Susan London

PHOENIX – The standard sequential approach to treatment of patients with isolated synchronous liver metastases of colorectal cancer, entailing up-front removal of the primary tumor, is associated with growth of the metastases, according to results from a retrospective cohort study.

A team led by Dr. Alistair Slesser, a surgical registrar at the Royal Marsden Hospital in London, studied 114 patients with colorectal cancer who had synchronous liver metastases, meaning ones identified within a year of the cancer diagnosis, and no other metastases.

Results showed that patients whose initial treatment was resection of the colorectal primary tumor had ninefold higher odds of progression of their liver metastases at 3 months, compared with patients whose initial treatment was chemotherapy, he reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Although liver metastases showed regression during 3-6 months of treatment in both groups, the rate was somewhat slower in the primary tumor resection group.

"Our findings suggest that an up-front primary tumor resection is actually an adverse prognostic factor. Indeed, our results have demonstrated that up-front primary tumor resection seemed to negate the effects of the adjuvant therapy on the treatment of the liver metastasis," Dr. Slesser commented.

"How does this apply clinically? We would recommend that patients who have limited metastatic disease, instead of having an up-front primary tumor resection perhaps [they should] be treated with neoadjuvant chemotherapy first. Or perhaps another surgical approach, like a simultaneous resection, should be considered to negate the adverse effects of a primary tumor resection on the metastatic disease," he said.

"When patients have lesions which are suspicious for liver metastases, we would recommend that these patients [be] thoroughly investigated, and if metastatic disease is confirmed, then again, we would recommend that they have chemotherapy prior to any subsequent intervention," he added.

The mechanism leading to growth of liver metastases after primary tumor resection is unknown, according to Dr. Slesser. "There is possibly an association for ... biological reasons. The other reason is that perhaps when a patient has an up-front primary tumor resection, there is a delay in getting chemotherapy, and that can cause the progression that we see."

Session attendee Dr. Gary Dunn, of the University of Oklahoma, Oklahoma City, asked how much time elapsed between up-front resection and receipt of adjuvant chemotherapy in that group, and the variance in this measure, noting, "That will significantly affect your outcome, if some patients started at 6 weeks and some patients started at 12 weeks postop."

"Usually, patients waited 6 weeks before they started chemotherapy postoperatively," Dr. Slesser explained. "The majority of patients who had primary tumor resection had the adjuvant chemotherapy after the postoperative scan; the 3-month scan tends to be the postoperative scan."

Dr. Dunn further wondered about the comparability between groups of the chemotherapy received, asking what agents were used.

"At the Royal Marsden, the chemotherapy regimes tend to be quite uniform," Dr. Slesser replied. "Generally, all patients are on capecitabine [Xeloda] and oxaliplatin, with a monoclonal agent such as bevacizumab [Avastin]. They tend to get that when they have neoadjuvant chemotherapy."

Another attendee said, "Excellent paper, very well presented data, particularly considering there are a lot of retrospective series out there that are showing the up-front resection as a favorable prognostic indicator, which I don’t believe. ... But I would like to see a little more information about how the patients were treated subsequently. Were these patients who they were planning to get to surgery for resection, or were these patients who were treated for palliative intent? Did they have symptomatic primaries?"

"In the majority of these patients, the intent was curative surgery," Dr. Slesser replied. "We tried to exclude patients who were clearly referred for palliative treatment because we really wanted to assess patients who were referred for curative treatment."

Attendee Dr. David Shibata, of the Moffitt Cancer Center in Tampa, commented, "I think a critical question is that you have done a primary tumor resection and the liver tumor has tended to grow, which is not entirely surprising, but then in those cases, how many became unresectable from a liver standpoint?"

"About 60% ended up having hepatectomies," Dr. Slesser said, noting that the data reported looked only at the short-term time frame. "We do have further results, which will be in the paper, pertaining to survival. But the real aim of this study was to look at initial radiological progression of disease, because we thought that the primary tumor resection may be associated with a sudden increase in the size of metastasis."

The finding of a better liver outcome with initial chemotherapy "makes sense," session comoderator Dr. Marylise Boutros, of McGill University in Montreal, said in an interview. "That’s something that we would expect, that you can treat the largest burden of the disease, which is the metastasis – it’s a systemic disease – with chemotherapy up-front."

"But it’s definitely a smaller study, and this needs to be looked at in a larger subset and in a prospective fashion," she added.

Giving some background to the research, Dr. Slesser noted that "the mainstay of surgical treatment for these patients with limited metastatic disease is a sequential resection. Patients tend to have an up-front primary tumor resection, followed by adjuvant chemotherapy, followed by hepatic resection if feasible. On the other hand, patients who have extensive metastatic disease tend to have neoadjuvant chemotherapy prior to a surgical intervention."

He and his coinvestigators studied patients with isolated synchronous colorectal liver metastases who were referred to the Royal Marsden Hospital for treatment between 2005 and 2010 and had imaging done at baseline, 3 months, and 6 months.

The mean age of the cohort was 64 years, and the ratio of men to women was about 2:1. In terms of treatment, 51% of the patients underwent primary tumor resection, while the other 49% received neoadjuvant chemotherapy.

In univariate analysis, the factor most strongly associated with progression of liver metastases – defined as an increase in their cumulative diameter of at least 20% – at 3 months was a primary tumor resection, according to Dr. Slesser.

In a multivariate analysis, relative to their counterparts in the neoadjuvant chemotherapy group, patients undergoing primary tumor resection had dramatically elevated odds of progression of liver metastases (odds ratio, 9.0; P = .001).

Additionally, metastatic burden showed an upward trend between baseline and 6 months in the group undergoing primary tumor resection (from 40 to 51 mm; P = .19), whereas it decreased significantly in the neoadjuvant chemotherapy group (from 96 to 52 mm; P = .001).

Overall, 93% of patients having a primary tumor resection went on to receive adjuvant chemotherapy, according to Dr. Slesser.

Comparing baseline to 3 months versus 3 months to 6 months, liver metastases began regressing in the primary tumor resection group, with the growth rate changing from 4.0 to –3.0 mm/month (P less than .001), reflecting the effect of the adjuvant chemotherapy, he said. Liver metastases in the neoadjuvant chemotherapy group continued to regress, albeit also at a slower pace, with the growth rate changing from –5.6 to –4.0 mm/month (P = .003).

Dr. Slesser disclosed no relevant conflicts of interest.

PHOENIX – The standard sequential approach to treatment of patients with isolated synchronous liver metastases of colorectal cancer, entailing up-front removal of the primary tumor, is associated with growth of the metastases, according to results from a retrospective cohort study.

A team led by Dr. Alistair Slesser, a surgical registrar at the Royal Marsden Hospital in London, studied 114 patients with colorectal cancer who had synchronous liver metastases, meaning ones identified within a year of the cancer diagnosis, and no other metastases.

Results showed that patients whose initial treatment was resection of the colorectal primary tumor had ninefold higher odds of progression of their liver metastases at 3 months, compared with patients whose initial treatment was chemotherapy, he reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Although liver metastases showed regression during 3-6 months of treatment in both groups, the rate was somewhat slower in the primary tumor resection group.

"Our findings suggest that an up-front primary tumor resection is actually an adverse prognostic factor. Indeed, our results have demonstrated that up-front primary tumor resection seemed to negate the effects of the adjuvant therapy on the treatment of the liver metastasis," Dr. Slesser commented.

"How does this apply clinically? We would recommend that patients who have limited metastatic disease, instead of having an up-front primary tumor resection perhaps [they should] be treated with neoadjuvant chemotherapy first. Or perhaps another surgical approach, like a simultaneous resection, should be considered to negate the adverse effects of a primary tumor resection on the metastatic disease," he said.

"When patients have lesions which are suspicious for liver metastases, we would recommend that these patients [be] thoroughly investigated, and if metastatic disease is confirmed, then again, we would recommend that they have chemotherapy prior to any subsequent intervention," he added.

The mechanism leading to growth of liver metastases after primary tumor resection is unknown, according to Dr. Slesser. "There is possibly an association for ... biological reasons. The other reason is that perhaps when a patient has an up-front primary tumor resection, there is a delay in getting chemotherapy, and that can cause the progression that we see."

Session attendee Dr. Gary Dunn, of the University of Oklahoma, Oklahoma City, asked how much time elapsed between up-front resection and receipt of adjuvant chemotherapy in that group, and the variance in this measure, noting, "That will significantly affect your outcome, if some patients started at 6 weeks and some patients started at 12 weeks postop."

"Usually, patients waited 6 weeks before they started chemotherapy postoperatively," Dr. Slesser explained. "The majority of patients who had primary tumor resection had the adjuvant chemotherapy after the postoperative scan; the 3-month scan tends to be the postoperative scan."

Dr. Dunn further wondered about the comparability between groups of the chemotherapy received, asking what agents were used.

"At the Royal Marsden, the chemotherapy regimes tend to be quite uniform," Dr. Slesser replied. "Generally, all patients are on capecitabine [Xeloda] and oxaliplatin, with a monoclonal agent such as bevacizumab [Avastin]. They tend to get that when they have neoadjuvant chemotherapy."

Another attendee said, "Excellent paper, very well presented data, particularly considering there are a lot of retrospective series out there that are showing the up-front resection as a favorable prognostic indicator, which I don’t believe. ... But I would like to see a little more information about how the patients were treated subsequently. Were these patients who they were planning to get to surgery for resection, or were these patients who were treated for palliative intent? Did they have symptomatic primaries?"

"In the majority of these patients, the intent was curative surgery," Dr. Slesser replied. "We tried to exclude patients who were clearly referred for palliative treatment because we really wanted to assess patients who were referred for curative treatment."

Attendee Dr. David Shibata, of the Moffitt Cancer Center in Tampa, commented, "I think a critical question is that you have done a primary tumor resection and the liver tumor has tended to grow, which is not entirely surprising, but then in those cases, how many became unresectable from a liver standpoint?"

"About 60% ended up having hepatectomies," Dr. Slesser said, noting that the data reported looked only at the short-term time frame. "We do have further results, which will be in the paper, pertaining to survival. But the real aim of this study was to look at initial radiological progression of disease, because we thought that the primary tumor resection may be associated with a sudden increase in the size of metastasis."

The finding of a better liver outcome with initial chemotherapy "makes sense," session comoderator Dr. Marylise Boutros, of McGill University in Montreal, said in an interview. "That’s something that we would expect, that you can treat the largest burden of the disease, which is the metastasis – it’s a systemic disease – with chemotherapy up-front."

"But it’s definitely a smaller study, and this needs to be looked at in a larger subset and in a prospective fashion," she added.

Giving some background to the research, Dr. Slesser noted that "the mainstay of surgical treatment for these patients with limited metastatic disease is a sequential resection. Patients tend to have an up-front primary tumor resection, followed by adjuvant chemotherapy, followed by hepatic resection if feasible. On the other hand, patients who have extensive metastatic disease tend to have neoadjuvant chemotherapy prior to a surgical intervention."

He and his coinvestigators studied patients with isolated synchronous colorectal liver metastases who were referred to the Royal Marsden Hospital for treatment between 2005 and 2010 and had imaging done at baseline, 3 months, and 6 months.

The mean age of the cohort was 64 years, and the ratio of men to women was about 2:1. In terms of treatment, 51% of the patients underwent primary tumor resection, while the other 49% received neoadjuvant chemotherapy.

In univariate analysis, the factor most strongly associated with progression of liver metastases – defined as an increase in their cumulative diameter of at least 20% – at 3 months was a primary tumor resection, according to Dr. Slesser.

In a multivariate analysis, relative to their counterparts in the neoadjuvant chemotherapy group, patients undergoing primary tumor resection had dramatically elevated odds of progression of liver metastases (odds ratio, 9.0; P = .001).

Additionally, metastatic burden showed an upward trend between baseline and 6 months in the group undergoing primary tumor resection (from 40 to 51 mm; P = .19), whereas it decreased significantly in the neoadjuvant chemotherapy group (from 96 to 52 mm; P = .001).

Overall, 93% of patients having a primary tumor resection went on to receive adjuvant chemotherapy, according to Dr. Slesser.

Comparing baseline to 3 months versus 3 months to 6 months, liver metastases began regressing in the primary tumor resection group, with the growth rate changing from 4.0 to –3.0 mm/month (P less than .001), reflecting the effect of the adjuvant chemotherapy, he said. Liver metastases in the neoadjuvant chemotherapy group continued to regress, albeit also at a slower pace, with the growth rate changing from –5.6 to –4.0 mm/month (P = .003).

Dr. Slesser disclosed no relevant conflicts of interest.

PHOENIX – The standard sequential approach to treatment of patients with isolated synchronous liver metastases of colorectal cancer, entailing up-front removal of the primary tumor, is associated with growth of the metastases, according to results from a retrospective cohort study.

A team led by Dr. Alistair Slesser, a surgical registrar at the Royal Marsden Hospital in London, studied 114 patients with colorectal cancer who had synchronous liver metastases, meaning ones identified within a year of the cancer diagnosis, and no other metastases.

Results showed that patients whose initial treatment was resection of the colorectal primary tumor had ninefold higher odds of progression of their liver metastases at 3 months, compared with patients whose initial treatment was chemotherapy, he reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Although liver metastases showed regression during 3-6 months of treatment in both groups, the rate was somewhat slower in the primary tumor resection group.

"Our findings suggest that an up-front primary tumor resection is actually an adverse prognostic factor. Indeed, our results have demonstrated that up-front primary tumor resection seemed to negate the effects of the adjuvant therapy on the treatment of the liver metastasis," Dr. Slesser commented.

"How does this apply clinically? We would recommend that patients who have limited metastatic disease, instead of having an up-front primary tumor resection perhaps [they should] be treated with neoadjuvant chemotherapy first. Or perhaps another surgical approach, like a simultaneous resection, should be considered to negate the adverse effects of a primary tumor resection on the metastatic disease," he said.

"When patients have lesions which are suspicious for liver metastases, we would recommend that these patients [be] thoroughly investigated, and if metastatic disease is confirmed, then again, we would recommend that they have chemotherapy prior to any subsequent intervention," he added.

The mechanism leading to growth of liver metastases after primary tumor resection is unknown, according to Dr. Slesser. "There is possibly an association for ... biological reasons. The other reason is that perhaps when a patient has an up-front primary tumor resection, there is a delay in getting chemotherapy, and that can cause the progression that we see."

Session attendee Dr. Gary Dunn, of the University of Oklahoma, Oklahoma City, asked how much time elapsed between up-front resection and receipt of adjuvant chemotherapy in that group, and the variance in this measure, noting, "That will significantly affect your outcome, if some patients started at 6 weeks and some patients started at 12 weeks postop."

"Usually, patients waited 6 weeks before they started chemotherapy postoperatively," Dr. Slesser explained. "The majority of patients who had primary tumor resection had the adjuvant chemotherapy after the postoperative scan; the 3-month scan tends to be the postoperative scan."

Dr. Dunn further wondered about the comparability between groups of the chemotherapy received, asking what agents were used.

"At the Royal Marsden, the chemotherapy regimes tend to be quite uniform," Dr. Slesser replied. "Generally, all patients are on capecitabine [Xeloda] and oxaliplatin, with a monoclonal agent such as bevacizumab [Avastin]. They tend to get that when they have neoadjuvant chemotherapy."

Another attendee said, "Excellent paper, very well presented data, particularly considering there are a lot of retrospective series out there that are showing the up-front resection as a favorable prognostic indicator, which I don’t believe. ... But I would like to see a little more information about how the patients were treated subsequently. Were these patients who they were planning to get to surgery for resection, or were these patients who were treated for palliative intent? Did they have symptomatic primaries?"

"In the majority of these patients, the intent was curative surgery," Dr. Slesser replied. "We tried to exclude patients who were clearly referred for palliative treatment because we really wanted to assess patients who were referred for curative treatment."

Attendee Dr. David Shibata, of the Moffitt Cancer Center in Tampa, commented, "I think a critical question is that you have done a primary tumor resection and the liver tumor has tended to grow, which is not entirely surprising, but then in those cases, how many became unresectable from a liver standpoint?"

"About 60% ended up having hepatectomies," Dr. Slesser said, noting that the data reported looked only at the short-term time frame. "We do have further results, which will be in the paper, pertaining to survival. But the real aim of this study was to look at initial radiological progression of disease, because we thought that the primary tumor resection may be associated with a sudden increase in the size of metastasis."

The finding of a better liver outcome with initial chemotherapy "makes sense," session comoderator Dr. Marylise Boutros, of McGill University in Montreal, said in an interview. "That’s something that we would expect, that you can treat the largest burden of the disease, which is the metastasis – it’s a systemic disease – with chemotherapy up-front."

"But it’s definitely a smaller study, and this needs to be looked at in a larger subset and in a prospective fashion," she added.

Giving some background to the research, Dr. Slesser noted that "the mainstay of surgical treatment for these patients with limited metastatic disease is a sequential resection. Patients tend to have an up-front primary tumor resection, followed by adjuvant chemotherapy, followed by hepatic resection if feasible. On the other hand, patients who have extensive metastatic disease tend to have neoadjuvant chemotherapy prior to a surgical intervention."

He and his coinvestigators studied patients with isolated synchronous colorectal liver metastases who were referred to the Royal Marsden Hospital for treatment between 2005 and 2010 and had imaging done at baseline, 3 months, and 6 months.

