Patrice Wendling

DETROIT – Patients with proximal pancreatic cancer should be reimaged before surgery if more than 3 weeks have passed since their most recent cross-sectional imaging study.

The recommendation is based on a retrospective analysis involving 487 patients that identified a significant, roughly twofold increase in unanticipated metastasis encountered at surgery if the interval between imaging and operation was more than 3 weeks.

Among 293 patients with proximal pancreatic cancer and precise imaging data, the frequency of occult metastasis was 12% when the imaging-to-operation interval (IOI) was 20 days or fewer, compared with 20% at an IOI of 21-27 days, 25% at 28-34 days, 35% at 35-41 days, 29% at 42-48 days, and 30% at 49-86 days.

There were no significant differences between patients in the various 1-week intervals in terms of sex, age, tumor size, percentage of poor grade tumors, lymph node positivity, vascular invasion, or perineural invasion, Dr. Jeffrey Glant said at the annual meeting of the Central Surgical Association.

In linear regression analysis, the relationship between frequency of unanticipated metastases and weekly IOI was statistically significant (P = .006) and had a correlation coefficient R² value of 0.99.

A similar relationship was not observed among 36 patients with distal pancreatic cancer and precise imaging data. The frequency of unanticipated metastasis among these patients was 0% at 0-6 days, 33% at 7-13 days, 38% at 14-20 days, 0% at 21-27 days, 0% at 28-34 days, 20% at 35-41 days, 33% at 42-48 days, and 25% at 49-87 days, said Dr. Glant of the department of surgery at Indiana University in Indianapolis.

Cross-sectional imaging is the primary preoperative staging modality in pancreatic cancer, which is the fourth most common cause of cancer death in the United States. The rate of encountering metastasis at operation is typically 10%-30%, he noted. The reasons for the delay in surgery could not be ascertained from the retrospective data.

Dr. Glant reported on 487 patients undergoing planned pancreatic resection for pancreatic ductal adenocarcinoma between January 2004 and December 2009 at the university’s high-volume pancreatic surgery center. Patients were excluded if they had received neoadjuvant therapy, prior pancreatic resection, or exploratory surgery for suspected metastatic disease.

Precise imaging data were available for 329 patients. Cross-sectional imaging was defined as dual-phase, contrast-enhanced CT, or MRI if CT was contraindicated.

Of the 285 patients (59%) who had their most recent imaging study performed at the university, 202 underwent resection and 83 were not resected. Metastasis was discovered at time of operation in 39 patients, he said.

Of the 202 (41%) patients whose most recent imaging study was performed at an outside institution, 139 underwent resection and 63 were not resected. Among the 202 patients, 35 had metastasis discovered at time of operation.

The overall frequency of unanticipated metastasis was statistically similar between patients who were imaged at the university and those who were imaged at an outside institution (14% vs. 17%), Dr. Glant said. This was true whether the patients had proximal (14% vs. 17%) or distal (15% vs. 25%) disease. Patients imaged at an outside venue, however, had significantly larger tumors than did those imaged at the university (3.4 cm vs. 3.1 cm; P = .05) and a higher rate of vascular invasion (73% vs. 61%; P = .03).

"It is appropriate and advisable to obtain more current imaging if the delay [in surgery] will exceed 3 weeks," Dr. Glant said.

Invited discussant Dr. Carl R. Schmidt of the Ohio State University, Columbus, said the size of the series, the robustness of the analysis, and the time period evaluated left no doubt in his mind about the use of modern imaging and the validity of the main finding. He asked what proportion of patients at the university undergoes staging laparoscopy, and what the distribution of metastasis was.

Coauthor Dr. Joshua A. Waters, also of Indiana University, replied that with just 16 patients undergoing staging laparoscopy in the entire series, the procedure is not routinely performed at the university in the setting of proximal pancreatic cancer. He also cited a recent study reporting a decrease in yield of staging laparoscopy from 1995 to 2005, particularly in those with proximal pancreatic cancers (J. Am. Coll. Surg. 2008;206:445-50). Regarding the distribution of the metastases, 80% were on the liver and 20% were at another location, primarily peritoneal implants, he said.

When asked whether any patients had undergone endobiliary stenting prior to resection, Dr. Waters said that a significant proportion of patients were stented prior to arrival at the hospital, and that stenting is known to affect the sensitivity of staging in terms of cross-sectional imaging.

Finally, audience member Dr. Fabrizio Michelassi, professor of surgery at Cornell University in New York City, asked how surgeons should use the data. Should they rush to operate on all patients within 2 weeks to avoid the discovery of more occult metastasis, or wait until 6 weeks for the metastases to declare themselves, since the incidence of occult metastasis appeared to stabilize by then at about 35%?

"One could suggest that if you really wait for 6 weeks, you could probably spare the morbidity of a large operation in 25% of patients who really don’t benefit from it," Dr. Michelassi said.

Dr. Waters said that for patients who are rescanned within 2-3 weeks of cross-sectional imaging and are subsequently found to have a metastatic focus or some evidence of progression, this may be evidence of a more aggressive biology. "This may be a subgroup of patients [whom you] would want to capture by rescanning and potentially not expose to a less than therapeutic laparotomy."

The authors reported no conflicts of interest.

DETROIT – Patients with proximal pancreatic cancer should be reimaged before surgery if more than 3 weeks have passed since their most recent cross-sectional imaging study.

The recommendation is based on a retrospective analysis involving 487 patients that identified a significant, roughly twofold increase in unanticipated metastasis encountered at surgery if the interval between imaging and operation was more than 3 weeks.

Among 293 patients with proximal pancreatic cancer and precise imaging data, the frequency of occult metastasis was 12% when the imaging-to-operation interval (IOI) was 20 days or fewer, compared with 20% at an IOI of 21-27 days, 25% at 28-34 days, 35% at 35-41 days, 29% at 42-48 days, and 30% at 49-86 days.

There were no significant differences between patients in the various 1-week intervals in terms of sex, age, tumor size, percentage of poor grade tumors, lymph node positivity, vascular invasion, or perineural invasion, Dr. Jeffrey Glant said at the annual meeting of the Central Surgical Association.

In linear regression analysis, the relationship between frequency of unanticipated metastases and weekly IOI was statistically significant (P = .006) and had a correlation coefficient R² value of 0.99.

A similar relationship was not observed among 36 patients with distal pancreatic cancer and precise imaging data. The frequency of unanticipated metastasis among these patients was 0% at 0-6 days, 33% at 7-13 days, 38% at 14-20 days, 0% at 21-27 days, 0% at 28-34 days, 20% at 35-41 days, 33% at 42-48 days, and 25% at 49-87 days, said Dr. Glant of the department of surgery at Indiana University in Indianapolis.

Cross-sectional imaging is the primary preoperative staging modality in pancreatic cancer, which is the fourth most common cause of cancer death in the United States. The rate of encountering metastasis at operation is typically 10%-30%, he noted. The reasons for the delay in surgery could not be ascertained from the retrospective data.

Dr. Glant reported on 487 patients undergoing planned pancreatic resection for pancreatic ductal adenocarcinoma between January 2004 and December 2009 at the university’s high-volume pancreatic surgery center. Patients were excluded if they had received neoadjuvant therapy, prior pancreatic resection, or exploratory surgery for suspected metastatic disease.

Precise imaging data were available for 329 patients. Cross-sectional imaging was defined as dual-phase, contrast-enhanced CT, or MRI if CT was contraindicated.

Of the 285 patients (59%) who had their most recent imaging study performed at the university, 202 underwent resection and 83 were not resected. Metastasis was discovered at time of operation in 39 patients, he said.

Of the 202 (41%) patients whose most recent imaging study was performed at an outside institution, 139 underwent resection and 63 were not resected. Among the 202 patients, 35 had metastasis discovered at time of operation.

The overall frequency of unanticipated metastasis was statistically similar between patients who were imaged at the university and those who were imaged at an outside institution (14% vs. 17%), Dr. Glant said. This was true whether the patients had proximal (14% vs. 17%) or distal (15% vs. 25%) disease. Patients imaged at an outside venue, however, had significantly larger tumors than did those imaged at the university (3.4 cm vs. 3.1 cm; P = .05) and a higher rate of vascular invasion (73% vs. 61%; P = .03).

"It is appropriate and advisable to obtain more current imaging if the delay [in surgery] will exceed 3 weeks," Dr. Glant said.

Invited discussant Dr. Carl R. Schmidt of the Ohio State University, Columbus, said the size of the series, the robustness of the analysis, and the time period evaluated left no doubt in his mind about the use of modern imaging and the validity of the main finding. He asked what proportion of patients at the university undergoes staging laparoscopy, and what the distribution of metastasis was.

Coauthor Dr. Joshua A. Waters, also of Indiana University, replied that with just 16 patients undergoing staging laparoscopy in the entire series, the procedure is not routinely performed at the university in the setting of proximal pancreatic cancer. He also cited a recent study reporting a decrease in yield of staging laparoscopy from 1995 to 2005, particularly in those with proximal pancreatic cancers (J. Am. Coll. Surg. 2008;206:445-50). Regarding the distribution of the metastases, 80% were on the liver and 20% were at another location, primarily peritoneal implants, he said.

When asked whether any patients had undergone endobiliary stenting prior to resection, Dr. Waters said that a significant proportion of patients were stented prior to arrival at the hospital, and that stenting is known to affect the sensitivity of staging in terms of cross-sectional imaging.

Finally, audience member Dr. Fabrizio Michelassi, professor of surgery at Cornell University in New York City, asked how surgeons should use the data. Should they rush to operate on all patients within 2 weeks to avoid the discovery of more occult metastasis, or wait until 6 weeks for the metastases to declare themselves, since the incidence of occult metastasis appeared to stabilize by then at about 35%?

"One could suggest that if you really wait for 6 weeks, you could probably spare the morbidity of a large operation in 25% of patients who really don’t benefit from it," Dr. Michelassi said.

Dr. Waters said that for patients who are rescanned within 2-3 weeks of cross-sectional imaging and are subsequently found to have a metastatic focus or some evidence of progression, this may be evidence of a more aggressive biology. "This may be a subgroup of patients [whom you] would want to capture by rescanning and potentially not expose to a less than therapeutic laparotomy."

The authors reported no conflicts of interest.

DETROIT – Patients with proximal pancreatic cancer should be reimaged before surgery if more than 3 weeks have passed since their most recent cross-sectional imaging study.

The recommendation is based on a retrospective analysis involving 487 patients that identified a significant, roughly twofold increase in unanticipated metastasis encountered at surgery if the interval between imaging and operation was more than 3 weeks.

Among 293 patients with proximal pancreatic cancer and precise imaging data, the frequency of occult metastasis was 12% when the imaging-to-operation interval (IOI) was 20 days or fewer, compared with 20% at an IOI of 21-27 days, 25% at 28-34 days, 35% at 35-41 days, 29% at 42-48 days, and 30% at 49-86 days.

There were no significant differences between patients in the various 1-week intervals in terms of sex, age, tumor size, percentage of poor grade tumors, lymph node positivity, vascular invasion, or perineural invasion, Dr. Jeffrey Glant said at the annual meeting of the Central Surgical Association.

In linear regression analysis, the relationship between frequency of unanticipated metastases and weekly IOI was statistically significant (P = .006) and had a correlation coefficient R² value of 0.99.

