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Neonatal hypothermia improves outcomes at age 6-7 years
Children born with perinatal asphyxia encephalopathy who received moderate hypothermia therapy showed superior neurocognitive outcomes at ages 6-7 years, compared with children who instead received usual care after birth, according to a report published online July 9 in the New England Journal of Medicine.
In the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial published in 2009, investigators found that affected neonates who had been treated with moderate (33-34° C) hypothermia using cooling blankets for 72 hours showed a lower rate of cerebral palsy and higher scores on measures of mental development, psychomotor development, and gross motor function when they reached 18 months of age than did a control group that received usual care.
To determine whether these benefits persisted longer term, they followed up 184 of these children at the age of 6-7 years, said Dr. Denis Azzopardi of the Centre for the Developing Brain at King’s College London and his associates (N. Engl. J. Med. 2014;371:140-9).
The 98 children in the intervention group and 86 in the control group were assessed by a psychologist and a pediatrician blinded to the study-group assignments who performed neurologic and neuropsychological examinations encompassing sensory function, cognition, memory, attention, and executive function. Parents and teachers also completed questionnaires regarding the children’s behavior, memory, and use of health care and educational services.
The primary outcome – frequency of survival with an IQ score of 85 or higher – was 52% in the hypothermia group, compared with only 39% in the control group. In addition, a significantly higher proportion of children in the hypothermia group (77%) than in the control group (63%) had IQ scores of 85 or higher. Significantly more children in the hypothermia group (45%) than the control group (28%) survived without neurologic abnormalities and had better scores on measures of gross motor function and manual ability, the investigators said.
"In conclusion, our study provides evidence that the benefits of moderate hypothermia after perinatal asphyxia persist into middle childhood," Dr. Azzopardi and his associates wrote.
This study was supported by the U.K. Medical Research Council, the National Institute for Health Research Biomedical Research Centres at Imperial College London, the University of Oxford, and King’s College London. Dr. Azzopardi reported no potential financial conflicts of interest; one of his associates reported receiving personal fees unrelated to this study from Novartis and Shire, and another reported receiving governmental research grants unrelated to this study.
Children born with perinatal asphyxia encephalopathy who received moderate hypothermia therapy showed superior neurocognitive outcomes at ages 6-7 years, compared with children who instead received usual care after birth, according to a report published online July 9 in the New England Journal of Medicine.
In the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial published in 2009, investigators found that affected neonates who had been treated with moderate (33-34° C) hypothermia using cooling blankets for 72 hours showed a lower rate of cerebral palsy and higher scores on measures of mental development, psychomotor development, and gross motor function when they reached 18 months of age than did a control group that received usual care.
To determine whether these benefits persisted longer term, they followed up 184 of these children at the age of 6-7 years, said Dr. Denis Azzopardi of the Centre for the Developing Brain at King’s College London and his associates (N. Engl. J. Med. 2014;371:140-9).
The 98 children in the intervention group and 86 in the control group were assessed by a psychologist and a pediatrician blinded to the study-group assignments who performed neurologic and neuropsychological examinations encompassing sensory function, cognition, memory, attention, and executive function. Parents and teachers also completed questionnaires regarding the children’s behavior, memory, and use of health care and educational services.
The primary outcome – frequency of survival with an IQ score of 85 or higher – was 52% in the hypothermia group, compared with only 39% in the control group. In addition, a significantly higher proportion of children in the hypothermia group (77%) than in the control group (63%) had IQ scores of 85 or higher. Significantly more children in the hypothermia group (45%) than the control group (28%) survived without neurologic abnormalities and had better scores on measures of gross motor function and manual ability, the investigators said.
"In conclusion, our study provides evidence that the benefits of moderate hypothermia after perinatal asphyxia persist into middle childhood," Dr. Azzopardi and his associates wrote.
This study was supported by the U.K. Medical Research Council, the National Institute for Health Research Biomedical Research Centres at Imperial College London, the University of Oxford, and King’s College London. Dr. Azzopardi reported no potential financial conflicts of interest; one of his associates reported receiving personal fees unrelated to this study from Novartis and Shire, and another reported receiving governmental research grants unrelated to this study.
Children born with perinatal asphyxia encephalopathy who received moderate hypothermia therapy showed superior neurocognitive outcomes at ages 6-7 years, compared with children who instead received usual care after birth, according to a report published online July 9 in the New England Journal of Medicine.