The mean age of the cohort was 64 years, and the ratio of men to women was about 2:1. In terms of treatment, 51% of the patients underwent primary tumor resection, while the other 49% received neoadjuvant chemotherapy.

In univariate analysis, the factor most strongly associated with progression of liver metastases – defined as an increase in their cumulative diameter of at least 20% – at 3 months was a primary tumor resection, according to Dr. Slesser.

In a multivariate analysis, relative to their counterparts in the neoadjuvant chemotherapy group, patients undergoing primary tumor resection had dramatically elevated odds of progression of liver metastases (odds ratio, 9.0; P = .001).

Additionally, metastatic burden showed an upward trend between baseline and 6 months in the group undergoing primary tumor resection (from 40 to 51 mm; P = .19), whereas it decreased significantly in the neoadjuvant chemotherapy group (from 96 to 52 mm; P = .001).

Overall, 93% of patients having a primary tumor resection went on to receive adjuvant chemotherapy, according to Dr. Slesser.

Comparing baseline to 3 months versus 3 months to 6 months, liver metastases began regressing in the primary tumor resection group, with the growth rate changing from 4.0 to –3.0 mm/month (P less than .001), reflecting the effect of the adjuvant chemotherapy, he said. Liver metastases in the neoadjuvant chemotherapy group continued to regress, albeit also at a slower pace, with the growth rate changing from –5.6 to –4.0 mm/month (P = .003).

Dr. Slesser disclosed no relevant conflicts of interest.

PHOENIX – When the entire colon cannot be examined during a colonoscopy, physicians should persevere in obtaining a full colonic evaluation because a sizable share of these patients will have an advanced polyp or cancer, a new study shows.

In the study, which used a prospective institutional database, about 1 in every 8 patients having an incomplete initial colonoscopy were subsequently found to have a clinically significant lesion after undergoing some other type of completion exam, lead investigator Dr. Timothy J. Ridolfi reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Patients with a personal history of polyps or cancer accounted for two-thirds of all patients who were found to have lesions on completion studies.

"Complete colonic evaluation in patients with an incomplete colonoscopy is important, and repeat colonoscopy is the most efficient way of achieving that," he commented. "Those with a personal history of polyps or cancer have the highest likelihood of a positive finding on repeat colonoscopy."

Session attendee Dr. Joshua Bleier, of the Hospital of the University of Pennsylvania, Philadelphia, asked, "Since you have this prospective database, was any chart review done to follow up on the patients who didn’t have completion evaluations?"

The investigators have not yet assessed outcomes among patients who were offered a completion study but skipped it, according to Dr. Ridolfi, who is a colorectal surgery fellow at the Cleveland Clinic. He noted that some patients may have had such studies done at outside institutions.

Commenting on the research in an interview, comoderator Dr. H. David Vargas, of the Ochsner Medical Center in New Orleans, said that although the study’s findings are not surprising, they are a good reminder to physicians of the need to follow through in cases where a colonoscopy cannot be completed.

Examining the entire colon "is really incumbent upon us. The onus is on us to complete it," he said. The study "confirms why we need to be thorough, if you will."

The investigators analyzed data from a prospective database that captured information on 25,645 colonoscopies performed by colorectal surgeons at the Cleveland Clinic between 1982 and 2009.

A total of 242 patients were identified as having an incomplete initial colonoscopy. The group had a mean age of 59 years, and 69% were women.

The leading reasons for an incomplete procedure were presence of stool, pain, and tortuosity, with the reason varying according to the anatomic extent of the procedure. Fully 71% of procedures were terminated at the splenic flexure or more distally, he reported.

Overall, 90% of the patients were offered some type of completion study, and 82% of this group complied and underwent the study.

The completion study was most commonly a barium enema (41%) or repeat colonoscopy (40%), and less commonly CT colonography (9%), colonoscopy under general anesthesia (5%), or indicated resection with intraoperative or perioperative colonoscopy (5%).

Some 12% of the patients undergoing a barium enema or CT colonography were found to have new abnormalities, according to Dr. Ridolfi.

In addition, 24% of the patients undergoing repeat colonoscopy were found to have polyps. Of the 32 polyps identified (21 located beyond the extent of the initial incomplete colonoscopy), 9 were advanced adenomas.

And 38% of the patients undergoing indicated resection were found to have some additional lesions on their intraoperative or perioperative colonoscopy.

Patients whose indication for the initial colonoscopy was a personal history of polyps or cancer were more likely than those with other indications – a family history, symptoms, or screening – to have lesions on their completion study. In fact, these patients made up 67% of all patients with positive findings.

Ultimately, 12% of the patients undergoing completion studies were determined to have clinically significant lesions that led to polypectomy or partial colectomy.

Dr. Ridolfi disclosed no relevant conflicts of interest.

PHOENIX – When the entire colon cannot be examined during a colonoscopy, physicians should persevere in obtaining a full colonic evaluation because a sizable share of these patients will have an advanced polyp or cancer, a new study shows.

In the study, which used a prospective institutional database, about 1 in every 8 patients having an incomplete initial colonoscopy were subsequently found to have a clinically significant lesion after undergoing some other type of completion exam, lead investigator Dr. Timothy J. Ridolfi reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Patients with a personal history of polyps or cancer accounted for two-thirds of all patients who were found to have lesions on completion studies.

"Complete colonic evaluation in patients with an incomplete colonoscopy is important, and repeat colonoscopy is the most efficient way of achieving that," he commented. "Those with a personal history of polyps or cancer have the highest likelihood of a positive finding on repeat colonoscopy."

Session attendee Dr. Joshua Bleier, of the Hospital of the University of Pennsylvania, Philadelphia, asked, "Since you have this prospective database, was any chart review done to follow up on the patients who didn’t have completion evaluations?"

The investigators have not yet assessed outcomes among patients who were offered a completion study but skipped it, according to Dr. Ridolfi, who is a colorectal surgery fellow at the Cleveland Clinic. He noted that some patients may have had such studies done at outside institutions.

Commenting on the research in an interview, comoderator Dr. H. David Vargas, of the Ochsner Medical Center in New Orleans, said that although the study’s findings are not surprising, they are a good reminder to physicians of the need to follow through in cases where a colonoscopy cannot be completed.

Examining the entire colon "is really incumbent upon us. The onus is on us to complete it," he said. The study "confirms why we need to be thorough, if you will."

The investigators analyzed data from a prospective database that captured information on 25,645 colonoscopies performed by colorectal surgeons at the Cleveland Clinic between 1982 and 2009.

A total of 242 patients were identified as having an incomplete initial colonoscopy. The group had a mean age of 59 years, and 69% were women.

The leading reasons for an incomplete procedure were presence of stool, pain, and tortuosity, with the reason varying according to the anatomic extent of the procedure. Fully 71% of procedures were terminated at the splenic flexure or more distally, he reported.

Overall, 90% of the patients were offered some type of completion study, and 82% of this group complied and underwent the study.

The completion study was most commonly a barium enema (41%) or repeat colonoscopy (40%), and less commonly CT colonography (9%), colonoscopy under general anesthesia (5%), or indicated resection with intraoperative or perioperative colonoscopy (5%).

Some 12% of the patients undergoing a barium enema or CT colonography were found to have new abnormalities, according to Dr. Ridolfi.

In addition, 24% of the patients undergoing repeat colonoscopy were found to have polyps. Of the 32 polyps identified (21 located beyond the extent of the initial incomplete colonoscopy), 9 were advanced adenomas.

And 38% of the patients undergoing indicated resection were found to have some additional lesions on their intraoperative or perioperative colonoscopy.

Patients whose indication for the initial colonoscopy was a personal history of polyps or cancer were more likely than those with other indications – a family history, symptoms, or screening – to have lesions on their completion study. In fact, these patients made up 67% of all patients with positive findings.

Ultimately, 12% of the patients undergoing completion studies were determined to have clinically significant lesions that led to polypectomy or partial colectomy.

Dr. Ridolfi disclosed no relevant conflicts of interest.

PHOENIX – When the entire colon cannot be examined during a colonoscopy, physicians should persevere in obtaining a full colonic evaluation because a sizable share of these patients will have an advanced polyp or cancer, a new study shows.

In the study, which used a prospective institutional database, about 1 in every 8 patients having an incomplete initial colonoscopy were subsequently found to have a clinically significant lesion after undergoing some other type of completion exam, lead investigator Dr. Timothy J. Ridolfi reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Patients with a personal history of polyps or cancer accounted for two-thirds of all patients who were found to have lesions on completion studies.

"Complete colonic evaluation in patients with an incomplete colonoscopy is important, and repeat colonoscopy is the most efficient way of achieving that," he commented. "Those with a personal history of polyps or cancer have the highest likelihood of a positive finding on repeat colonoscopy."

Session attendee Dr. Joshua Bleier, of the Hospital of the University of Pennsylvania, Philadelphia, asked, "Since you have this prospective database, was any chart review done to follow up on the patients who didn’t have completion evaluations?"

The investigators have not yet assessed outcomes among patients who were offered a completion study but skipped it, according to Dr. Ridolfi, who is a colorectal surgery fellow at the Cleveland Clinic. He noted that some patients may have had such studies done at outside institutions.

Commenting on the research in an interview, comoderator Dr. H. David Vargas, of the Ochsner Medical Center in New Orleans, said that although the study’s findings are not surprising, they are a good reminder to physicians of the need to follow through in cases where a colonoscopy cannot be completed.

Examining the entire colon "is really incumbent upon us. The onus is on us to complete it," he said. The study "confirms why we need to be thorough, if you will."

The investigators analyzed data from a prospective database that captured information on 25,645 colonoscopies performed by colorectal surgeons at the Cleveland Clinic between 1982 and 2009.

A total of 242 patients were identified as having an incomplete initial colonoscopy. The group had a mean age of 59 years, and 69% were women.

The leading reasons for an incomplete procedure were presence of stool, pain, and tortuosity, with the reason varying according to the anatomic extent of the procedure. Fully 71% of procedures were terminated at the splenic flexure or more distally, he reported.

Overall, 90% of the patients were offered some type of completion study, and 82% of this group complied and underwent the study.

The completion study was most commonly a barium enema (41%) or repeat colonoscopy (40%), and less commonly CT colonography (9%), colonoscopy under general anesthesia (5%), or indicated resection with intraoperative or perioperative colonoscopy (5%).

Some 12% of the patients undergoing a barium enema or CT colonography were found to have new abnormalities, according to Dr. Ridolfi.

In addition, 24% of the patients undergoing repeat colonoscopy were found to have polyps. Of the 32 polyps identified (21 located beyond the extent of the initial incomplete colonoscopy), 9 were advanced adenomas.

And 38% of the patients undergoing indicated resection were found to have some additional lesions on their intraoperative or perioperative colonoscopy.

Patients whose indication for the initial colonoscopy was a personal history of polyps or cancer were more likely than those with other indications – a family history, symptoms, or screening – to have lesions on their completion study. In fact, these patients made up 67% of all patients with positive findings.

Ultimately, 12% of the patients undergoing completion studies were determined to have clinically significant lesions that led to polypectomy or partial colectomy.

Dr. Ridolfi disclosed no relevant conflicts of interest.

SAN FRANCISCO – New drugs aimed at treating the nonpsychotic symptoms of schizophrenia that impair patients’ daily functioning are likely to move into the clinic soon, predicts Dr. Stephen R. Marder, professor and director of the section on psychosis at the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles.

Antipsychotics have been available since the early 1950s, but functional impairments for people with schizophrenia continue to persist, he said. In fact, fewer than 20% are able to work independently, he said at the annual meeting of the American Psychiatric Association. Until recently, "clinical practice was focused on what drugs were able to do, which was to dampen the psychotic symptoms of schizophrenia, and drug development was at a halt," said Dr. Marder, who also serves as director of the Mental Illness Research, Education, and Clinical Center, Los Angeles.

But that has changed, thanks to MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia), a collaborative effort of about 300 investigators focused on facilitating drug development for nonpsychotic symptoms.

"If the goal is to be able to improve the functioning in schizophrenia – for people to be able to work, live independently, participate in family and social life – there are some attractive targets: basic cognition, negative symptoms, and social cognition," Dr. Marder explained.

Roughly a half-dozen agents targeting these symptoms are now in phase II or III clinical trials. "We are at a stage where ... it’s conceivable that in late 2014 or 2015, we will actually have a drug for negative symptoms, with other drugs for cognition following shortly thereafter," he said "So it’s a time of optimism."

A relatively new area of research focus in schizophrenia is impairment of social cognition and the ability to read other people based on cues such as body language, facial expressions, and tone of voice.

Emerging data suggest that the naturally occurring hormone and neurotransmitter oxytocin, long used in obstetrics, is beneficial in this context.

"It is involved in multiple aspects of social behavior and related emotions," Dr. Marder noted. Administration to mentally healthy individuals has been associated with increased trust when playing games and increased sensitivity to social signals.

In a phase II trial, patients with schizophrenia had better uptake of social cognition training when given intranasal oxytocin, as compared with placebo, shortly before training began.

Relative to placebo, oxytocin did not improve low-level function, such as ability to interpret facial expressions. However, it did improve high-level function, such as the ability to detect sarcasm, assessed in the study with a test of empathic accuracy. Moreover, the effect was sustained, lasting at least a month.

Thus, an old drug might eventually find new use to treat a complex symptom of schizophrenia, he said.

"We are feeling relatively optimistic that these efforts are going to lead, in the relatively near future, to better treatment," Dr. Marder said.

Dr. Marder disclosed that he is on the advisory boards of numerous pharmaceutical companies, including Abbott, Amgen, Roche, Shire, Otsuka, Wyeth, Pfizer, and Lundbeck, and that he receives research support from Novartis, GlaxoSmithKline, Sunovion, and PsychoGenics.

SAN FRANCISCO – New drugs aimed at treating the nonpsychotic symptoms of schizophrenia that impair patients’ daily functioning are likely to move into the clinic soon, predicts Dr. Stephen R. Marder, professor and director of the section on psychosis at the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles.

Antipsychotics have been available since the early 1950s, but functional impairments for people with schizophrenia continue to persist, he said. In fact, fewer than 20% are able to work independently, he said at the annual meeting of the American Psychiatric Association. Until recently, "clinical practice was focused on what drugs were able to do, which was to dampen the psychotic symptoms of schizophrenia, and drug development was at a halt," said Dr. Marder, who also serves as director of the Mental Illness Research, Education, and Clinical Center, Los Angeles.

But that has changed, thanks to MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia), a collaborative effort of about 300 investigators focused on facilitating drug development for nonpsychotic symptoms.

"If the goal is to be able to improve the functioning in schizophrenia – for people to be able to work, live independently, participate in family and social life – there are some attractive targets: basic cognition, negative symptoms, and social cognition," Dr. Marder explained.

Roughly a half-dozen agents targeting these symptoms are now in phase II or III clinical trials. "We are at a stage where ... it’s conceivable that in late 2014 or 2015, we will actually have a drug for negative symptoms, with other drugs for cognition following shortly thereafter," he said "So it’s a time of optimism."

A relatively new area of research focus in schizophrenia is impairment of social cognition and the ability to read other people based on cues such as body language, facial expressions, and tone of voice.

Emerging data suggest that the naturally occurring hormone and neurotransmitter oxytocin, long used in obstetrics, is beneficial in this context.

"It is involved in multiple aspects of social behavior and related emotions," Dr. Marder noted. Administration to mentally healthy individuals has been associated with increased trust when playing games and increased sensitivity to social signals.

In a phase II trial, patients with schizophrenia had better uptake of social cognition training when given intranasal oxytocin, as compared with placebo, shortly before training began.

Relative to placebo, oxytocin did not improve low-level function, such as ability to interpret facial expressions. However, it did improve high-level function, such as the ability to detect sarcasm, assessed in the study with a test of empathic accuracy. Moreover, the effect was sustained, lasting at least a month.

Thus, an old drug might eventually find new use to treat a complex symptom of schizophrenia, he said.

"We are feeling relatively optimistic that these efforts are going to lead, in the relatively near future, to better treatment," Dr. Marder said.

Dr. Marder disclosed that he is on the advisory boards of numerous pharmaceutical companies, including Abbott, Amgen, Roche, Shire, Otsuka, Wyeth, Pfizer, and Lundbeck, and that he receives research support from Novartis, GlaxoSmithKline, Sunovion, and PsychoGenics.

SAN FRANCISCO – New drugs aimed at treating the nonpsychotic symptoms of schizophrenia that impair patients’ daily functioning are likely to move into the clinic soon, predicts Dr. Stephen R. Marder, professor and director of the section on psychosis at the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles.

Antipsychotics have been available since the early 1950s, but functional impairments for people with schizophrenia continue to persist, he said. In fact, fewer than 20% are able to work independently, he said at the annual meeting of the American Psychiatric Association. Until recently, "clinical practice was focused on what drugs were able to do, which was to dampen the psychotic symptoms of schizophrenia, and drug development was at a halt," said Dr. Marder, who also serves as director of the Mental Illness Research, Education, and Clinical Center, Los Angeles.

But that has changed, thanks to MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia), a collaborative effort of about 300 investigators focused on facilitating drug development for nonpsychotic symptoms.

"If the goal is to be able to improve the functioning in schizophrenia – for people to be able to work, live independently, participate in family and social life – there are some attractive targets: basic cognition, negative symptoms, and social cognition," Dr. Marder explained.