A similar relationship was not observed among 36 patients with distal pancreatic cancer and precise imaging data. The frequency of unanticipated metastasis among these patients was 0% at 0-6 days, 33% at 7-13 days, 38% at 14-20 days, 0% at 21-27 days, 0% at 28-34 days, 20% at 35-41 days, 33% at 42-48 days, and 25% at 49-87 days, said Dr. Glant of the department of surgery at Indiana University in Indianapolis.

Cross-sectional imaging is the primary preoperative staging modality in pancreatic cancer, which is the fourth most common cause of cancer death in the United States. The rate of encountering metastasis at operation is typically 10%-30%, he noted. The reasons for the delay in surgery could not be ascertained from the retrospective data.

Dr. Glant reported on 487 patients undergoing planned pancreatic resection for pancreatic ductal adenocarcinoma between January 2004 and December 2009 at the university’s high-volume pancreatic surgery center. Patients were excluded if they had received neoadjuvant therapy, prior pancreatic resection, or exploratory surgery for suspected metastatic disease.

Precise imaging data were available for 329 patients. Cross-sectional imaging was defined as dual-phase, contrast-enhanced CT, or MRI if CT was contraindicated.

Of the 285 patients (59%) who had their most recent imaging study performed at the university, 202 underwent resection and 83 were not resected. Metastasis was discovered at time of operation in 39 patients, he said.

Of the 202 (41%) patients whose most recent imaging study was performed at an outside institution, 139 underwent resection and 63 were not resected. Among the 202 patients, 35 had metastasis discovered at time of operation.

The overall frequency of unanticipated metastasis was statistically similar between patients who were imaged at the university and those who were imaged at an outside institution (14% vs. 17%), Dr. Glant said. This was true whether the patients had proximal (14% vs. 17%) or distal (15% vs. 25%) disease. Patients imaged at an outside venue, however, had significantly larger tumors than did those imaged at the university (3.4 cm vs. 3.1 cm; P = .05) and a higher rate of vascular invasion (73% vs. 61%; P = .03).

"It is appropriate and advisable to obtain more current imaging if the delay [in surgery] will exceed 3 weeks," Dr. Glant said.

Invited discussant Dr. Carl R. Schmidt of the Ohio State University, Columbus, said the size of the series, the robustness of the analysis, and the time period evaluated left no doubt in his mind about the use of modern imaging and the validity of the main finding. He asked what proportion of patients at the university undergoes staging laparoscopy, and what the distribution of metastasis was.

Coauthor Dr. Joshua A. Waters, also of Indiana University, replied that with just 16 patients undergoing staging laparoscopy in the entire series, the procedure is not routinely performed at the university in the setting of proximal pancreatic cancer. He also cited a recent study reporting a decrease in yield of staging laparoscopy from 1995 to 2005, particularly in those with proximal pancreatic cancers (J. Am. Coll. Surg. 2008;206:445-50). Regarding the distribution of the metastases, 80% were on the liver and 20% were at another location, primarily peritoneal implants, he said.

When asked whether any patients had undergone endobiliary stenting prior to resection, Dr. Waters said that a significant proportion of patients were stented prior to arrival at the hospital, and that stenting is known to affect the sensitivity of staging in terms of cross-sectional imaging.

Finally, audience member Dr. Fabrizio Michelassi, professor of surgery at Cornell University in New York City, asked how surgeons should use the data. Should they rush to operate on all patients within 2 weeks to avoid the discovery of more occult metastasis, or wait until 6 weeks for the metastases to declare themselves, since the incidence of occult metastasis appeared to stabilize by then at about 35%?

"One could suggest that if you really wait for 6 weeks, you could probably spare the morbidity of a large operation in 25% of patients who really don’t benefit from it," Dr. Michelassi said.

Dr. Waters said that for patients who are rescanned within 2-3 weeks of cross-sectional imaging and are subsequently found to have a metastatic focus or some evidence of progression, this may be evidence of a more aggressive biology. "This may be a subgroup of patients [whom you] would want to capture by rescanning and potentially not expose to a less than therapeutic laparotomy."

The authors reported no conflicts of interest.

DETROIT – Patients with proximal pancreatic cancer should be reimaged before surgery if more than 3 weeks have passed since their most recent cross-sectional imaging study.

The recommendation is based on a retrospective analysis involving 487 patients that identified a significant, roughly twofold increase in unanticipated metastasis encountered at surgery if the interval between imaging and operation was more than 3 weeks.

Among 293 patients with proximal pancreatic cancer and precise imaging data, the frequency of occult metastasis was 12% when the imaging-to-operation interval (IOI) was 20 days or fewer, compared with 20% at an IOI of 21-27 days, 25% at 28-34 days, 35% at 35-41 days, 29% at 42-48 days, and 30% at 49-86 days.

There were no significant differences between patients in the various 1-week intervals in terms of sex, age, tumor size, percentage of poor grade tumors, lymph node positivity, vascular invasion, or perineural invasion, Dr. Jeffrey Glant said at the annual meeting of the Central Surgical Association.

In linear regression analysis, the relationship between frequency of unanticipated metastases and weekly IOI was statistically significant (P = .006) and had a correlation coefficient R² value of 0.99.

A similar relationship was not observed among 36 patients with distal pancreatic cancer and precise imaging data. The frequency of unanticipated metastasis among these patients was 0% at 0-6 days, 33% at 7-13 days, 38% at 14-20 days, 0% at 21-27 days, 0% at 28-34 days, 20% at 35-41 days, 33% at 42-48 days, and 25% at 49-87 days, said Dr. Glant of the department of surgery at Indiana University in Indianapolis.

Cross-sectional imaging is the primary preoperative staging modality in pancreatic cancer, which is the fourth most common cause of cancer death in the United States. The rate of encountering metastasis at operation is typically 10%-30%, he noted. The reasons for the delay in surgery could not be ascertained from the retrospective data.

Dr. Glant reported on 487 patients undergoing planned pancreatic resection for pancreatic ductal adenocarcinoma between January 2004 and December 2009 at the university’s high-volume pancreatic surgery center. Patients were excluded if they had received neoadjuvant therapy, prior pancreatic resection, or exploratory surgery for suspected metastatic disease.

Precise imaging data were available for 329 patients. Cross-sectional imaging was defined as dual-phase, contrast-enhanced CT, or MRI if CT was contraindicated.

Of the 285 patients (59%) who had their most recent imaging study performed at the university, 202 underwent resection and 83 were not resected. Metastasis was discovered at time of operation in 39 patients, he said.

Of the 202 (41%) patients whose most recent imaging study was performed at an outside institution, 139 underwent resection and 63 were not resected. Among the 202 patients, 35 had metastasis discovered at time of operation.

The overall frequency of unanticipated metastasis was statistically similar between patients who were imaged at the university and those who were imaged at an outside institution (14% vs. 17%), Dr. Glant said. This was true whether the patients had proximal (14% vs. 17%) or distal (15% vs. 25%) disease. Patients imaged at an outside venue, however, had significantly larger tumors than did those imaged at the university (3.4 cm vs. 3.1 cm; P = .05) and a higher rate of vascular invasion (73% vs. 61%; P = .03).

"It is appropriate and advisable to obtain more current imaging if the delay [in surgery] will exceed 3 weeks," Dr. Glant said.

Invited discussant Dr. Carl R. Schmidt of the Ohio State University, Columbus, said the size of the series, the robustness of the analysis, and the time period evaluated left no doubt in his mind about the use of modern imaging and the validity of the main finding. He asked what proportion of patients at the university undergoes staging laparoscopy, and what the distribution of metastasis was.

Coauthor Dr. Joshua A. Waters, also of Indiana University, replied that with just 16 patients undergoing staging laparoscopy in the entire series, the procedure is not routinely performed at the university in the setting of proximal pancreatic cancer. He also cited a recent study reporting a decrease in yield of staging laparoscopy from 1995 to 2005, particularly in those with proximal pancreatic cancers (J. Am. Coll. Surg. 2008;206:445-50). Regarding the distribution of the metastases, 80% were on the liver and 20% were at another location, primarily peritoneal implants, he said.

When asked whether any patients had undergone endobiliary stenting prior to resection, Dr. Waters said that a significant proportion of patients were stented prior to arrival at the hospital, and that stenting is known to affect the sensitivity of staging in terms of cross-sectional imaging.

Finally, audience member Dr. Fabrizio Michelassi, professor of surgery at Cornell University in New York City, asked how surgeons should use the data. Should they rush to operate on all patients within 2 weeks to avoid the discovery of more occult metastasis, or wait until 6 weeks for the metastases to declare themselves, since the incidence of occult metastasis appeared to stabilize by then at about 35%?

"One could suggest that if you really wait for 6 weeks, you could probably spare the morbidity of a large operation in 25% of patients who really don’t benefit from it," Dr. Michelassi said.

Dr. Waters said that for patients who are rescanned within 2-3 weeks of cross-sectional imaging and are subsequently found to have a metastatic focus or some evidence of progression, this may be evidence of a more aggressive biology. "This may be a subgroup of patients [whom you] would want to capture by rescanning and potentially not expose to a less than therapeutic laparotomy."

The authors reported no conflicts of interest.

DETROIT – Patients with proximal pancreatic cancer should be reimaged before surgery if more than 3 weeks have passed since their most recent cross-sectional imaging study.

The recommendation is based on a retrospective analysis involving 487 patients that identified a significant, roughly twofold increase in unanticipated metastasis encountered at surgery if the interval between imaging and operation was more than 3 weeks.

Among 293 patients with proximal pancreatic cancer and precise imaging data, the frequency of occult metastasis was 12% when the imaging-to-operation interval (IOI) was 20 days or fewer, compared with 20% at an IOI of 21-27 days, 25% at 28-34 days, 35% at 35-41 days, 29% at 42-48 days, and 30% at 49-86 days.

There were no significant differences between patients in the various 1-week intervals in terms of sex, age, tumor size, percentage of poor grade tumors, lymph node positivity, vascular invasion, or perineural invasion, Dr. Jeffrey Glant said at the annual meeting of the Central Surgical Association.

In linear regression analysis, the relationship between frequency of unanticipated metastases and weekly IOI was statistically significant (P = .006) and had a correlation coefficient R² value of 0.99.

A similar relationship was not observed among 36 patients with distal pancreatic cancer and precise imaging data. The frequency of unanticipated metastasis among these patients was 0% at 0-6 days, 33% at 7-13 days, 38% at 14-20 days, 0% at 21-27 days, 0% at 28-34 days, 20% at 35-41 days, 33% at 42-48 days, and 25% at 49-87 days, said Dr. Glant of the department of surgery at Indiana University in Indianapolis.

Cross-sectional imaging is the primary preoperative staging modality in pancreatic cancer, which is the fourth most common cause of cancer death in the United States. The rate of encountering metastasis at operation is typically 10%-30%, he noted. The reasons for the delay in surgery could not be ascertained from the retrospective data.

Dr. Glant reported on 487 patients undergoing planned pancreatic resection for pancreatic ductal adenocarcinoma between January 2004 and December 2009 at the university’s high-volume pancreatic surgery center. Patients were excluded if they had received neoadjuvant therapy, prior pancreatic resection, or exploratory surgery for suspected metastatic disease.

Precise imaging data were available for 329 patients. Cross-sectional imaging was defined as dual-phase, contrast-enhanced CT, or MRI if CT was contraindicated.

Of the 285 patients (59%) who had their most recent imaging study performed at the university, 202 underwent resection and 83 were not resected. Metastasis was discovered at time of operation in 39 patients, he said.

Of the 202 (41%) patients whose most recent imaging study was performed at an outside institution, 139 underwent resection and 63 were not resected. Among the 202 patients, 35 had metastasis discovered at time of operation.

