistent and negative impact on survival. Smoking, diabetes, dialysis-dependent renal failure – their negative impact increases over time. ... Some early important risk factors, like shock, emergency status, and reoperation are not predictors of late outcomes."

Dr. Edwards and. Dr. Shahian reported no relevant financial relationships.

FT. LAUDERDALE, FLA. – Coronary artery bypass graft surgery shows a clear long-term survival advantage in certain high-risk groups over percutaneous coronary intervention, based on results of the largest study of real-world data so far.

The survival advantage for a composite high-risk group – including patients aged 75 years and older, patients with diabetes, those with ejection fractions (EF) less than 50%, and those with a glomerular filtration rate (GFR) less than 60 mL/min per 1.73 m² – was 28% at 4 years, Dr. Fred H. Edwards reported at the annual meeting of the Society of Thoracic Surgeons.

The findings come from the ASCERT (The American College of Cardiology Foundation – The Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies) study, in which researchers compared catheter- and surgery-based procedures using the existing ACC and STS databases, as well as the Centers for Medicare and Medicaid Services 100% denominator file data. The study was designed to identify specific patient characteristics that favor one mode of treatment over the other.

The ACC and the STS both have large registries containing detailed clinical information on millions of procedures. However, the information in these databases extends to only 1 month after the procedure. The researchers linked this short-term clinical information with the administrative data registry from the CMS to provide long-term mortality, rehospitalization, and resource utilization outcomes. The 3- to 5-year outcomes after coronary artery bypass graft (CABG) surgery are being compared with those after percutaneous coronary intervention (PCI) – primarily using drug-eluting coronary stents, from the STS and ACC databases, respectively. In addition to survival, researchers are assessing the need for additional procedures and hospitalizations, new cardiac disease conditions, and the medications being taken at various points in time after the coronary artery procedure.

Patients in this CMS population were at least 65 years of age with two- to three-vessel disease. Patients with either single-vessel disease or left-main disease were excluded.

"[This study has] a population that is actually 10 times greater than the sum total of all patients ever having been enrolled in randomized [revascularization] trials," said Dr. Edwards, who is medical director of cardiothoracic surgery at the University of Florida/Shands Jacksonville,and chairman of the STS National Database.

Data from both the STS and ACC databases were linked to data from the CMS. A propensity score – the probability of having CABG – was calculated for each patient, and clinically important subgroups were identified before the files were linked. The propensity scores and inverse weighting were used to calculate adjusted survival curves. "Then we compared the survival for coronary bypass and percutaneous intervention for groups having very similar characteristics," said Dr. Edwards.

High- and Low-Risk Groups Identified

This analysis included a total of 189,793 patients, of which 103,549 received PCI. Dr. Edwards presented the survival results for high-risk subgroups; the overall results will be presented at the ACC’s Annual Scientific Session in March, he said.

High-risk subgroups include patients who were aged 75 years and older, had diabetes, had EFs less than 50%, and had a GFR less than 60 mL/min per 1.73 m².

For those aged 75 years and older, the mortality risk ratio at 4 years was 0.78 favoring surgery. Correspondingly, the survival advantage in this group for surgery was 22%. For patients with three-vessel disease, the survival advantage at 4 years was 25%. Patients with insulin-dependent diabetes had a 28% survival advantage at 4 years with CABG, compared with PCI. For patients with EFs less than 50%, the survival advantage with surgery was 30% at 4 years.

However, there appears to be a survival advantage with PCI in these groups at up to 1 year of follow-up. "We should keep in mind that in many of these subgroups, the survival with percutaneous intervention is better than surgery in that first 6-10 months after the procedure. The reason for that, of course, is the procedural mortality," Dr. Edwards said.

They also defined a low-risk population (about 20% of the total population). They looked at survival advantages at years 1-4. "I think this is important because it illustrates that surgery really does start to declare its advantage in year 1 to year 2. Then it looks like it begins to plateau off a little bit," he said. "Still, at 4 years for both high-risk and low-risk patients, you’ve got more than a 25% survival advantage for surgery."

He noted that "this is a Medicare population, so we would be on shaky ground if we tried to extrapolate these results to a global population."

He concluded by saying that "the results should improve the quality of care for patients with coronary disease, and it should clarify the indications for intervention in the subgroups that we’ve presented here."

