Thoracic Surgery News (Archived)

CHICAGO - A small study provides compelling data that both the genotype and phenotype of non-small cell lung cancers can transform with acquired resistance to tyrosine kinase inhibitors.

Repeat tumor biopsies revealed that the histologic diagnosis of the tumor shifted from adenocarcinoma to small cell lung cancer (SCLC) in 14% of 37 consecutive patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) and acquired tyrosine kinase inhibitor (TKI) resistance, Dr. Lecia Sequist said at the Multidisciplinary Syposium on Thoracic Oncology.

The L858R mutation or E 19 deletion was retained in all cases. In one patient, an additional PIK3CA mutation was seen only when the tumor shifted to SCLC.
Although other groups have documented sporadictransformation, Dr. Sequist called the 14% transformation rate remarkable. “I think this points to a broader conceptual model of acquired resistance, and we need to think very carefully about doing more repeat biopsies in patients,” she said.

EGFR-mutant NSCLC is highly sensitive to EGFR TKI therapy, but acquired resistance develops at about 9-12 months due to T790M mutations in half of patients and MET amplification in 10% to 15%, said Dr. Sequist of Massachusetts General Hospital Cancer Center, Boston.

Although re-biopsy is not common practice, invited discussant Dr. Mark Socinski said it should be on the clinician's radar because it can alter the therapeutic course of refractory disease and arguably the clinical benefit.

“I think the message here is to consider re-biopsy more often in selected patients until we have a better understanding of this one disease we call non-small lung cancer that we realize is an incredibly heterogenous disease,” said Dr. Socinski, director of the thoracic oncology program at the Lineberger Comprehensive Cancer Center at the University of North Carolina-Chapel Hill.
 
Among the five patients whose cancer transformed, two maintained a slow, indolent course after SCLC transformation, while three had a change around the time of their biopsy to an explosive growth pattern more clinically reminiscent of SCLC, Dr. Sequist said. Four patients were treated with SCLC-like chemotherapy regimens, and three responded with marked partial responses.

Longitudinal data from fluorescent in situ hybridization analysis for MET and EGFR gene copy number suggest that the resistant tumor is distinct from the original tumor and that MET amplification lies in a distinct subpopulation of the cell and is selected out under pressure from TKI therapy, she said.

Multiple biopsies over time also identified a waxing and waning of genotypic and phenotypic findings in response to TKI therapy. This pattern was most pronounced in a case that transformed from EGFR TKI-sensitive adenocarcinoma to resistant SCLC while on erlotinib (Tarceva) for more than 1 year, switched back to TKI-sensitive adenocarcinoma following treatment with chemotherapy and radiation and a 9- to 10-month break from erlotinib, and then after a very successful, but short-lived re-response to erlotinib, shifted back to SCLC a second time upon clinical resistance.

“It's showing us that if you do repeat biopsies, it can direct patients towards clinical trials that they have a higher likelihood of benefiting from,” she said.

The population comprised 15 men and 22 women, median age 60 years. All had responded to either gefitinib (Iressa) or erlotinib, with a median of 18.4 months of initial EGFR TKI therapy. The majority (81%) remained on TKI at the time of repeat biopsy. Repeat biopsy showed T790m mutations in 49%, PIK3CA in 5%, MET amplification in 5%, and an unknown mechanism in 30%, reported Dr. Sequist.

Dr. Sequist and Dr. Socinski disclosed no relevant conflicts.

CHICAGO - A small study provides compelling data that both the genotype and phenotype of non-small cell lung cancers can transform with acquired resistance to tyrosine kinase inhibitors.

Repeat tumor biopsies revealed that the histologic diagnosis of the tumor shifted from adenocarcinoma to small cell lung cancer (SCLC) in 14% of 37 consecutive patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) and acquired tyrosine kinase inhibitor (TKI) resistance, Dr. Lecia Sequist said at the Multidisciplinary Syposium on Thoracic Oncology.

The L858R mutation or E 19 deletion was retained in all cases. In one patient, an additional PIK3CA mutation was seen only when the tumor shifted to SCLC.
Although other groups have documented sporadictransformation, Dr. Sequist called the 14% transformation rate remarkable. “I think this points to a broader conceptual model of acquired resistance, and we need to think very carefully about doing more repeat biopsies in patients,” she said.

EGFR-mutant NSCLC is highly sensitive to EGFR TKI therapy, but acquired resistance develops at about 9-12 months due to T790M mutations in half of patients and MET amplification in 10% to 15%, said Dr. Sequist of Massachusetts General Hospital Cancer Center, Boston.

Although re-biopsy is not common practice, invited discussant Dr. Mark Socinski said it should be on the clinician's radar because it can alter the therapeutic course of refractory disease and arguably the clinical benefit.

“I think the message here is to consider re-biopsy more often in selected patients until we have a better understanding of this one disease we call non-small lung cancer that we realize is an incredibly heterogenous disease,” said Dr. Socinski, director of the thoracic oncology program at the Lineberger Comprehensive Cancer Center at the University of North Carolina-Chapel Hill.
 
Among the five patients whose cancer transformed, two maintained a slow, indolent course after SCLC transformation, while three had a change around the time of their biopsy to an explosive growth pattern more clinically reminiscent of SCLC, Dr. Sequist said. Four patients were treated with SCLC-like chemotherapy regimens, and three responded with marked partial responses.

Longitudinal data from fluorescent in situ hybridization analysis for MET and EGFR gene copy number suggest that the resistant tumor is distinct from the original tumor and that MET amplification lies in a distinct subpopulation of the cell and is selected out under pressure from TKI therapy, she said.

Multiple biopsies over time also identified a waxing and waning of genotypic and phenotypic findings in response to TKI therapy. This pattern was most pronounced in a case that transformed from EGFR TKI-sensitive adenocarcinoma to resistant SCLC while on erlotinib (Tarceva) for more than 1 year, switched back to TKI-sensitive adenocarcinoma following treatment with chemotherapy and radiation and a 9- to 10-month break from erlotinib, and then after a very successful, but short-lived re-response to erlotinib, shifted back to SCLC a second time upon clinical resistance.