The overall frequency of unanticipated metastasis was statistically similar between patients who were imaged at the university and those who were imaged at an outside institution (14% vs. 17%), Dr. Glant said. This was true whether the patients had proximal (14% vs. 17%) or distal (15% vs. 25%) disease. Patients imaged at an outside venue, however, had significantly larger tumors than did those imaged at the university (3.4 cm vs. 3.1 cm; P = .05) and a higher rate of vascular invasion (73% vs. 61%; P = .03).

"It is appropriate and advisable to obtain more current imaging if the delay [in surgery] will exceed 3 weeks," Dr. Glant said.

Invited discussant Dr. Carl R. Schmidt of the Ohio State University, Columbus, said the size of the series, the robustness of the analysis, and the time period evaluated left no doubt in his mind about the use of modern imaging and the validity of the main finding. He asked what proportion of patients at the university undergoes staging laparoscopy, and what the distribution of metastasis was.

Coauthor Dr. Joshua A. Waters, also of Indiana University, replied that with just 16 patients undergoing staging laparoscopy in the entire series, the procedure is not routinely performed at the university in the setting of proximal pancreatic cancer. He also cited a recent study reporting a decrease in yield of staging laparoscopy from 1995 to 2005, particularly in those with proximal pancreatic cancers (J. Am. Coll. Surg. 2008;206:445-50). Regarding the distribution of the metastases, 80% were on the liver and 20% were at another location, primarily peritoneal implants, he said.

When asked whether any patients had undergone endobiliary stenting prior to resection, Dr. Waters said that a significant proportion of patients were stented prior to arrival at the hospital, and that stenting is known to affect the sensitivity of staging in terms of cross-sectional imaging.

Finally, audience member Dr. Fabrizio Michelassi, professor of surgery at Cornell University in New York City, asked how surgeons should use the data. Should they rush to operate on all patients within 2 weeks to avoid the discovery of more occult metastasis, or wait until 6 weeks for the metastases to declare themselves, since the incidence of occult metastasis appeared to stabilize by then at about 35%?

"One could suggest that if you really wait for 6 weeks, you could probably spare the morbidity of a large operation in 25% of patients who really don’t benefit from it," Dr. Michelassi said.

Dr. Waters said that for patients who are rescanned within 2-3 weeks of cross-sectional imaging and are subsequently found to have a metastatic focus or some evidence of progression, this may be evidence of a more aggressive biology. "This may be a subgroup of patients [whom you] would want to capture by rescanning and potentially not expose to a less than therapeutic laparotomy."

The authors reported no conflicts of interest.

DETROIT – Patients with proximal pancreatic cancer should be reimaged before surgery if more than 3 weeks have passed since their most recent cross-sectional imaging study.

The recommendation is based on a retrospective analysis involving 487 patients that identified a significant, roughly twofold increase in unanticipated metastasis encountered at surgery if the interval between imaging and operation was more than 3 weeks.

Among 293 patients with proximal pancreatic cancer and precise imaging data, the frequency of occult metastasis was 12% when the imaging-to-operation interval (IOI) was 20 days or fewer, compared with 20% at an IOI of 21-27 days, 25% at 28-34 days, 35% at 35-41 days, 29% at 42-48 days, and 30% at 49-86 days.

There were no significant differences between patients in the various 1-week intervals in terms of sex, age, tumor size, percentage of poor grade tumors, lymph node positivity, vascular invasion, or perineural invasion, Dr. Jeffrey Glant said at the annual meeting of the Central Surgical Association.

In linear regression analysis, the relationship between frequency of unanticipated metastases and weekly IOI was statistically significant (P = .006) and had a correlation coefficient R² value of 0.99.

A similar relationship was not observed among 36 patients with distal pancreatic cancer and precise imaging data. The frequency of unanticipated metastasis among these patients was 0% at 0-6 days, 33% at 7-13 days, 38% at 14-20 days, 0% at 21-27 days, 0% at 28-34 days, 20% at 35-41 days, 33% at 42-48 days, and 25% at 49-87 days, said Dr. Glant of the department of surgery at Indiana University in Indianapolis.

Cross-sectional imaging is the primary preoperative staging modality in pancreatic cancer, which is the fourth most common cause of cancer death in the United States. The rate of encountering metastasis at operation is typically 10%-30%, he noted. The reasons for the delay in surgery could not be ascertained from the retrospective data.

Dr. Glant reported on 487 patients undergoing planned pancreatic resection for pancreatic ductal adenocarcinoma between January 2004 and December 2009 at the university’s high-volume pancreatic surgery center. Patients were excluded if they had received neoadjuvant therapy, prior pancreatic resection, or exploratory surgery for suspected metastatic disease.

Precise imaging data were available for 329 patients. Cross-sectional imaging was defined as dual-phase, contrast-enhanced CT, or MRI if CT was contraindicated.

Of the 285 patients (59%) who had their most recent imaging study performed at the university, 202 underwent resection and 83 were not resected. Metastasis was discovered at time of operation in 39 patients, he said.

Of the 202 (41%) patients whose most recent imaging study was performed at an outside institution, 139 underwent resection and 63 were not resected. Among the 202 patients, 35 had metastasis discovered at time of operation.

The overall frequency of unanticipated metastasis was statistically similar between patients who were imaged at the university and those who were imaged at an outside institution (14% vs. 17%), Dr. Glant said. This was true whether the patients had proximal (14% vs. 17%) or distal (15% vs. 25%) disease. Patients imaged at an outside venue, however, had significantly larger tumors than did those imaged at the university (3.4 cm vs. 3.1 cm; P = .05) and a higher rate of vascular invasion (73% vs. 61%; P = .03).

"It is appropriate and advisable to obtain more current imaging if the delay [in surgery] will exceed 3 weeks," Dr. Glant said.

Invited discussant Dr. Carl R. Schmidt of the Ohio State University, Columbus, said the size of the series, the robustness of the analysis, and the time period evaluated left no doubt in his mind about the use of modern imaging and the validity of the main finding. He asked what proportion of patients at the university undergoes staging laparoscopy, and what the distribution of metastasis was.

Coauthor Dr. Joshua A. Waters, also of Indiana University, replied that with just 16 patients undergoing staging laparoscopy in the entire series, the procedure is not routinely performed at the university in the setting of proximal pancreatic cancer. He also cited a recent study reporting a decrease in yield of staging laparoscopy from 1995 to 2005, particularly in those with proximal pancreatic cancers (J. Am. Coll. Surg. 2008;206:445-50). Regarding the distribution of the metastases, 80% were on the liver and 20% were at another location, primarily peritoneal implants, he said.

When asked whether any patients had undergone endobiliary stenting prior to resection, Dr. Waters said that a significant proportion of patients were stented prior to arrival at the hospital, and that stenting is known to affect the sensitivity of staging in terms of cross-sectional imaging.

Finally, audience member Dr. Fabrizio Michelassi, professor of surgery at Cornell University in New York City, asked how surgeons should use the data. Should they rush to operate on all patients within 2 weeks to avoid the discovery of more occult metastasis, or wait until 6 weeks for the metastases to declare themselves, since the incidence of occult metastasis appeared to stabilize by then at about 35%?

"One could suggest that if you really wait for 6 weeks, you could probably spare the morbidity of a large operation in 25% of patients who really don’t benefit from it," Dr. Michelassi said.

Dr. Waters said that for patients who are rescanned within 2-3 weeks of cross-sectional imaging and are subsequently found to have a metastatic focus or some evidence of progression, this may be evidence of a more aggressive biology. "This may be a subgroup of patients [whom you] would want to capture by rescanning and potentially not expose to a less than therapeutic laparotomy."

The authors reported no conflicts of interest.

DETROIT – Patients with proximal pancreatic cancer should be reimaged before surgery if more than 3 weeks have passed since their most recent cross-sectional imaging study.

The recommendation is based on a retrospective analysis involving 487 patients that identified a significant, roughly twofold increase in unanticipated metastasis encountered at surgery if the interval between imaging and operation was more than 3 weeks.

Among 293 patients with proximal pancreatic cancer and precise imaging data, the frequency of occult metastasis was 12% when the imaging-to-operation interval (IOI) was 20 days or fewer, compared with 20% at an IOI of 21-27 days, 25% at 28-34 days, 35% at 35-41 days, 29% at 42-48 days, and 30% at 49-86 days.

There were no significant differences between patients in the various 1-week intervals in terms of sex, age, tumor size, percentage of poor grade tumors, lymph node positivity, vascular invasion, or perineural invasion, Dr. Jeffrey Glant said at the annual meeting of the Central Surgical Association.

In linear regression analysis, the relationship between frequency of unanticipated metastases and weekly IOI was statistically significant (P = .006) and had a correlation coefficient R² value of 0.99.

A similar relationship was not observed among 36 patients with distal pancreatic cancer and precise imaging data. The frequency of unanticipated metastasis among these patients was 0% at 0-6 days, 33% at 7-13 days, 38% at 14-20 days, 0% at 21-27 days, 0% at 28-34 days, 20% at 35-41 days, 33% at 42-48 days, and 25% at 49-87 days, said Dr. Glant of the department of surgery at Indiana University in Indianapolis.

Cross-sectional imaging is the primary preoperative staging modality in pancreatic cancer, which is the fourth most common cause of cancer death in the United States. The rate of encountering metastasis at operation is typically 10%-30%, he noted. The reasons for the delay in surgery could not be ascertained from the retrospective data.

Dr. Glant reported on 487 patients undergoing planned pancreatic resection for pancreatic ductal adenocarcinoma between January 2004 and December 2009 at the university’s high-volume pancreatic surgery center. Patients were excluded if they had received neoadjuvant therapy, prior pancreatic resection, or exploratory surgery for suspected metastatic disease.

Precise imaging data were available for 329 patients. Cross-sectional imaging was defined as dual-phase, contrast-enhanced CT, or MRI if CT was contraindicated.

Of the 285 patients (59%) who had their most recent imaging study performed at the university, 202 underwent resection and 83 were not resected. Metastasis was discovered at time of operation in 39 patients, he said.

Of the 202 (41%) patients whose most recent imaging study was performed at an outside institution, 139 underwent resection and 63 were not resected. Among the 202 patients, 35 had metastasis discovered at time of operation.

The overall frequency of unanticipated metastasis was statistically similar between patients who were imaged at the university and those who were imaged at an outside institution (14% vs. 17%), Dr. Glant said. This was true whether the patients had proximal (14% vs. 17%) or distal (15% vs. 25%) disease. Patients imaged at an outside venue, however, had significantly larger tumors than did those imaged at the university (3.4 cm vs. 3.1 cm; P = .05) and a higher rate of vascular invasion (73% vs. 61%; P = .03).

"It is appropriate and advisable to obtain more current imaging if the delay [in surgery] will exceed 3 weeks," Dr. Glant said.

Invited discussant Dr. Carl R. Schmidt of the Ohio State University, Columbus, said the size of the series, the robustness of the analysis, and the time period evaluated left no doubt in his mind about the use of modern imaging and the validity of the main finding. He asked what proportion of patients at the university undergoes staging laparoscopy, and what the distribution of metastasis was.

Coauthor Dr. Joshua A. Waters, also of Indiana University, replied that with just 16 patients undergoing staging laparoscopy in the entire series, the procedure is not routinely performed at the university in the setting of proximal pancreatic cancer. He also cited a recent study reporting a decrease in yield of staging laparoscopy from 1995 to 2005, particularly in those with proximal pancreatic cancers (J. Am. Coll. Surg. 2008;206:445-50). Regarding the distribution of the metastases, 80% were on the liver and 20% were at another location, primarily peritoneal implants, he said.