Prediction Models Gleaned From Data

During the same presentation, Dr. David M. Shahian reported on long-term prediction models of death and nonfatal events for both CABG and PCI. "Longer term outcomes are clearly going to be necessary if we’re really going to determine the true comparative effectiveness of these various strategies." he said.

The researchers looked at all isolated CABG patients at STS-participating hospitals who were discharged between the beginning of 2002 and the end of 2007. STS procedural records were linked to CMS claims and denominator files.

The final cohort included 348,341 CABG patients at 917 sites. Follow-up was through 2008 (median follow-up, 4 years). Long-term variables were based on those from short-term CABG models and clinical experience. Separate hazard ratios were estimated for each of these variables for four time intervals: 0-30 days, 31-80 days, 181-730 days, and more than 2 years.

Kaplan-Meier estimated mortality rates for CABG were 3% at 30 days, 6% at 180 days, 8% at 1 year, 11% at 2 years, and 23% at 3 years. Predicted mortality rates were superimposable with observed mortality rates, said Dr. Shahian, who is a cardiothoracic surgeon at Harvard Medical School in Boston. Dr. Shahian is also the chair of the STS Adult Cardiac Surgery Database and the STS Quality Measurement Task Force.

"We did observe the obesity paradox here. It’s the frail, almost cachectic individuals, who do the worst, while the more obese individuals tend to do better over time," he said.

The impact of some predictors changed over time. For example, patients with an acute MI have an increased initial mortality risk, which becomes generally insignificant over 1-2 years. In addition, early reoperation, shock, and emergency status have high up-front risks that decrease over time. However, preoperative atrial fibrillation progressively increases risk over time, he said.

"Among hospital survivors, higher ejection fraction and higher [body mass index] are protective at all time periods. A past history of stroke ... [and] chronic lung-disease immunosuppression have a persistent and negative impact on survival. Smoking, diabetes, dialysis-dependent renal failure – their negative impact increases over time. ... Some early important risk factors, like shock, emergency status, and reoperation are not predictors of late outcomes."

Dr. Edwards and. Dr. Shahian reported no relevant financial relationships.

FT. LAUDERDALE, FLA. – Coronary artery bypass graft surgery shows a clear long-term survival advantage in certain high-risk groups over percutaneous coronary intervention, based on results of the largest study of real-world data so far.

The survival advantage for a composite high-risk group – including patients aged 75 years and older, patients with diabetes, those with ejection fractions (EF) less than 50%, and those with a glomerular filtration rate (GFR) less than 60 mL/min per 1.73 m² – was 28% at 4 years, Dr. Fred H. Edwards reported at the annual meeting of the Society of Thoracic Surgeons.

The findings come from the ASCERT (The American College of Cardiology Foundation – The Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies) study, in which researchers compared catheter- and surgery-based procedures using the existing ACC and STS databases, as well as the Centers for Medicare and Medicaid Services 100% denominator file data. The study was designed to identify specific patient characteristics that favor one mode of treatment over the other.

The ACC and the STS both have large registries containing detailed clinical information on millions of procedures. However, the information in these databases extends to only 1 month after the procedure. The researchers linked this short-term clinical information with the administrative data registry from the CMS to provide long-term mortality, rehospitalization, and resource utilization outcomes. The 3- to 5-year outcomes after coronary artery bypass graft (CABG) surgery are being compared with those after percutaneous coronary intervention (PCI) – primarily using drug-eluting coronary stents, from the STS and ACC databases, respectively. In addition to survival, researchers are assessing the need for additional procedures and hospitalizations, new cardiac disease conditions, and the medications being taken at various points in time after the coronary artery procedure.

Patients in this CMS population were at least 65 years of age with two- to three-vessel disease. Patients with either single-vessel disease or left-main disease were excluded.

"[This study has] a population that is actually 10 times greater than the sum total of all patients ever having been enrolled in randomized [revascularization] trials," said Dr. Edwards, who is medical director of cardiothoracic surgery at the University of Florida/Shands Jacksonville,and chairman of the STS National Database.

Data from both the STS and ACC databases were linked to data from the CMS. A propensity score – the probability of having CABG – was calculated for each patient, and clinically important subgroups were identified before the files were linked. The propensity scores and inverse weighting were used to calculate adjusted survival curves. "Then we compared the survival for coronary bypass and percutaneous intervention for groups having very similar characteristics," said Dr. Edwards.