Roughly a half-dozen agents targeting these symptoms are now in phase II or III clinical trials. "We are at a stage where ... it’s conceivable that in late 2014 or 2015, we will actually have a drug for negative symptoms, with other drugs for cognition following shortly thereafter," he said "So it’s a time of optimism."

A relatively new area of research focus in schizophrenia is impairment of social cognition and the ability to read other people based on cues such as body language, facial expressions, and tone of voice.

Emerging data suggest that the naturally occurring hormone and neurotransmitter oxytocin, long used in obstetrics, is beneficial in this context.

"It is involved in multiple aspects of social behavior and related emotions," Dr. Marder noted. Administration to mentally healthy individuals has been associated with increased trust when playing games and increased sensitivity to social signals.

In a phase II trial, patients with schizophrenia had better uptake of social cognition training when given intranasal oxytocin, as compared with placebo, shortly before training began.

Relative to placebo, oxytocin did not improve low-level function, such as ability to interpret facial expressions. However, it did improve high-level function, such as the ability to detect sarcasm, assessed in the study with a test of empathic accuracy. Moreover, the effect was sustained, lasting at least a month.

Thus, an old drug might eventually find new use to treat a complex symptom of schizophrenia, he said.

"We are feeling relatively optimistic that these efforts are going to lead, in the relatively near future, to better treatment," Dr. Marder said.

Dr. Marder disclosed that he is on the advisory boards of numerous pharmaceutical companies, including Abbott, Amgen, Roche, Shire, Otsuka, Wyeth, Pfizer, and Lundbeck, and that he receives research support from Novartis, GlaxoSmithKline, Sunovion, and PsychoGenics.

SAN FRANCISCO – Changes to the psychosis section of the long-awaited fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) are hardly dramatic, but they are still likely to advance the field and make the classification system more clinically relevant and easier to use, according to the authors.

Representatives of the 12-member Work Group on Psychotic Disorders detailed some of the revised elements of this section of the new manual, which was released with the start of the annual meeting of the American Psychiatric Association.

Key changes are outlined

"When we were approaching the DSM-5, we thought we learned so much in the last 20 years about the nature of all these psychotic disorders – such incredible advances in imaging and genetics and all these different areas of neurobiology – that, somehow, we were going to revolutionize diagnosis with an etiopathophysiological classification, if you will," commented Dr. Rajiv Tandon of the University of Florida, Gainesville. "And relatively early in the process, we recognized that that was impossible to accomplish, because although we learned a lot, we didn’t know enough yet to be able to do that."

Still, the new edition differs from its predecessor, the DSM-IV, released nearly a decade ago, in a variety of key respects, he said.

For example, gone are the subtypes of schizophrenia, along with shared psychotic disorder. Newly added is catatonia not elsewhere classified, referring to a fully defined catatonic syndrome in the absence of an identifiable medical disorder.

The DSM-5 also sees the debut of assessment of the dimensions of psychosis, which captures the presence and severity of various symptoms. In addition, the criteria for diagnosing schizoaffective disorder have been modified, and catatonia is now treated more uniformly across the manual.

"What we have come up with regard to psychotic disorders are iterative changes, modest improvements, improved clinical utility, simplicity – we have actually reduced the number of disorders in our section by about 20%," Dr. Tandon said. "Very importantly, in addition to improved clinical utility and incorporating the new information we have learned to the extent possible, the DSM-5 look at psychotic disorders provides a much better platform to a future etiopathophysiological classification."

DSM, RDoC called complementary

The DSM-5’s new dimensional approach to assessing psychotic disorders will not only help advance the study of these disorders, but will also help to track their course in patients over time and ensure appropriate treatment, said Dr. Dolores Malaspina of the NYU Langone Medical Center in New York.

Clinicians will rate the presence and severity of eight symptoms – hallucinations, delusions, disorganized speech, psychomotor behavior, negative symptoms, impaired cognition, depression, and mania – on a scale from 0 to 4.

In particular, this approach will promote patient-centered care, she maintained. "We want our treatments to be person specific. For a treatment to be person specific, it’s not simply based on a diagnosis."

Dr. Malaspina further noted that dimensional assessment addresses some of the National Institute of Mental Health’s reservations about the DSM classification system.

"The NIMH has come to see the categories of the DSM as getting in the way of progress forward," she explained. The NIMH, therefore, developed its own classification system, called Research Domain Criteria (RDoC).

"Their goal is to do studies where symptoms have been assessed along a continuum. This approach is not antagonistic to the DSM – there is actually no dueling that will take place in the Moscone Center," she quipped, referring to the location of the APA meeting in San Francisco. "There actually is a great amount of agreement. The future of psychiatric assessment should see that the DSM-5 and the RDoC are complementary, not competing frameworks."

Cognitive impairment left out

Patients with schizophrenia commonly have impaired cognition, so clinicians might be surprised to find that this feature is still not listed as a core feature in the DSM-5, noted Dr. Raquel E. Gur of the University of Pennsylvania, Philadelphia.

"To meet the core features of hallucinations, delusions, and disorganized thinking, you must have impaired cognition, otherwise you will not perceive events around you differently than other people. There is something that happens in the brains of these people that make them distort reality, and those things are measurable," she commented.

Moreover, cognitive status is important when assessing the ability of patients to engage in treatment and when it comes to setting realistic goals of care.

To be sure, the DSM-5 describes assessment of cognitive status as vital to the differential diagnosis when distinguishing entities on the schizophrenia spectrum from other psychotic disorders.

The work group, however, stopped short of including it among core features because of its uncertain specificity to schizophrenia, lack of agreed-on measures that can be readily used in the real world, and absence of evidence that assessment is clinically indicated and applicable in this setting. In other words, more research is needed in this area, Dr. Gur said.

APS inclusion proves controversial

One of the most controversial aspects of the DSM-5 is its inclusion of attenuated psychosis syndrome (APS), acknowledged Dr. Ming T. Tsuang of the University of California, San Diego.

About a third of patients with this constellation of symptoms develop a full-blown psychotic disorder, raising hopes that the APS diagnosis could help identify patients who will benefit from early intervention.

Some, however, have expressed concern that adding APS to the classification system might lead to inappropriate antipsychotic therapy.

"From our experience, that is not the case," Dr. Tsuang said. "Actually, the APS category may educate clinicians about the relative lack of utility of antipsychotic medication in this population. So we hope that if we have this category, inappropriate antipsychotic use among youth may be reduced."

"In the end, our task force decided not to put APS into the main body of the DSM-5, but rather into the appendix, because more research needs to be done to really test its validity and usefulness, particularly for clinicians," he concluded. "For the DSM-6, once we have more experience in this area and [more information from research], we may be able to put this condition in the main body. At that time, the name may change."

Closer to ICD but still distinct

The DSM-5 is likely to share much with the psychosis section of the forthcoming International Classification of Diseases, 11th revision (ICD-11), of the World Health Organization, expected out in 2015. Yet the two will still have their differences.

For example, both classification systems have deleted schizophrenia subtypes, replacing them with dimensional assessments in the case of DSM-5 and symptom specifiers in the case of ICD-11, noted Dr. Wolfgang Gaebel of the Heinrich Heine University Düsseldorf in Germany.

The two differ, though, with respect to diagnostic criteria, such as the requirement for functional impairment to make a diagnosis of schizophrenia and the inclusion of longitudinal criteria to make a diagnosis of schizoaffective disorder.

"There is some harmonization," he commented, while adding that there is still justification for having two classification systems, even if they are generally converging over time.

"Of course, on one hand, we would like to see one system which fits all. On the other hand, the two systems have different foci and always have," Dr. Gaebel said. "ICD is the system which has been used worldwide, mainly for administrative reasons. Some countries, in the clinical situation, use DSM, whereas many other countries use ICD, but when it comes to research, they use in addition DSM, also for publication because, of course, many papers you want to submit to Anglo-American journals that prefer the DSM. And I think the DSM has – this is my personal opinion – a more research-based focus.

"But I think the two systems profit from each other. I doubt for various, and I would say political, reasons that in the future we will have one system, although it would be very good to have it," he concluded.

Dr. Tandon, Dr. Malaspina, Dr. Gur, and Dr. Tsuang disclosed no relevant conflicts of interest. Dr. Gaebel disclosed that he is on the scientific advisory board of Lundbeck International Neuroscience Foundation and receives symposium support from Lilly Germany and Janssen Cilag Germany.

SAN FRANCISCO – Changes to the psychosis section of the long-awaited fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) are hardly dramatic, but they are still likely to advance the field and make the classification system more clinically relevant and easier to use, according to the authors.

Representatives of the 12-member Work Group on Psychotic Disorders detailed some of the revised elements of this section of the new manual, which was released with the start of the annual meeting of the American Psychiatric Association.

Key changes are outlined

"When we were approaching the DSM-5, we thought we learned so much in the last 20 years about the nature of all these psychotic disorders – such incredible advances in imaging and genetics and all these different areas of neurobiology – that, somehow, we were going to revolutionize diagnosis with an etiopathophysiological classification, if you will," commented Dr. Rajiv Tandon of the University of Florida, Gainesville. "And relatively early in the process, we recognized that that was impossible to accomplish, because although we learned a lot, we didn’t know enough yet to be able to do that."

Still, the new edition differs from its predecessor, the DSM-IV, released nearly a decade ago, in a variety of key respects, he said.

For example, gone are the subtypes of schizophrenia, along with shared psychotic disorder. Newly added is catatonia not elsewhere classified, referring to a fully defined catatonic syndrome in the absence of an identifiable medical disorder.

The DSM-5 also sees the debut of assessment of the dimensions of psychosis, which captures the presence and severity of various symptoms. In addition, the criteria for diagnosing schizoaffective disorder have been modified, and catatonia is now treated more uniformly across the manual.

"What we have come up with regard to psychotic disorders are iterative changes, modest improvements, improved clinical utility, simplicity – we have actually reduced the number of disorders in our section by about 20%," Dr. Tandon said. "Very importantly, in addition to improved clinical utility and incorporating the new information we have learned to the extent possible, the DSM-5 look at psychotic disorders provides a much better platform to a future etiopathophysiological classification."

DSM, RDoC called complementary

The DSM-5’s new dimensional approach to assessing psychotic disorders will not only help advance the study of these disorders, but will also help to track their course in patients over time and ensure appropriate treatment, said Dr. Dolores Malaspina of the NYU Langone Medical Center in New York.

Clinicians will rate the presence and severity of eight symptoms – hallucinations, delusions, disorganized speech, psychomotor behavior, negative symptoms, impaired cognition, depression, and mania – on a scale from 0 to 4.

In particular, this approach will promote patient-centered care, she maintained. "We want our treatments to be person specific. For a treatment to be person specific, it’s not simply based on a diagnosis."

Dr. Malaspina further noted that dimensional assessment addresses some of the National Institute of Mental Health’s reservations about the DSM classification system.

"The NIMH has come to see the categories of the DSM as getting in the way of progress forward," she explained. The NIMH, therefore, developed its own classification system, called Research Domain Criteria (RDoC).

"Their goal is to do studies where symptoms have been assessed along a continuum. This approach is not antagonistic to the DSM – there is actually no dueling that will take place in the Moscone Center," she quipped, referring to the location of the APA meeting in San Francisco. "There actually is a great amount of agreement. The future of psychiatric assessment should see that the DSM-5 and the RDoC are complementary, not competing frameworks."

Cognitive impairment left out

Patients with schizophrenia commonly have impaired cognition, so clinicians might be surprised to find that this feature is still not listed as a core feature in the DSM-5, noted Dr. Raquel E. Gur of the University of Pennsylvania, Philadelphia.

"To meet the core features of hallucinations, delusions, and disorganized thinking, you must have impaired cognition, otherwise you will not perceive events around you differently than other people. There is something that happens in the brains of these people that make them distort reality, and those things are measurable," she commented.

Moreover, cognitive status is important when assessing the ability of patients to engage in treatment and when it comes to setting realistic goals of care.

To be sure, the DSM-5 describes assessment of cognitive status as vital to the differential diagnosis when distinguishing entities on the schizophrenia spectrum from other psychotic disorders.

The work group, however, stopped short of including it among core features because of its uncertain specificity to schizophrenia, lack of agreed-on measures that can be readily used in the real world, and absence of evidence that assessment is clinically indicated and applicable in this setting. In other words, more research is needed in this area, Dr. Gur said.

APS inclusion proves controversial

One of the most controversial aspects of the DSM-5 is its inclusion of attenuated psychosis syndrome (APS), acknowledged Dr. Ming T. Tsuang of the University of California, San Diego.

About a third of patients with this constellation of symptoms develop a full-blown psychotic disorder, raising hopes that the APS diagnosis could help identify patients who will benefit from early intervention.

Some, however, have expressed concern that adding APS to the classification system might lead to inappropriate antipsychotic therapy.

"From our experience, that is not the case," Dr. Tsuang said. "Actually, the APS category may educate clinicians about the relative lack of utility of antipsychotic medication in this population. So we hope that if we have this category, inappropriate antipsychotic use among youth may be reduced."

"In the end, our task force decided not to put APS into the main body of the DSM-5, but rather into the appendix, because more research needs to be done to really test its validity and usefulness, particularly for clinicians," he concluded. "For the DSM-6, once we have more experience in this area and [more information from research], we may be able to put this condition in the main body. At that time, the name may change."

Closer to ICD but still distinct

The DSM-5 is likely to share much with the psychosis section of the forthcoming International Classification of Diseases, 11th revision (ICD-11), of the World Health Organization, expected out in 2015. Yet the two will still have their differences.

For example, both classification systems have deleted schizophrenia subtypes, replacing them with dimensional assessments in the case of DSM-5 and symptom specifiers in the case of ICD-11, noted Dr. Wolfgang Gaebel of the Heinrich Heine University Düsseldorf in Germany.

The two differ, though, with respect to diagnostic criteria, such as the requirement for functional impairment to make a diagnosis of schizophrenia and the inclusion of longitudinal criteria to make a diagnosis of schizoaffective disorder.

"There is some harmonization," he commented, while adding that there is still justification for having two classification systems, even if they are generally converging over time.

"Of course, on one hand, we would like to see one system which fits all. On the other hand, the two systems have different foci and always have," Dr. Gaebel said. "ICD is the system which has been used worldwide, mainly for administrative reasons. Some countries, in the clinical situation, use DSM, whereas many other countries use ICD, but when it comes to research, they use in addition DSM, also for publication because, of course, many papers you want to submit to Anglo-American journals that prefer the DSM. And I think the DSM has – this is my personal opinion – a more research-based focus.

"But I think the two systems profit from each other. I doubt for various, and I would say political, reasons that in the future we will have one system, although it would be very good to have it," he concluded.

Dr. Tandon, Dr. Malaspina, Dr. Gur, and Dr. Tsuang disclosed no relevant conflicts of interest. Dr. Gaebel disclosed that he is on the scientific advisory board of Lundbeck International Neuroscience Foundation and receives symposium support from Lilly Germany and Janssen Cilag Germany.

SAN FRANCISCO – Changes to the psychosis section of the long-awaited fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) are hardly dramatic, but they are still likely to advance the field and make the classification system more clinically relevant and easier to use, according to the authors.

Representatives of the 12-member Work Group on Psychotic Disorders detailed some of the revised elements of this section of the new manual, which was released with the start of the annual meeting of the American Psychiatric Association.

Key changes are outlined

"When we were approaching the DSM-5, we thought we learned so much in the last 20 years about the nature of all these psychotic disorders – such incredible advances in imaging and genetics and all these different areas of neurobiology – that, somehow, we were going to revolutionize diagnosis with an etiopathophysiological classification, if you will," commented Dr. Rajiv Tandon of the University of Florida, Gainesville. "And relatively early in the process, we recognized that that was impossible to accomplish, because although we learned a lot, we didn’t know enough yet to be able to do that."

Still, the new edition differs from its predecessor, the DSM-IV, released nearly a decade ago, in a variety of key respects, he said.

For example, gone are the subtypes of schizophrenia, along with shared psychotic disorder. Newly added is catatonia not elsewhere classified, referring to a fully defined catatonic syndrome in the absence of an identifiable medical disorder.

The DSM-5 also sees the debut of assessment of the dimensions of psychosis, which captures the presence and severity of various symptoms. In addition, the criteria for diagnosing schizoaffective disorder have been modified, and catatonia is now treated more uniformly across the manual.

"What we have come up with regard to psychotic disorders are iterative changes, modest improvements, improved clinical utility, simplicity – we have actually reduced the number of disorders in our section by about 20%," Dr. Tandon said. "Very importantly, in addition to improved clinical utility and incorporating the new information we have learned to the extent possible, the DSM-5 look at psychotic disorders provides a much better platform to a future etiopathophysiological classification."

DSM, RDoC called complementary

The DSM-5’s new dimensional approach to assessing psychotic disorders will not only help advance the study of these disorders, but will also help to track their course in patients over time and ensure appropriate treatment, said Dr. Dolores Malaspina of the NYU Langone Medical Center in New York.

Clinicians will rate the presence and severity of eight symptoms – hallucinations, delusions, disorganized speech, psychomotor behavior, negative symptoms, impaired cognition, depression, and mania – on a scale from 0 to 4.

In particular, this approach will promote patient-centered care, she maintained. "We want our treatments to be person specific. For a treatment to be person specific, it’s not simply based on a diagnosis."

Dr. Malaspina further noted that dimensional assessment addresses some of the National Institute of Mental Health’s reservations about the DSM classification system.