In the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial published in 2009, investigators found that affected neonates who had been treated with moderate (33-34° C) hypothermia using cooling blankets for 72 hours showed a lower rate of cerebral palsy and higher scores on measures of mental development, psychomotor development, and gross motor function when they reached 18 months of age than did a control group that received usual care.
To determine whether these benefits persisted longer term, they followed up 184 of these children at the age of 6-7 years, said Dr. Denis Azzopardi of the Centre for the Developing Brain at King’s College London and his associates (N. Engl. J. Med. 2014;371:140-9).
The 98 children in the intervention group and 86 in the control group were assessed by a psychologist and a pediatrician blinded to the study-group assignments who performed neurologic and neuropsychological examinations encompassing sensory function, cognition, memory, attention, and executive function. Parents and teachers also completed questionnaires regarding the children’s behavior, memory, and use of health care and educational services.
The primary outcome – frequency of survival with an IQ score of 85 or higher – was 52% in the hypothermia group, compared with only 39% in the control group. In addition, a significantly higher proportion of children in the hypothermia group (77%) than in the control group (63%) had IQ scores of 85 or higher. Significantly more children in the hypothermia group (45%) than the control group (28%) survived without neurologic abnormalities and had better scores on measures of gross motor function and manual ability, the investigators said.
"In conclusion, our study provides evidence that the benefits of moderate hypothermia after perinatal asphyxia persist into middle childhood," Dr. Azzopardi and his associates wrote.
This study was supported by the U.K. Medical Research Council, the National Institute for Health Research Biomedical Research Centres at Imperial College London, the University of Oxford, and King’s College London. Dr. Azzopardi reported no potential financial conflicts of interest; one of his associates reported receiving personal fees unrelated to this study from Novartis and Shire, and another reported receiving governmental research grants unrelated to this study.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Major finding: The frequency of survival with an IQ score of 85 or higher was 52% in the hypothermia group and 39% in the control group.
Data source: Long-term follow-up of 184 children aged 6-7 years who had been born with perinatal asphyxia encephalopathy and treated with either usual care or hypothermia therapy for 72 hours.
Disclosures: This study was supported by the U.K. Medical Research Council, the National Institute for Health Research Biomedical Research Centres at Imperial College London, the University of Oxford, and King’s College London. Dr. Azzopardi reported no potential financial conflicts of interest. One of his associates reported receiving personal fees unrelated to this study from Novartis and Shire, and another reported receiving governmental research grants unrelated to this study.
Dupilumab produces dramatic improvement in atopic dermatitis
The monoclonal antibody dupilumab, which blocks the action of the type 2 helper T-cell (Th2) cytokines interleukin-4 and interleukin-13, produced rapid and significant improvement in all signs, symptoms, and biomarkers of atopic dermatitis in four industry-sponsored randomized clinical trials. The data were reported online July 9 in the New England Journal of Medicine.
In particular, once-weekly subcutaneous injections of dupilumab quickly yielded substantial reductions in pruritus, "a major contributor to reduced quality of life experienced by patients with atopic dermatitis," said Dr. Lisa A. Beck of the department of dermatology, University of Rochester (N.Y.) Medical Center, and her associates.
These findings "extend the potential benefit of this new biologic therapy beyond asthma to a second atopic disorder" and suggest that the treatment may be beneficial for other atopic disorders as well, they noted (N. Engl. J. Med. 2014;371:130-9 [doi:10.1056/NEJMoa1314768]).
The four double-blind, placebo-controlled trials involved a total of 207 adults aged 18 years and older in the United States and Europe who had poorly controlled moderate to severe atopic dermatitis of at least 2 years’ duration. Two studies assessed 4 weeks of monotherapy with dupilumab, one assessed 12 weeks of monotherapy, and the fourth assessed 4 weeks of dupilumab added to topical glucocorticoids.
In all four studies, dupilumab induced rapid, dose-dependent improvements in an investigator’s global assessment score, a measure of the percentage of affected body-surface area, scores on the Eczema Area and Severity Index, and scores on both the 5-D pruritus scale and an additional numerical-rating scale of pruritus. In the 12-week trial, for example, 85% of patients given dupilumab achieved at least a 50% reduction in EASI scores, and mean scores on the pruritus rating scale declined by 56%.