High- and Low-Risk Groups Identified

This analysis included a total of 189,793 patients, of which 103,549 received PCI. Dr. Edwards presented the survival results for high-risk subgroups; the overall results will be presented at the ACC’s Annual Scientific Session in March, he said.

High-risk subgroups include patients who were aged 75 years and older, had diabetes, had EFs less than 50%, and had a GFR less than 60 mL/min per 1.73 m².

For those aged 75 years and older, the mortality risk ratio at 4 years was 0.78 favoring surgery. Correspondingly, the survival advantage in this group for surgery was 22%. For patients with three-vessel disease, the survival advantage at 4 years was 25%. Patients with insulin-dependent diabetes had a 28% survival advantage at 4 years with CABG, compared with PCI. For patients with EFs less than 50%, the survival advantage with surgery was 30% at 4 years.

However, there appears to be a survival advantage with PCI in these groups at up to 1 year of follow-up. "We should keep in mind that in many of these subgroups, the survival with percutaneous intervention is better than surgery in that first 6-10 months after the procedure. The reason for that, of course, is the procedural mortality," Dr. Edwards said.

They also defined a low-risk population (about 20% of the total population). They looked at survival advantages at years 1-4. "I think this is important because it illustrates that surgery really does start to declare its advantage in year 1 to year 2. Then it looks like it begins to plateau off a little bit," he said. "Still, at 4 years for both high-risk and low-risk patients, you’ve got more than a 25% survival advantage for surgery."

He noted that "this is a Medicare population, so we would be on shaky ground if we tried to extrapolate these results to a global population."

He concluded by saying that "the results should improve the quality of care for patients with coronary disease, and it should clarify the indications for intervention in the subgroups that we’ve presented here."

Prediction Models Gleaned From Data

During the same presentation, Dr. David M. Shahian reported on long-term prediction models of death and nonfatal events for both CABG and PCI. "Longer term outcomes are clearly going to be necessary if we’re really going to determine the true comparative effectiveness of these various strategies." he said.

The researchers looked at all isolated CABG patients at STS-participating hospitals who were discharged between the beginning of 2002 and the end of 2007. STS procedural records were linked to CMS claims and denominator files.

The final cohort included 348,341 CABG patients at 917 sites. Follow-up was through 2008 (median follow-up, 4 years). Long-term variables were based on those from short-term CABG models and clinical experience. Separate hazard ratios were estimated for each of these variables for four time intervals: 0-30 days, 31-80 days, 181-730 days, and more than 2 years.

Kaplan-Meier estimated mortality rates for CABG were 3% at 30 days, 6% at 180 days, 8% at 1 year, 11% at 2 years, and 23% at 3 years. Predicted mortality rates were superimposable with observed mortality rates, said Dr. Shahian, who is a cardiothoracic surgeon at Harvard Medical School in Boston. Dr. Shahian is also the chair of the STS Adult Cardiac Surgery Database and the STS Quality Measurement Task Force.

"We did observe the obesity paradox here. It’s the frail, almost cachectic individuals, who do the worst, while the more obese individuals tend to do better over time," he said.

The impact of some predictors changed over time. For example, patients with an acute MI have an increased initial mortality risk, which becomes generally insignificant over 1-2 years. In addition, early reoperation, shock, and emergency status have high up-front risks that decrease over time. However, preoperative atrial fibrillation progressively increases risk over time, he said.

"Among hospital survivors, higher ejection fraction and higher [body mass index] are protective at all time periods. A past history of stroke ... [and] chronic lung-disease immunosuppression have a persistent and negative impact on survival. Smoking, diabetes, dialysis-dependent renal failure – their negative impact increases over time. ... Some early important risk factors, like shock, emergency status, and reoperation are not predictors of late outcomes."

Dr. Edwards and. Dr. Shahian reported no relevant financial relationships.

FT. LAUDERDALE, FLA. – Coronary artery bypass graft surgery shows a clear long-term survival advantage in certain high-risk groups over percutaneous coronary intervention, based on results of the largest study of real-world data so far.

The survival advantage for a composite high-risk group – including patients aged 75 years and older, patients with diabetes, those with ejection fractions (EF) less than 50%, and those with a glomerular filtration rate (GFR) less than 60 mL/min per 1.73 m² – was 28% at 4 years, Dr. Fred H. Edwards reported at the annual meeting of the Society of Thoracic Surgeons.