When asked whether any patients had undergone endobiliary stenting prior to resection, Dr. Waters said that a significant proportion of patients were stented prior to arrival at the hospital, and that stenting is known to affect the sensitivity of staging in terms of cross-sectional imaging.

Finally, audience member Dr. Fabrizio Michelassi, professor of surgery at Cornell University in New York City, asked how surgeons should use the data. Should they rush to operate on all patients within 2 weeks to avoid the discovery of more occult metastasis, or wait until 6 weeks for the metastases to declare themselves, since the incidence of occult metastasis appeared to stabilize by then at about 35%?

"One could suggest that if you really wait for 6 weeks, you could probably spare the morbidity of a large operation in 25% of patients who really don’t benefit from it," Dr. Michelassi said.

Dr. Waters said that for patients who are rescanned within 2-3 weeks of cross-sectional imaging and are subsequently found to have a metastatic focus or some evidence of progression, this may be evidence of a more aggressive biology. "This may be a subgroup of patients [whom you] would want to capture by rescanning and potentially not expose to a less than therapeutic laparotomy."

The authors reported no conflicts of interest.

DETROIT – Patients with proximal pancreatic cancer should be reimaged before surgery if more than 3 weeks have passed since their most recent cross-sectional imaging study.

The recommendation is based on a retrospective analysis involving 487 patients that identified a significant, roughly twofold increase in unanticipated metastasis encountered at surgery if the interval between imaging and operation was more than 3 weeks.

Among 293 patients with proximal pancreatic cancer and precise imaging data, the frequency of occult metastasis was 12% when the imaging-to-operation interval (IOI) was 20 days or fewer, compared with 20% at an IOI of 21-27 days, 25% at 28-34 days, 35% at 35-41 days, 29% at 42-48 days, and 30% at 49-86 days.

There were no significant differences between patients in the various 1-week intervals in terms of sex, age, tumor size, percentage of poor grade tumors, lymph node positivity, vascular invasion, or perineural invasion, Dr. Jeffrey Glant said at the annual meeting of the Central Surgical Association.

In linear regression analysis, the relationship between frequency of unanticipated metastases and weekly IOI was statistically significant (P = .006) and had a correlation coefficient R² value of 0.99.

A similar relationship was not observed among 36 patients with distal pancreatic cancer and precise imaging data. The frequency of unanticipated metastasis among these patients was 0% at 0-6 days, 33% at 7-13 days, 38% at 14-20 days, 0% at 21-27 days, 0% at 28-34 days, 20% at 35-41 days, 33% at 42-48 days, and 25% at 49-87 days, said Dr. Glant of the department of surgery at Indiana University in Indianapolis.

Cross-sectional imaging is the primary preoperative staging modality in pancreatic cancer, which is the fourth most common cause of cancer death in the United States. The rate of encountering metastasis at operation is typically 10%-30%, he noted. The reasons for the delay in surgery could not be ascertained from the retrospective data.

Dr. Glant reported on 487 patients undergoing planned pancreatic resection for pancreatic ductal adenocarcinoma between January 2004 and December 2009 at the university’s high-volume pancreatic surgery center. Patients were excluded if they had received neoadjuvant therapy, prior pancreatic resection, or exploratory surgery for suspected metastatic disease.

Precise imaging data were available for 329 patients. Cross-sectional imaging was defined as dual-phase, contrast-enhanced CT, or MRI if CT was contraindicated.

Of the 285 patients (59%) who had their most recent imaging study performed at the university, 202 underwent resection and 83 were not resected. Metastasis was discovered at time of operation in 39 patients, he said.

Of the 202 (41%) patients whose most recent imaging study was performed at an outside institution, 139 underwent resection and 63 were not resected. Among the 202 patients, 35 had metastasis discovered at time of operation.

The overall frequency of unanticipated metastasis was statistically similar between patients who were imaged at the university and those who were imaged at an outside institution (14% vs. 17%), Dr. Glant said. This was true whether the patients had proximal (14% vs. 17%) or distal (15% vs. 25%) disease. Patients imaged at an outside venue, however, had significantly larger tumors than did those imaged at the university (3.4 cm vs. 3.1 cm; P = .05) and a higher rate of vascular invasion (73% vs. 61%; P = .03).

"It is appropriate and advisable to obtain more current imaging if the delay [in surgery] will exceed 3 weeks," Dr. Glant said.

Invited discussant Dr. Carl R. Schmidt of the Ohio State University, Columbus, said the size of the series, the robustness of the analysis, and the time period evaluated left no doubt in his mind about the use of modern imaging and the validity of the main finding. He asked what proportion of patients at the university undergoes staging laparoscopy, and what the distribution of metastasis was.

Coauthor Dr. Joshua A. Waters, also of Indiana University, replied that with just 16 patients undergoing staging laparoscopy in the entire series, the procedure is not routinely performed at the university in the setting of proximal pancreatic cancer. He also cited a recent study reporting a decrease in yield of staging laparoscopy from 1995 to 2005, particularly in those with proximal pancreatic cancers (J. Am. Coll. Surg. 2008;206:445-50). Regarding the distribution of the metastases, 80% were on the liver and 20% were at another location, primarily peritoneal implants, he said.

When asked whether any patients had undergone endobiliary stenting prior to resection, Dr. Waters said that a significant proportion of patients were stented prior to arrival at the hospital, and that stenting is known to affect the sensitivity of staging in terms of cross-sectional imaging.

Finally, audience member Dr. Fabrizio Michelassi, professor of surgery at Cornell University in New York City, asked how surgeons should use the data. Should they rush to operate on all patients within 2 weeks to avoid the discovery of more occult metastasis, or wait until 6 weeks for the metastases to declare themselves, since the incidence of occult metastasis appeared to stabilize by then at about 35%?

"One could suggest that if you really wait for 6 weeks, you could probably spare the morbidity of a large operation in 25% of patients who really don’t benefit from it," Dr. Michelassi said.

Dr. Waters said that for patients who are rescanned within 2-3 weeks of cross-sectional imaging and are subsequently found to have a metastatic focus or some evidence of progression, this may be evidence of a more aggressive biology. "This may be a subgroup of patients [whom you] would want to capture by rescanning and potentially not expose to a less than therapeutic laparotomy."

The authors reported no conflicts of interest.

DETROIT – Patients with proximal pancreatic cancer should be reimaged before surgery if more than 3 weeks have passed since their most recent cross-sectional imaging study.

The recommendation is based on a retrospective analysis involving 487 patients that identified a significant, roughly twofold increase in unanticipated metastasis encountered at surgery if the interval between imaging and operation was more than 3 weeks.

Among 293 patients with proximal pancreatic cancer and precise imaging data, the frequency of occult metastasis was 12% when the imaging-to-operation interval (IOI) was 20 days or fewer, compared with 20% at an IOI of 21-27 days, 25% at 28-34 days, 35% at 35-41 days, 29% at 42-48 days, and 30% at 49-86 days.

There were no significant differences between patients in the various 1-week intervals in terms of sex, age, tumor size, percentage of poor grade tumors, lymph node positivity, vascular invasion, or perineural invasion, Dr. Jeffrey Glant said at the annual meeting of the Central Surgical Association.

In linear regression analysis, the relationship between frequency of unanticipated metastases and weekly IOI was statistically significant (P = .006) and had a correlation coefficient R² value of 0.99.

A similar relationship was not observed among 36 patients with distal pancreatic cancer and precise imaging data. The frequency of unanticipated metastasis among these patients was 0% at 0-6 days, 33% at 7-13 days, 38% at 14-20 days, 0% at 21-27 days, 0% at 28-34 days, 20% at 35-41 days, 33% at 42-48 days, and 25% at 49-87 days, said Dr. Glant of the department of surgery at Indiana University in Indianapolis.

Cross-sectional imaging is the primary preoperative staging modality in pancreatic cancer, which is the fourth most common cause of cancer death in the United States. The rate of encountering metastasis at operation is typically 10%-30%, he noted. The reasons for the delay in surgery could not be ascertained from the retrospective data.

Dr. Glant reported on 487 patients undergoing planned pancreatic resection for pancreatic ductal adenocarcinoma between January 2004 and December 2009 at the university’s high-volume pancreatic surgery center. Patients were excluded if they had received neoadjuvant therapy, prior pancreatic resection, or exploratory surgery for suspected metastatic disease.

Precise imaging data were available for 329 patients. Cross-sectional imaging was defined as dual-phase, contrast-enhanced CT, or MRI if CT was contraindicated.

Of the 285 patients (59%) who had their most recent imaging study performed at the university, 202 underwent resection and 83 were not resected. Metastasis was discovered at time of operation in 39 patients, he said.

Of the 202 (41%) patients whose most recent imaging study was performed at an outside institution, 139 underwent resection and 63 were not resected. Among the 202 patients, 35 had metastasis discovered at time of operation.

The overall frequency of unanticipated metastasis was statistically similar between patients who were imaged at the university and those who were imaged at an outside institution (14% vs. 17%), Dr. Glant said. This was true whether the patients had proximal (14% vs. 17%) or distal (15% vs. 25%) disease. Patients imaged at an outside venue, however, had significantly larger tumors than did those imaged at the university (3.4 cm vs. 3.1 cm; P = .05) and a higher rate of vascular invasion (73% vs. 61%; P = .03).

"It is appropriate and advisable to obtain more current imaging if the delay [in surgery] will exceed 3 weeks," Dr. Glant said.

Invited discussant Dr. Carl R. Schmidt of the Ohio State University, Columbus, said the size of the series, the robustness of the analysis, and the time period evaluated left no doubt in his mind about the use of modern imaging and the validity of the main finding. He asked what proportion of patients at the university undergoes staging laparoscopy, and what the distribution of metastasis was.

Coauthor Dr. Joshua A. Waters, also of Indiana University, replied that with just 16 patients undergoing staging laparoscopy in the entire series, the procedure is not routinely performed at the university in the setting of proximal pancreatic cancer. He also cited a recent study reporting a decrease in yield of staging laparoscopy from 1995 to 2005, particularly in those with proximal pancreatic cancers (J. Am. Coll. Surg. 2008;206:445-50). Regarding the distribution of the metastases, 80% were on the liver and 20% were at another location, primarily peritoneal implants, he said.

When asked whether any patients had undergone endobiliary stenting prior to resection, Dr. Waters said that a significant proportion of patients were stented prior to arrival at the hospital, and that stenting is known to affect the sensitivity of staging in terms of cross-sectional imaging.

Finally, audience member Dr. Fabrizio Michelassi, professor of surgery at Cornell University in New York City, asked how surgeons should use the data. Should they rush to operate on all patients within 2 weeks to avoid the discovery of more occult metastasis, or wait until 6 weeks for the metastases to declare themselves, since the incidence of occult metastasis appeared to stabilize by then at about 35%?

"One could suggest that if you really wait for 6 weeks, you could probably spare the morbidity of a large operation in 25% of patients who really don’t benefit from it," Dr. Michelassi said.

Dr. Waters said that for patients who are rescanned within 2-3 weeks of cross-sectional imaging and are subsequently found to have a metastatic focus or some evidence of progression, this may be evidence of a more aggressive biology. "This may be a subgroup of patients [whom you] would want to capture by rescanning and potentially not expose to a less than therapeutic laparotomy."

The authors reported no conflicts of interest.

Major Finding: Prostate-specific antigen progression was observed at 6 months in 10% of the androgen suppression arm (ADT) vs. 1% of the ADT plus docetaxel arm (P = .002) of the trial.