Adverse events in all study groups were generally mild and transient: Nasopharyngitis and headache were reported more frequently in the active-treatment groups than in the placebo groups. However, serious adverse events and adverse events leading to treatment withdrawal – chiefly skin infections and exacerbations of the underlying dermatitis – were more common in the placebo groups and were related to lack of efficacy.
This study was funded by Regeneron Pharmaceuticals and Sanofi, which also performed data analysis and assisted with writing the report. Dr. Beck reported other ties to Regeneron; her associates reported ties to numerous industry sources.
The monoclonal antibody dupilumab, which blocks the action of the type 2 helper T-cell (Th2) cytokines interleukin-4 and interleukin-13, produced rapid and significant improvement in all signs, symptoms, and biomarkers of atopic dermatitis in four industry-sponsored randomized clinical trials. The data were reported online July 9 in the New England Journal of Medicine.
In particular, once-weekly subcutaneous injections of dupilumab quickly yielded substantial reductions in pruritus, "a major contributor to reduced quality of life experienced by patients with atopic dermatitis," said Dr. Lisa A. Beck of the department of dermatology, University of Rochester (N.Y.) Medical Center, and her associates.
These findings "extend the potential benefit of this new biologic therapy beyond asthma to a second atopic disorder" and suggest that the treatment may be beneficial for other atopic disorders as well, they noted (N. Engl. J. Med. 2014;371:130-9 [doi:10.1056/NEJMoa1314768]).
The four double-blind, placebo-controlled trials involved a total of 207 adults aged 18 years and older in the United States and Europe who had poorly controlled moderate to severe atopic dermatitis of at least 2 years’ duration. Two studies assessed 4 weeks of monotherapy with dupilumab, one assessed 12 weeks of monotherapy, and the fourth assessed 4 weeks of dupilumab added to topical glucocorticoids.
In all four studies, dupilumab induced rapid, dose-dependent improvements in an investigator’s global assessment score, a measure of the percentage of affected body-surface area, scores on the Eczema Area and Severity Index, and scores on both the 5-D pruritus scale and an additional numerical-rating scale of pruritus. In the 12-week trial, for example, 85% of patients given dupilumab achieved at least a 50% reduction in EASI scores, and mean scores on the pruritus rating scale declined by 56%.
Adverse events in all study groups were generally mild and transient: Nasopharyngitis and headache were reported more frequently in the active-treatment groups than in the placebo groups. However, serious adverse events and adverse events leading to treatment withdrawal – chiefly skin infections and exacerbations of the underlying dermatitis – were more common in the placebo groups and were related to lack of efficacy.
This study was funded by Regeneron Pharmaceuticals and Sanofi, which also performed data analysis and assisted with writing the report. Dr. Beck reported other ties to Regeneron; her associates reported ties to numerous industry sources.
The monoclonal antibody dupilumab, which blocks the action of the type 2 helper T-cell (Th2) cytokines interleukin-4 and interleukin-13, produced rapid and significant improvement in all signs, symptoms, and biomarkers of atopic dermatitis in four industry-sponsored randomized clinical trials. The data were reported online July 9 in the New England Journal of Medicine.
In particular, once-weekly subcutaneous injections of dupilumab quickly yielded substantial reductions in pruritus, "a major contributor to reduced quality of life experienced by patients with atopic dermatitis," said Dr. Lisa A. Beck of the department of dermatology, University of Rochester (N.Y.) Medical Center, and her associates.
These findings "extend the potential benefit of this new biologic therapy beyond asthma to a second atopic disorder" and suggest that the treatment may be beneficial for other atopic disorders as well, they noted (N. Engl. J. Med. 2014;371:130-9 [doi:10.1056/NEJMoa1314768]).
The four double-blind, placebo-controlled trials involved a total of 207 adults aged 18 years and older in the United States and Europe who had poorly controlled moderate to severe atopic dermatitis of at least 2 years’ duration. Two studies assessed 4 weeks of monotherapy with dupilumab, one assessed 12 weeks of monotherapy, and the fourth assessed 4 weeks of dupilumab added to topical glucocorticoids.
In all four studies, dupilumab induced rapid, dose-dependent improvements in an investigator’s global assessment score, a measure of the percentage of affected body-surface area, scores on the Eczema Area and Severity Index, and scores on both the 5-D pruritus scale and an additional numerical-rating scale of pruritus. In the 12-week trial, for example, 85% of patients given dupilumab achieved at least a 50% reduction in EASI scores, and mean scores on the pruritus rating scale declined by 56%.