The findings come from the ASCERT (The American College of Cardiology Foundation – The Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies) study, in which researchers compared catheter- and surgery-based procedures using the existing ACC and STS databases, as well as the Centers for Medicare and Medicaid Services 100% denominator file data. The study was designed to identify specific patient characteristics that favor one mode of treatment over the other.

The ACC and the STS both have large registries containing detailed clinical information on millions of procedures. However, the information in these databases extends to only 1 month after the procedure. The researchers linked this short-term clinical information with the administrative data registry from the CMS to provide long-term mortality, rehospitalization, and resource utilization outcomes. The 3- to 5-year outcomes after coronary artery bypass graft (CABG) surgery are being compared with those after percutaneous coronary intervention (PCI) – primarily using drug-eluting coronary stents, from the STS and ACC databases, respectively. In addition to survival, researchers are assessing the need for additional procedures and hospitalizations, new cardiac disease conditions, and the medications being taken at various points in time after the coronary artery procedure.

Patients in this CMS population were at least 65 years of age with two- to three-vessel disease. Patients with either single-vessel disease or left-main disease were excluded.

"[This study has] a population that is actually 10 times greater than the sum total of all patients ever having been enrolled in randomized [revascularization] trials," said Dr. Edwards, who is medical director of cardiothoracic surgery at the University of Florida/Shands Jacksonville,and chairman of the STS National Database.

Data from both the STS and ACC databases were linked to data from the CMS. A propensity score – the probability of having CABG – was calculated for each patient, and clinically important subgroups were identified before the files were linked. The propensity scores and inverse weighting were used to calculate adjusted survival curves. "Then we compared the survival for coronary bypass and percutaneous intervention for groups having very similar characteristics," said Dr. Edwards.

High- and Low-Risk Groups Identified

This analysis included a total of 189,793 patients, of which 103,549 received PCI. Dr. Edwards presented the survival results for high-risk subgroups; the overall results will be presented at the ACC’s Annual Scientific Session in March, he said.

High-risk subgroups include patients who were aged 75 years and older, had diabetes, had EFs less than 50%, and had a GFR less than 60 mL/min per 1.73 m².

For those aged 75 years and older, the mortality risk ratio at 4 years was 0.78 favoring surgery. Correspondingly, the survival advantage in this group for surgery was 22%. For patients with three-vessel disease, the survival advantage at 4 years was 25%. Patients with insulin-dependent diabetes had a 28% survival advantage at 4 years with CABG, compared with PCI. For patients with EFs less than 50%, the survival advantage with surgery was 30% at 4 years.

However, there appears to be a survival advantage with PCI in these groups at up to 1 year of follow-up. "We should keep in mind that in many of these subgroups, the survival with percutaneous intervention is better than surgery in that first 6-10 months after the procedure. The reason for that, of course, is the procedural mortality," Dr. Edwards said.

They also defined a low-risk population (about 20% of the total population). They looked at survival advantages at years 1-4. "I think this is important because it illustrates that surgery really does start to declare its advantage in year 1 to year 2. Then it looks like it begins to plateau off a little bit," he said. "Still, at 4 years for both high-risk and low-risk patients, you’ve got more than a 25% survival advantage for surgery."

He noted that "this is a Medicare population, so we would be on shaky ground if we tried to extrapolate these results to a global population."

He concluded by saying that "the results should improve the quality of care for patients with coronary disease, and it should clarify the indications for intervention in the subgroups that we’ve presented here."

Prediction Models Gleaned From Data

During the same presentation, Dr. David M. Shahian reported on long-term prediction models of death and nonfatal events for both CABG and PCI. "Longer term outcomes are clearly going to be necessary if we’re really going to determine the true comparative effectiveness of these various strategies." he said.

The researchers looked at all isolated CABG patients at STS-participating hospitals who were discharged between the beginning of 2002 and the end of 2007. STS procedural records were linked to CMS claims and denominator files.

The final cohort included 348,341 CABG patients at 917 sites. Follow-up was through 2008 (median follow-up, 4 years). Long-term variables were based on those from short-term CABG models and clinical experience. Separate hazard ratios were estimated for each of these variables for four time intervals: 0-30 days, 31-80 days, 181-730 days, and more than 2 years.

Kaplan-Meier estimated mortality rates for CABG were 3% at 30 days, 6% at 180 days, 8% at 1 year, 11% at 2 years, and 23% at 3 years. Predicted mortality rates were superimposable with observed mortality rates, said Dr. Shahian, who is a cardiothoracic surgeon at Harvard Medical School in Boston. Dr. Shahian is also the chair of the STS Adult Cardiac Surgery Database and the STS Quality Measurement Task Force.