“It's showing us that if you do repeat biopsies, it can direct patients towards clinical trials that they have a higher likelihood of benefiting from,” she said.

The population comprised 15 men and 22 women, median age 60 years. All had responded to either gefitinib (Iressa) or erlotinib, with a median of 18.4 months of initial EGFR TKI therapy. The majority (81%) remained on TKI at the time of repeat biopsy. Repeat biopsy showed T790m mutations in 49%, PIK3CA in 5%, MET amplification in 5%, and an unknown mechanism in 30%, reported Dr. Sequist.

Dr. Sequist and Dr. Socinski disclosed no relevant conflicts.

CHICAGO - A small study provides compelling data that both the genotype and phenotype of non-small cell lung cancers can transform with acquired resistance to tyrosine kinase inhibitors.

Repeat tumor biopsies revealed that the histologic diagnosis of the tumor shifted from adenocarcinoma to small cell lung cancer (SCLC) in 14% of 37 consecutive patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) and acquired tyrosine kinase inhibitor (TKI) resistance, Dr. Lecia Sequist said at the Multidisciplinary Syposium on Thoracic Oncology.

The L858R mutation or E 19 deletion was retained in all cases. In one patient, an additional PIK3CA mutation was seen only when the tumor shifted to SCLC.
Although other groups have documented sporadictransformation, Dr. Sequist called the 14% transformation rate remarkable. “I think this points to a broader conceptual model of acquired resistance, and we need to think very carefully about doing more repeat biopsies in patients,” she said.

EGFR-mutant NSCLC is highly sensitive to EGFR TKI therapy, but acquired resistance develops at about 9-12 months due to T790M mutations in half of patients and MET amplification in 10% to 15%, said Dr. Sequist of Massachusetts General Hospital Cancer Center, Boston.

Although re-biopsy is not common practice, invited discussant Dr. Mark Socinski said it should be on the clinician's radar because it can alter the therapeutic course of refractory disease and arguably the clinical benefit.

“I think the message here is to consider re-biopsy more often in selected patients until we have a better understanding of this one disease we call non-small lung cancer that we realize is an incredibly heterogenous disease,” said Dr. Socinski, director of the thoracic oncology program at the Lineberger Comprehensive Cancer Center at the University of North Carolina-Chapel Hill.
 
Among the five patients whose cancer transformed, two maintained a slow, indolent course after SCLC transformation, while three had a change around the time of their biopsy to an explosive growth pattern more clinically reminiscent of SCLC, Dr. Sequist said. Four patients were treated with SCLC-like chemotherapy regimens, and three responded with marked partial responses.

Longitudinal data from fluorescent in situ hybridization analysis for MET and EGFR gene copy number suggest that the resistant tumor is distinct from the original tumor and that MET amplification lies in a distinct subpopulation of the cell and is selected out under pressure from TKI therapy, she said.

Multiple biopsies over time also identified a waxing and waning of genotypic and phenotypic findings in response to TKI therapy. This pattern was most pronounced in a case that transformed from EGFR TKI-sensitive adenocarcinoma to resistant SCLC while on erlotinib (Tarceva) for more than 1 year, switched back to TKI-sensitive adenocarcinoma following treatment with chemotherapy and radiation and a 9- to 10-month break from erlotinib, and then after a very successful, but short-lived re-response to erlotinib, shifted back to SCLC a second time upon clinical resistance.

“It's showing us that if you do repeat biopsies, it can direct patients towards clinical trials that they have a higher likelihood of benefiting from,” she said.

The population comprised 15 men and 22 women, median age 60 years. All had responded to either gefitinib (Iressa) or erlotinib, with a median of 18.4 months of initial EGFR TKI therapy. The majority (81%) remained on TKI at the time of repeat biopsy. Repeat biopsy showed T790m mutations in 49%, PIK3CA in 5%, MET amplification in 5%, and an unknown mechanism in 30%, reported Dr. Sequist.

Dr. Sequist and Dr. Socinski disclosed no relevant conflicts.

CHICAGO - Nonsurgical approaches are beginning to dominate the management of acute esophageal perforations.

An analysis of 81 consecutive acute esophageal perforation cases between June 1989 and March 2009 revealed that nonsurgical management jumped from 0% during the first 4 years of the study to 75% in the last 4 years.

The average length of stay declined significantly over the same period, from 26 days to 20 days , while complications trended downward, from 50% to 33%, Dr. Michal Hubka reported on behalf of lead author Dr. Madhan Kumar Kuppusamy and their colleagues at Virginia Mason Medical Center in Seattle.

In all, 33 patients were managed nonoperatively and 48 surgically. Primary repair was the most common surgical approach (34 cases). Nonsurgical treatments included endoscopic stenting (11 cases), drainage procedures including mediastinal drainage (13 cases), total parenteral nutrition (7 cases), Dobhoff feeding tube (5 cases), gastrostomy (5 cases), endoscopic repair with clips or glue (3 cases), and feeding jejunostomy (3 cases).

"Nonoperative treatment options are increasing and surgeons must be able to apply these techniques to improve outcomes,” Dr. Hubka said at the annual meeting of the Western Surgical Society.

Hybrid-type management was performed in 21% of patients and most often took the form of endoscopic stents or drainage at the time of open or thoracoscopic drainage or decortication.

The nonoperative group was less likely than the operative group to experience pneumonia (4 patients vs. 7 patients) and dysrhythmias (4 patients vs. 11 patients), but more likely to experience persistent leak at the 14th day (3 vs. 2), stent migration (3 vs. 0), sepsis (1 vs. 0), and renal failure (1 vs. 0), Dr. Hubka said. Deep vein thrombosis occurred in one patient in each group.