Adverse events in all study groups were generally mild and transient: Nasopharyngitis and headache were reported more frequently in the active-treatment groups than in the placebo groups. However, serious adverse events and adverse events leading to treatment withdrawal – chiefly skin infections and exacerbations of the underlying dermatitis – were more common in the placebo groups and were related to lack of efficacy.
This study was funded by Regeneron Pharmaceuticals and Sanofi, which also performed data analysis and assisted with writing the report. Dr. Beck reported other ties to Regeneron; her associates reported ties to numerous industry sources.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: By reducing pruritus, dupilumab could improve quality of life.
Major finding: In a 12-week trial, 85% of patients given dupilumab achieved at least a 50% reduction in EASI scores, and the mean scores on the pruritus rating scale declined by 56%.
Data source: Four separate double-blind randomized trials comparing 4 weeks or 12 weeks of weekly subcutaneous injections of dupilumab against placebo in 207 American and European adults with poorly controlled moderate to severe atopic dermatitis.
Disclosures: This study was funded by Regeneron Pharmaceuticals and Sanofi, which also performed data analysis and assisted with writing the report. Dr. Beck reported other ties to Regeneron; her associates reported ties to numerous industry sources.
Initial cholecystectomy bests standard approach for suspected common duct stone
For patients at intermediate risk for having a common duct stone, initial cholecystectomy resulted in a shorter hospital stay, fewer invasive procedures, and no increase in morbidity, compared with the standard approach of doing a common duct exploration via endoscopic ultrasound followed by (if indicated) endoscopic retrograde cholangiopancreatography and cholecystectomy, according to a report published online July 8 in JAMA.
At present there are no specific guidelines as to the initial treatment approach for patients who present to the emergency department with suspected choledocholithiasis and who are at intermediate risk for retaining a common duct stone. In contrast, guidelines recommend initial laparoscopic cholecystectomy for patients at low risk for a retained common duct stone and preoperative endoscopic retrograde cholangiopancreatography (ERCP) followed by cholecystectomy for those at high risk, said Dr. Pouya Iranmanesh of the divisions of digestive surgery and transplant surgery, Geneva University Hospital, and his associates.
They performed a single-center randomized clinical trial comparing these two approaches in 100 intermediate-risk patients who presented to the emergency department during a 2-year period with sudden abdominal pain in the right upper quadrant and/or epigastric region, which was associated with elevated liver enzymes and the presence of a gallstone on ultrasound. Patients were included in the study whether they had associated acute cholecystitis or not and were randomly assigned to undergo either initial emergency laparoscopic cholecystectomy with intraoperative cholangiogram (50 patients) or initial common duct ultrasound exploration followed by (if indicated) ERCP and cholecystectomy (50 control subjects).
The median length of hospital stay was significantly shorter for the initial-cholecystectomy group (5 days) than for the control group (8 days), and the total number of procedures (endoscopic ultrasounds, magnetic resonance cholangiopancreatographies, and ERCPs) also was significantly smaller (25 vs. 71). In particular, the number of endoscopic ultrasounds was only 10 in the initial-cholecystectomy group, compared with 54 in the control group. All 50 patients in the control group (100%) underwent at least one common duct investigation exclusive of the intraoperative cholangiogram, compared with only 20 patients (40%) in the initial-cholecystectomy group, the investigators reported (JAMA 2014 July 8 [doi:10.1001/jama.2014.7587]).
The two study groups had similar rates of conversion to laparotomy, similar operation times, a similar number of failed intraoperative cholangiograms, and similar results on quality of life measures at 1 month and 6 months after hospital discharge. The rates of complications (8% vs 14%) and of severe complications (4% vs 8%) were approximately twice as high in the control group as in the initial-cholecystectomy group.
Since 30 (60%) of the patients in the initial-cholecystectomy group never needed any common duct investigation, it follows that many intermediate-risk patients in real-world practice are undergoing unnecessary common duct procedures. A policy of performing a cholecystectomy first ensures that only patients who retain common duct stones will undergo such invasive procedures, Dr. Iranmanesh and his associates said.
Dr. Iranmanesh and his associates reported no relevant financial disclosures.
For patients at intermediate risk for having a common duct stone, initial cholecystectomy resulted in a shorter hospital stay, fewer invasive procedures, and no increase in morbidity, compared with the standard approach of doing a common duct exploration via endoscopic ultrasound followed by (if indicated) endoscopic retrograde cholangiopancreatography and cholecystectomy, according to a report published online July 8 in JAMA.