"The NIMH has come to see the categories of the DSM as getting in the way of progress forward," she explained. The NIMH, therefore, developed its own classification system, called Research Domain Criteria (RDoC).

"Their goal is to do studies where symptoms have been assessed along a continuum. This approach is not antagonistic to the DSM – there is actually no dueling that will take place in the Moscone Center," she quipped, referring to the location of the APA meeting in San Francisco. "There actually is a great amount of agreement. The future of psychiatric assessment should see that the DSM-5 and the RDoC are complementary, not competing frameworks."

Cognitive impairment left out

Patients with schizophrenia commonly have impaired cognition, so clinicians might be surprised to find that this feature is still not listed as a core feature in the DSM-5, noted Dr. Raquel E. Gur of the University of Pennsylvania, Philadelphia.

"To meet the core features of hallucinations, delusions, and disorganized thinking, you must have impaired cognition, otherwise you will not perceive events around you differently than other people. There is something that happens in the brains of these people that make them distort reality, and those things are measurable," she commented.

Moreover, cognitive status is important when assessing the ability of patients to engage in treatment and when it comes to setting realistic goals of care.

To be sure, the DSM-5 describes assessment of cognitive status as vital to the differential diagnosis when distinguishing entities on the schizophrenia spectrum from other psychotic disorders.

The work group, however, stopped short of including it among core features because of its uncertain specificity to schizophrenia, lack of agreed-on measures that can be readily used in the real world, and absence of evidence that assessment is clinically indicated and applicable in this setting. In other words, more research is needed in this area, Dr. Gur said.

APS inclusion proves controversial

One of the most controversial aspects of the DSM-5 is its inclusion of attenuated psychosis syndrome (APS), acknowledged Dr. Ming T. Tsuang of the University of California, San Diego.

About a third of patients with this constellation of symptoms develop a full-blown psychotic disorder, raising hopes that the APS diagnosis could help identify patients who will benefit from early intervention.

Some, however, have expressed concern that adding APS to the classification system might lead to inappropriate antipsychotic therapy.

"From our experience, that is not the case," Dr. Tsuang said. "Actually, the APS category may educate clinicians about the relative lack of utility of antipsychotic medication in this population. So we hope that if we have this category, inappropriate antipsychotic use among youth may be reduced."

"In the end, our task force decided not to put APS into the main body of the DSM-5, but rather into the appendix, because more research needs to be done to really test its validity and usefulness, particularly for clinicians," he concluded. "For the DSM-6, once we have more experience in this area and [more information from research], we may be able to put this condition in the main body. At that time, the name may change."

Closer to ICD but still distinct

The DSM-5 is likely to share much with the psychosis section of the forthcoming International Classification of Diseases, 11th revision (ICD-11), of the World Health Organization, expected out in 2015. Yet the two will still have their differences.

For example, both classification systems have deleted schizophrenia subtypes, replacing them with dimensional assessments in the case of DSM-5 and symptom specifiers in the case of ICD-11, noted Dr. Wolfgang Gaebel of the Heinrich Heine University Düsseldorf in Germany.

The two differ, though, with respect to diagnostic criteria, such as the requirement for functional impairment to make a diagnosis of schizophrenia and the inclusion of longitudinal criteria to make a diagnosis of schizoaffective disorder.

"There is some harmonization," he commented, while adding that there is still justification for having two classification systems, even if they are generally converging over time.

"Of course, on one hand, we would like to see one system which fits all. On the other hand, the two systems have different foci and always have," Dr. Gaebel said. "ICD is the system which has been used worldwide, mainly for administrative reasons. Some countries, in the clinical situation, use DSM, whereas many other countries use ICD, but when it comes to research, they use in addition DSM, also for publication because, of course, many papers you want to submit to Anglo-American journals that prefer the DSM. And I think the DSM has – this is my personal opinion – a more research-based focus.

"But I think the two systems profit from each other. I doubt for various, and I would say political, reasons that in the future we will have one system, although it would be very good to have it," he concluded.

Dr. Tandon, Dr. Malaspina, Dr. Gur, and Dr. Tsuang disclosed no relevant conflicts of interest. Dr. Gaebel disclosed that he is on the scientific advisory board of Lundbeck International Neuroscience Foundation and receives symposium support from Lilly Germany and Janssen Cilag Germany.

SAN FRANCISCO – A simple, low-cost intervention reduces the rate of suicide intent by about one-third among veterans at moderate risk who are discharged from the emergency department, according to a study presented at the annual meeting of the American Psychiatric Association.

The two-part intervention – known as the Suicide Assessment and Follow-up Engagement: Veteran Emergency Treatment project (SAFE VET) – consists of a safety plan developed in the emergency department plus structured weekly follow-up monitoring post discharge.

Among the 124 veterans included in an interim analysis, about 15% of those in the intervention group had suicide intent at 1 month after discharge, compared with 22% of those in a risk-matched group receiving usual care, reported lead investigator Barbara Stanley, Ph.D., professor and research scientist at Columbia University, New York.

Nearly two-thirds of the veterans in the intervention group reported that they had used their safety plan to avert a suicidal crisis. Furthermore, in comments, the veterans described the intervention as life saving.

"Does SAFE VET ultimately prevent suicide? That question, of course, is out. Do people think this is very, very helpful to them? Very much so," Dr. Stanley commented. "And if you think about this, overall, the expenditure of time is, maximum, 3 hours."

One person attending the session questioned the level of training needed for professionals who help develop the safety plans. "You made it sound pretty easy, and I just wondered, when you are talking about moderate suicide risk patients who are seen cross sectionally, that’s very complicated," he said.

Dr. Stanley responded that doing a safety plan is far easier than conducting a good risk assessment "because you train in it and follow a particular pattern. We have trained people from the level of volunteers answering hotlines up to psychiatrists. If somebody has judged the person is okay to be let go [from the hospital], once you go from that point on, it does not require a lot of professional expertise to do it."

Another attendee asked, "Did you stratify effectiveness by diagnosis or impairment? For example, I could see that cognitively impaired people would do better with a program that reaches out to them, rather than wait for them to come to us."

"No, we kind of took an effectiveness approach in this study; we just took all comers. So if the staff had decided that this person is moderate risk and doesn’t need to be hospitalized, we would include them, period," Dr. Stanley said. "I’m not saying that there won’t be a difference [by diagnosis], because there could be."

SAFE VET intervention

There is good rationale for using ED-based suicide interventions, as the ED is often suicidal patients’ main or only contact with the health care system and many will not follow through with or will have a wait in accessing care after discharge, according to Dr. Stanley.

She contrasted the typical ED approach to suicidal patients and patients with obvious fractures, noting that the latter would never be sent on their way for treatment of the problem at a later time.

"We should figure out a way to have time enough in the ED to do an intervention for our suicidal veterans or suicidal patients, the equivalent of applying a cast in the ED," she maintained.

The safety plan component of SAFE VET is a short prioritized list of coping strategies and resources for use before or during a suicidal crisis that is crafted jointly by the patient and clinician in the ED, but in the patient’s own words (Am. J. Public Health 2012;102[Suppl. 1]:S33-7). It aims to reduce risk, enhance coping, increase treatment motivation, and promote linkages.

The plan has six steps: recognize warning signs, use internal coping strategies, socialize with others who can offer support and distraction, contact family members or friends who can help, contact a mental health agency or professional, and reduce the potential for use of lethal means such as firearms.

The plan has been adopted nationwide at Veterans Affairs Medical Centers in the United States, where a template is used.

With a safety plan in place, "patients feel like they don’t have to ‘white knuckle’ their suicidal episodes anymore because, in the past, what they just did was try to survive it, knowing that time in a certain sense is their friend because the suicidal feelings eventually go away," Dr. Stanley explained. "This gives them something they can do in order to help them through that period of time."

The other component of SAFE VET is structured follow-up monitoring after the patient leaves the ED, typically in the form of weekly telephone calls.

The caller – ideally the same clinician who helped the patient develop the safety plan in the ED – checks on the patient’s mood and risk, reviews and revises the safety plan, discusses access to means, and discusses treatment engagement and helps problem-solve obstacles to getting into treatment.

"Follow-up is important, because this is a very high-risk period. We are potentially saving lives during this period," Dr. Stanley noted. "It’s very low cost – it’s phone contact." On the other hand, "it’s some burden. The big problem is that it requires a shift in the system: Provider systems are not set up for follow-up phone contact," she said.

Study details

The 222 veterans studied were 46 years old on average, and 89% were male. Overall, about one-fourth had a high school education or less and slightly more than half were unemployed.

Interim data among the 124 veterans having adequate follow-up showed that those in the SAFE VET intervention group received a mean of 7.2 follow-up calls.

Compared with their peers in the control group, veterans in the intervention group were less likely at 1 month to have suicidal intent with or without a plan (15% vs. 22%), but the difference diminished thereafter.

"It seems like we are getting our biggest effects at 1 month and then at around 3 months; the groups appear to be equal," commented Dr. Stanley.

In interviews conducted several months after the intervention, 55% of veterans in that group said that it was very helpful for staying safe; 69% and 76% were very satisfied with the safety planning and the follow-up monitoring, respectively, she reported.

Fully 61% of veterans in the intervention group had used their safety plan to avert a suicidal crisis. These users said that the plan helped them contact a professional (50%), contact social support (39%), use an internal coping strategy (26%), and recognize a warning sign of suicidal crisis (21%).

Veterans said that the most helpful aspect of the follow-up calls was regularly checking in (75%) and feeling cared for (58%).

The research was funded by the U.S. Department of Defense and the U.S. Veterans Health Administration.

SAN FRANCISCO – A simple, low-cost intervention reduces the rate of suicide intent by about one-third among veterans at moderate risk who are discharged from the emergency department, according to a study presented at the annual meeting of the American Psychiatric Association.

The two-part intervention – known as the Suicide Assessment and Follow-up Engagement: Veteran Emergency Treatment project (SAFE VET) – consists of a safety plan developed in the emergency department plus structured weekly follow-up monitoring post discharge.

Among the 124 veterans included in an interim analysis, about 15% of those in the intervention group had suicide intent at 1 month after discharge, compared with 22% of those in a risk-matched group receiving usual care, reported lead investigator Barbara Stanley, Ph.D., professor and research scientist at Columbia University, New York.

Nearly two-thirds of the veterans in the intervention group reported that they had used their safety plan to avert a suicidal crisis. Furthermore, in comments, the veterans described the intervention as life saving.

"Does SAFE VET ultimately prevent suicide? That question, of course, is out. Do people think this is very, very helpful to them? Very much so," Dr. Stanley commented. "And if you think about this, overall, the expenditure of time is, maximum, 3 hours."

One person attending the session questioned the level of training needed for professionals who help develop the safety plans. "You made it sound pretty easy, and I just wondered, when you are talking about moderate suicide risk patients who are seen cross sectionally, that’s very complicated," he said.

Dr. Stanley responded that doing a safety plan is far easier than conducting a good risk assessment "because you train in it and follow a particular pattern. We have trained people from the level of volunteers answering hotlines up to psychiatrists. If somebody has judged the person is okay to be let go [from the hospital], once you go from that point on, it does not require a lot of professional expertise to do it."

Another attendee asked, "Did you stratify effectiveness by diagnosis or impairment? For example, I could see that cognitively impaired people would do better with a program that reaches out to them, rather than wait for them to come to us."

"No, we kind of took an effectiveness approach in this study; we just took all comers. So if the staff had decided that this person is moderate risk and doesn’t need to be hospitalized, we would include them, period," Dr. Stanley said. "I’m not saying that there won’t be a difference [by diagnosis], because there could be."

SAFE VET intervention

There is good rationale for using ED-based suicide interventions, as the ED is often suicidal patients’ main or only contact with the health care system and many will not follow through with or will have a wait in accessing care after discharge, according to Dr. Stanley.

She contrasted the typical ED approach to suicidal patients and patients with obvious fractures, noting that the latter would never be sent on their way for treatment of the problem at a later time.

"We should figure out a way to have time enough in the ED to do an intervention for our suicidal veterans or suicidal patients, the equivalent of applying a cast in the ED," she maintained.

The safety plan component of SAFE VET is a short prioritized list of coping strategies and resources for use before or during a suicidal crisis that is crafted jointly by the patient and clinician in the ED, but in the patient’s own words (Am. J. Public Health 2012;102[Suppl. 1]:S33-7). It aims to reduce risk, enhance coping, increase treatment motivation, and promote linkages.

The plan has six steps: recognize warning signs, use internal coping strategies, socialize with others who can offer support and distraction, contact family members or friends who can help, contact a mental health agency or professional, and reduce the potential for use of lethal means such as firearms.

The plan has been adopted nationwide at Veterans Affairs Medical Centers in the United States, where a template is used.

With a safety plan in place, "patients feel like they don’t have to ‘white knuckle’ their suicidal episodes anymore because, in the past, what they just did was try to survive it, knowing that time in a certain sense is their friend because the suicidal feelings eventually go away," Dr. Stanley explained. "This gives them something they can do in order to help them through that period of time."

The other component of SAFE VET is structured follow-up monitoring after the patient leaves the ED, typically in the form of weekly telephone calls.

The caller – ideally the same clinician who helped the patient develop the safety plan in the ED – checks on the patient’s mood and risk, reviews and revises the safety plan, discusses access to means, and discusses treatment engagement and helps problem-solve obstacles to getting into treatment.

"Follow-up is important, because this is a very high-risk period. We are potentially saving lives during this period," Dr. Stanley noted. "It’s very low cost – it’s phone contact." On the other hand, "it’s some burden. The big problem is that it requires a shift in the system: Provider systems are not set up for follow-up phone contact," she said.

Study details

The 222 veterans studied were 46 years old on average, and 89% were male. Overall, about one-fourth had a high school education or less and slightly more than half were unemployed.

Interim data among the 124 veterans having adequate follow-up showed that those in the SAFE VET intervention group received a mean of 7.2 follow-up calls.

Compared with their peers in the control group, veterans in the intervention group were less likely at 1 month to have suicidal intent with or without a plan (15% vs. 22%), but the difference diminished thereafter.

"It seems like we are getting our biggest effects at 1 month and then at around 3 months; the groups appear to be equal," commented Dr. Stanley.

In interviews conducted several months after the intervention, 55% of veterans in that group said that it was very helpful for staying safe; 69% and 76% were very satisfied with the safety planning and the follow-up monitoring, respectively, she reported.

Fully 61% of veterans in the intervention group had used their safety plan to avert a suicidal crisis. These users said that the plan helped them contact a professional (50%), contact social support (39%), use an internal coping strategy (26%), and recognize a warning sign of suicidal crisis (21%).

Veterans said that the most helpful aspect of the follow-up calls was regularly checking in (75%) and feeling cared for (58%).

The research was funded by the U.S. Department of Defense and the U.S. Veterans Health Administration.

SAN FRANCISCO – A simple, low-cost intervention reduces the rate of suicide intent by about one-third among veterans at moderate risk who are discharged from the emergency department, according to a study presented at the annual meeting of the American Psychiatric Association.

The two-part intervention – known as the Suicide Assessment and Follow-up Engagement: Veteran Emergency Treatment project (SAFE VET) – consists of a safety plan developed in the emergency department plus structured weekly follow-up monitoring post discharge.

Among the 124 veterans included in an interim analysis, about 15% of those in the intervention group had suicide intent at 1 month after discharge, compared with 22% of those in a risk-matched group receiving usual care, reported lead investigator Barbara Stanley, Ph.D., professor and research scientist at Columbia University, New York.

Nearly two-thirds of the veterans in the intervention group reported that they had used their safety plan to avert a suicidal crisis. Furthermore, in comments, the veterans described the intervention as life saving.

"Does SAFE VET ultimately prevent suicide? That question, of course, is out. Do people think this is very, very helpful to them? Very much so," Dr. Stanley commented. "And if you think about this, overall, the expenditure of time is, maximum, 3 hours."

One person attending the session questioned the level of training needed for professionals who help develop the safety plans. "You made it sound pretty easy, and I just wondered, when you are talking about moderate suicide risk patients who are seen cross sectionally, that’s very complicated," he said.

Dr. Stanley responded that doing a safety plan is far easier than conducting a good risk assessment "because you train in it and follow a particular pattern. We have trained people from the level of volunteers answering hotlines up to psychiatrists. If somebody has judged the person is okay to be let go [from the hospital], once you go from that point on, it does not require a lot of professional expertise to do it."

Another attendee asked, "Did you stratify effectiveness by diagnosis or impairment? For example, I could see that cognitively impaired people would do better with a program that reaches out to them, rather than wait for them to come to us."

"No, we kind of took an effectiveness approach in this study; we just took all comers. So if the staff had decided that this person is moderate risk and doesn’t need to be hospitalized, we would include them, period," Dr. Stanley said. "I’m not saying that there won’t be a difference [by diagnosis], because there could be."

SAFE VET intervention

There is good rationale for using ED-based suicide interventions, as the ED is often suicidal patients’ main or only contact with the health care system and many will not follow through with or will have a wait in accessing care after discharge, according to Dr. Stanley.

She contrasted the typical ED approach to suicidal patients and patients with obvious fractures, noting that the latter would never be sent on their way for treatment of the problem at a later time.

"We should figure out a way to have time enough in the ED to do an intervention for our suicidal veterans or suicidal patients, the equivalent of applying a cast in the ED," she maintained.