Data Source: Phase III GETUG-AFU 15/0403 study in 385 men with hormone-naive metastatic prostate cancer.

Disclosures: The trial was supported by grants from the French Health Ministry, Sanofi-Aventis, AstraZeneca, and Amgen. Dr. Gravis and coauthors reported that they had no disclosures.

ORLANDO – The addition of docetaxel to androgen deprivation therapy significantly reduces PSA progression but is coupled with significant toxicity in hormone-naive metastatic prostate cancer, according to results of a phase III multicenter trial from France and Belgium.

Progression of prostate-specific antigen (PSA), defined as at least a 25% increase from baseline, was observed in 8% of the androgen suppression arm (ADT), versus 3% of the ADT plus docetaxel (Taxotere) arm at 3 months (P value = .08) and in 10% vs. 1%, respectively, after 6 months (P = .002), Dr. Gwenaelle Gravis reported at the symposium.

The addition of docetaxel also significantly increased the likelihood of a PSA response, defined as a decrease of at least 50% from baseline. A PSA response was achieved in 91% of the ADT plus docetaxel arm vs. 80% of the ADT arm at 3 months (P = .008) and in 95% vs. 86% when assessed at 6 months (P = .01), said Dr. Gravis of Institut Paoli-Calmettes, Marseille, France.

Although the data on the study's primary end point of overall survival are not yet available, these current findings are noteworthy in light of recent work by the Southwest Oncology Group demonstrating that PSA progression at 7 months is a strong predictor of death in patients who have metastatic hormone-sensitive and castration-resistant prostate cancer (J. Clin. Oncol. 2009;27:2450-6).

The French researchers randomized 192 patients to ADT plus docetaxel 75 mg/m

The patients were stratified according to prior systemic treatment and Glass risk group.

After the accrual of 215 patients, three toxic deaths occurred – two as a result of neutropenic fever and one from general impairment. This prompted the internal monitoring committee to recommend the use of granulocyte-colony stimulating factor from day 5 to day 10 after each docetaxel administration, with no subsequent deaths occurring, Dr. Gravis said.

Grades 3/4 hematologic toxicity in 188 evaluable ADT plus docetaxel patients include anemia (2%), neutropenia (32%), febrile neutropenia (7%) and septic death (1%), while only 1% anemia was reported in 185 evaluable ADT-only patients.

Other notable grade 3/4 toxicities occurring in the ADT plus docetaxel vs. ADT alone arms included fatigue (7% vs. 1%), erectile dysfunction (9% vs. 8%), decreased libido (6% vs. 5%) and hot flushes (4% vs. 2%).

“Docetaxel was associated with a significant increased, but manageable toxicity,” Dr. Gravis said at the symposium, which was cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

Global quality of life scores were equivalent in both arms at 12 months in the GETUG-AFU 15/0403 study, sponsored by the National Federation of Comprehensive Cancer Centers with the collaboration of the French Association of Urology (AFU).

At baseline, the patients had a median age of 63 years and roughly half had a good performance status. The median PSA was 27 ng/mL, median Karnofsky score was 100 and 58% had a Gleason score of 8 or more.

Less than 30% received radical prostatectomy or radiotherapy and less than 10% received systemic treatment with chemotherapy or hormonal therapy. Most patients had up-front metastatic disease, with bone metastases present in 81% and nodes metastases in 55%, Dr. Gravis said.

View on the News

Questions of Survival Benefit Still Remain

This study supports the consideration of chemotherapy further up the treatment sequence, but there are Food and Drug Administration–approved alternatives such as Sipuleucel T, which has lower toxicity and need only be administered for three injections vs. nine cycles of docetaxel.

The survival benefit of androgen deprivation therapy and docetaxel in hormone-sensitive patients still needs to be demonstrated. Since PSA response was associated with survival benefit in the trials using docetaxel in the castration-resistant setting, it is reasonable to expect a survival benefit in those who are still hormone sensitive as well.

This still must be demonstrated, however, particularly if regulatory approval for this indication is sought. At the very least, this study provides some proof that the institution of chemotherapy can provide some benefit, even in patients who are hormone sensitive.

DR. BADRINATH R. KONETY is an ACS Fellow and chair of the department of urology, University of Minnesota, Minneapolis.

Major Finding: Prostate-specific antigen progression was observed at 6 months in 10% of the androgen suppression arm (ADT) vs. 1% of the ADT plus docetaxel arm (P = .002) of the trial.

Data Source: Phase III GETUG-AFU 15/0403 study in 385 men with hormone-naive metastatic prostate cancer.

Disclosures: The trial was supported by grants from the French Health Ministry, Sanofi-Aventis, AstraZeneca, and Amgen. Dr. Gravis and coauthors reported that they had no disclosures.

ORLANDO – The addition of docetaxel to androgen deprivation therapy significantly reduces PSA progression but is coupled with significant toxicity in hormone-naive metastatic prostate cancer, according to results of a phase III multicenter trial from France and Belgium.

Progression of prostate-specific antigen (PSA), defined as at least a 25% increase from baseline, was observed in 8% of the androgen suppression arm (ADT), versus 3% of the ADT plus docetaxel (Taxotere) arm at 3 months (P value = .08) and in 10% vs. 1%, respectively, after 6 months (P = .002), Dr. Gwenaelle Gravis reported at the symposium.

The addition of docetaxel also significantly increased the likelihood of a PSA response, defined as a decrease of at least 50% from baseline. A PSA response was achieved in 91% of the ADT plus docetaxel arm vs. 80% of the ADT arm at 3 months (P = .008) and in 95% vs. 86% when assessed at 6 months (P = .01), said Dr. Gravis of Institut Paoli-Calmettes, Marseille, France.

Although the data on the study's primary end point of overall survival are not yet available, these current findings are noteworthy in light of recent work by the Southwest Oncology Group demonstrating that PSA progression at 7 months is a strong predictor of death in patients who have metastatic hormone-sensitive and castration-resistant prostate cancer (J. Clin. Oncol. 2009;27:2450-6).

The French researchers randomized 192 patients to ADT plus docetaxel 75 mg/m

The patients were stratified according to prior systemic treatment and Glass risk group.

After the accrual of 215 patients, three toxic deaths occurred – two as a result of neutropenic fever and one from general impairment. This prompted the internal monitoring committee to recommend the use of granulocyte-colony stimulating factor from day 5 to day 10 after each docetaxel administration, with no subsequent deaths occurring, Dr. Gravis said.

Grades 3/4 hematologic toxicity in 188 evaluable ADT plus docetaxel patients include anemia (2%), neutropenia (32%), febrile neutropenia (7%) and septic death (1%), while only 1% anemia was reported in 185 evaluable ADT-only patients.

Other notable grade 3/4 toxicities occurring in the ADT plus docetaxel vs. ADT alone arms included fatigue (7% vs. 1%), erectile dysfunction (9% vs. 8%), decreased libido (6% vs. 5%) and hot flushes (4% vs. 2%).

“Docetaxel was associated with a significant increased, but manageable toxicity,” Dr. Gravis said at the symposium, which was cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

Global quality of life scores were equivalent in both arms at 12 months in the GETUG-AFU 15/0403 study, sponsored by the National Federation of Comprehensive Cancer Centers with the collaboration of the French Association of Urology (AFU).

At baseline, the patients had a median age of 63 years and roughly half had a good performance status. The median PSA was 27 ng/mL, median Karnofsky score was 100 and 58% had a Gleason score of 8 or more.

Less than 30% received radical prostatectomy or radiotherapy and less than 10% received systemic treatment with chemotherapy or hormonal therapy. Most patients had up-front metastatic disease, with bone metastases present in 81% and nodes metastases in 55%, Dr. Gravis said.

View on the News

Questions of Survival Benefit Still Remain

This study supports the consideration of chemotherapy further up the treatment sequence, but there are Food and Drug Administration–approved alternatives such as Sipuleucel T, which has lower toxicity and need only be administered for three injections vs. nine cycles of docetaxel.

The survival benefit of androgen deprivation therapy and docetaxel in hormone-sensitive patients still needs to be demonstrated. Since PSA response was associated with survival benefit in the trials using docetaxel in the castration-resistant setting, it is reasonable to expect a survival benefit in those who are still hormone sensitive as well.

This still must be demonstrated, however, particularly if regulatory approval for this indication is sought. At the very least, this study provides some proof that the institution of chemotherapy can provide some benefit, even in patients who are hormone sensitive.

DR. BADRINATH R. KONETY is an ACS Fellow and chair of the department of urology, University of Minnesota, Minneapolis.

Major Finding: Prostate-specific antigen progression was observed at 6 months in 10% of the androgen suppression arm (ADT) vs. 1% of the ADT plus docetaxel arm (P = .002) of the trial.

Data Source: Phase III GETUG-AFU 15/0403 study in 385 men with hormone-naive metastatic prostate cancer.

Disclosures: The trial was supported by grants from the French Health Ministry, Sanofi-Aventis, AstraZeneca, and Amgen. Dr. Gravis and coauthors reported that they had no disclosures.

ORLANDO – The addition of docetaxel to androgen deprivation therapy significantly reduces PSA progression but is coupled with significant toxicity in hormone-naive metastatic prostate cancer, according to results of a phase III multicenter trial from France and Belgium.

Progression of prostate-specific antigen (PSA), defined as at least a 25% increase from baseline, was observed in 8% of the androgen suppression arm (ADT), versus 3% of the ADT plus docetaxel (Taxotere) arm at 3 months (P value = .08) and in 10% vs. 1%, respectively, after 6 months (P = .002), Dr. Gwenaelle Gravis reported at the symposium.

The addition of docetaxel also significantly increased the likelihood of a PSA response, defined as a decrease of at least 50% from baseline. A PSA response was achieved in 91% of the ADT plus docetaxel arm vs. 80% of the ADT arm at 3 months (P = .008) and in 95% vs. 86% when assessed at 6 months (P = .01), said Dr. Gravis of Institut Paoli-Calmettes, Marseille, France.

Although the data on the study's primary end point of overall survival are not yet available, these current findings are noteworthy in light of recent work by the Southwest Oncology Group demonstrating that PSA progression at 7 months is a strong predictor of death in patients who have metastatic hormone-sensitive and castration-resistant prostate cancer (J. Clin. Oncol. 2009;27:2450-6).

The French researchers randomized 192 patients to ADT plus docetaxel 75 mg/m

The patients were stratified according to prior systemic treatment and Glass risk group.

After the accrual of 215 patients, three toxic deaths occurred – two as a result of neutropenic fever and one from general impairment. This prompted the internal monitoring committee to recommend the use of granulocyte-colony stimulating factor from day 5 to day 10 after each docetaxel administration, with no subsequent deaths occurring, Dr. Gravis said.

Grades 3/4 hematologic toxicity in 188 evaluable ADT plus docetaxel patients include anemia (2%), neutropenia (32%), febrile neutropenia (7%) and septic death (1%), while only 1% anemia was reported in 185 evaluable ADT-only patients.

Other notable grade 3/4 toxicities occurring in the ADT plus docetaxel vs. ADT alone arms included fatigue (7% vs. 1%), erectile dysfunction (9% vs. 8%), decreased libido (6% vs. 5%) and hot flushes (4% vs. 2%).

“Docetaxel was associated with a significant increased, but manageable toxicity,” Dr. Gravis said at the symposium, which was cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

Global quality of life scores were equivalent in both arms at 12 months in the GETUG-AFU 15/0403 study, sponsored by the National Federation of Comprehensive Cancer Centers with the collaboration of the French Association of Urology (AFU).