Two patients managed medically died vs. one treated surgically (6% vs. 2%), for an overall mortality rate of 3.7%. A historical comparison of nine other studies involving nonoperative management of esophageal perforations presented by Dr. Hubka showed mortality rates reaching a high of 24% between 1973 and 1993 and a low of 3.8% between 1990 and 2001.

One of those nine studies identified a stepwise increase in mortality as time from perforation to diagnosis increased, with 5% of 75 patients dying with an immediate diagnosis vs. 14% with a diagnosis within 24 hours and 44% if the diagnosis occurred after 24 hours (Eur. J. Cardiothorac. Surg. 2003;23:799-804).

In all, 57 patients in the current analysis were treated within 24 hours and 24 were treated after 24 hours. Length of stay was significantly shorter in the early-treatment group at 15.6 days vs. 29.4 days in the late-treatment group. In the early-treatment group, complications occurred in 20 and death in 1; in the late-treatment group, 11 had complications and 2 died, Dr. Hubka said.

"Time to diagnosis continues to be important; however, management in an experienced center facile with all current management techniques is the major issue affecting outcomes,” he said.

The percentage of cases referred to the tertiary referral center was 50% from 1989 to 1992 and 79% from 2005 to 2009. Referred patients were significantly more likely to be treated more than 24 hours after perforation.

The improvement in outcomes is likely related to increasing diversity of treatment techniques and management in specialty centers, Dr. Hubka said.

Invited discussant Dr. Jeffrey Peters from the University of Rochester (N.Y.) Medical Center, said, "What you heard was an increasing chorus of a paradigm change, if you will, that's sort of paradoxical to most of us - that someone with a hole in their esophagus does better if you don't operate on them. I still struggle trying not to do that when patients present in the emergency room with these issues.”

Still, he described the improvement in outcomes as true progress for patients. Dr. Peters noted that the etiology of acute perforations has changed over time, with most now iatrogenic, and thus the benefit of early treatment may not be as critical as in years past. He said referral to a tertiary center is important, but that the paper did not prove a causal effect.

Based on the findings, Dr. Peters asked when surgeons should operate, how the size of the injury and presence of underlying disease should be taken into account in treatment decisions, and when surgery should be considered if nonoperative therapy fails.

Dr. Hubka said patients with larger esophageal tears or injuries and moderate mediastinal pleural contamination who can tolerate surgery are the ones who proceed to the operating room. He suggested that the study's operative rate would likely have been higher if patients with perforations due to neoplasia or cancer had been included and that the presence of such underlying disease would surely push them toward operative management in clinical practice. Finally, if a patient becomes unstable or their level of contamination increases despite nonsurgical management, they would proceed to surgery and decontamination.

"A point of our study is that this management, whether it's endoscopic or operative, should be performed by surgeons because we have all the tools to manage all patients appropriately,” Dr. Hubka said.

The study authors and discussant said that they had no financial disclosures.

CHICAGO - Nonsurgical approaches are beginning to dominate the management of acute esophageal perforations.

An analysis of 81 consecutive acute esophageal perforation cases between June 1989 and March 2009 revealed that nonsurgical management jumped from 0% during the first 4 years of the study to 75% in the last 4 years.

The average length of stay declined significantly over the same period, from 26 days to 20 days , while complications trended downward, from 50% to 33%, Dr. Michal Hubka reported on behalf of lead author Dr. Madhan Kumar Kuppusamy and their colleagues at Virginia Mason Medical Center in Seattle.

In all, 33 patients were managed nonoperatively and 48 surgically. Primary repair was the most common surgical approach (34 cases). Nonsurgical treatments included endoscopic stenting (11 cases), drainage procedures including mediastinal drainage (13 cases), total parenteral nutrition (7 cases), Dobhoff feeding tube (5 cases), gastrostomy (5 cases), endoscopic repair with clips or glue (3 cases), and feeding jejunostomy (3 cases).

"Nonoperative treatment options are increasing and surgeons must be able to apply these techniques to improve outcomes,” Dr. Hubka said at the annual meeting of the Western Surgical Society.

Hybrid-type management was performed in 21% of patients and most often took the form of endoscopic stents or drainage at the time of open or thoracoscopic drainage or decortication.

The nonoperative group was less likely than the operative group to experience pneumonia (4 patients vs. 7 patients) and dysrhythmias (4 patients vs. 11 patients), but more likely to experience persistent leak at the 14th day (3 vs. 2), stent migration (3 vs. 0), sepsis (1 vs. 0), and renal failure (1 vs. 0), Dr. Hubka said. Deep vein thrombosis occurred in one patient in each group.

Two patients managed medically died vs. one treated surgically (6% vs. 2%), for an overall mortality rate of 3.7%. A historical comparison of nine other studies involving nonoperative management of esophageal perforations presented by Dr. Hubka showed mortality rates reaching a high of 24% between 1973 and 1993 and a low of 3.8% between 1990 and 2001.

One of those nine studies identified a stepwise increase in mortality as time from perforation to diagnosis increased, with 5% of 75 patients dying with an immediate diagnosis vs. 14% with a diagnosis within 24 hours and 44% if the diagnosis occurred after 24 hours (Eur. J. Cardiothorac. Surg. 2003;23:799-804).

In all, 57 patients in the current analysis were treated within 24 hours and 24 were treated after 24 hours. Length of stay was significantly shorter in the early-treatment group at 15.6 days vs. 29.4 days in the late-treatment group. In the early-treatment group, complications occurred in 20 and death in 1; in the late-treatment group, 11 had complications and 2 died, Dr. Hubka said.

"Time to diagnosis continues to be important; however, management in an experienced center facile with all current management techniques is the major issue affecting outcomes,” he said.

The percentage of cases referred to the tertiary referral center was 50% from 1989 to 1992 and 79% from 2005 to 2009. Referred patients were significantly more likely to be treated more than 24 hours after perforation.

The improvement in outcomes is likely related to increasing diversity of treatment techniques and management in specialty centers, Dr. Hubka said.