The safety plan component of SAFE VET is a short prioritized list of coping strategies and resources for use before or during a suicidal crisis that is crafted jointly by the patient and clinician in the ED, but in the patient’s own words (Am. J. Public Health 2012;102[Suppl. 1]:S33-7). It aims to reduce risk, enhance coping, increase treatment motivation, and promote linkages.

The plan has six steps: recognize warning signs, use internal coping strategies, socialize with others who can offer support and distraction, contact family members or friends who can help, contact a mental health agency or professional, and reduce the potential for use of lethal means such as firearms.

The plan has been adopted nationwide at Veterans Affairs Medical Centers in the United States, where a template is used.

With a safety plan in place, "patients feel like they don’t have to ‘white knuckle’ their suicidal episodes anymore because, in the past, what they just did was try to survive it, knowing that time in a certain sense is their friend because the suicidal feelings eventually go away," Dr. Stanley explained. "This gives them something they can do in order to help them through that period of time."

The other component of SAFE VET is structured follow-up monitoring after the patient leaves the ED, typically in the form of weekly telephone calls.

The caller – ideally the same clinician who helped the patient develop the safety plan in the ED – checks on the patient’s mood and risk, reviews and revises the safety plan, discusses access to means, and discusses treatment engagement and helps problem-solve obstacles to getting into treatment.

"Follow-up is important, because this is a very high-risk period. We are potentially saving lives during this period," Dr. Stanley noted. "It’s very low cost – it’s phone contact." On the other hand, "it’s some burden. The big problem is that it requires a shift in the system: Provider systems are not set up for follow-up phone contact," she said.

Study details

The 222 veterans studied were 46 years old on average, and 89% were male. Overall, about one-fourth had a high school education or less and slightly more than half were unemployed.

Interim data among the 124 veterans having adequate follow-up showed that those in the SAFE VET intervention group received a mean of 7.2 follow-up calls.

Compared with their peers in the control group, veterans in the intervention group were less likely at 1 month to have suicidal intent with or without a plan (15% vs. 22%), but the difference diminished thereafter.

"It seems like we are getting our biggest effects at 1 month and then at around 3 months; the groups appear to be equal," commented Dr. Stanley.

In interviews conducted several months after the intervention, 55% of veterans in that group said that it was very helpful for staying safe; 69% and 76% were very satisfied with the safety planning and the follow-up monitoring, respectively, she reported.

Fully 61% of veterans in the intervention group had used their safety plan to avert a suicidal crisis. These users said that the plan helped them contact a professional (50%), contact social support (39%), use an internal coping strategy (26%), and recognize a warning sign of suicidal crisis (21%).

Veterans said that the most helpful aspect of the follow-up calls was regularly checking in (75%) and feeling cared for (58%).

The research was funded by the U.S. Department of Defense and the U.S. Veterans Health Administration.

LOS ANGELES – A modified frailty index strongly predicts morbidity and mortality after esophagectomy, based on a study of more than 2,000 patients in a national database.

Both the rate of serious complications and the rate of death rose steadily and significantly with the index, which is derived from 11 common clinical variables.

Compared with their counterparts having the lowest index, patients having the highest index were 31 times more likely to die in the first postoperative month even after confounders were taken into account, according to data reported at the annual meeting of the Society of Thoracic Surgeons (STS).

"The modified frailty index appears to be an important predictor of morbidity and mortality. It can be used to guide surgeons in making more accurate predictions of complications. It also provides an objective guide for patients in decision making," commented lead investigator Dr. Arielle Hodari, a thoracic surgery resident at the Henry Ford Hospital in Detroit.

In the study, the investigators calculated a preoperative modified frailty index for 2,095 patients who underwent esophagectomy between 2005 and 2010. The index contains 11 variables chosen by mapping those used in the Canadian Study of Health and Aging Frailty Index (CMAJ 2005;173:489-95) onto those available in the National Surgical Quality Improvement Program (NSQIP) database.

The 11 variables in the index were (1) nonindependent functional status, (2) diabetes, (3) chronic obstructive pulmonary disease or pneumonia, (4) congestive heart failure, (5) myocardial infarction, (6) percutaneous coronary intervention, cardiac surgery, or angina, (7) hypertension, (8) peripheral vascular disease, (9) impaired sensorium, (10) transient ischemic attack or stroke without residual deficit, and (11) stroke with deficit.

The study patients had indexes ranging from a low of 0 (meaning 0 of 11 variables) to a high of 0.45 (5 of 11 variables). The large majority clustered at the lower end of the spectrum; only about 1% had an index of 0.45.

The main results showed that as the index increased from 0 to 0.45, there was also an increase in the rate of Clavien 4 complications from 18% to 62% (P less than .001), which are life-threatening complications leading to ICU admission, as well as an increase in the rate of 30-day mortality from 2% to 23% (P less than .001).

The findings were similar for respiratory complications and for cardiovascular complications individually, according to Dr. Hodari.

In a multivariate analysis, patients with the highest index had sharply elevated odds of death relative to their counterparts with the lowest index (odds ratio, 31.8; P = .015).

"The NSQIP data does not differentiate between pathology (squamous cell carcinoma vs. adenocarcinoma) or surgical modality," Dr. Hodari commented, discussing the study’s limitations. "We also need validation in a prospective study."

During the discussion following the presentation of the data, Dr. Hodari was asked about the number of patients who had received neoadjuvant/induction therapy before coming to surgery.

"What I find in my own personal practice is that it’s hard sometimes to say no [to surgery] altogether. So if somebody is T3 or N1, I’ll let them get some induction therapy and then get them back to reevaluate them," he said. "I’d be particularly interested in this type of analysis being applied then, because a lot of times [the patients] haven’t really been improved by that process, and maybe it just shows that I’ve procrastinated in making a difficult decision and probably made it even harder by putting it off until after their induction therapy. Do you know anything about the status of induction therapy in these patients, whether the frailness that was measured was in part due to the induction therapy and how that might affect your results?"

"Unfortunately, that is not available in NSQIP, so we don’t know which patients had neoadjuvant treatment," Dr. Hodari replied.

Regarding questions about the use of 30-day mortality as an endpoint, he responded, "I think it’s worthwhile – maybe it’s not in the database – to look at these figures at 90 days, because, of course, the high-risk patients die within 30 days. But there is a big increase in mortality, almost doubling, at 90 days."

An attendee noted that the original frailty index includes unintentional weight loss, but the modified one does not. "Why was that done for this particular patient population, because with esophageal cancer and dysphagia and unintentional weight loss being a big component of the comorbidity these patients have, wouldn’t you think that would be important to include that?"

That choice was made on the basis of data constraints, Dr. Hodari replied. "We chose variables by going through NSQIP and finding something that corresponds with the Canadian system," she explained.

Dr. Mark Krasna, a thoracic surgeon with Meridian Surgical Associates in Neptune, N.J., expressed reservations about using the NSQIP database to assess the outcomes of thoracic surgery.

"How many thoracic surgeons participate in the NSQIP data?" he asked. In the STS database, "I think we have a robust series of esophagectomists who are thoracic surgeons, and we know what those data are. But, for example, data that were presented from NSQIP [at another conference] were primarily from nonthoracic esophageal surgeons [and were associated] with a much higher mortality and morbidity. Personally, I’m not a NSQIP participant, and I don’t know if many people in this room are. Do you know how many of these were thoracic surgeons?"

"I know the majority of NSQIP esophagectomies are done by general surgeons. I don’t know the exact number," Dr. Hodari replied.

Dr. Krasna asked the audience to raise their hands if they participated in NSQIP, and only about half did so. "I would just say perhaps it’s worthwhile to reassess this [index] based on the STS database because I think you may actually find some change" in the results, he commented.

Dr. Hodari disclosed no relevant conflicts of interest.

LOS ANGELES – A modified frailty index strongly predicts morbidity and mortality after esophagectomy, based on a study of more than 2,000 patients in a national database.

Both the rate of serious complications and the rate of death rose steadily and significantly with the index, which is derived from 11 common clinical variables.

Compared with their counterparts having the lowest index, patients having the highest index were 31 times more likely to die in the first postoperative month even after confounders were taken into account, according to data reported at the annual meeting of the Society of Thoracic Surgeons (STS).

"The modified frailty index appears to be an important predictor of morbidity and mortality. It can be used to guide surgeons in making more accurate predictions of complications. It also provides an objective guide for patients in decision making," commented lead investigator Dr. Arielle Hodari, a thoracic surgery resident at the Henry Ford Hospital in Detroit.

In the study, the investigators calculated a preoperative modified frailty index for 2,095 patients who underwent esophagectomy between 2005 and 2010. The index contains 11 variables chosen by mapping those used in the Canadian Study of Health and Aging Frailty Index (CMAJ 2005;173:489-95) onto those available in the National Surgical Quality Improvement Program (NSQIP) database.

The 11 variables in the index were (1) nonindependent functional status, (2) diabetes, (3) chronic obstructive pulmonary disease or pneumonia, (4) congestive heart failure, (5) myocardial infarction, (6) percutaneous coronary intervention, cardiac surgery, or angina, (7) hypertension, (8) peripheral vascular disease, (9) impaired sensorium, (10) transient ischemic attack or stroke without residual deficit, and (11) stroke with deficit.

The study patients had indexes ranging from a low of 0 (meaning 0 of 11 variables) to a high of 0.45 (5 of 11 variables). The large majority clustered at the lower end of the spectrum; only about 1% had an index of 0.45.

The main results showed that as the index increased from 0 to 0.45, there was also an increase in the rate of Clavien 4 complications from 18% to 62% (P less than .001), which are life-threatening complications leading to ICU admission, as well as an increase in the rate of 30-day mortality from 2% to 23% (P less than .001).

The findings were similar for respiratory complications and for cardiovascular complications individually, according to Dr. Hodari.

In a multivariate analysis, patients with the highest index had sharply elevated odds of death relative to their counterparts with the lowest index (odds ratio, 31.8; P = .015).

"The NSQIP data does not differentiate between pathology (squamous cell carcinoma vs. adenocarcinoma) or surgical modality," Dr. Hodari commented, discussing the study’s limitations. "We also need validation in a prospective study."

During the discussion following the presentation of the data, Dr. Hodari was asked about the number of patients who had received neoadjuvant/induction therapy before coming to surgery.

"What I find in my own personal practice is that it’s hard sometimes to say no [to surgery] altogether. So if somebody is T3 or N1, I’ll let them get some induction therapy and then get them back to reevaluate them," he said. "I’d be particularly interested in this type of analysis being applied then, because a lot of times [the patients] haven’t really been improved by that process, and maybe it just shows that I’ve procrastinated in making a difficult decision and probably made it even harder by putting it off until after their induction therapy. Do you know anything about the status of induction therapy in these patients, whether the frailness that was measured was in part due to the induction therapy and how that might affect your results?"

"Unfortunately, that is not available in NSQIP, so we don’t know which patients had neoadjuvant treatment," Dr. Hodari replied.

Regarding questions about the use of 30-day mortality as an endpoint, he responded, "I think it’s worthwhile – maybe it’s not in the database – to look at these figures at 90 days, because, of course, the high-risk patients die within 30 days. But there is a big increase in mortality, almost doubling, at 90 days."

An attendee noted that the original frailty index includes unintentional weight loss, but the modified one does not. "Why was that done for this particular patient population, because with esophageal cancer and dysphagia and unintentional weight loss being a big component of the comorbidity these patients have, wouldn’t you think that would be important to include that?"

That choice was made on the basis of data constraints, Dr. Hodari replied. "We chose variables by going through NSQIP and finding something that corresponds with the Canadian system," she explained.

Dr. Mark Krasna, a thoracic surgeon with Meridian Surgical Associates in Neptune, N.J., expressed reservations about using the NSQIP database to assess the outcomes of thoracic surgery.

"How many thoracic surgeons participate in the NSQIP data?" he asked. In the STS database, "I think we have a robust series of esophagectomists who are thoracic surgeons, and we know what those data are. But, for example, data that were presented from NSQIP [at another conference] were primarily from nonthoracic esophageal surgeons [and were associated] with a much higher mortality and morbidity. Personally, I’m not a NSQIP participant, and I don’t know if many people in this room are. Do you know how many of these were thoracic surgeons?"

"I know the majority of NSQIP esophagectomies are done by general surgeons. I don’t know the exact number," Dr. Hodari replied.

Dr. Krasna asked the audience to raise their hands if they participated in NSQIP, and only about half did so. "I would just say perhaps it’s worthwhile to reassess this [index] based on the STS database because I think you may actually find some change" in the results, he commented.

Dr. Hodari disclosed no relevant conflicts of interest.

LOS ANGELES – A modified frailty index strongly predicts morbidity and mortality after esophagectomy, based on a study of more than 2,000 patients in a national database.

Both the rate of serious complications and the rate of death rose steadily and significantly with the index, which is derived from 11 common clinical variables.

Compared with their counterparts having the lowest index, patients having the highest index were 31 times more likely to die in the first postoperative month even after confounders were taken into account, according to data reported at the annual meeting of the Society of Thoracic Surgeons (STS).

"The modified frailty index appears to be an important predictor of morbidity and mortality. It can be used to guide surgeons in making more accurate predictions of complications. It also provides an objective guide for patients in decision making," commented lead investigator Dr. Arielle Hodari, a thoracic surgery resident at the Henry Ford Hospital in Detroit.

In the study, the investigators calculated a preoperative modified frailty index for 2,095 patients who underwent esophagectomy between 2005 and 2010. The index contains 11 variables chosen by mapping those used in the Canadian Study of Health and Aging Frailty Index (CMAJ 2005;173:489-95) onto those available in the National Surgical Quality Improvement Program (NSQIP) database.

The 11 variables in the index were (1) nonindependent functional status, (2) diabetes, (3) chronic obstructive pulmonary disease or pneumonia, (4) congestive heart failure, (5) myocardial infarction, (6) percutaneous coronary intervention, cardiac surgery, or angina, (7) hypertension, (8) peripheral vascular disease, (9) impaired sensorium, (10) transient ischemic attack or stroke without residual deficit, and (11) stroke with deficit.

The study patients had indexes ranging from a low of 0 (meaning 0 of 11 variables) to a high of 0.45 (5 of 11 variables). The large majority clustered at the lower end of the spectrum; only about 1% had an index of 0.45.

The main results showed that as the index increased from 0 to 0.45, there was also an increase in the rate of Clavien 4 complications from 18% to 62% (P less than .001), which are life-threatening complications leading to ICU admission, as well as an increase in the rate of 30-day mortality from 2% to 23% (P less than .001).

The findings were similar for respiratory complications and for cardiovascular complications individually, according to Dr. Hodari.

In a multivariate analysis, patients with the highest index had sharply elevated odds of death relative to their counterparts with the lowest index (odds ratio, 31.8; P = .015).

"The NSQIP data does not differentiate between pathology (squamous cell carcinoma vs. adenocarcinoma) or surgical modality," Dr. Hodari commented, discussing the study’s limitations. "We also need validation in a prospective study."

During the discussion following the presentation of the data, Dr. Hodari was asked about the number of patients who had received neoadjuvant/induction therapy before coming to surgery.

"What I find in my own personal practice is that it’s hard sometimes to say no [to surgery] altogether. So if somebody is T3 or N1, I’ll let them get some induction therapy and then get them back to reevaluate them," he said. "I’d be particularly interested in this type of analysis being applied then, because a lot of times [the patients] haven’t really been improved by that process, and maybe it just shows that I’ve procrastinated in making a difficult decision and probably made it even harder by putting it off until after their induction therapy. Do you know anything about the status of induction therapy in these patients, whether the frailness that was measured was in part due to the induction therapy and how that might affect your results?"

"Unfortunately, that is not available in NSQIP, so we don’t know which patients had neoadjuvant treatment," Dr. Hodari replied.

Regarding questions about the use of 30-day mortality as an endpoint, he responded, "I think it’s worthwhile – maybe it’s not in the database – to look at these figures at 90 days, because, of course, the high-risk patients die within 30 days. But there is a big increase in mortality, almost doubling, at 90 days."

An attendee noted that the original frailty index includes unintentional weight loss, but the modified one does not. "Why was that done for this particular patient population, because with esophageal cancer and dysphagia and unintentional weight loss being a big component of the comorbidity these patients have, wouldn’t you think that would be important to include that?"

That choice was made on the basis of data constraints, Dr. Hodari replied. "We chose variables by going through NSQIP and finding something that corresponds with the Canadian system," she explained.

Dr. Mark Krasna, a thoracic surgeon with Meridian Surgical Associates in Neptune, N.J., expressed reservations about using the NSQIP database to assess the outcomes of thoracic surgery.

"How many thoracic surgeons participate in the NSQIP data?" he asked. In the STS database, "I think we have a robust series of esophagectomists who are thoracic surgeons, and we know what those data are. But, for example, data that were presented from NSQIP [at another conference] were primarily from nonthoracic esophageal surgeons [and were associated] with a much higher mortality and morbidity. Personally, I’m not a NSQIP participant, and I don’t know if many people in this room are. Do you know how many of these were thoracic surgeons?"

"I know the majority of NSQIP esophagectomies are done by general surgeons. I don’t know the exact number," Dr. Hodari replied.

Dr. Krasna asked the audience to raise their hands if they participated in NSQIP, and only about half did so. "I would just say perhaps it’s worthwhile to reassess this [index] based on the STS database because I think you may actually find some change" in the results, he commented.

Dr. Hodari disclosed no relevant conflicts of interest.