At baseline, the patients had a median age of 63 years and roughly half had a good performance status. The median PSA was 27 ng/mL, median Karnofsky score was 100 and 58% had a Gleason score of 8 or more.

Less than 30% received radical prostatectomy or radiotherapy and less than 10% received systemic treatment with chemotherapy or hormonal therapy. Most patients had up-front metastatic disease, with bone metastases present in 81% and nodes metastases in 55%, Dr. Gravis said.

View on the News

Questions of Survival Benefit Still Remain

This study supports the consideration of chemotherapy further up the treatment sequence, but there are Food and Drug Administration–approved alternatives such as Sipuleucel T, which has lower toxicity and need only be administered for three injections vs. nine cycles of docetaxel.

The survival benefit of androgen deprivation therapy and docetaxel in hormone-sensitive patients still needs to be demonstrated. Since PSA response was associated with survival benefit in the trials using docetaxel in the castration-resistant setting, it is reasonable to expect a survival benefit in those who are still hormone sensitive as well.

This still must be demonstrated, however, particularly if regulatory approval for this indication is sought. At the very least, this study provides some proof that the institution of chemotherapy can provide some benefit, even in patients who are hormone sensitive.

DR. BADRINATH R. KONETY is an ACS Fellow and chair of the department of urology, University of Minnesota, Minneapolis.

Major Finding: Taking dutasteride 0.5 mg daily reduced relative risk of prostate cancer progression by 38.9% vs. placebo.

Data Source: Phase III REDEEM trial in 302 men with low-risk, early stage prostate cancer followed with active surveillance.

Disclosures: GlaxoSmithKline sponsored the study. The investigators disclosed relationships with GSK, including consultant/advisory roles, employment/stock ownership, and research support and honoraria. Dr. Vogelzang disclosed financial relationships with multiple pharmaceutical companies.

Dutasteride slowed the time to prostate cancer progression in men with low-risk, early-stage disease who were followed with active surveillance in the phase III REDEEM study.

Of the 302 patients who were randomized, 38% of men given dutasteride (Avodart) 0.5 mg daily and 49% of those given placebo experienced some progression of their cancer.

This resulted in a relative risk reduction of 38.9% in the dutasteride group, lead author Dr. Neil Fleshner said during a press briefing that was held in advance of the Genitourinary Cancers Symposium.

The aggregate primary end point of the Reduction With Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) study was time to either therapeutic or pathological progression. Therapeutic progression was defined as prostatectomy, radiation, or hormonal therapy. Pathological progression was defined as at least four positive biopsy cores, at least 50% of any one core positive, or a Gleason pattern of 4 or more.

At final biopsy, 36% of 140 men receiving dutasteride had no cancer vs. 23% of 136 men on placebo (P = .024). “This is a statistically, and I think, clinically significant improvement,” said Dr. Fleshner, head of urology at University Health Network in Toronto.

There was no evidence of increased Gleason score progression in patients given dutasteride in the three-year trial, he said. At final biopsy, 12% of men given dutasteride and 14% of those given placebo had a Gleason score of 7, and 2% of men in both groups had a Gleason score of 8.

This is noteworthy as an increase in high-grade prostate cancers was observed in men treated with dutasteride compared with those on placebo in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.

Avodart's maker, GlaxoSmithKline, filed for a chemoprevention indication for dutasteride in the United States and Europe based mainly on the results of REDUCE, a 4-year study of 8,231 men aged 50–75 years considered at an increased risk of prostate cancer because of an elevated PSA (2.5–10 ng/mL) and one negative biopsy.

The company has since announced receiving a Complete Response Letter from the Food and Drug Administration, which signals that the indication has not been approved.

Dutasteride and finasteride, another 5-alpha reductase inhibitor, were shot down as prostate chemoprevention agents in December 2010 by the FDA's Oncologic Drugs Advisory Committee on the basis that the risk-benefit profile for either drug is not favorable when it is used to reduce the risk of prostate cancer.

The current results will not resurrect GSK's attempt to gain a chemoprevention indication for dutasteride. “They are not going to apply for it,” Dr. Fleshner told reporters at the meeting.

“This was not a registration trial, and the time required to reassemble and complete another one will not fit in with their patent expiration. So, I don't think we will see a formal indication for surveillance,” he said.

A separate cost-utility analysis published in February showed that dutasteride at a cost of $626 per year, down from the current $1,400, was unlikely to be cost effective for chemoprevention use in men at elevated risk for prostate cancer (Cancer Prev. Res. 2011;4:277-83).

The moderator of the press briefing, Dr. Nicholas Vogelzang of Las Vegas, who is with US Oncology, said that the paper is important because of the increased anxiety experienced by the growing number of men under watchful waiting.

“With this drug, dutasteride, the PSA [prostate-specific antigen] drops by about 50%; it makes the gland smaller, so they have [fewer] urinary symptoms,” he said.

“Now we have learned that this seems to reduce the amount of cancer in the gland, and we are now able to offer the patients who wish to have watchful waiting an active treatment option. I think it's an important step forward,” Dr. Vogelzang noted.

Dutasteride was approved for benign prostatic hypertrophy in men with an enlarged prostate in 2001. Currently, no drug is approved for prevention of prostate cancer.

At baseline, men in the REDEEM study were aged 48–82 years, they had a PSA level of less than 11 ng/mL, a Gleason score of 6 or less, and clinical stage T1c-T2a disease.

The data were formally presented at the symposium, which is sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

'This is a statistically, and I think, clinically significant improvement.'

Source DR. FLESHNER

Major Finding: Taking dutasteride 0.5 mg daily reduced relative risk of prostate cancer progression by 38.9% vs. placebo.

Data Source: Phase III REDEEM trial in 302 men with low-risk, early stage prostate cancer followed with active surveillance.

Disclosures: GlaxoSmithKline sponsored the study. The investigators disclosed relationships with GSK, including consultant/advisory roles, employment/stock ownership, and research support and honoraria. Dr. Vogelzang disclosed financial relationships with multiple pharmaceutical companies.

Dutasteride slowed the time to prostate cancer progression in men with low-risk, early-stage disease who were followed with active surveillance in the phase III REDEEM study.

Of the 302 patients who were randomized, 38% of men given dutasteride (Avodart) 0.5 mg daily and 49% of those given placebo experienced some progression of their cancer.

This resulted in a relative risk reduction of 38.9% in the dutasteride group, lead author Dr. Neil Fleshner said during a press briefing that was held in advance of the Genitourinary Cancers Symposium.

The aggregate primary end point of the Reduction With Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) study was time to either therapeutic or pathological progression. Therapeutic progression was defined as prostatectomy, radiation, or hormonal therapy. Pathological progression was defined as at least four positive biopsy cores, at least 50% of any one core positive, or a Gleason pattern of 4 or more.

At final biopsy, 36% of 140 men receiving dutasteride had no cancer vs. 23% of 136 men on placebo (P = .024). “This is a statistically, and I think, clinically significant improvement,” said Dr. Fleshner, head of urology at University Health Network in Toronto.

There was no evidence of increased Gleason score progression in patients given dutasteride in the three-year trial, he said. At final biopsy, 12% of men given dutasteride and 14% of those given placebo had a Gleason score of 7, and 2% of men in both groups had a Gleason score of 8.

This is noteworthy as an increase in high-grade prostate cancers was observed in men treated with dutasteride compared with those on placebo in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.

Avodart's maker, GlaxoSmithKline, filed for a chemoprevention indication for dutasteride in the United States and Europe based mainly on the results of REDUCE, a 4-year study of 8,231 men aged 50–75 years considered at an increased risk of prostate cancer because of an elevated PSA (2.5–10 ng/mL) and one negative biopsy.

The company has since announced receiving a Complete Response Letter from the Food and Drug Administration, which signals that the indication has not been approved.

Dutasteride and finasteride, another 5-alpha reductase inhibitor, were shot down as prostate chemoprevention agents in December 2010 by the FDA's Oncologic Drugs Advisory Committee on the basis that the risk-benefit profile for either drug is not favorable when it is used to reduce the risk of prostate cancer.

The current results will not resurrect GSK's attempt to gain a chemoprevention indication for dutasteride. “They are not going to apply for it,” Dr. Fleshner told reporters at the meeting.

“This was not a registration trial, and the time required to reassemble and complete another one will not fit in with their patent expiration. So, I don't think we will see a formal indication for surveillance,” he said.

A separate cost-utility analysis published in February showed that dutasteride at a cost of $626 per year, down from the current $1,400, was unlikely to be cost effective for chemoprevention use in men at elevated risk for prostate cancer (Cancer Prev. Res. 2011;4:277-83).

The moderator of the press briefing, Dr. Nicholas Vogelzang of Las Vegas, who is with US Oncology, said that the paper is important because of the increased anxiety experienced by the growing number of men under watchful waiting.

“With this drug, dutasteride, the PSA [prostate-specific antigen] drops by about 50%; it makes the gland smaller, so they have [fewer] urinary symptoms,” he said.

“Now we have learned that this seems to reduce the amount of cancer in the gland, and we are now able to offer the patients who wish to have watchful waiting an active treatment option. I think it's an important step forward,” Dr. Vogelzang noted.

Dutasteride was approved for benign prostatic hypertrophy in men with an enlarged prostate in 2001. Currently, no drug is approved for prevention of prostate cancer.

At baseline, men in the REDEEM study were aged 48–82 years, they had a PSA level of less than 11 ng/mL, a Gleason score of 6 or less, and clinical stage T1c-T2a disease.

The data were formally presented at the symposium, which is sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

'This is a statistically, and I think, clinically significant improvement.'

Source DR. FLESHNER

Major Finding: Taking dutasteride 0.5 mg daily reduced relative risk of prostate cancer progression by 38.9% vs. placebo.

Data Source: Phase III REDEEM trial in 302 men with low-risk, early stage prostate cancer followed with active surveillance.

Disclosures: GlaxoSmithKline sponsored the study. The investigators disclosed relationships with GSK, including consultant/advisory roles, employment/stock ownership, and research support and honoraria. Dr. Vogelzang disclosed financial relationships with multiple pharmaceutical companies.

Dutasteride slowed the time to prostate cancer progression in men with low-risk, early-stage disease who were followed with active surveillance in the phase III REDEEM study.

Of the 302 patients who were randomized, 38% of men given dutasteride (Avodart) 0.5 mg daily and 49% of those given placebo experienced some progression of their cancer.

This resulted in a relative risk reduction of 38.9% in the dutasteride group, lead author Dr. Neil Fleshner said during a press briefing that was held in advance of the Genitourinary Cancers Symposium.

The aggregate primary end point of the Reduction With Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) study was time to either therapeutic or pathological progression. Therapeutic progression was defined as prostatectomy, radiation, or hormonal therapy. Pathological progression was defined as at least four positive biopsy cores, at least 50% of any one core positive, or a Gleason pattern of 4 or more.

At final biopsy, 36% of 140 men receiving dutasteride had no cancer vs. 23% of 136 men on placebo (P = .024). “This is a statistically, and I think, clinically significant improvement,” said Dr. Fleshner, head of urology at University Health Network in Toronto.

There was no evidence of increased Gleason score progression in patients given dutasteride in the three-year trial, he said. At final biopsy, 12% of men given dutasteride and 14% of those given placebo had a Gleason score of 7, and 2% of men in both groups had a Gleason score of 8.

This is noteworthy as an increase in high-grade prostate cancers was observed in men treated with dutasteride compared with those on placebo in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.