At present there are no specific guidelines as to the initial treatment approach for patients who present to the emergency department with suspected choledocholithiasis and who are at intermediate risk for retaining a common duct stone. In contrast, guidelines recommend initial laparoscopic cholecystectomy for patients at low risk for a retained common duct stone and preoperative endoscopic retrograde cholangiopancreatography (ERCP) followed by cholecystectomy for those at high risk, said Dr. Pouya Iranmanesh of the divisions of digestive surgery and transplant surgery, Geneva University Hospital, and his associates.
They performed a single-center randomized clinical trial comparing these two approaches in 100 intermediate-risk patients who presented to the emergency department during a 2-year period with sudden abdominal pain in the right upper quadrant and/or epigastric region, which was associated with elevated liver enzymes and the presence of a gallstone on ultrasound. Patients were included in the study whether they had associated acute cholecystitis or not and were randomly assigned to undergo either initial emergency laparoscopic cholecystectomy with intraoperative cholangiogram (50 patients) or initial common duct ultrasound exploration followed by (if indicated) ERCP and cholecystectomy (50 control subjects).
The median length of hospital stay was significantly shorter for the initial-cholecystectomy group (5 days) than for the control group (8 days), and the total number of procedures (endoscopic ultrasounds, magnetic resonance cholangiopancreatographies, and ERCPs) also was significantly smaller (25 vs. 71). In particular, the number of endoscopic ultrasounds was only 10 in the initial-cholecystectomy group, compared with 54 in the control group. All 50 patients in the control group (100%) underwent at least one common duct investigation exclusive of the intraoperative cholangiogram, compared with only 20 patients (40%) in the initial-cholecystectomy group, the investigators reported (JAMA 2014 July 8 [doi:10.1001/jama.2014.7587]).
The two study groups had similar rates of conversion to laparotomy, similar operation times, a similar number of failed intraoperative cholangiograms, and similar results on quality of life measures at 1 month and 6 months after hospital discharge. The rates of complications (8% vs 14%) and of severe complications (4% vs 8%) were approximately twice as high in the control group as in the initial-cholecystectomy group.
Since 30 (60%) of the patients in the initial-cholecystectomy group never needed any common duct investigation, it follows that many intermediate-risk patients in real-world practice are undergoing unnecessary common duct procedures. A policy of performing a cholecystectomy first ensures that only patients who retain common duct stones will undergo such invasive procedures, Dr. Iranmanesh and his associates said.
Dr. Iranmanesh and his associates reported no relevant financial disclosures.
For patients at intermediate risk for having a common duct stone, initial cholecystectomy resulted in a shorter hospital stay, fewer invasive procedures, and no increase in morbidity, compared with the standard approach of doing a common duct exploration via endoscopic ultrasound followed by (if indicated) endoscopic retrograde cholangiopancreatography and cholecystectomy, according to a report published online July 8 in JAMA.
At present there are no specific guidelines as to the initial treatment approach for patients who present to the emergency department with suspected choledocholithiasis and who are at intermediate risk for retaining a common duct stone. In contrast, guidelines recommend initial laparoscopic cholecystectomy for patients at low risk for a retained common duct stone and preoperative endoscopic retrograde cholangiopancreatography (ERCP) followed by cholecystectomy for those at high risk, said Dr. Pouya Iranmanesh of the divisions of digestive surgery and transplant surgery, Geneva University Hospital, and his associates.
They performed a single-center randomized clinical trial comparing these two approaches in 100 intermediate-risk patients who presented to the emergency department during a 2-year period with sudden abdominal pain in the right upper quadrant and/or epigastric region, which was associated with elevated liver enzymes and the presence of a gallstone on ultrasound. Patients were included in the study whether they had associated acute cholecystitis or not and were randomly assigned to undergo either initial emergency laparoscopic cholecystectomy with intraoperative cholangiogram (50 patients) or initial common duct ultrasound exploration followed by (if indicated) ERCP and cholecystectomy (50 control subjects).
The median length of hospital stay was significantly shorter for the initial-cholecystectomy group (5 days) than for the control group (8 days), and the total number of procedures (endoscopic ultrasounds, magnetic resonance cholangiopancreatographies, and ERCPs) also was significantly smaller (25 vs. 71). In particular, the number of endoscopic ultrasounds was only 10 in the initial-cholecystectomy group, compared with 54 in the control group. All 50 patients in the control group (100%) underwent at least one common duct investigation exclusive of the intraoperative cholangiogram, compared with only 20 patients (40%) in the initial-cholecystectomy group, the investigators reported (JAMA 2014 July 8 [doi:10.1001/jama.2014.7587]).