LOS ANGELES – Aortic valve interventions rose sharply in the United Kingdom during a recent 5-year period, largely due to a spike in procedures among elderly patients, researchers reported at the annual meeting of the Society of Thoracic Surgeons.

In the study, the combined U.K. Cardiac Surgical and Transcatheter Aortic Valve Implantation (TAVI) Registries – known as SATIRE for short – the team analyzed data from 37,020 patients nationwide who underwent aortic valve interventions (excluding balloon valvuloplasty) between 2006 and 2010.

Results showed that the annual number of these procedures increased by 32% over the course of the study, with about half of the increase due to procedures among patients aged 80 years and older, reported lead investigator Dr. Neil E. Moat, a cardiac surgeon and codirector of the Transcatheter Valve Programme at the Royal Brompton Hospital in London.

Overall, the annual number of aortic valve interventions increased during the study period, from 6,217 in 2006 to 8,201 in 2010. This was driven largely by a near doubling in interventions among patients aged 80 years or older, from 1,055 to 2,035.

"In 2010, 25% of all aortic valve interventions in the U.K. were performed in patients aged 80 or over," Dr. Moat noted.

By type of intervention, there was an increase in the annual number of TAVIs (from none to 749) and conventional surgeries (from 6,217 to 7,252), although the latter stabilized toward the end of the period.

"This is the first time in the whole history – 35 years of collecting U.K. cardiac surgical data – that these numbers have plateaued," he commented.

As of 2010, TAVIs accounted for 9% of all aortic valve interventions studied.

Not surprisingly, patients undergoing TAVI surgery were older than their counterparts undergoing conventional surgery, had a higher risk profile, and had poorer postoperative survival, but their lengths of hospital stay were statistically indistinguishable.

Importantly, two scores used in Europe to predict mortality after such interventions showed differential performance.

"The logistic EuroSCORE does not predict operative outcomes of surgery or TAVI" and should not be used, Dr. Moat advised. "The EuroSCORE II is probably quite good for conventional surgery but again is rather poor for predicting mortality outcomes from TAVI. And I suppose on this side of the pond, you will be pleased to hear that the STS [U.S. Society of Thoracic Surgeons] score is far better than either of these European scores in our population."

In the discussion after the presentation of the study, Dr. Paul A. Kurlansky, a cardiothoracic surgeon from Miami, remarked, "Maybe our risk score is better on this side of the pond, but we do not have the merging of databases that you guys have over there [in the U.K.], or the completion of them. One opportunity that I was wondering if you had taken or are planning to take advantage of is the ability to do propensity score matching or use other statistical tools in order to really match patients so that you can compare outcomes."

"That’s a very interesting question and something that we have debated long and hard," Dr. Moat replied, citing reservations given by the study’s statisticians. "They are very firm in their belief that whilst you can apply those statistical techniques, they are actually not valid because you have so much confounding by indication that [you are unable] to propensity-match populations. So it’s a deliberate decision not to pursue that."

Main analyses in the study used prospectively collected registry data for 35,392 patients undergoing conventional surgery – either aortic valve replacement (AVR) alone or combined with coronary artery bypass grafting (CABG) – and 1,628 TAVIs.

"Because [the registries] are national and publicly funded, they are free from any commercial bias. These are mandatory registries and therefore free of any selection bias," Dr. Moat pointed out. Furthermore, there is good standardization of definitions and long-term follow-up of mortality.

"All cardiac surgical procedures and all TAVIs in the U.K. are entered into national registries hosted by the National Institute for Cardiovascular Outcomes Research. The data set and databases of all of these registries are designed to be compatible and comparable," he added.

Overall, compared with patients undergoing surgery, patients undergoing TAVI were on average older and had a higher risk profile in terms of cardiovascular measures and comorbidities, although there was substantial overlap.

The median postoperative length of stay was 8 days after conventional surgery and 7 days after TAVI. "Despite the TAVI patients being older and at increased risk, there was no difference in postoperative length of stay. If anything, it was marginally lower in the TAVI group," Dr. Moat commented. The distribution of length of stay was also much the same. "You see a substantial numbers of these elderly, frail, and high-risk patients [in the TAVI group] being discharged before day 6," he added.

Actuarial analyses in the study population overall showed poorer survival after TAVI than after conventional surgery (whether AVR alone or combined with CABG), both in the first year and longer term. However, the gaps between curves were smaller among patients aged 80 years or older.

Among the patients undergoing TAVI, longer-term survival after aortic valve intervention did not differ according to the number of diseased vessels treated.

"An interesting observation worthy of further study is that we are well aware that patients having combined AVR and CABG have worse earlier and late survival than patients having isolated AVR. But it would seem that the presence of concomitant coronary artery disease – despite much of it being left untreated – did not affect early or late survival following TAVI," Dr. Moat commented.

The EuroSCORE was a poor predictor of mortality after both conventional surgery and TAVI, but the EuroSCORE II performed fairly well after conventional surgery, whether isolated AVR (observed:expected ratio, 0.87; area under the curve, 0.78) or AVR plus CABG (observed:expected ratio, 1.0; area under the curve, 0.73).

Dr. Moat disclosed that he is on the speakers bureau for, and receives honoraria from, Abbott Laboratories, and sits on the consultant/advisory board of Medtronic.

LOS ANGELES – Aortic valve interventions rose sharply in the United Kingdom during a recent 5-year period, largely due to a spike in procedures among elderly patients, researchers reported at the annual meeting of the Society of Thoracic Surgeons.

In the study, the combined U.K. Cardiac Surgical and Transcatheter Aortic Valve Implantation (TAVI) Registries – known as SATIRE for short – the team analyzed data from 37,020 patients nationwide who underwent aortic valve interventions (excluding balloon valvuloplasty) between 2006 and 2010.

Results showed that the annual number of these procedures increased by 32% over the course of the study, with about half of the increase due to procedures among patients aged 80 years and older, reported lead investigator Dr. Neil E. Moat, a cardiac surgeon and codirector of the Transcatheter Valve Programme at the Royal Brompton Hospital in London.

Overall, the annual number of aortic valve interventions increased during the study period, from 6,217 in 2006 to 8,201 in 2010. This was driven largely by a near doubling in interventions among patients aged 80 years or older, from 1,055 to 2,035.

"In 2010, 25% of all aortic valve interventions in the U.K. were performed in patients aged 80 or over," Dr. Moat noted.

By type of intervention, there was an increase in the annual number of TAVIs (from none to 749) and conventional surgeries (from 6,217 to 7,252), although the latter stabilized toward the end of the period.

"This is the first time in the whole history – 35 years of collecting U.K. cardiac surgical data – that these numbers have plateaued," he commented.

As of 2010, TAVIs accounted for 9% of all aortic valve interventions studied.

Not surprisingly, patients undergoing TAVI surgery were older than their counterparts undergoing conventional surgery, had a higher risk profile, and had poorer postoperative survival, but their lengths of hospital stay were statistically indistinguishable.

Importantly, two scores used in Europe to predict mortality after such interventions showed differential performance.

"The logistic EuroSCORE does not predict operative outcomes of surgery or TAVI" and should not be used, Dr. Moat advised. "The EuroSCORE II is probably quite good for conventional surgery but again is rather poor for predicting mortality outcomes from TAVI. And I suppose on this side of the pond, you will be pleased to hear that the STS [U.S. Society of Thoracic Surgeons] score is far better than either of these European scores in our population."

In the discussion after the presentation of the study, Dr. Paul A. Kurlansky, a cardiothoracic surgeon from Miami, remarked, "Maybe our risk score is better on this side of the pond, but we do not have the merging of databases that you guys have over there [in the U.K.], or the completion of them. One opportunity that I was wondering if you had taken or are planning to take advantage of is the ability to do propensity score matching or use other statistical tools in order to really match patients so that you can compare outcomes."

"That’s a very interesting question and something that we have debated long and hard," Dr. Moat replied, citing reservations given by the study’s statisticians. "They are very firm in their belief that whilst you can apply those statistical techniques, they are actually not valid because you have so much confounding by indication that [you are unable] to propensity-match populations. So it’s a deliberate decision not to pursue that."

Main analyses in the study used prospectively collected registry data for 35,392 patients undergoing conventional surgery – either aortic valve replacement (AVR) alone or combined with coronary artery bypass grafting (CABG) – and 1,628 TAVIs.

"Because [the registries] are national and publicly funded, they are free from any commercial bias. These are mandatory registries and therefore free of any selection bias," Dr. Moat pointed out. Furthermore, there is good standardization of definitions and long-term follow-up of mortality.

"All cardiac surgical procedures and all TAVIs in the U.K. are entered into national registries hosted by the National Institute for Cardiovascular Outcomes Research. The data set and databases of all of these registries are designed to be compatible and comparable," he added.

Overall, compared with patients undergoing surgery, patients undergoing TAVI were on average older and had a higher risk profile in terms of cardiovascular measures and comorbidities, although there was substantial overlap.

The median postoperative length of stay was 8 days after conventional surgery and 7 days after TAVI. "Despite the TAVI patients being older and at increased risk, there was no difference in postoperative length of stay. If anything, it was marginally lower in the TAVI group," Dr. Moat commented. The distribution of length of stay was also much the same. "You see a substantial numbers of these elderly, frail, and high-risk patients [in the TAVI group] being discharged before day 6," he added.

Actuarial analyses in the study population overall showed poorer survival after TAVI than after conventional surgery (whether AVR alone or combined with CABG), both in the first year and longer term. However, the gaps between curves were smaller among patients aged 80 years or older.

Among the patients undergoing TAVI, longer-term survival after aortic valve intervention did not differ according to the number of diseased vessels treated.

"An interesting observation worthy of further study is that we are well aware that patients having combined AVR and CABG have worse earlier and late survival than patients having isolated AVR. But it would seem that the presence of concomitant coronary artery disease – despite much of it being left untreated – did not affect early or late survival following TAVI," Dr. Moat commented.

The EuroSCORE was a poor predictor of mortality after both conventional surgery and TAVI, but the EuroSCORE II performed fairly well after conventional surgery, whether isolated AVR (observed:expected ratio, 0.87; area under the curve, 0.78) or AVR plus CABG (observed:expected ratio, 1.0; area under the curve, 0.73).

Dr. Moat disclosed that he is on the speakers bureau for, and receives honoraria from, Abbott Laboratories, and sits on the consultant/advisory board of Medtronic.

LOS ANGELES – Aortic valve interventions rose sharply in the United Kingdom during a recent 5-year period, largely due to a spike in procedures among elderly patients, researchers reported at the annual meeting of the Society of Thoracic Surgeons.

In the study, the combined U.K. Cardiac Surgical and Transcatheter Aortic Valve Implantation (TAVI) Registries – known as SATIRE for short – the team analyzed data from 37,020 patients nationwide who underwent aortic valve interventions (excluding balloon valvuloplasty) between 2006 and 2010.

Results showed that the annual number of these procedures increased by 32% over the course of the study, with about half of the increase due to procedures among patients aged 80 years and older, reported lead investigator Dr. Neil E. Moat, a cardiac surgeon and codirector of the Transcatheter Valve Programme at the Royal Brompton Hospital in London.

Overall, the annual number of aortic valve interventions increased during the study period, from 6,217 in 2006 to 8,201 in 2010. This was driven largely by a near doubling in interventions among patients aged 80 years or older, from 1,055 to 2,035.

"In 2010, 25% of all aortic valve interventions in the U.K. were performed in patients aged 80 or over," Dr. Moat noted.

By type of intervention, there was an increase in the annual number of TAVIs (from none to 749) and conventional surgeries (from 6,217 to 7,252), although the latter stabilized toward the end of the period.

"This is the first time in the whole history – 35 years of collecting U.K. cardiac surgical data – that these numbers have plateaued," he commented.

As of 2010, TAVIs accounted for 9% of all aortic valve interventions studied.

Not surprisingly, patients undergoing TAVI surgery were older than their counterparts undergoing conventional surgery, had a higher risk profile, and had poorer postoperative survival, but their lengths of hospital stay were statistically indistinguishable.

Importantly, two scores used in Europe to predict mortality after such interventions showed differential performance.

"The logistic EuroSCORE does not predict operative outcomes of surgery or TAVI" and should not be used, Dr. Moat advised. "The EuroSCORE II is probably quite good for conventional surgery but again is rather poor for predicting mortality outcomes from TAVI. And I suppose on this side of the pond, you will be pleased to hear that the STS [U.S. Society of Thoracic Surgeons] score is far better than either of these European scores in our population."

In the discussion after the presentation of the study, Dr. Paul A. Kurlansky, a cardiothoracic surgeon from Miami, remarked, "Maybe our risk score is better on this side of the pond, but we do not have the merging of databases that you guys have over there [in the U.K.], or the completion of them. One opportunity that I was wondering if you had taken or are planning to take advantage of is the ability to do propensity score matching or use other statistical tools in order to really match patients so that you can compare outcomes."

"That’s a very interesting question and something that we have debated long and hard," Dr. Moat replied, citing reservations given by the study’s statisticians. "They are very firm in their belief that whilst you can apply those statistical techniques, they are actually not valid because you have so much confounding by indication that [you are unable] to propensity-match populations. So it’s a deliberate decision not to pursue that."

Main analyses in the study used prospectively collected registry data for 35,392 patients undergoing conventional surgery – either aortic valve replacement (AVR) alone or combined with coronary artery bypass grafting (CABG) – and 1,628 TAVIs.

"Because [the registries] are national and publicly funded, they are free from any commercial bias. These are mandatory registries and therefore free of any selection bias," Dr. Moat pointed out. Furthermore, there is good standardization of definitions and long-term follow-up of mortality.

"All cardiac surgical procedures and all TAVIs in the U.K. are entered into national registries hosted by the National Institute for Cardiovascular Outcomes Research. The data set and databases of all of these registries are designed to be compatible and comparable," he added.

Overall, compared with patients undergoing surgery, patients undergoing TAVI were on average older and had a higher risk profile in terms of cardiovascular measures and comorbidities, although there was substantial overlap.

The median postoperative length of stay was 8 days after conventional surgery and 7 days after TAVI. "Despite the TAVI patients being older and at increased risk, there was no difference in postoperative length of stay. If anything, it was marginally lower in the TAVI group," Dr. Moat commented. The distribution of length of stay was also much the same. "You see a substantial numbers of these elderly, frail, and high-risk patients [in the TAVI group] being discharged before day 6," he added.

Actuarial analyses in the study population overall showed poorer survival after TAVI than after conventional surgery (whether AVR alone or combined with CABG), both in the first year and longer term. However, the gaps between curves were smaller among patients aged 80 years or older.

Among the patients undergoing TAVI, longer-term survival after aortic valve intervention did not differ according to the number of diseased vessels treated.

"An interesting observation worthy of further study is that we are well aware that patients having combined AVR and CABG have worse earlier and late survival than patients having isolated AVR. But it would seem that the presence of concomitant coronary artery disease – despite much of it being left untreated – did not affect early or late survival following TAVI," Dr. Moat commented.

The EuroSCORE was a poor predictor of mortality after both conventional surgery and TAVI, but the EuroSCORE II performed fairly well after conventional surgery, whether isolated AVR (observed:expected ratio, 0.87; area under the curve, 0.78) or AVR plus CABG (observed:expected ratio, 1.0; area under the curve, 0.73).

Dr. Moat disclosed that he is on the speakers bureau for, and receives honoraria from, Abbott Laboratories, and sits on the consultant/advisory board of Medtronic.

LOS ANGELES – A palliative care consultation within the last month of life improves a variety of end-of-life outcomes in patients dying from gynecologic cancers, based on a retrospective analysis.

Among the 100 patients studied, about one-fourth had a timely palliative care consultation, defined in one study as 14 days before death and in another study as 30 days before death, lead investigator Dr. Nicole S. Nevadunsky of Montefiore Medical Center, New York, reported at the annual meeting of the Society of Gynecologic Oncology.

Compared with their counterparts who had late or no consultations, patients who had timely consultations had lower scores for aggressive end-of-life events such as emergency department visits, chemotherapy, and death in an acute care setting.

In addition, in their last 14 days of life, this group had median direct inpatient hospital costs that were $5,106 less, and they were half as likely to be admitted.

"Our data suggest that early palliative medicine consultation results in decreased aggressive measures at the end of life [and] was associated with decreased direct inpatient costs for women who died from gynecologic malignancies," Dr. Nevadunsky noted. "Further research is needed to evaluate the quality of life in relation to [the aggressiveness of care] for patients and their families."

While it is unclear how many gynecologic oncologists are also board certified in palliative care, "I think more clinicians actually do palliative medicine as part of their everyday practice," Dr. Nevadunsky said. Also, palliative care is truly a multidisciplinary undertaking involving, for example, nurses, pastoral care personnel, social workers, and others.

"As far as the best metric for palliative medicine, I think it is quality of life. But how to define that is extremely complicated and still evolving," she added.

"I think it’s an experience where the patient is getting what they want most out of things, and sometimes that’s saying to the patient, ‘If we can’t cure you, what is the most important thing to you?’ " she replied. "Each patient is different, and that’s what makes (defining quality of life) so complicated."

The American Society of Clinical Oncology recommends consideration of palliative care early in the course of metastatic or symptomatic disease.

"This is a very vague recommendation: who, what, when, where, how? How will patients respond to this? Who’s going to pay for this? What’s the patient going to get out of this?" Dr. Nevadunsky commented.

She and her colleagues studied 100 consecutive patients who died from gynecologic cancer between 2006 and 2009 and received care at Montefiore in the year before death.