"We did observe the obesity paradox here. It’s the frail, almost cachectic individuals, who do the worst, while the more obese individuals tend to do better over time," he said.

The impact of some predictors changed over time. For example, patients with an acute MI have an increased initial mortality risk, which becomes generally insignificant over 1-2 years. In addition, early reoperation, shock, and emergency status have high up-front risks that decrease over time. However, preoperative atrial fibrillation progressively increases risk over time, he said.

"Among hospital survivors, higher ejection fraction and higher [body mass index] are protective at all time periods. A past history of stroke ... [and] chronic lung-disease immunosuppression have a persistent and negative impact on survival. Smoking, diabetes, dialysis-dependent renal failure – their negative impact increases over time. ... Some early important risk factors, like shock, emergency status, and reoperation are not predictors of late outcomes."

Dr. Edwards and. Dr. Shahian reported no relevant financial relationships.

FT. LAUDERDALE, FLA. – Coronary artery bypass graft surgery shows a clear long-term survival advantage in certain high-risk groups over percutaneous coronary intervention, based on results of the largest study of real-world data so far.

The survival advantage for a composite high-risk group – including patients aged 75 years and older, patients with diabetes, those with ejection fractions (EF) less than 50%, and those with a glomerular filtration rate (GFR) less than 60 mL/min per 1.73 m² – was 28% at 4 years, Dr. Fred H. Edwards reported at the annual meeting of the Society of Thoracic Surgeons.

The findings come from the ASCERT (The American College of Cardiology Foundation – The Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies) study, in which researchers compared catheter- and surgery-based procedures using the existing ACC and STS databases, as well as the Centers for Medicare and Medicaid Services 100% denominator file data. The study was designed to identify specific patient characteristics that favor one mode of treatment over the other.

The ACC and the STS both have large registries containing detailed clinical information on millions of procedures. However, the information in these databases extends to only 1 month after the procedure. The researchers linked this short-term clinical information with the administrative data registry from the CMS to provide long-term mortality, rehospitalization, and resource utilization outcomes. The 3- to 5-year outcomes after coronary artery bypass graft (CABG) surgery are being compared with those after percutaneous coronary intervention (PCI) – primarily using drug-eluting coronary stents, from the STS and ACC databases, respectively. In addition to survival, researchers are assessing the need for additional procedures and hospitalizations, new cardiac disease conditions, and the medications being taken at various points in time after the coronary artery procedure.

Patients in this CMS population were at least 65 years of age with two- to three-vessel disease. Patients with either single-vessel disease or left-main disease were excluded.

"[This study has] a population that is actually 10 times greater than the sum total of all patients ever having been enrolled in randomized [revascularization] trials," said Dr. Edwards, who is medical director of cardiothoracic surgery at the University of Florida/Shands Jacksonville,and chairman of the STS National Database.

Data from both the STS and ACC databases were linked to data from the CMS. A propensity score – the probability of having CABG – was calculated for each patient, and clinically important subgroups were identified before the files were linked. The propensity scores and inverse weighting were used to calculate adjusted survival curves. "Then we compared the survival for coronary bypass and percutaneous intervention for groups having very similar characteristics," said Dr. Edwards.

High- and Low-Risk Groups Identified

This analysis included a total of 189,793 patients, of which 103,549 received PCI. Dr. Edwards presented the survival results for high-risk subgroups; the overall results will be presented at the ACC’s Annual Scientific Session in March, he said.

High-risk subgroups include patients who were aged 75 years and older, had diabetes, had EFs less than 50%, and had a GFR less than 60 mL/min per 1.73 m².

For those aged 75 years and older, the mortality risk ratio at 4 years was 0.78 favoring surgery. Correspondingly, the survival advantage in this group for surgery was 22%. For patients with three-vessel disease, the survival advantage at 4 years was 25%. Patients with insulin-dependent diabetes had a 28% survival advantage at 4 years with CABG, compared with PCI. For patients with EFs less than 50%, the survival advantage with surgery was 30% at 4 years.

However, there appears to be a survival advantage with PCI in these groups at up to 1 year of follow-up. "We should keep in mind that in many of these subgroups, the survival with percutaneous intervention is better than surgery in that first 6-10 months after the procedure. The reason for that, of course, is the procedural mortality," Dr. Edwards said.