Invited discussant Dr. Jeffrey Peters from the University of Rochester (N.Y.) Medical Center, said, "What you heard was an increasing chorus of a paradigm change, if you will, that's sort of paradoxical to most of us - that someone with a hole in their esophagus does better if you don't operate on them. I still struggle trying not to do that when patients present in the emergency room with these issues.”

Still, he described the improvement in outcomes as true progress for patients. Dr. Peters noted that the etiology of acute perforations has changed over time, with most now iatrogenic, and thus the benefit of early treatment may not be as critical as in years past. He said referral to a tertiary center is important, but that the paper did not prove a causal effect.

Based on the findings, Dr. Peters asked when surgeons should operate, how the size of the injury and presence of underlying disease should be taken into account in treatment decisions, and when surgery should be considered if nonoperative therapy fails.

Dr. Hubka said patients with larger esophageal tears or injuries and moderate mediastinal pleural contamination who can tolerate surgery are the ones who proceed to the operating room. He suggested that the study's operative rate would likely have been higher if patients with perforations due to neoplasia or cancer had been included and that the presence of such underlying disease would surely push them toward operative management in clinical practice. Finally, if a patient becomes unstable or their level of contamination increases despite nonsurgical management, they would proceed to surgery and decontamination.

"A point of our study is that this management, whether it's endoscopic or operative, should be performed by surgeons because we have all the tools to manage all patients appropriately,” Dr. Hubka said.

The study authors and discussant said that they had no financial disclosures.

CHICAGO - Nonsurgical approaches are beginning to dominate the management of acute esophageal perforations.

An analysis of 81 consecutive acute esophageal perforation cases between June 1989 and March 2009 revealed that nonsurgical management jumped from 0% during the first 4 years of the study to 75% in the last 4 years.

The average length of stay declined significantly over the same period, from 26 days to 20 days , while complications trended downward, from 50% to 33%, Dr. Michal Hubka reported on behalf of lead author Dr. Madhan Kumar Kuppusamy and their colleagues at Virginia Mason Medical Center in Seattle.

In all, 33 patients were managed nonoperatively and 48 surgically. Primary repair was the most common surgical approach (34 cases). Nonsurgical treatments included endoscopic stenting (11 cases), drainage procedures including mediastinal drainage (13 cases), total parenteral nutrition (7 cases), Dobhoff feeding tube (5 cases), gastrostomy (5 cases), endoscopic repair with clips or glue (3 cases), and feeding jejunostomy (3 cases).

"Nonoperative treatment options are increasing and surgeons must be able to apply these techniques to improve outcomes,” Dr. Hubka said at the annual meeting of the Western Surgical Society.

Hybrid-type management was performed in 21% of patients and most often took the form of endoscopic stents or drainage at the time of open or thoracoscopic drainage or decortication.

The nonoperative group was less likely than the operative group to experience pneumonia (4 patients vs. 7 patients) and dysrhythmias (4 patients vs. 11 patients), but more likely to experience persistent leak at the 14th day (3 vs. 2), stent migration (3 vs. 0), sepsis (1 vs. 0), and renal failure (1 vs. 0), Dr. Hubka said. Deep vein thrombosis occurred in one patient in each group.

Two patients managed medically died vs. one treated surgically (6% vs. 2%), for an overall mortality rate of 3.7%. A historical comparison of nine other studies involving nonoperative management of esophageal perforations presented by Dr. Hubka showed mortality rates reaching a high of 24% between 1973 and 1993 and a low of 3.8% between 1990 and 2001.

One of those nine studies identified a stepwise increase in mortality as time from perforation to diagnosis increased, with 5% of 75 patients dying with an immediate diagnosis vs. 14% with a diagnosis within 24 hours and 44% if the diagnosis occurred after 24 hours (Eur. J. Cardiothorac. Surg. 2003;23:799-804).

In all, 57 patients in the current analysis were treated within 24 hours and 24 were treated after 24 hours. Length of stay was significantly shorter in the early-treatment group at 15.6 days vs. 29.4 days in the late-treatment group. In the early-treatment group, complications occurred in 20 and death in 1; in the late-treatment group, 11 had complications and 2 died, Dr. Hubka said.

"Time to diagnosis continues to be important; however, management in an experienced center facile with all current management techniques is the major issue affecting outcomes,” he said.

The percentage of cases referred to the tertiary referral center was 50% from 1989 to 1992 and 79% from 2005 to 2009. Referred patients were significantly more likely to be treated more than 24 hours after perforation.

The improvement in outcomes is likely related to increasing diversity of treatment techniques and management in specialty centers, Dr. Hubka said.

Invited discussant Dr. Jeffrey Peters from the University of Rochester (N.Y.) Medical Center, said, "What you heard was an increasing chorus of a paradigm change, if you will, that's sort of paradoxical to most of us - that someone with a hole in their esophagus does better if you don't operate on them. I still struggle trying not to do that when patients present in the emergency room with these issues.”

Still, he described the improvement in outcomes as true progress for patients. Dr. Peters noted that the etiology of acute perforations has changed over time, with most now iatrogenic, and thus the benefit of early treatment may not be as critical as in years past. He said referral to a tertiary center is important, but that the paper did not prove a causal effect.

Based on the findings, Dr. Peters asked when surgeons should operate, how the size of the injury and presence of underlying disease should be taken into account in treatment decisions, and when surgery should be considered if nonoperative therapy fails.

Dr. Hubka said patients with larger esophageal tears or injuries and moderate mediastinal pleural contamination who can tolerate surgery are the ones who proceed to the operating room. He suggested that the study's operative rate would likely have been higher if patients with perforations due to neoplasia or cancer had been included and that the presence of such underlying disease would surely push them toward operative management in clinical practice. Finally, if a patient becomes unstable or their level of contamination increases despite nonsurgical management, they would proceed to surgery and decontamination.

"A point of our study is that this management, whether it's endoscopic or operative, should be performed by surgeons because we have all the tools to manage all patients appropriately,” Dr. Hubka said.