In the first study, they defined a timely palliative care consultation as one occurring more than 30 days before death.

"The ideal timing for palliative medicine consultation is unknown; however, 30 days was chosen as the minimal exposure time because the standard metrics utilized to compare aggressive measures at the end of life included a minimum of 30 days," Dr. Nevadunsky explained.

"Overall, I was surprised to find that 49 of the 100 women actually had a palliative medicine consultation at some time or another during their care," she said.

However, the median number of days between consultation and death was 16, and only 18% of patients had a timely consultation.

Late diagnosis did not explain this finding, as less than 10% of patients received their diagnosis in the month before they died.

"The scope of this study was not inclusive to determine why this [late palliative care consultation] was happening," Dr. Nevadunsky said. Data showed that although the two groups were demographically similar, the patients who received a timely consultation were more likely to be married.

The group with timely consultations were less likely to receive aggressive end-of-life care, based on measures of eight indicators of aggressive care (0 vs. 2, P = .025).

The difference between those patients who had timely consultation and those with untimely or no consultation was greatest for the indicators of a hospital stay lasting more than 14 days in the last month of life (22% vs. 40%) and death in the acute care setting (28% vs. 45%).

In the second study, the investigators found that 29% of patients had a timely palliative care consultation, defined in this case as one occurring 14 days or more before death.

Patients with a timely consultation had lower median direct hospital inpatient costs per day in the last 30 days of life ($613 vs. $702, P = .02). They also had lower median direct hospital inpatient costs in the last 14 days overall ($0 vs. $5,106, P = .007) and on a per-day basis ($0 vs. $676, P = .007).

"The patients who had the timely consultations actually weren’t admitted to the hospital as often," Dr. Nevadunsky noted. In fact, they were half as likely to be admitted in the last 14 days (35% vs. 71%, P = .001).

"Shortcomings [of the study] include small numbers and the retrospective collection of data. Also, our study did not account for outpatient costs, including those assumed by families, or for those costs incurred by loss of time out of work by families to care for the patient," acknowledged Dr. Nevadunsky, who disclosed no relevant conflicts of interest.

LOS ANGELES – A palliative care consultation within the last month of life improves a variety of end-of-life outcomes in patients dying from gynecologic cancers, based on a retrospective analysis.

Among the 100 patients studied, about one-fourth had a timely palliative care consultation, defined in one study as 14 days before death and in another study as 30 days before death, lead investigator Dr. Nicole S. Nevadunsky of Montefiore Medical Center, New York, reported at the annual meeting of the Society of Gynecologic Oncology.

Compared with their counterparts who had late or no consultations, patients who had timely consultations had lower scores for aggressive end-of-life events such as emergency department visits, chemotherapy, and death in an acute care setting.

In addition, in their last 14 days of life, this group had median direct inpatient hospital costs that were $5,106 less, and they were half as likely to be admitted.

"Our data suggest that early palliative medicine consultation results in decreased aggressive measures at the end of life [and] was associated with decreased direct inpatient costs for women who died from gynecologic malignancies," Dr. Nevadunsky noted. "Further research is needed to evaluate the quality of life in relation to [the aggressiveness of care] for patients and their families."

While it is unclear how many gynecologic oncologists are also board certified in palliative care, "I think more clinicians actually do palliative medicine as part of their everyday practice," Dr. Nevadunsky said. Also, palliative care is truly a multidisciplinary undertaking involving, for example, nurses, pastoral care personnel, social workers, and others.

"As far as the best metric for palliative medicine, I think it is quality of life. But how to define that is extremely complicated and still evolving," she added.

"I think it’s an experience where the patient is getting what they want most out of things, and sometimes that’s saying to the patient, ‘If we can’t cure you, what is the most important thing to you?’ " she replied. "Each patient is different, and that’s what makes (defining quality of life) so complicated."

The American Society of Clinical Oncology recommends consideration of palliative care early in the course of metastatic or symptomatic disease.

"This is a very vague recommendation: who, what, when, where, how? How will patients respond to this? Who’s going to pay for this? What’s the patient going to get out of this?" Dr. Nevadunsky commented.

She and her colleagues studied 100 consecutive patients who died from gynecologic cancer between 2006 and 2009 and received care at Montefiore in the year before death.

In the first study, they defined a timely palliative care consultation as one occurring more than 30 days before death.

"The ideal timing for palliative medicine consultation is unknown; however, 30 days was chosen as the minimal exposure time because the standard metrics utilized to compare aggressive measures at the end of life included a minimum of 30 days," Dr. Nevadunsky explained.

"Overall, I was surprised to find that 49 of the 100 women actually had a palliative medicine consultation at some time or another during their care," she said.

However, the median number of days between consultation and death was 16, and only 18% of patients had a timely consultation.

Late diagnosis did not explain this finding, as less than 10% of patients received their diagnosis in the month before they died.

"The scope of this study was not inclusive to determine why this [late palliative care consultation] was happening," Dr. Nevadunsky said. Data showed that although the two groups were demographically similar, the patients who received a timely consultation were more likely to be married.

The group with timely consultations were less likely to receive aggressive end-of-life care, based on measures of eight indicators of aggressive care (0 vs. 2, P = .025).

The difference between those patients who had timely consultation and those with untimely or no consultation was greatest for the indicators of a hospital stay lasting more than 14 days in the last month of life (22% vs. 40%) and death in the acute care setting (28% vs. 45%).

In the second study, the investigators found that 29% of patients had a timely palliative care consultation, defined in this case as one occurring 14 days or more before death.

Patients with a timely consultation had lower median direct hospital inpatient costs per day in the last 30 days of life ($613 vs. $702, P = .02). They also had lower median direct hospital inpatient costs in the last 14 days overall ($0 vs. $5,106, P = .007) and on a per-day basis ($0 vs. $676, P = .007).

"The patients who had the timely consultations actually weren’t admitted to the hospital as often," Dr. Nevadunsky noted. In fact, they were half as likely to be admitted in the last 14 days (35% vs. 71%, P = .001).

"Shortcomings [of the study] include small numbers and the retrospective collection of data. Also, our study did not account for outpatient costs, including those assumed by families, or for those costs incurred by loss of time out of work by families to care for the patient," acknowledged Dr. Nevadunsky, who disclosed no relevant conflicts of interest.

LOS ANGELES – A palliative care consultation within the last month of life improves a variety of end-of-life outcomes in patients dying from gynecologic cancers, based on a retrospective analysis.

Among the 100 patients studied, about one-fourth had a timely palliative care consultation, defined in one study as 14 days before death and in another study as 30 days before death, lead investigator Dr. Nicole S. Nevadunsky of Montefiore Medical Center, New York, reported at the annual meeting of the Society of Gynecologic Oncology.

Compared with their counterparts who had late or no consultations, patients who had timely consultations had lower scores for aggressive end-of-life events such as emergency department visits, chemotherapy, and death in an acute care setting.

In addition, in their last 14 days of life, this group had median direct inpatient hospital costs that were $5,106 less, and they were half as likely to be admitted.

"Our data suggest that early palliative medicine consultation results in decreased aggressive measures at the end of life [and] was associated with decreased direct inpatient costs for women who died from gynecologic malignancies," Dr. Nevadunsky noted. "Further research is needed to evaluate the quality of life in relation to [the aggressiveness of care] for patients and their families."

While it is unclear how many gynecologic oncologists are also board certified in palliative care, "I think more clinicians actually do palliative medicine as part of their everyday practice," Dr. Nevadunsky said. Also, palliative care is truly a multidisciplinary undertaking involving, for example, nurses, pastoral care personnel, social workers, and others.

"As far as the best metric for palliative medicine, I think it is quality of life. But how to define that is extremely complicated and still evolving," she added.

"I think it’s an experience where the patient is getting what they want most out of things, and sometimes that’s saying to the patient, ‘If we can’t cure you, what is the most important thing to you?’ " she replied. "Each patient is different, and that’s what makes (defining quality of life) so complicated."

The American Society of Clinical Oncology recommends consideration of palliative care early in the course of metastatic or symptomatic disease.

"This is a very vague recommendation: who, what, when, where, how? How will patients respond to this? Who’s going to pay for this? What’s the patient going to get out of this?" Dr. Nevadunsky commented.

She and her colleagues studied 100 consecutive patients who died from gynecologic cancer between 2006 and 2009 and received care at Montefiore in the year before death.

In the first study, they defined a timely palliative care consultation as one occurring more than 30 days before death.

"The ideal timing for palliative medicine consultation is unknown; however, 30 days was chosen as the minimal exposure time because the standard metrics utilized to compare aggressive measures at the end of life included a minimum of 30 days," Dr. Nevadunsky explained.

"Overall, I was surprised to find that 49 of the 100 women actually had a palliative medicine consultation at some time or another during their care," she said.

However, the median number of days between consultation and death was 16, and only 18% of patients had a timely consultation.

Late diagnosis did not explain this finding, as less than 10% of patients received their diagnosis in the month before they died.

"The scope of this study was not inclusive to determine why this [late palliative care consultation] was happening," Dr. Nevadunsky said. Data showed that although the two groups were demographically similar, the patients who received a timely consultation were more likely to be married.

The group with timely consultations were less likely to receive aggressive end-of-life care, based on measures of eight indicators of aggressive care (0 vs. 2, P = .025).

The difference between those patients who had timely consultation and those with untimely or no consultation was greatest for the indicators of a hospital stay lasting more than 14 days in the last month of life (22% vs. 40%) and death in the acute care setting (28% vs. 45%).

In the second study, the investigators found that 29% of patients had a timely palliative care consultation, defined in this case as one occurring 14 days or more before death.

Patients with a timely consultation had lower median direct hospital inpatient costs per day in the last 30 days of life ($613 vs. $702, P = .02). They also had lower median direct hospital inpatient costs in the last 14 days overall ($0 vs. $5,106, P = .007) and on a per-day basis ($0 vs. $676, P = .007).

"The patients who had the timely consultations actually weren’t admitted to the hospital as often," Dr. Nevadunsky noted. In fact, they were half as likely to be admitted in the last 14 days (35% vs. 71%, P = .001).

"Shortcomings [of the study] include small numbers and the retrospective collection of data. Also, our study did not account for outpatient costs, including those assumed by families, or for those costs incurred by loss of time out of work by families to care for the patient," acknowledged Dr. Nevadunsky, who disclosed no relevant conflicts of interest.

LOS ANGELES – Patients with resected advanced ovarian cancer and low-volume residual disease fare better in the long term with intraperitoneal chemotherapy instead of intravenous chemotherapy.

A team led by Dr. Devansu Tewari assessed outcomes in 876 women from two key Gynecologic Oncology Group trials: GOG 114 and GOG 172. Combined median follow-up in those trials approached 11 years.

Compared with their peers given intravenous chemotherapy, women given intraperitoneal (IP) chemotherapy had a 16% lower risk of progression or death and a 17% lower risk of death, according to results reported at the annual meeting of the Society of Gynecologic Oncology.

Benefit was evident regardless of the extent of residual disease. Also, each additional cycle of IP chemotherapy reduced the risk of death by 12%.

"A strength of this study is that it is a combined analysis of these two major IP trials that looked at long-term follow-up and showed survival outcomes that are quite significant. The defining difference between the two groups is that one received IP therapy and one did not, as it is very unlikely that IP therapy would have been administered in the recurrent setting," Dr. Tewari commented.

Although more than 7 years have elapsed since the National Cancer Institute recommended consideration of IP chemotherapy for advanced-stage low-volume ovarian cancer, uptake of this therapy has been limited given lingering questions about efficacy, safety, and issues such as the ideal regimen, noted Dr. Tewari, who is director of gynecologic oncology for the Southern California Permanente Medical Group in Orange County, California, and assistant professor of ob.gyn. at the University of California, Irvine.

"We have now updated the results of GOG 172 and GOG 114. But we also acknowledge that in the last 7 years, a lot has changed in the treatment of ovarian cancer in which these advantages may be further enhanced," he noted, for example, through use of bevacizumab (Avastin) and dose-dense therapy.

In particular, oncologists are awaiting results of the recently completed GOG 262 trial (assessing the role of bevacizumab and dose-dense paclitaxel) and the GOG 252 trial (assessing the role of IP carboplatin, bevacizumab, and dose-dense paclitaxel).

"We hope that the results of these studies, combined with the findings before, will bring in the foundation that we need to move forward in terms of laying the groundwork for treating women individually and tailoring their treatment for this cancer specifically for them," Dr. Tewari said.

One session attendee, noting the IP regimens used in the trials studied, asked, "Is it the dose-dense treatment or the IP that actually matters?"

"That’s a very good question. The whole issue with GOG 172 was essentially partial deployment of dose dense because patients [in the IP arm] received [an additional] day 8 treatment, so it has to be acknowledged," Dr. Tewari replied. "I think the answer is going to really come about when we see the findings of GOG 252."

Attendee Dr. Joan Walker of the University of Oklahoma, Oklahoma City, said, "I want to thank the presenters for emphasizing IP chemotherapy with cisplatin, and I think that it still needs to be emphasized."

She noted that the long-term survival gains being seen with IP chemotherapy are "just amazing. And we don’t know why that is, but obviously if GOG 104, 114, and 172 all show the same thing, it can’t necessarily be that the Taxol [paclitaxel] IP is the only contributing factor," she said.

"I think the future is bright for women and their survival, and it may be the bone marrow preservation of cisplatin that’s really causing the long-term effect because we know that patients get treated with multiple agents over and over again," Dr. Walker speculated.

The two trials that Dr. Tewari’s group studied – GOG 114 and GOG 172 – enrolled patients with resected stage III epithelial ovarian or peritoneal carcinoma who had residual disease measuring 1.0 cm or less.

The former trial compared IV carboplatin and paclitaxel with IP cisplatin; the latter trial compared IV paclitaxel with IP cisplatin and paclitaxel. About two-thirds of the women had macroscopic residual disease.

With a median follow-up of 10.7 years, relative to their counterparts given IV chemotherapy, women given IP chemotherapy had better progression-free survival (25 vs. 20 months; hazard ratio, 0.84; P = .03) and overall survival (62 vs. 51 months; hazard ratio, 0.83; P = .048).

The survival benefit of IP over IV chemotherapy was evident among both women with microscopic residual disease (5-year survival, 65% vs. 58%) and women with macroscopic residual disease (44% vs. 35%).

"There has been a lot of debate regarding the role of IP therapy in microscopic and macroscopic residual disease, and we saw an advantage in this cohort in both specific groups," commented Dr. Tewari.

Overall, half of patients given IP chemotherapy completed all six cycles of that chemotherapy. The risk of death fell with each additional cycle of IP chemotherapy (hazard ratio, 0.88, P less than .001).

Dr. Tewari disclosed no conflicts of interest related to the research.

LOS ANGELES – Patients with resected advanced ovarian cancer and low-volume residual disease fare better in the long term with intraperitoneal chemotherapy instead of intravenous chemotherapy.

A team led by Dr. Devansu Tewari assessed outcomes in 876 women from two key Gynecologic Oncology Group trials: GOG 114 and GOG 172. Combined median follow-up in those trials approached 11 years.

Compared with their peers given intravenous chemotherapy, women given intraperitoneal (IP) chemotherapy had a 16% lower risk of progression or death and a 17% lower risk of death, according to results reported at the annual meeting of the Society of Gynecologic Oncology.

Benefit was evident regardless of the extent of residual disease. Also, each additional cycle of IP chemotherapy reduced the risk of death by 12%.

"A strength of this study is that it is a combined analysis of these two major IP trials that looked at long-term follow-up and showed survival outcomes that are quite significant. The defining difference between the two groups is that one received IP therapy and one did not, as it is very unlikely that IP therapy would have been administered in the recurrent setting," Dr. Tewari commented.

Although more than 7 years have elapsed since the National Cancer Institute recommended consideration of IP chemotherapy for advanced-stage low-volume ovarian cancer, uptake of this therapy has been limited given lingering questions about efficacy, safety, and issues such as the ideal regimen, noted Dr. Tewari, who is director of gynecologic oncology for the Southern California Permanente Medical Group in Orange County, California, and assistant professor of ob.gyn. at the University of California, Irvine.

"We have now updated the results of GOG 172 and GOG 114. But we also acknowledge that in the last 7 years, a lot has changed in the treatment of ovarian cancer in which these advantages may be further enhanced," he noted, for example, through use of bevacizumab (Avastin) and dose-dense therapy.

In particular, oncologists are awaiting results of the recently completed GOG 262 trial (assessing the role of bevacizumab and dose-dense paclitaxel) and the GOG 252 trial (assessing the role of IP carboplatin, bevacizumab, and dose-dense paclitaxel).

"We hope that the results of these studies, combined with the findings before, will bring in the foundation that we need to move forward in terms of laying the groundwork for treating women individually and tailoring their treatment for this cancer specifically for them," Dr. Tewari said.

One session attendee, noting the IP regimens used in the trials studied, asked, "Is it the dose-dense treatment or the IP that actually matters?"

"That’s a very good question. The whole issue with GOG 172 was essentially partial deployment of dose dense because patients [in the IP arm] received [an additional] day 8 treatment, so it has to be acknowledged," Dr. Tewari replied. "I think the answer is going to really come about when we see the findings of GOG 252."

Attendee Dr. Joan Walker of the University of Oklahoma, Oklahoma City, said, "I want to thank the presenters for emphasizing IP chemotherapy with cisplatin, and I think that it still needs to be emphasized."