Avodart's maker, GlaxoSmithKline, filed for a chemoprevention indication for dutasteride in the United States and Europe based mainly on the results of REDUCE, a 4-year study of 8,231 men aged 50–75 years considered at an increased risk of prostate cancer because of an elevated PSA (2.5–10 ng/mL) and one negative biopsy.

The company has since announced receiving a Complete Response Letter from the Food and Drug Administration, which signals that the indication has not been approved.

Dutasteride and finasteride, another 5-alpha reductase inhibitor, were shot down as prostate chemoprevention agents in December 2010 by the FDA's Oncologic Drugs Advisory Committee on the basis that the risk-benefit profile for either drug is not favorable when it is used to reduce the risk of prostate cancer.

The current results will not resurrect GSK's attempt to gain a chemoprevention indication for dutasteride. “They are not going to apply for it,” Dr. Fleshner told reporters at the meeting.

“This was not a registration trial, and the time required to reassemble and complete another one will not fit in with their patent expiration. So, I don't think we will see a formal indication for surveillance,” he said.

A separate cost-utility analysis published in February showed that dutasteride at a cost of $626 per year, down from the current $1,400, was unlikely to be cost effective for chemoprevention use in men at elevated risk for prostate cancer (Cancer Prev. Res. 2011;4:277-83).

The moderator of the press briefing, Dr. Nicholas Vogelzang of Las Vegas, who is with US Oncology, said that the paper is important because of the increased anxiety experienced by the growing number of men under watchful waiting.

“With this drug, dutasteride, the PSA [prostate-specific antigen] drops by about 50%; it makes the gland smaller, so they have [fewer] urinary symptoms,” he said.

“Now we have learned that this seems to reduce the amount of cancer in the gland, and we are now able to offer the patients who wish to have watchful waiting an active treatment option. I think it's an important step forward,” Dr. Vogelzang noted.

Dutasteride was approved for benign prostatic hypertrophy in men with an enlarged prostate in 2001. Currently, no drug is approved for prevention of prostate cancer.

At baseline, men in the REDEEM study were aged 48–82 years, they had a PSA level of less than 11 ng/mL, a Gleason score of 6 or less, and clinical stage T1c-T2a disease.

The data were formally presented at the symposium, which is sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

'This is a statistically, and I think, clinically significant improvement.'

Source DR. FLESHNER

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.

DETROIT - Rural hospitals will need to devise unique strategies to enhance hiring and retention in the face of a looming shortage of almost 30,000 surgeons over the next 20 years.

"We think this shortage will result in competition between urban and rural hospitals, maybe perpetuating in bidding wars," Dr. Thomas E. Williams Jr. said at the annual meeting of the Central Surgical Association.

"In a sense, this shortage could be a perfect storm; an imperative for both the urban and rural hospitals we see in America today."

The researchers previously reported that an estimated 101,838 surgeons will need to be trained by 2030 to address a projected shortage in the United States of 29,138 surgeons in seven surgical specialties: obstetrics and gynecology, orthopedic surgery, general surgery, otolaryngology, urology, neurosurgery, and thoracic surgery (Ann. Surg. 2009;250:590-7)

The current analysis went one step further, focusing on the average recruitment needs for the seven specialties in rural vs. urban hospitals in light of the projected U.S. population of 364 million by 2030. The model assumed that there will be equal population growth in urban and rural areas; that rural hospitals will need to recruit obstetric/gynecologic, orthopedic, and general surgeons; and that the percentage of the population receiving care at urban and rural hospitals will remain constant, Dr. Williams explained.

Currently, the American Hospital Association estimates that there are 3,012 urban hospitals in the United States. serving 82% of the population or 253 million Americans, and 1,998 rural hospitals serving 18% or 56 million Americans.

Based on these assumptions, the total number of surgical hires over the next 19 years will be 83,507 for urban hospitals and 13,953 for rural hospitals. This means urban hospitals must hire and retain 4,175 surgeons per year or 27.7 surgeons per hospital, while rural hospitals will need to hire 698 surgeons per year or 7 surgeons per hospital, said Dr. Williams of the department of surgery at Ohio State University in Columbus.

While the recruitment goals for urban hospitals might appear more daunting, rural hospitals are already facing a dramatic loss of general surgeons.

"In rural hospitals, general surgery is essential," he said. "[General surgeons] account for 60% of the revenue. What’s happening now is that about 34% of general surgeons are notifying their administrators of retiring or leaving in 2 years. Thirty-three percent of rural hospitals are recruiting now."

Factors that might make rural recruitment more difficult include professional and social isolation, cross coverage, insufficient training for the variety of procedures performed and pathologies encountered, and women’s preference for urban areas, he said.

Factors that positively influence rural recruitment include the chance to be a critical part of the community, independence, the wide spectrum of procedures, and hailing from a rural area.

One strategy that can tip a surgeon toward a rural hospital is doing a residency in a rural training program. The researchers estimate that half of general surgery residents who rotate through such a program will go on to practice in rural towns.

"It’s to the advantage of rural hospital administrators to establish rotations with medical schools in their hospitals, so they can have the opportunity to recruit some of the people that rotate through their rural hospitals," Dr. Williams said.

Consideration of the needs of the surgeon’s family is another factor. Typically, this will be a two-income family that values education and will need either good public schools or the means to pay for private schools. Most couples will also have educational debts, some as high as $400,000 for a two-physician couple. Thus, educational loan repayment could be a potential "trump card" for rural hospitals in the future, he said.

Rural hospitals are already throwing out the welcome mat. Most offer hiring incentives such as a relocation allowance; signing bonus; health, disability, and life insurance; and malpractice coverage. Educational loan forgiveness was offered by 38% of hospitals last year, up 7% from 2009, Dr. Williams said. Still, competition for new hires is fierce.

"In many general surgery programs in the United States, senior residents are receiving as many as 50 offers for employment today," he said.

To illustrate the point, Dr. Williams showed a recent classified ad in the New England Journal of Medicine offering a starting base salary of $600,000 for an orthopedic surgeon in coastal Georgia plus a sign-on and relocation bonus, full benefits, and a high-yield bonus. This is nearly double the median starting salary of $370,000 for an orthopedic surgeon identified in a recent Cejka Executive Search survey, he pointed out.

Median starting salaries for the seven surgical specialties studied ranged from a low of $260,000 for a general surgeon to a high of $450,000 for a neurosurgeon in the Cejka survey.

Invited discussant Dr. Nathaniel Soper, chair of the department of surgery at Northwestern University in Chicago, said, "It may end up being ultimately that these bidding wars are good for general surgeons, but I think it’s not going to be good for the population we serve, as there is going to be a shortage unless something is done."

Dr. Sober suggested that the basic problem is not so much the division between rural vs. urban, but the supply of surgeons, and asked what can be done to meet the estimated shortfall. He also questioned the model’s assumption that the population would remain equal in rural and urban areas.

Co-author and colleague Dr. Bhagwan Satiani replied that the analysis included a simplified version of the federal model used to calculate supply and demand, but added that every projection in the last 50-75 years has been wrong. "You have to look at this model and say, ‘This is the best we can do right now," he said.

According to Dr. Satiani, one of the best ways to increase the rural surgeon supply is through a comprehensive medical school rural program (MSRP). "If you took 10 medical students out of the class and put them into the MSRP program, you could double the number of rural surgeons. That’s how important that is," said Dr. Satiani, medical director of the vascular surgery laboratory and a professor of clinical surgery at Ohio State University.

A recently published report from the Physician Shortage Area Program (PSAP) at Jefferson Medical College in Philadelphia provides a similar calculation for rural physicians and reports that 79%-87% of graduates from the two MSRPs with long-range rural outcomes – the PSAP and University of Minnesota at Duluth – remained in rural practice for up to 20 years (Acad. Med. 2011;86:272). It also notes that the Affordable Care Act authorized a new Rural Physician Training Grants program to provide grants to medical schools to develop or expand MSRPs.

Only 25 of the roughly 250 medical schools have general surgery programs, and just 10% of these could be considered programs that attract rural surgeons, according to Dr. Satiani. "I think American surgery is going to have to give this a separate tract within residency programs."

Audience member Dr. Mark Malangoni, associate executive director of the American Board of Surgery in Philadelphia, pointed out that in such rural areas as Wyoming, the closest medical school is more than 1,000 miles away in Washington state. He suggested that one way to link rural hospitals and to counteract the professional isolation experienced by some rural physicians is through Web-based surgeon-to-surgeon consultations, an idea strongly supported by a recent survey of American College of Surgeons fellows.

If a new medical school were located in a rural area, Dr. Satiani said it could feed two to three nearby states, but not one of the new medical schools built in the last 5 years has been in truly rural areas.

Finally, several audience members suggested that efforts need to be made to eliminate the perception among residents that surgical specialists are somehow better than general surgeons.

"It’s the one-on-one thing that’s going to work with the residents, because all they see are these super-specialists," Dr. Satiani said. "I think it has to come from the programs and the leadership; defining general surgery better, even going as far as changing the name, if that becomes an important issue."

When asked in an interview what that new name might be, Dr. Satiani said the terms "master surgeon" and "omni surgeon" have been floated, with master surgeon more likely to resonate with the general public.

The authors reported no conflicts of interest.

DETROIT - Rural hospitals will need to devise unique strategies to enhance hiring and retention in the face of a looming shortage of almost 30,000 surgeons over the next 20 years.

"We think this shortage will result in competition between urban and rural hospitals, maybe perpetuating in bidding wars," Dr. Thomas E. Williams Jr. said at the annual meeting of the Central Surgical Association.

"In a sense, this shortage could be a perfect storm; an imperative for both the urban and rural hospitals we see in America today."

The researchers previously reported that an estimated 101,838 surgeons will need to be trained by 2030 to address a projected shortage in the United States of 29,138 surgeons in seven surgical specialties: obstetrics and gynecology, orthopedic surgery, general surgery, otolaryngology, urology, neurosurgery, and thoracic surgery (Ann. Surg. 2009;250:590-7)

The current analysis went one step further, focusing on the average recruitment needs for the seven specialties in rural vs. urban hospitals in light of the projected U.S. population of 364 million by 2030. The model assumed that there will be equal population growth in urban and rural areas; that rural hospitals will need to recruit obstetric/gynecologic, orthopedic, and general surgeons; and that the percentage of the population receiving care at urban and rural hospitals will remain constant, Dr. Williams explained.

Currently, the American Hospital Association estimates that there are 3,012 urban hospitals in the United States. serving 82% of the population or 253 million Americans, and 1,998 rural hospitals serving 18% or 56 million Americans.

Based on these assumptions, the total number of surgical hires over the next 19 years will be 83,507 for urban hospitals and 13,953 for rural hospitals. This means urban hospitals must hire and retain 4,175 surgeons per year or 27.7 surgeons per hospital, while rural hospitals will need to hire 698 surgeons per year or 7 surgeons per hospital, said Dr. Williams of the department of surgery at Ohio State University in Columbus.

While the recruitment goals for urban hospitals might appear more daunting, rural hospitals are already facing a dramatic loss of general surgeons.

"In rural hospitals, general surgery is essential," he said. "[General surgeons] account for 60% of the revenue. What’s happening now is that about 34% of general surgeons are notifying their administrators of retiring or leaving in 2 years. Thirty-three percent of rural hospitals are recruiting now."

Factors that might make rural recruitment more difficult include professional and social isolation, cross coverage, insufficient training for the variety of procedures performed and pathologies encountered, and women’s preference for urban areas, he said.