The study authors and discussant said that they had no financial disclosures.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

CHICAGO - A small study provides compelling data that both the genotype and phenotype of non-small cell lung cancers can transform with acquired resistance to tyrosine kinase inhibitors.

Repeat tumor biopsies revealed that the histologic diagnosis of the tumor shifted from adenocarcinoma to small cell lung cancer (SCLC) in 14% of 37 consecutive patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) and acquired tyrosine kinase inhibitor (TKI) resistance, Dr. Lecia Sequist said at the Multidisciplinary Syposium on Thoracic Oncology.

The L858R mutation or E 19 deletion was retained in all cases. In one patient, an additional PIK3CA mutation was seen only when the tumor shifted to SCLC.
Although other groups have documented sporadictransformation, Dr. Sequist called the 14% transformation rate remarkable. “I think this points to a broader conceptual model of acquired resistance, and we need to think very carefully about doing more repeat biopsies in patients,” she said.

EGFR-mutant NSCLC is highly sensitive to EGFR TKI therapy, but acquired resistance develops at about 9-12 months due to T790M mutations in half of patients and MET amplification in 10% to 15%, said Dr. Sequist of Massachusetts General Hospital Cancer Center, Boston.

Although re-biopsy is not common practice, invited discussant Dr. Mark Socinski said it should be on the clinician's radar because it can alter the therapeutic course of refractory disease and arguably the clinical benefit.

“I think the message here is to consider re-biopsy more often in selected patients until we have a better understanding of this one disease we call non-small lung cancer that we realize is an incredibly heterogenous disease,” said Dr. Socinski, director of the thoracic oncology program at the Lineberger Comprehensive Cancer Center at the University of North Carolina-Chapel Hill.
 
Among the five patients whose cancer transformed, two maintained a slow, indolent course after SCLC transformation, while three had a change around the time of their biopsy to an explosive growth pattern more clinically reminiscent of SCLC, Dr. Sequist said. Four patients were treated with SCLC-like chemotherapy regimens, and three responded with marked partial responses.

Longitudinal data from fluorescent in situ hybridization analysis for MET and EGFR gene copy number suggest that the resistant tumor is distinct from the original tumor and that MET amplification lies in a distinct subpopulation of the cell and is selected out under pressure from TKI therapy, she said.

Multiple biopsies over time also identified a waxing and waning of genotypic and phenotypic findings in response to TKI therapy. This pattern was most pronounced in a case that transformed from EGFR TKI-sensitive adenocarcinoma to resistant SCLC while on erlotinib (Tarceva) for more than 1 year, switched back to TKI-sensitive adenocarcinoma following treatment with chemotherapy and radiation and a 9- to 10-month break from erlotinib, and then after a very successful, but short-lived re-response to erlotinib, shifted back to SCLC a second time upon clinical resistance.

“It's showing us that if you do repeat biopsies, it can direct patients towards clinical trials that they have a higher likelihood of benefiting from,” she said.

The population comprised 15 men and 22 women, median age 60 years. All had responded to either gefitinib (Iressa) or erlotinib, with a median of 18.4 months of initial EGFR TKI therapy. The majority (81%) remained on TKI at the time of repeat biopsy. Repeat biopsy showed T790m mutations in 49%, PIK3CA in 5%, MET amplification in 5%, and an unknown mechanism in 30%, reported Dr. Sequist.

Dr. Sequist and Dr. Socinski disclosed no relevant conflicts.

CHICAGO - A small study provides compelling data that both the genotype and phenotype of non-small cell lung cancers can transform with acquired resistance to tyrosine kinase inhibitors.

Repeat tumor biopsies revealed that the histologic diagnosis of the tumor shifted from adenocarcinoma to small cell lung cancer (SCLC) in 14% of 37 consecutive patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) and acquired tyrosine kinase inhibitor (TKI) resistance, Dr. Lecia Sequist said at the Multidisciplinary Syposium on Thoracic Oncology.

The L858R mutation or E 19 deletion was retained in all cases. In one patient, an additional PIK3CA mutation was seen only when the tumor shifted to SCLC.
Although other groups have documented sporadictransformation, Dr. Sequist called the 14% transformation rate remarkable. “I think this points to a broader conceptual model of acquired resistance, and we need to think very carefully about doing more repeat biopsies in patients,” she said.

EGFR-mutant NSCLC is highly sensitive to EGFR TKI therapy, but acquired resistance develops at about 9-12 months due to T790M mutations in half of patients and MET amplification in 10% to 15%, said Dr. Sequist of Massachusetts General Hospital Cancer Center, Boston.

Although re-biopsy is not common practice, invited discussant Dr. Mark Socinski said it should be on the clinician's radar because it can alter the therapeutic course of refractory disease and arguably the clinical benefit.

“I think the message here is to consider re-biopsy more often in selected patients until we have a better understanding of this one disease we call non-small lung cancer that we realize is an incredibly heterogenous disease,” said Dr. Socinski, director of the thoracic oncology program at the Lineberger Comprehensive Cancer Center at the University of North Carolina-Chapel Hill.
 
Among the five patients whose cancer transformed, two maintained a slow, indolent course after SCLC transformation, while three had a change around the time of their biopsy to an explosive growth pattern more clinically reminiscent of SCLC, Dr. Sequist said. Four patients were treated with SCLC-like chemotherapy regimens, and three responded with marked partial responses.

Longitudinal data from fluorescent in situ hybridization analysis for MET and EGFR gene copy number suggest that the resistant tumor is distinct from the original tumor and that MET amplification lies in a distinct subpopulation of the cell and is selected out under pressure from TKI therapy, she said.

Multiple biopsies over time also identified a waxing and waning of genotypic and phenotypic findings in response to TKI therapy. This pattern was most pronounced in a case that transformed from EGFR TKI-sensitive adenocarcinoma to resistant SCLC while on erlotinib (Tarceva) for more than 1 year, switched back to TKI-sensitive adenocarcinoma following treatment with chemotherapy and radiation and a 9- to 10-month break from erlotinib, and then after a very successful, but short-lived re-response to erlotinib, shifted back to SCLC a second time upon clinical resistance.