She noted that the long-term survival gains being seen with IP chemotherapy are "just amazing. And we don’t know why that is, but obviously if GOG 104, 114, and 172 all show the same thing, it can’t necessarily be that the Taxol [paclitaxel] IP is the only contributing factor," she said.

"I think the future is bright for women and their survival, and it may be the bone marrow preservation of cisplatin that’s really causing the long-term effect because we know that patients get treated with multiple agents over and over again," Dr. Walker speculated.

The two trials that Dr. Tewari’s group studied – GOG 114 and GOG 172 – enrolled patients with resected stage III epithelial ovarian or peritoneal carcinoma who had residual disease measuring 1.0 cm or less.

The former trial compared IV carboplatin and paclitaxel with IP cisplatin; the latter trial compared IV paclitaxel with IP cisplatin and paclitaxel. About two-thirds of the women had macroscopic residual disease.

With a median follow-up of 10.7 years, relative to their counterparts given IV chemotherapy, women given IP chemotherapy had better progression-free survival (25 vs. 20 months; hazard ratio, 0.84; P = .03) and overall survival (62 vs. 51 months; hazard ratio, 0.83; P = .048).

The survival benefit of IP over IV chemotherapy was evident among both women with microscopic residual disease (5-year survival, 65% vs. 58%) and women with macroscopic residual disease (44% vs. 35%).

"There has been a lot of debate regarding the role of IP therapy in microscopic and macroscopic residual disease, and we saw an advantage in this cohort in both specific groups," commented Dr. Tewari.

Overall, half of patients given IP chemotherapy completed all six cycles of that chemotherapy. The risk of death fell with each additional cycle of IP chemotherapy (hazard ratio, 0.88, P less than .001).

Dr. Tewari disclosed no conflicts of interest related to the research.

LOS ANGELES – Patients with resected advanced ovarian cancer and low-volume residual disease fare better in the long term with intraperitoneal chemotherapy instead of intravenous chemotherapy.

A team led by Dr. Devansu Tewari assessed outcomes in 876 women from two key Gynecologic Oncology Group trials: GOG 114 and GOG 172. Combined median follow-up in those trials approached 11 years.

Compared with their peers given intravenous chemotherapy, women given intraperitoneal (IP) chemotherapy had a 16% lower risk of progression or death and a 17% lower risk of death, according to results reported at the annual meeting of the Society of Gynecologic Oncology.

Benefit was evident regardless of the extent of residual disease. Also, each additional cycle of IP chemotherapy reduced the risk of death by 12%.

"A strength of this study is that it is a combined analysis of these two major IP trials that looked at long-term follow-up and showed survival outcomes that are quite significant. The defining difference between the two groups is that one received IP therapy and one did not, as it is very unlikely that IP therapy would have been administered in the recurrent setting," Dr. Tewari commented.

Although more than 7 years have elapsed since the National Cancer Institute recommended consideration of IP chemotherapy for advanced-stage low-volume ovarian cancer, uptake of this therapy has been limited given lingering questions about efficacy, safety, and issues such as the ideal regimen, noted Dr. Tewari, who is director of gynecologic oncology for the Southern California Permanente Medical Group in Orange County, California, and assistant professor of ob.gyn. at the University of California, Irvine.

"We have now updated the results of GOG 172 and GOG 114. But we also acknowledge that in the last 7 years, a lot has changed in the treatment of ovarian cancer in which these advantages may be further enhanced," he noted, for example, through use of bevacizumab (Avastin) and dose-dense therapy.

In particular, oncologists are awaiting results of the recently completed GOG 262 trial (assessing the role of bevacizumab and dose-dense paclitaxel) and the GOG 252 trial (assessing the role of IP carboplatin, bevacizumab, and dose-dense paclitaxel).

"We hope that the results of these studies, combined with the findings before, will bring in the foundation that we need to move forward in terms of laying the groundwork for treating women individually and tailoring their treatment for this cancer specifically for them," Dr. Tewari said.

One session attendee, noting the IP regimens used in the trials studied, asked, "Is it the dose-dense treatment or the IP that actually matters?"

"That’s a very good question. The whole issue with GOG 172 was essentially partial deployment of dose dense because patients [in the IP arm] received [an additional] day 8 treatment, so it has to be acknowledged," Dr. Tewari replied. "I think the answer is going to really come about when we see the findings of GOG 252."

Attendee Dr. Joan Walker of the University of Oklahoma, Oklahoma City, said, "I want to thank the presenters for emphasizing IP chemotherapy with cisplatin, and I think that it still needs to be emphasized."

She noted that the long-term survival gains being seen with IP chemotherapy are "just amazing. And we don’t know why that is, but obviously if GOG 104, 114, and 172 all show the same thing, it can’t necessarily be that the Taxol [paclitaxel] IP is the only contributing factor," she said.

"I think the future is bright for women and their survival, and it may be the bone marrow preservation of cisplatin that’s really causing the long-term effect because we know that patients get treated with multiple agents over and over again," Dr. Walker speculated.

The two trials that Dr. Tewari’s group studied – GOG 114 and GOG 172 – enrolled patients with resected stage III epithelial ovarian or peritoneal carcinoma who had residual disease measuring 1.0 cm or less.

The former trial compared IV carboplatin and paclitaxel with IP cisplatin; the latter trial compared IV paclitaxel with IP cisplatin and paclitaxel. About two-thirds of the women had macroscopic residual disease.

With a median follow-up of 10.7 years, relative to their counterparts given IV chemotherapy, women given IP chemotherapy had better progression-free survival (25 vs. 20 months; hazard ratio, 0.84; P = .03) and overall survival (62 vs. 51 months; hazard ratio, 0.83; P = .048).

The survival benefit of IP over IV chemotherapy was evident among both women with microscopic residual disease (5-year survival, 65% vs. 58%) and women with macroscopic residual disease (44% vs. 35%).

"There has been a lot of debate regarding the role of IP therapy in microscopic and macroscopic residual disease, and we saw an advantage in this cohort in both specific groups," commented Dr. Tewari.

Overall, half of patients given IP chemotherapy completed all six cycles of that chemotherapy. The risk of death fell with each additional cycle of IP chemotherapy (hazard ratio, 0.88, P less than .001).

Dr. Tewari disclosed no conflicts of interest related to the research.

LOS ANGELES – An investigational type of photodynamic therapy appears promising for treating early cervical intraepithelial neoplasia, finds a phase 2b trial reported at the annual meeting of the Society of Gynecologic Oncology.

A team led by Dr. Mark H. Einstein undertook a dose-finding study of hexaminolevulinate (HAL) gel coupled with photodynamic therapy in 262 patients with grade 1 or 2 cervical intraepithelial neoplasia (CIN1, CIN2).

Among patients with CIN2, nearly all of those treated with the highest dose of HAL and photodynamic therapy had a response at 3 months, compared with roughly half of their counterparts treated with placebo.

The therapy was associated with a higher rate of local reactions, but none had to discontinue treatment.

"The 5% HAL photodynamic therapy was effective in treating patients with CIN2. There seems to be a signal of efficacy in patients who have HPV 16 and 18 as well," which may help inform the design of future phase III trials, commented Dr. Einstein, who is director of clinical research for women’s health and gynecologic oncology at the Montefiore Medical Center, New York.

"This device was very easy to use and was very well tolerated by this patient population, with essentially self-limiting reactions," he added.

Dr. Einstein noted that new approaches are needed for dealing with CIN, given that it commonly occurs in young women of childbearing age, and that some current treatments aimed at obliterating these lesions make subsequent colposcopies difficult and increase the risk of preterm birth.

For photodynamic therapy, a photosensitizing agent is applied to the cervix and accumulates in the premalignant cells, he explained. When the area is illuminated at a specific energy, reactive oxygen species are generated, killing the cells.

"The hypothesized mechanism of photodynamic therapy in cervical lesions is that once the HAL is applied and light is emitted for about 5 hours, this induces some local apoptosis, and that will release a lot of HPV antigens from these dying cells. These are then presented to naive T cells in the locoregional lymph nodes, which then stimulates even more of a cell-mediated immune response and inflammatory response that then further increases apoptosis of local cells," Dr. Einstein elaborated. "And then, hypothetically, in other areas of the cervical and vaginal tract, you are going to get a big cell-mediated immune response."

Women in the trial, which was sponsored by Photocure, had pathologically confirmed, previously untreated CIN1 or CIN2.

They were randomized evenly to four groups treated with HAL 5%, 1%, or 0.2%, or placebo, and photodynamic therapy.

A gynecologist placed the integrated drug and device (Cevira, manufactured by Photocure) in the outpatient setting. Five hours after placement, the device self-activated and delivered photodynamic therapy for roughly 5 hours. The patients removed the device themselves thereafter.

The patients had a median age of 27 years, and 46% had CIN2. About half of those tested were found to have a high-risk type of HPV.

Among patients with CIN2, 5% HAL photodynamic therapy yielded a higher 3-month rate of response (based on histology, cytology, and HPV status) than did placebo, both overall (95% vs. 56%; P = .01) and in the subset who were positive for any type of HPV (92% vs. 50%; P = .02).

"Clearly, the placebo effect was very large in this group, and this is expected in young women who have CIN1 and CIN2. That being said, this was significant efficacy when compared to placebo," said Dr. Einstein, who disclosed that his institution has received funding from Photocure for educational speaking activities and research.

Additionally, among the patients with CIN2 who had HPV 16 or 18 infection, those treated with 5% HAL photodynamic therapy were more likely than were those treated with placebo to have clearance of the virus (83% vs. 0%; P = .02).

There was no significant benefit among women with CIN1 or among women treated with the lower doses of HAL.

Relative to their counterparts treated with placebo, patients treated with 5% HAL photodynamic therapy had a higher rate of self-limiting local reactions (54% vs. 32%); the most common were vaginal discharge and local discomfort. None of the patients discontinued treatment because of these reactions.

A total of five pregnancies were reported among study patients in the 3 months after treatment. All of these women delivered normal full-term infants.

LOS ANGELES – An investigational type of photodynamic therapy appears promising for treating early cervical intraepithelial neoplasia, finds a phase 2b trial reported at the annual meeting of the Society of Gynecologic Oncology.

A team led by Dr. Mark H. Einstein undertook a dose-finding study of hexaminolevulinate (HAL) gel coupled with photodynamic therapy in 262 patients with grade 1 or 2 cervical intraepithelial neoplasia (CIN1, CIN2).

Among patients with CIN2, nearly all of those treated with the highest dose of HAL and photodynamic therapy had a response at 3 months, compared with roughly half of their counterparts treated with placebo.

The therapy was associated with a higher rate of local reactions, but none had to discontinue treatment.

"The 5% HAL photodynamic therapy was effective in treating patients with CIN2. There seems to be a signal of efficacy in patients who have HPV 16 and 18 as well," which may help inform the design of future phase III trials, commented Dr. Einstein, who is director of clinical research for women’s health and gynecologic oncology at the Montefiore Medical Center, New York.

"This device was very easy to use and was very well tolerated by this patient population, with essentially self-limiting reactions," he added.

Dr. Einstein noted that new approaches are needed for dealing with CIN, given that it commonly occurs in young women of childbearing age, and that some current treatments aimed at obliterating these lesions make subsequent colposcopies difficult and increase the risk of preterm birth.

For photodynamic therapy, a photosensitizing agent is applied to the cervix and accumulates in the premalignant cells, he explained. When the area is illuminated at a specific energy, reactive oxygen species are generated, killing the cells.

"The hypothesized mechanism of photodynamic therapy in cervical lesions is that once the HAL is applied and light is emitted for about 5 hours, this induces some local apoptosis, and that will release a lot of HPV antigens from these dying cells. These are then presented to naive T cells in the locoregional lymph nodes, which then stimulates even more of a cell-mediated immune response and inflammatory response that then further increases apoptosis of local cells," Dr. Einstein elaborated. "And then, hypothetically, in other areas of the cervical and vaginal tract, you are going to get a big cell-mediated immune response."

Women in the trial, which was sponsored by Photocure, had pathologically confirmed, previously untreated CIN1 or CIN2.

They were randomized evenly to four groups treated with HAL 5%, 1%, or 0.2%, or placebo, and photodynamic therapy.

A gynecologist placed the integrated drug and device (Cevira, manufactured by Photocure) in the outpatient setting. Five hours after placement, the device self-activated and delivered photodynamic therapy for roughly 5 hours. The patients removed the device themselves thereafter.

The patients had a median age of 27 years, and 46% had CIN2. About half of those tested were found to have a high-risk type of HPV.

Among patients with CIN2, 5% HAL photodynamic therapy yielded a higher 3-month rate of response (based on histology, cytology, and HPV status) than did placebo, both overall (95% vs. 56%; P = .01) and in the subset who were positive for any type of HPV (92% vs. 50%; P = .02).

"Clearly, the placebo effect was very large in this group, and this is expected in young women who have CIN1 and CIN2. That being said, this was significant efficacy when compared to placebo," said Dr. Einstein, who disclosed that his institution has received funding from Photocure for educational speaking activities and research.

Additionally, among the patients with CIN2 who had HPV 16 or 18 infection, those treated with 5% HAL photodynamic therapy were more likely than were those treated with placebo to have clearance of the virus (83% vs. 0%; P = .02).

There was no significant benefit among women with CIN1 or among women treated with the lower doses of HAL.

Relative to their counterparts treated with placebo, patients treated with 5% HAL photodynamic therapy had a higher rate of self-limiting local reactions (54% vs. 32%); the most common were vaginal discharge and local discomfort. None of the patients discontinued treatment because of these reactions.

A total of five pregnancies were reported among study patients in the 3 months after treatment. All of these women delivered normal full-term infants.

LOS ANGELES – An investigational type of photodynamic therapy appears promising for treating early cervical intraepithelial neoplasia, finds a phase 2b trial reported at the annual meeting of the Society of Gynecologic Oncology.

A team led by Dr. Mark H. Einstein undertook a dose-finding study of hexaminolevulinate (HAL) gel coupled with photodynamic therapy in 262 patients with grade 1 or 2 cervical intraepithelial neoplasia (CIN1, CIN2).

Among patients with CIN2, nearly all of those treated with the highest dose of HAL and photodynamic therapy had a response at 3 months, compared with roughly half of their counterparts treated with placebo.

The therapy was associated with a higher rate of local reactions, but none had to discontinue treatment.

"The 5% HAL photodynamic therapy was effective in treating patients with CIN2. There seems to be a signal of efficacy in patients who have HPV 16 and 18 as well," which may help inform the design of future phase III trials, commented Dr. Einstein, who is director of clinical research for women’s health and gynecologic oncology at the Montefiore Medical Center, New York.

"This device was very easy to use and was very well tolerated by this patient population, with essentially self-limiting reactions," he added.

Dr. Einstein noted that new approaches are needed for dealing with CIN, given that it commonly occurs in young women of childbearing age, and that some current treatments aimed at obliterating these lesions make subsequent colposcopies difficult and increase the risk of preterm birth.

For photodynamic therapy, a photosensitizing agent is applied to the cervix and accumulates in the premalignant cells, he explained. When the area is illuminated at a specific energy, reactive oxygen species are generated, killing the cells.

"The hypothesized mechanism of photodynamic therapy in cervical lesions is that once the HAL is applied and light is emitted for about 5 hours, this induces some local apoptosis, and that will release a lot of HPV antigens from these dying cells. These are then presented to naive T cells in the locoregional lymph nodes, which then stimulates even more of a cell-mediated immune response and inflammatory response that then further increases apoptosis of local cells," Dr. Einstein elaborated. "And then, hypothetically, in other areas of the cervical and vaginal tract, you are going to get a big cell-mediated immune response."

Women in the trial, which was sponsored by Photocure, had pathologically confirmed, previously untreated CIN1 or CIN2.

They were randomized evenly to four groups treated with HAL 5%, 1%, or 0.2%, or placebo, and photodynamic therapy.

A gynecologist placed the integrated drug and device (Cevira, manufactured by Photocure) in the outpatient setting. Five hours after placement, the device self-activated and delivered photodynamic therapy for roughly 5 hours. The patients removed the device themselves thereafter.

The patients had a median age of 27 years, and 46% had CIN2. About half of those tested were found to have a high-risk type of HPV.

Among patients with CIN2, 5% HAL photodynamic therapy yielded a higher 3-month rate of response (based on histology, cytology, and HPV status) than did placebo, both overall (95% vs. 56%; P = .01) and in the subset who were positive for any type of HPV (92% vs. 50%; P = .02).

"Clearly, the placebo effect was very large in this group, and this is expected in young women who have CIN1 and CIN2. That being said, this was significant efficacy when compared to placebo," said Dr. Einstein, who disclosed that his institution has received funding from Photocure for educational speaking activities and research.

Additionally, among the patients with CIN2 who had HPV 16 or 18 infection, those treated with 5% HAL photodynamic therapy were more likely than were those treated with placebo to have clearance of the virus (83% vs. 0%; P = .02).

There was no significant benefit among women with CIN1 or among women treated with the lower doses of HAL.

Relative to their counterparts treated with placebo, patients treated with 5% HAL photodynamic therapy had a higher rate of self-limiting local reactions (54% vs. 32%); the most common were vaginal discharge and local discomfort. None of the patients discontinued treatment because of these reactions.

A total of five pregnancies were reported among study patients in the 3 months after treatment. All of these women delivered normal full-term infants.