The two study groups had similar rates of conversion to laparotomy, similar operation times, a similar number of failed intraoperative cholangiograms, and similar results on quality of life measures at 1 month and 6 months after hospital discharge. The rates of complications (8% vs 14%) and of severe complications (4% vs 8%) were approximately twice as high in the control group as in the initial-cholecystectomy group.
Since 30 (60%) of the patients in the initial-cholecystectomy group never needed any common duct investigation, it follows that many intermediate-risk patients in real-world practice are undergoing unnecessary common duct procedures. A policy of performing a cholecystectomy first ensures that only patients who retain common duct stones will undergo such invasive procedures, Dr. Iranmanesh and his associates said.
Dr. Iranmanesh and his associates reported no relevant financial disclosures.
FROM JAMA
Key clinical point: Initial cholecystectomy for patients at intermediate risk for common duct stone results in shorter hospital stays and fewer invasive procedures.
Major finding: The median length of hospital stay was significantly shorter for the initial-cholecystectomy group (5 days) than for the control group (8 days), and the total number of procedures (endoscopic ultrasounds, magnetic resonance cholangiopancreatographies, and ERCPs) also was significantly smaller (25 vs. 71).
Data source: A single-center randomized clinical trial comparing 50 patients who had initial cholecystectomy with 50 who had common duct exploration followed by ERCP and cholecystectomy; follow-up was done at 1 and 6 months.
Disclosures: Dr. Iranmanesh and his associates reported no relevant financial conflicts of interest.
Initial cholecystectomy bests standard approach for suspected common duct stone
For patients at intermediate risk for having a common duct stone, initial cholecystectomy resulted in a shorter hospital stay, fewer invasive procedures, and no increase in morbidity, compared with the standard approach of doing a common duct exploration via endoscopic ultrasound followed by (if indicated) endoscopic retrograde cholangiopancreatography and cholecystectomy, according to a report published online July 8 in JAMA.
At present there are no specific guidelines as to the initial treatment approach for patients who present to the emergency department with suspected choledocholithiasis and who are at intermediate risk for retaining a common duct stone. In contrast, guidelines recommend initial laparoscopic cholecystectomy for patients at low risk for a retained common duct stone and preoperative endoscopic retrograde cholangiopancreatography (ERCP) followed by cholecystectomy for those at high risk, said Dr. Pouya Iranmanesh of the divisions of digestive surgery and transplant surgery, Geneva University Hospital, and his associates.
They performed a single-center randomized clinical trial comparing these two approaches in 100 intermediate-risk patients who presented to the emergency department during a 2-year period with sudden abdominal pain in the right upper quadrant and/or epigastric region, which was associated with elevated liver enzymes and the presence of a gallstone on ultrasound. Patients were included in the study whether they had associated acute cholecystitis or not and were randomly assigned to undergo either initial emergency laparoscopic cholecystectomy with intraoperative cholangiogram (50 patients) or initial common duct ultrasound exploration followed by (if indicated) ERCP and cholecystectomy (50 control subjects).
The median length of hospital stay was significantly shorter for the initial-cholecystectomy group (5 days) than for the control group (8 days), and the total number of procedures (endoscopic ultrasounds, magnetic resonance cholangiopancreatographies, and ERCPs) also was significantly smaller (25 vs. 71). In particular, the number of endoscopic ultrasounds was only 10 in the initial-cholecystectomy group, compared with 54 in the control group. All 50 patients in the control group (100%) underwent at least one common duct investigation exclusive of the intraoperative cholangiogram, compared with only 20 patients (40%) in the initial-cholecystectomy group, the investigators reported (JAMA 2014 July 8 [doi:10.1001/jama.2014.7587]).
The two study groups had similar rates of conversion to laparotomy, similar operation times, a similar number of failed intraoperative cholangiograms, and similar results on quality of life measures at 1 month and 6 months after hospital discharge. The rates of complications (8% vs 14%) and of severe complications (4% vs 8%) were approximately twice as high in the control group as in the initial-cholecystectomy group.