Factors that positively influence rural recruitment include the chance to be a critical part of the community, independence, the wide spectrum of procedures, and hailing from a rural area.

One strategy that can tip a surgeon toward a rural hospital is doing a residency in a rural training program. The researchers estimate that half of general surgery residents who rotate through such a program will go on to practice in rural towns.

"It’s to the advantage of rural hospital administrators to establish rotations with medical schools in their hospitals, so they can have the opportunity to recruit some of the people that rotate through their rural hospitals," Dr. Williams said.

Consideration of the needs of the surgeon’s family is another factor. Typically, this will be a two-income family that values education and will need either good public schools or the means to pay for private schools. Most couples will also have educational debts, some as high as $400,000 for a two-physician couple. Thus, educational loan repayment could be a potential "trump card" for rural hospitals in the future, he said.

Rural hospitals are already throwing out the welcome mat. Most offer hiring incentives such as a relocation allowance; signing bonus; health, disability, and life insurance; and malpractice coverage. Educational loan forgiveness was offered by 38% of hospitals last year, up 7% from 2009, Dr. Williams said. Still, competition for new hires is fierce.

"In many general surgery programs in the United States, senior residents are receiving as many as 50 offers for employment today," he said.

To illustrate the point, Dr. Williams showed a recent classified ad in the New England Journal of Medicine offering a starting base salary of $600,000 for an orthopedic surgeon in coastal Georgia plus a sign-on and relocation bonus, full benefits, and a high-yield bonus. This is nearly double the median starting salary of $370,000 for an orthopedic surgeon identified in a recent Cejka Executive Search survey, he pointed out.

Median starting salaries for the seven surgical specialties studied ranged from a low of $260,000 for a general surgeon to a high of $450,000 for a neurosurgeon in the Cejka survey.

Invited discussant Dr. Nathaniel Soper, chair of the department of surgery at Northwestern University in Chicago, said, "It may end up being ultimately that these bidding wars are good for general surgeons, but I think it’s not going to be good for the population we serve, as there is going to be a shortage unless something is done."

Dr. Sober suggested that the basic problem is not so much the division between rural vs. urban, but the supply of surgeons, and asked what can be done to meet the estimated shortfall. He also questioned the model’s assumption that the population would remain equal in rural and urban areas.

Co-author and colleague Dr. Bhagwan Satiani replied that the analysis included a simplified version of the federal model used to calculate supply and demand, but added that every projection in the last 50-75 years has been wrong. "You have to look at this model and say, ‘This is the best we can do right now," he said.

According to Dr. Satiani, one of the best ways to increase the rural surgeon supply is through a comprehensive medical school rural program (MSRP). "If you took 10 medical students out of the class and put them into the MSRP program, you could double the number of rural surgeons. That’s how important that is," said Dr. Satiani, medical director of the vascular surgery laboratory and a professor of clinical surgery at Ohio State University.

A recently published report from the Physician Shortage Area Program (PSAP) at Jefferson Medical College in Philadelphia provides a similar calculation for rural physicians and reports that 79%-87% of graduates from the two MSRPs with long-range rural outcomes – the PSAP and University of Minnesota at Duluth – remained in rural practice for up to 20 years (Acad. Med. 2011;86:272). It also notes that the Affordable Care Act authorized a new Rural Physician Training Grants program to provide grants to medical schools to develop or expand MSRPs.

Only 25 of the roughly 250 medical schools have general surgery programs, and just 10% of these could be considered programs that attract rural surgeons, according to Dr. Satiani. "I think American surgery is going to have to give this a separate tract within residency programs."

Audience member Dr. Mark Malangoni, associate executive director of the American Board of Surgery in Philadelphia, pointed out that in such rural areas as Wyoming, the closest medical school is more than 1,000 miles away in Washington state. He suggested that one way to link rural hospitals and to counteract the professional isolation experienced by some rural physicians is through Web-based surgeon-to-surgeon consultations, an idea strongly supported by a recent survey of American College of Surgeons fellows.

If a new medical school were located in a rural area, Dr. Satiani said it could feed two to three nearby states, but not one of the new medical schools built in the last 5 years has been in truly rural areas.

Finally, several audience members suggested that efforts need to be made to eliminate the perception among residents that surgical specialists are somehow better than general surgeons.

"It’s the one-on-one thing that’s going to work with the residents, because all they see are these super-specialists," Dr. Satiani said. "I think it has to come from the programs and the leadership; defining general surgery better, even going as far as changing the name, if that becomes an important issue."

When asked in an interview what that new name might be, Dr. Satiani said the terms "master surgeon" and "omni surgeon" have been floated, with master surgeon more likely to resonate with the general public.

The authors reported no conflicts of interest.

DETROIT - Rural hospitals will need to devise unique strategies to enhance hiring and retention in the face of a looming shortage of almost 30,000 surgeons over the next 20 years.

"We think this shortage will result in competition between urban and rural hospitals, maybe perpetuating in bidding wars," Dr. Thomas E. Williams Jr. said at the annual meeting of the Central Surgical Association.

"In a sense, this shortage could be a perfect storm; an imperative for both the urban and rural hospitals we see in America today."

The researchers previously reported that an estimated 101,838 surgeons will need to be trained by 2030 to address a projected shortage in the United States of 29,138 surgeons in seven surgical specialties: obstetrics and gynecology, orthopedic surgery, general surgery, otolaryngology, urology, neurosurgery, and thoracic surgery (Ann. Surg. 2009;250:590-7)

The current analysis went one step further, focusing on the average recruitment needs for the seven specialties in rural vs. urban hospitals in light of the projected U.S. population of 364 million by 2030. The model assumed that there will be equal population growth in urban and rural areas; that rural hospitals will need to recruit obstetric/gynecologic, orthopedic, and general surgeons; and that the percentage of the population receiving care at urban and rural hospitals will remain constant, Dr. Williams explained.

Currently, the American Hospital Association estimates that there are 3,012 urban hospitals in the United States. serving 82% of the population or 253 million Americans, and 1,998 rural hospitals serving 18% or 56 million Americans.

Based on these assumptions, the total number of surgical hires over the next 19 years will be 83,507 for urban hospitals and 13,953 for rural hospitals. This means urban hospitals must hire and retain 4,175 surgeons per year or 27.7 surgeons per hospital, while rural hospitals will need to hire 698 surgeons per year or 7 surgeons per hospital, said Dr. Williams of the department of surgery at Ohio State University in Columbus.

While the recruitment goals for urban hospitals might appear more daunting, rural hospitals are already facing a dramatic loss of general surgeons.

"In rural hospitals, general surgery is essential," he said. "[General surgeons] account for 60% of the revenue. What’s happening now is that about 34% of general surgeons are notifying their administrators of retiring or leaving in 2 years. Thirty-three percent of rural hospitals are recruiting now."

Factors that might make rural recruitment more difficult include professional and social isolation, cross coverage, insufficient training for the variety of procedures performed and pathologies encountered, and women’s preference for urban areas, he said.

Factors that positively influence rural recruitment include the chance to be a critical part of the community, independence, the wide spectrum of procedures, and hailing from a rural area.

One strategy that can tip a surgeon toward a rural hospital is doing a residency in a rural training program. The researchers estimate that half of general surgery residents who rotate through such a program will go on to practice in rural towns.

"It’s to the advantage of rural hospital administrators to establish rotations with medical schools in their hospitals, so they can have the opportunity to recruit some of the people that rotate through their rural hospitals," Dr. Williams said.

Consideration of the needs of the surgeon’s family is another factor. Typically, this will be a two-income family that values education and will need either good public schools or the means to pay for private schools. Most couples will also have educational debts, some as high as $400,000 for a two-physician couple. Thus, educational loan repayment could be a potential "trump card" for rural hospitals in the future, he said.

Rural hospitals are already throwing out the welcome mat. Most offer hiring incentives such as a relocation allowance; signing bonus; health, disability, and life insurance; and malpractice coverage. Educational loan forgiveness was offered by 38% of hospitals last year, up 7% from 2009, Dr. Williams said. Still, competition for new hires is fierce.

"In many general surgery programs in the United States, senior residents are receiving as many as 50 offers for employment today," he said.

To illustrate the point, Dr. Williams showed a recent classified ad in the New England Journal of Medicine offering a starting base salary of $600,000 for an orthopedic surgeon in coastal Georgia plus a sign-on and relocation bonus, full benefits, and a high-yield bonus. This is nearly double the median starting salary of $370,000 for an orthopedic surgeon identified in a recent Cejka Executive Search survey, he pointed out.

Median starting salaries for the seven surgical specialties studied ranged from a low of $260,000 for a general surgeon to a high of $450,000 for a neurosurgeon in the Cejka survey.

Invited discussant Dr. Nathaniel Soper, chair of the department of surgery at Northwestern University in Chicago, said, "It may end up being ultimately that these bidding wars are good for general surgeons, but I think it’s not going to be good for the population we serve, as there is going to be a shortage unless something is done."

Dr. Sober suggested that the basic problem is not so much the division between rural vs. urban, but the supply of surgeons, and asked what can be done to meet the estimated shortfall. He also questioned the model’s assumption that the population would remain equal in rural and urban areas.

Co-author and colleague Dr. Bhagwan Satiani replied that the analysis included a simplified version of the federal model used to calculate supply and demand, but added that every projection in the last 50-75 years has been wrong. "You have to look at this model and say, ‘This is the best we can do right now," he said.

According to Dr. Satiani, one of the best ways to increase the rural surgeon supply is through a comprehensive medical school rural program (MSRP). "If you took 10 medical students out of the class and put them into the MSRP program, you could double the number of rural surgeons. That’s how important that is," said Dr. Satiani, medical director of the vascular surgery laboratory and a professor of clinical surgery at Ohio State University.

A recently published report from the Physician Shortage Area Program (PSAP) at Jefferson Medical College in Philadelphia provides a similar calculation for rural physicians and reports that 79%-87% of graduates from the two MSRPs with long-range rural outcomes – the PSAP and University of Minnesota at Duluth – remained in rural practice for up to 20 years (Acad. Med. 2011;86:272). It also notes that the Affordable Care Act authorized a new Rural Physician Training Grants program to provide grants to medical schools to develop or expand MSRPs.

Only 25 of the roughly 250 medical schools have general surgery programs, and just 10% of these could be considered programs that attract rural surgeons, according to Dr. Satiani. "I think American surgery is going to have to give this a separate tract within residency programs."

Audience member Dr. Mark Malangoni, associate executive director of the American Board of Surgery in Philadelphia, pointed out that in such rural areas as Wyoming, the closest medical school is more than 1,000 miles away in Washington state. He suggested that one way to link rural hospitals and to counteract the professional isolation experienced by some rural physicians is through Web-based surgeon-to-surgeon consultations, an idea strongly supported by a recent survey of American College of Surgeons fellows.

If a new medical school were located in a rural area, Dr. Satiani said it could feed two to three nearby states, but not one of the new medical schools built in the last 5 years has been in truly rural areas.

Finally, several audience members suggested that efforts need to be made to eliminate the perception among residents that surgical specialists are somehow better than general surgeons.

"It’s the one-on-one thing that’s going to work with the residents, because all they see are these super-specialists," Dr. Satiani said. "I think it has to come from the programs and the leadership; defining general surgery better, even going as far as changing the name, if that becomes an important issue."

When asked in an interview what that new name might be, Dr. Satiani said the terms "master surgeon" and "omni surgeon" have been floated, with master surgeon more likely to resonate with the general public.

The authors reported no conflicts of interest.