They also defined a low-risk population (about 20% of the total population). They looked at survival advantages at years 1-4. "I think this is important because it illustrates that surgery really does start to declare its advantage in year 1 to year 2. Then it looks like it begins to plateau off a little bit," he said. "Still, at 4 years for both high-risk and low-risk patients, you’ve got more than a 25% survival advantage for surgery."

He noted that "this is a Medicare population, so we would be on shaky ground if we tried to extrapolate these results to a global population."

He concluded by saying that "the results should improve the quality of care for patients with coronary disease, and it should clarify the indications for intervention in the subgroups that we’ve presented here."

Prediction Models Gleaned From Data

During the same presentation, Dr. David M. Shahian reported on long-term prediction models of death and nonfatal events for both CABG and PCI. "Longer term outcomes are clearly going to be necessary if we’re really going to determine the true comparative effectiveness of these various strategies." he said.

The researchers looked at all isolated CABG patients at STS-participating hospitals who were discharged between the beginning of 2002 and the end of 2007. STS procedural records were linked to CMS claims and denominator files.

The final cohort included 348,341 CABG patients at 917 sites. Follow-up was through 2008 (median follow-up, 4 years). Long-term variables were based on those from short-term CABG models and clinical experience. Separate hazard ratios were estimated for each of these variables for four time intervals: 0-30 days, 31-80 days, 181-730 days, and more than 2 years.

Kaplan-Meier estimated mortality rates for CABG were 3% at 30 days, 6% at 180 days, 8% at 1 year, 11% at 2 years, and 23% at 3 years. Predicted mortality rates were superimposable with observed mortality rates, said Dr. Shahian, who is a cardiothoracic surgeon at Harvard Medical School in Boston. Dr. Shahian is also the chair of the STS Adult Cardiac Surgery Database and the STS Quality Measurement Task Force.

"We did observe the obesity paradox here. It’s the frail, almost cachectic individuals, who do the worst, while the more obese individuals tend to do better over time," he said.

The impact of some predictors changed over time. For example, patients with an acute MI have an increased initial mortality risk, which becomes generally insignificant over 1-2 years. In addition, early reoperation, shock, and emergency status have high up-front risks that decrease over time. However, preoperative atrial fibrillation progressively increases risk over time, he said.

"Among hospital survivors, higher ejection fraction and higher [body mass index] are protective at all time periods. A past history of stroke ... [and] chronic lung-disease immunosuppression have a persistent and negative impact on survival. Smoking, diabetes, dialysis-dependent renal failure – their negative impact increases over time. ... Some early important risk factors, like shock, emergency status, and reoperation are not predictors of late outcomes."

Dr. Edwards and. Dr. Shahian reported no relevant financial relationships.

FT. LAUDERDALE, FLA. – Coronary artery bypass graft surgery shows a clear long-term survival advantage in certain high-risk groups over percutaneous coronary intervention, based on results of the largest study of real-world data so far.

The survival advantage for a composite high-risk group – including patients aged 75 years and older, patients with diabetes, those with ejection fractions (EF) less than 50%, and those with a glomerular filtration rate (GFR) less than 60 mL/min per 1.73 m² – was 28% at 4 years, Dr. Fred H. Edwards reported at the annual meeting of the Society of Thoracic Surgeons.

The findings come from the ASCERT (The American College of Cardiology Foundation – The Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies) study, in which researchers compared catheter- and surgery-based procedures using the existing ACC and STS databases, as well as the Centers for Medicare and Medicaid Services 100% denominator file data. The study was designed to identify specific patient characteristics that favor one mode of treatment over the other.

The ACC and the STS both have large registries containing detailed clinical information on millions of procedures. However, the information in these databases extends to only 1 month after the procedure. The researchers linked this short-term clinical information with the administrative data registry from the CMS to provide long-term mortality, rehospitalization, and resource utilization outcomes. The 3- to 5-year outcomes after coronary artery bypass graft (CABG) surgery are being compared with those after percutaneous coronary intervention (PCI) – primarily using drug-eluting coronary stents, from the STS and ACC databases, respectively. In addition to survival, researchers are assessing the need for additional procedures and hospitalizations, new cardiac disease conditions, and the medications being taken at various points in time after the coronary artery procedure.

Patients in this CMS population were at least 65 years of age with two- to three-vessel disease. Patients with either single-vessel disease or left-main disease were excluded.