Since 30 (60%) of the patients in the initial-cholecystectomy group never needed any common duct investigation, it follows that many intermediate-risk patients in real-world practice are undergoing unnecessary common duct procedures. A policy of performing a cholecystectomy first ensures that only patients who retain common duct stones will undergo such invasive procedures, Dr. Iranmanesh and his associates said.
Dr. Iranmanesh and his associates reported no relevant financial disclosures.
For patients at intermediate risk for having a common duct stone, initial cholecystectomy resulted in a shorter hospital stay, fewer invasive procedures, and no increase in morbidity, compared with the standard approach of doing a common duct exploration via endoscopic ultrasound followed by (if indicated) endoscopic retrograde cholangiopancreatography and cholecystectomy, according to a report published online July 8 in JAMA.
At present there are no specific guidelines as to the initial treatment approach for patients who present to the emergency department with suspected choledocholithiasis and who are at intermediate risk for retaining a common duct stone. In contrast, guidelines recommend initial laparoscopic cholecystectomy for patients at low risk for a retained common duct stone and preoperative endoscopic retrograde cholangiopancreatography (ERCP) followed by cholecystectomy for those at high risk, said Dr. Pouya Iranmanesh of the divisions of digestive surgery and transplant surgery, Geneva University Hospital, and his associates.
They performed a single-center randomized clinical trial comparing these two approaches in 100 intermediate-risk patients who presented to the emergency department during a 2-year period with sudden abdominal pain in the right upper quadrant and/or epigastric region, which was associated with elevated liver enzymes and the presence of a gallstone on ultrasound. Patients were included in the study whether they had associated acute cholecystitis or not and were randomly assigned to undergo either initial emergency laparoscopic cholecystectomy with intraoperative cholangiogram (50 patients) or initial common duct ultrasound exploration followed by (if indicated) ERCP and cholecystectomy (50 control subjects).
The median length of hospital stay was significantly shorter for the initial-cholecystectomy group (5 days) than for the control group (8 days), and the total number of procedures (endoscopic ultrasounds, magnetic resonance cholangiopancreatographies, and ERCPs) also was significantly smaller (25 vs. 71). In particular, the number of endoscopic ultrasounds was only 10 in the initial-cholecystectomy group, compared with 54 in the control group. All 50 patients in the control group (100%) underwent at least one common duct investigation exclusive of the intraoperative cholangiogram, compared with only 20 patients (40%) in the initial-cholecystectomy group, the investigators reported (JAMA 2014 July 8 [doi:10.1001/jama.2014.7587]).
The two study groups had similar rates of conversion to laparotomy, similar operation times, a similar number of failed intraoperative cholangiograms, and similar results on quality of life measures at 1 month and 6 months after hospital discharge. The rates of complications (8% vs 14%) and of severe complications (4% vs 8%) were approximately twice as high in the control group as in the initial-cholecystectomy group.
Since 30 (60%) of the patients in the initial-cholecystectomy group never needed any common duct investigation, it follows that many intermediate-risk patients in real-world practice are undergoing unnecessary common duct procedures. A policy of performing a cholecystectomy first ensures that only patients who retain common duct stones will undergo such invasive procedures, Dr. Iranmanesh and his associates said.
Dr. Iranmanesh and his associates reported no relevant financial disclosures.
For patients at intermediate risk for having a common duct stone, initial cholecystectomy resulted in a shorter hospital stay, fewer invasive procedures, and no increase in morbidity, compared with the standard approach of doing a common duct exploration via endoscopic ultrasound followed by (if indicated) endoscopic retrograde cholangiopancreatography and cholecystectomy, according to a report published online July 8 in JAMA.
At present there are no specific guidelines as to the initial treatment approach for patients who present to the emergency department with suspected choledocholithiasis and who are at intermediate risk for retaining a common duct stone. In contrast, guidelines recommend initial laparoscopic cholecystectomy for patients at low risk for a retained common duct stone and preoperative endoscopic retrograde cholangiopancreatography (ERCP) followed by cholecystectomy for those at high risk, said Dr. Pouya Iranmanesh of the divisions of digestive surgery and transplant surgery, Geneva University Hospital, and his associates.
They performed a single-center randomized clinical trial comparing these two approaches in 100 intermediate-risk patients who presented to the emergency department during a 2-year period with sudden abdominal pain in the right upper quadrant and/or epigastric region, which was associated with elevated liver enzymes and the presence of a gallstone on ultrasound. Patients were included in the study whether they had associated acute cholecystitis or not and were randomly assigned to undergo either initial emergency laparoscopic cholecystectomy with intraoperative cholangiogram (50 patients) or initial common duct ultrasound exploration followed by (if indicated) ERCP and cholecystectomy (50 control subjects).