“It's showing us that if you do repeat biopsies, it can direct patients towards clinical trials that they have a higher likelihood of benefiting from,” she said.

The population comprised 15 men and 22 women, median age 60 years. All had responded to either gefitinib (Iressa) or erlotinib, with a median of 18.4 months of initial EGFR TKI therapy. The majority (81%) remained on TKI at the time of repeat biopsy. Repeat biopsy showed T790m mutations in 49%, PIK3CA in 5%, MET amplification in 5%, and an unknown mechanism in 30%, reported Dr. Sequist.

Dr. Sequist and Dr. Socinski disclosed no relevant conflicts.

CHICAGO - A small study provides compelling data that both the genotype and phenotype of non-small cell lung cancers can transform with acquired resistance to tyrosine kinase inhibitors.

Repeat tumor biopsies revealed that the histologic diagnosis of the tumor shifted from adenocarcinoma to small cell lung cancer (SCLC) in 14% of 37 consecutive patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) and acquired tyrosine kinase inhibitor (TKI) resistance, Dr. Lecia Sequist said at the Multidisciplinary Syposium on Thoracic Oncology.

The L858R mutation or E 19 deletion was retained in all cases. In one patient, an additional PIK3CA mutation was seen only when the tumor shifted to SCLC.
Although other groups have documented sporadictransformation, Dr. Sequist called the 14% transformation rate remarkable. “I think this points to a broader conceptual model of acquired resistance, and we need to think very carefully about doing more repeat biopsies in patients,” she said.

EGFR-mutant NSCLC is highly sensitive to EGFR TKI therapy, but acquired resistance develops at about 9-12 months due to T790M mutations in half of patients and MET amplification in 10% to 15%, said Dr. Sequist of Massachusetts General Hospital Cancer Center, Boston.

Although re-biopsy is not common practice, invited discussant Dr. Mark Socinski said it should be on the clinician's radar because it can alter the therapeutic course of refractory disease and arguably the clinical benefit.

“I think the message here is to consider re-biopsy more often in selected patients until we have a better understanding of this one disease we call non-small lung cancer that we realize is an incredibly heterogenous disease,” said Dr. Socinski, director of the thoracic oncology program at the Lineberger Comprehensive Cancer Center at the University of North Carolina-Chapel Hill.
 
Among the five patients whose cancer transformed, two maintained a slow, indolent course after SCLC transformation, while three had a change around the time of their biopsy to an explosive growth pattern more clinically reminiscent of SCLC, Dr. Sequist said. Four patients were treated with SCLC-like chemotherapy regimens, and three responded with marked partial responses.

Longitudinal data from fluorescent in situ hybridization analysis for MET and EGFR gene copy number suggest that the resistant tumor is distinct from the original tumor and that MET amplification lies in a distinct subpopulation of the cell and is selected out under pressure from TKI therapy, she said.

Multiple biopsies over time also identified a waxing and waning of genotypic and phenotypic findings in response to TKI therapy. This pattern was most pronounced in a case that transformed from EGFR TKI-sensitive adenocarcinoma to resistant SCLC while on erlotinib (Tarceva) for more than 1 year, switched back to TKI-sensitive adenocarcinoma following treatment with chemotherapy and radiation and a 9- to 10-month break from erlotinib, and then after a very successful, but short-lived re-response to erlotinib, shifted back to SCLC a second time upon clinical resistance.

“It's showing us that if you do repeat biopsies, it can direct patients towards clinical trials that they have a higher likelihood of benefiting from,” she said.

The population comprised 15 men and 22 women, median age 60 years. All had responded to either gefitinib (Iressa) or erlotinib, with a median of 18.4 months of initial EGFR TKI therapy. The majority (81%) remained on TKI at the time of repeat biopsy. Repeat biopsy showed T790m mutations in 49%, PIK3CA in 5%, MET amplification in 5%, and an unknown mechanism in 30%, reported Dr. Sequist.

Dr. Sequist and Dr. Socinski disclosed no relevant conflicts.

CHICAGO - Nonsurgical approaches are beginning to dominate the management of acute esophageal perforations.

An analysis of 81 consecutive acute esophageal perforation cases between June 1989 and March 2009 revealed that nonsurgical management jumped from 0% during the first 4 years of the study to 75% in the last 4 years.

The average length of stay declined significantly over the same period, from 26 days to 20 days , while complications trended downward, from 50% to 33%, Dr. Michal Hubka reported on behalf of lead author Dr. Madhan Kumar Kuppusamy and their colleagues at Virginia Mason Medical Center in Seattle.

In all, 33 patients were managed nonoperatively and 48 surgically. Primary repair was the most common surgical approach (34 cases). Nonsurgical treatments included endoscopic stenting (11 cases), drainage procedures including mediastinal drainage (13 cases), total parenteral nutrition (7 cases), Dobhoff feeding tube (5 cases), gastrostomy (5 cases), endoscopic repair with clips or glue (3 cases), and feeding jejunostomy (3 cases).

"Nonoperative treatment options are increasing and surgeons must be able to apply these techniques to improve outcomes,” Dr. Hubka said at the annual meeting of the Western Surgical Society.

Hybrid-type management was performed in 21% of patients and most often took the form of endoscopic stents or drainage at the time of open or thoracoscopic drainage or decortication.

The nonoperative group was less likely than the operative group to experience pneumonia (4 patients vs. 7 patients) and dysrhythmias (4 patients vs. 11 patients), but more likely to experience persistent leak at the 14th day (3 vs. 2), stent migration (3 vs. 0), sepsis (1 vs. 0), and renal failure (1 vs. 0), Dr. Hubka said. Deep vein thrombosis occurred in one patient in each group.