"[This study has] a population that is actually 10 times greater than the sum total of all patients ever having been enrolled in randomized [revascularization] trials," said Dr. Edwards, who is medical director of cardiothoracic surgery at the University of Florida/Shands Jacksonville,and chairman of the STS National Database.

Data from both the STS and ACC databases were linked to data from the CMS. A propensity score – the probability of having CABG – was calculated for each patient, and clinically important subgroups were identified before the files were linked. The propensity scores and inverse weighting were used to calculate adjusted survival curves. "Then we compared the survival for coronary bypass and percutaneous intervention for groups having very similar characteristics," said Dr. Edwards.

High- and Low-Risk Groups Identified

This analysis included a total of 189,793 patients, of which 103,549 received PCI. Dr. Edwards presented the survival results for high-risk subgroups; the overall results will be presented at the ACC’s Annual Scientific Session in March, he said.

High-risk subgroups include patients who were aged 75 years and older, had diabetes, had EFs less than 50%, and had a GFR less than 60 mL/min per 1.73 m².

For those aged 75 years and older, the mortality risk ratio at 4 years was 0.78 favoring surgery. Correspondingly, the survival advantage in this group for surgery was 22%. For patients with three-vessel disease, the survival advantage at 4 years was 25%. Patients with insulin-dependent diabetes had a 28% survival advantage at 4 years with CABG, compared with PCI. For patients with EFs less than 50%, the survival advantage with surgery was 30% at 4 years.

However, there appears to be a survival advantage with PCI in these groups at up to 1 year of follow-up. "We should keep in mind that in many of these subgroups, the survival with percutaneous intervention is better than surgery in that first 6-10 months after the procedure. The reason for that, of course, is the procedural mortality," Dr. Edwards said.

They also defined a low-risk population (about 20% of the total population). They looked at survival advantages at years 1-4. "I think this is important because it illustrates that surgery really does start to declare its advantage in year 1 to year 2. Then it looks like it begins to plateau off a little bit," he said. "Still, at 4 years for both high-risk and low-risk patients, you’ve got more than a 25% survival advantage for surgery."

He noted that "this is a Medicare population, so we would be on shaky ground if we tried to extrapolate these results to a global population."

He concluded by saying that "the results should improve the quality of care for patients with coronary disease, and it should clarify the indications for intervention in the subgroups that we’ve presented here."

Prediction Models Gleaned From Data

During the same presentation, Dr. David M. Shahian reported on long-term prediction models of death and nonfatal events for both CABG and PCI. "Longer term outcomes are clearly going to be necessary if we’re really going to determine the true comparative effectiveness of these various strategies." he said.

The researchers looked at all isolated CABG patients at STS-participating hospitals who were discharged between the beginning of 2002 and the end of 2007. STS procedural records were linked to CMS claims and denominator files.

The final cohort included 348,341 CABG patients at 917 sites. Follow-up was through 2008 (median follow-up, 4 years). Long-term variables were based on those from short-term CABG models and clinical experience. Separate hazard ratios were estimated for each of these variables for four time intervals: 0-30 days, 31-80 days, 181-730 days, and more than 2 years.

Kaplan-Meier estimated mortality rates for CABG were 3% at 30 days, 6% at 180 days, 8% at 1 year, 11% at 2 years, and 23% at 3 years. Predicted mortality rates were superimposable with observed mortality rates, said Dr. Shahian, who is a cardiothoracic surgeon at Harvard Medical School in Boston. Dr. Shahian is also the chair of the STS Adult Cardiac Surgery Database and the STS Quality Measurement Task Force.

"We did observe the obesity paradox here. It’s the frail, almost cachectic individuals, who do the worst, while the more obese individuals tend to do better over time," he said.

The impact of some predictors changed over time. For example, patients with an acute MI have an increased initial mortality risk, which becomes generally insignificant over 1-2 years. In addition, early reoperation, shock, and emergency status have high up-front risks that decrease over time. However, preoperative atrial fibrillation progressively increases risk over time, he said.

"Among hospital survivors, higher ejection fraction and higher [body mass index] are protective at all time periods. A past history of stroke ... [and] chronic lung-disease immunosuppression have a persistent and negative impact on survival. Smoking, diabetes, dialysis-dependent renal failure – their negative impact increases over time. ... Some early important risk factors, like shock, emergency status, and reoperation are not predictors of late outcomes."

Dr. Edwards and. Dr. Shahian reported no relevant financial relationships.