Two patients managed medically died vs. one treated surgically (6% vs. 2%), for an overall mortality rate of 3.7%. A historical comparison of nine other studies involving nonoperative management of esophageal perforations presented by Dr. Hubka showed mortality rates reaching a high of 24% between 1973 and 1993 and a low of 3.8% between 1990 and 2001.

One of those nine studies identified a stepwise increase in mortality as time from perforation to diagnosis increased, with 5% of 75 patients dying with an immediate diagnosis vs. 14% with a diagnosis within 24 hours and 44% if the diagnosis occurred after 24 hours (Eur. J. Cardiothorac. Surg. 2003;23:799-804).

In all, 57 patients in the current analysis were treated within 24 hours and 24 were treated after 24 hours. Length of stay was significantly shorter in the early-treatment group at 15.6 days vs. 29.4 days in the late-treatment group. In the early-treatment group, complications occurred in 20 and death in 1; in the late-treatment group, 11 had complications and 2 died, Dr. Hubka said.

"Time to diagnosis continues to be important; however, management in an experienced center facile with all current management techniques is the major issue affecting outcomes,” he said.

The percentage of cases referred to the tertiary referral center was 50% from 1989 to 1992 and 79% from 2005 to 2009. Referred patients were significantly more likely to be treated more than 24 hours after perforation.

The improvement in outcomes is likely related to increasing diversity of treatment techniques and management in specialty centers, Dr. Hubka said.

Invited discussant Dr. Jeffrey Peters from the University of Rochester (N.Y.) Medical Center, said, "What you heard was an increasing chorus of a paradigm change, if you will, that's sort of paradoxical to most of us - that someone with a hole in their esophagus does better if you don't operate on them. I still struggle trying not to do that when patients present in the emergency room with these issues.”

Still, he described the improvement in outcomes as true progress for patients. Dr. Peters noted that the etiology of acute perforations has changed over time, with most now iatrogenic, and thus the benefit of early treatment may not be as critical as in years past. He said referral to a tertiary center is important, but that the paper did not prove a causal effect.

Based on the findings, Dr. Peters asked when surgeons should operate, how the size of the injury and presence of underlying disease should be taken into account in treatment decisions, and when surgery should be considered if nonoperative therapy fails.

Dr. Hubka said patients with larger esophageal tears or injuries and moderate mediastinal pleural contamination who can tolerate surgery are the ones who proceed to the operating room. He suggested that the study's operative rate would likely have been higher if patients with perforations due to neoplasia or cancer had been included and that the presence of such underlying disease would surely push them toward operative management in clinical practice. Finally, if a patient becomes unstable or their level of contamination increases despite nonsurgical management, they would proceed to surgery and decontamination.

"A point of our study is that this management, whether it's endoscopic or operative, should be performed by surgeons because we have all the tools to manage all patients appropriately,” Dr. Hubka said.

The study authors and discussant said that they had no financial disclosures.

CHICAGO - Nonsurgical approaches are beginning to dominate the management of acute esophageal perforations.

An analysis of 81 consecutive acute esophageal perforation cases between June 1989 and March 2009 revealed that nonsurgical management jumped from 0% during the first 4 years of the study to 75% in the last 4 years.

The average length of stay declined significantly over the same period, from 26 days to 20 days , while complications trended downward, from 50% to 33%, Dr. Michal Hubka reported on behalf of lead author Dr. Madhan Kumar Kuppusamy and their colleagues at Virginia Mason Medical Center in Seattle.

In all, 33 patients were managed nonoperatively and 48 surgically. Primary repair was the most common surgical approach (34 cases). Nonsurgical treatments included endoscopic stenting (11 cases), drainage procedures including mediastinal drainage (13 cases), total parenteral nutrition (7 cases), Dobhoff feeding tube (5 cases), gastrostomy (5 cases), endoscopic repair with clips or glue (3 cases), and feeding jejunostomy (3 cases).

"Nonoperative treatment options are increasing and surgeons must be able to apply these techniques to improve outcomes,” Dr. Hubka said at the annual meeting of the Western Surgical Society.

Hybrid-type management was performed in 21% of patients and most often took the form of endoscopic stents or drainage at the time of open or thoracoscopic drainage or decortication.

The nonoperative group was less likely than the operative group to experience pneumonia (4 patients vs. 7 patients) and dysrhythmias (4 patients vs. 11 patients), but more likely to experience persistent leak at the 14th day (3 vs. 2), stent migration (3 vs. 0), sepsis (1 vs. 0), and renal failure (1 vs. 0), Dr. Hubka said. Deep vein thrombosis occurred in one patient in each group.

Two patients managed medically died vs. one treated surgically (6% vs. 2%), for an overall mortality rate of 3.7%. A historical comparison of nine other studies involving nonoperative management of esophageal perforations presented by Dr. Hubka showed mortality rates reaching a high of 24% between 1973 and 1993 and a low of 3.8% between 1990 and 2001.

One of those nine studies identified a stepwise increase in mortality as time from perforation to diagnosis increased, with 5% of 75 patients dying with an immediate diagnosis vs. 14% with a diagnosis within 24 hours and 44% if the diagnosis occurred after 24 hours (Eur. J. Cardiothorac. Surg. 2003;23:799-804).

In all, 57 patients in the current analysis were treated within 24 hours and 24 were treated after 24 hours. Length of stay was significantly shorter in the early-treatment group at 15.6 days vs. 29.4 days in the late-treatment group. In the early-treatment group, complications occurred in 20 and death in 1; in the late-treatment group, 11 had complications and 2 died, Dr. Hubka said.

"Time to diagnosis continues to be important; however, management in an experienced center facile with all current management techniques is the major issue affecting outcomes,” he said.

The percentage of cases referred to the tertiary referral center was 50% from 1989 to 1992 and 79% from 2005 to 2009. Referred patients were significantly more likely to be treated more than 24 hours after perforation.

The improvement in outcomes is likely related to increasing diversity of treatment techniques and management in specialty centers, Dr. Hubka said.

Invited discussant Dr. Jeffrey Peters from the University of Rochester (N.Y.) Medical Center, said, "What you heard was an increasing chorus of a paradigm change, if you will, that's sort of paradoxical to most of us - that someone with a hole in their esophagus does better if you don't operate on them. I still struggle trying not to do that when patients present in the emergency room with these issues.”

Still, he described the improvement in outcomes as true progress for patients. Dr. Peters noted that the etiology of acute perforations has changed over time, with most now iatrogenic, and thus the benefit of early treatment may not be as critical as in years past. He said referral to a tertiary center is important, but that the paper did not prove a causal effect.

Based on the findings, Dr. Peters asked when surgeons should operate, how the size of the injury and presence of underlying disease should be taken into account in treatment decisions, and when surgery should be considered if nonoperative therapy fails.

Dr. Hubka said patients with larger esophageal tears or injuries and moderate mediastinal pleural contamination who can tolerate surgery are the ones who proceed to the operating room. He suggested that the study's operative rate would likely have been higher if patients with perforations due to neoplasia or cancer had been included and that the presence of such underlying disease would surely push them toward operative management in clinical practice. Finally, if a patient becomes unstable or their level of contamination increases despite nonsurgical management, they would proceed to surgery and decontamination.

"A point of our study is that this management, whether it's endoscopic or operative, should be performed by surgeons because we have all the tools to manage all patients appropriately,” Dr. Hubka said.

The study authors and discussant said that they had no financial disclosures.

CHICAGO - Nonsurgical approaches are beginning to dominate the management of acute esophageal perforations.

An analysis of 81 consecutive acute esophageal perforation cases between June 1989 and March 2009 revealed that nonsurgical management jumped from 0% during the first 4 years of the study to 75% in the last 4 years.

The average length of stay declined significantly over the same period, from 26 days to 20 days , while complications trended downward, from 50% to 33%, Dr. Michal Hubka reported on behalf of lead author Dr. Madhan Kumar Kuppusamy and their colleagues at Virginia Mason Medical Center in Seattle.

In all, 33 patients were managed nonoperatively and 48 surgically. Primary repair was the most common surgical approach (34 cases). Nonsurgical treatments included endoscopic stenting (11 cases), drainage procedures including mediastinal drainage (13 cases), total parenteral nutrition (7 cases), Dobhoff feeding tube (5 cases), gastrostomy (5 cases), endoscopic repair with clips or glue (3 cases), and feeding jejunostomy (3 cases).

"Nonoperative treatment options are increasing and surgeons must be able to apply these techniques to improve outcomes,” Dr. Hubka said at the annual meeting of the Western Surgical Society.

Hybrid-type management was performed in 21% of patients and most often took the form of endoscopic stents or drainage at the time of open or thoracoscopic drainage or decortication.

The nonoperative group was less likely than the operative group to experience pneumonia (4 patients vs. 7 patients) and dysrhythmias (4 patients vs. 11 patients), but more likely to experience persistent leak at the 14th day (3 vs. 2), stent migration (3 vs. 0), sepsis (1 vs. 0), and renal failure (1 vs. 0), Dr. Hubka said. Deep vein thrombosis occurred in one patient in each group.

Two patients managed medically died vs. one treated surgically (6% vs. 2%), for an overall mortality rate of 3.7%. A historical comparison of nine other studies involving nonoperative management of esophageal perforations presented by Dr. Hubka showed mortality rates reaching a high of 24% between 1973 and 1993 and a low of 3.8% between 1990 and 2001.

One of those nine studies identified a stepwise increase in mortality as time from perforation to diagnosis increased, with 5% of 75 patients dying with an immediate diagnosis vs. 14% with a diagnosis within 24 hours and 44% if the diagnosis occurred after 24 hours (Eur. J. Cardiothorac. Surg. 2003;23:799-804).

In all, 57 patients in the current analysis were treated within 24 hours and 24 were treated after 24 hours. Length of stay was significantly shorter in the early-treatment group at 15.6 days vs. 29.4 days in the late-treatment group. In the early-treatment group, complications occurred in 20 and death in 1; in the late-treatment group, 11 had complications and 2 died, Dr. Hubka said.

"Time to diagnosis continues to be important; however, management in an experienced center facile with all current management techniques is the major issue affecting outcomes,” he said.

The percentage of cases referred to the tertiary referral center was 50% from 1989 to 1992 and 79% from 2005 to 2009. Referred patients were significantly more likely to be treated more than 24 hours after perforation.

The improvement in outcomes is likely related to increasing diversity of treatment techniques and management in specialty centers, Dr. Hubka said.

Invited discussant Dr. Jeffrey Peters from the University of Rochester (N.Y.) Medical Center, said, "What you heard was an increasing chorus of a paradigm change, if you will, that's sort of paradoxical to most of us - that someone with a hole in their esophagus does better if you don't operate on them. I still struggle trying not to do that when patients present in the emergency room with these issues.”

Still, he described the improvement in outcomes as true progress for patients. Dr. Peters noted that the etiology of acute perforations has changed over time, with most now iatrogenic, and thus the benefit of early treatment may not be as critical as in years past. He said referral to a tertiary center is important, but that the paper did not prove a causal effect.

Based on the findings, Dr. Peters asked when surgeons should operate, how the size of the injury and presence of underlying disease should be taken into account in treatment decisions, and when surgery should be considered if nonoperative therapy fails.

Dr. Hubka said patients with larger esophageal tears or injuries and moderate mediastinal pleural contamination who can tolerate surgery are the ones who proceed to the operating room. He suggested that the study's operative rate would likely have been higher if patients with perforations due to neoplasia or cancer had been included and that the presence of such underlying disease would surely push them toward operative management in clinical practice. Finally, if a patient becomes unstable or their level of contamination increases despite nonsurgical management, they would proceed to surgery and decontamination.

"A point of our study is that this management, whether it's endoscopic or operative, should be performed by surgeons because we have all the tools to manage all patients appropriately,” Dr. Hubka said.

The study authors and discussant said that they had no financial disclosures.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.