The median length of hospital stay was significantly shorter for the initial-cholecystectomy group (5 days) than for the control group (8 days), and the total number of procedures (endoscopic ultrasounds, magnetic resonance cholangiopancreatographies, and ERCPs) also was significantly smaller (25 vs. 71). In particular, the number of endoscopic ultrasounds was only 10 in the initial-cholecystectomy group, compared with 54 in the control group. All 50 patients in the control group (100%) underwent at least one common duct investigation exclusive of the intraoperative cholangiogram, compared with only 20 patients (40%) in the initial-cholecystectomy group, the investigators reported (JAMA 2014 July 8 [doi:10.1001/jama.2014.7587]).
The two study groups had similar rates of conversion to laparotomy, similar operation times, a similar number of failed intraoperative cholangiograms, and similar results on quality of life measures at 1 month and 6 months after hospital discharge. The rates of complications (8% vs 14%) and of severe complications (4% vs 8%) were approximately twice as high in the control group as in the initial-cholecystectomy group.
Since 30 (60%) of the patients in the initial-cholecystectomy group never needed any common duct investigation, it follows that many intermediate-risk patients in real-world practice are undergoing unnecessary common duct procedures. A policy of performing a cholecystectomy first ensures that only patients who retain common duct stones will undergo such invasive procedures, Dr. Iranmanesh and his associates said.
Dr. Iranmanesh and his associates reported no relevant financial disclosures.
FROM JAMA
Key clinical point: Initial cholecystectomy for patients at intermediate risk for common duct stone results in shorter hospital stays and fewer invasive procedures.
Major finding: The median length of hospital stay was significantly shorter for the initial-cholecystectomy group (5 days) than for the control group (8 days), and the total number of procedures (endoscopic ultrasounds, magnetic resonance cholangiopancreatographies, and ERCPs) also was significantly smaller (25 vs. 71).
Data source: A single-center randomized clinical trial comparing 50 patients who had initial cholecystectomy with 50 who had common duct exploration followed by ERCP and cholecystectomy; follow-up was done at 1 and 6 months.
Disclosures: Dr. Iranmanesh and his associates reported no relevant financial conflicts of interest.
USPSTF: Don’t screen general population for carotid stenosis
Asymptomatic adults in the general population who have no history of stroke, transient ischemic attack, or neurologic signs or symptoms should not be screened for carotid artery stenosis, according to a U.S. Preventive Services Task Force recommendation published online July 7 in Annals of Internal Medicine.
All screening strategies, even a noninvasive one that has minimal harmful effects such as ultrasonography, are insufficiently sensitive for detecting the condition. And all of them can lead to unnecessary treatment or can themselves induce serious harms including death, stroke, and myocardial infarction. Therefore, at this time, "the harms of screening for asymptomatic carotid artery stenosis outweigh the benefits," said Dr. Michael L. LeFevre of the University of Missouri, Columbia, and his associates with the USPSTF.
The recommendation is an update of the previous one issued in 2007, which also concluded that screening the general population for carotid stenosis was unwarranted. For this update, the USPSTF performed an exhaustive review and meta-analysis of the data that have accrued since that time, which addressed advances in screening tests, risk stratification tools, both screening and treatment using carotid endarterectomy (CEA) and carotid angioplasty and stenting (CAAS), and optimal medical therapies.
Dr. LeFevre, a cochair of USPSTF, and his colleagues reviewed recent randomized controlled trials, meta-analyses, and cohort studies of these topics. They found that the prevalence of carotid artery stenosis is only 0.5%-1% in the general population of adults. The most feasible screen for the condition is duplex ultrasonography; but in real-world practice, even this screen yields many false-positive results in such patients, and so exposes them to harm.
There also is no evidence that another noninvasive screen for carotid artery stenosis – auscultation of the neck to detect carotid bruits – is accurate or provides any benefit. Only four studies examined this strategy; none of them used angiography as a gold standard for diagnosis, and only two involved patients from the general population.
Moreover, even when screening of asymptomatic patients leads to detection and early intervention, "the magnitude of benefit is small to none." In particular, adding medications to current optimal medical management does not appear to convey any benefit, Dr. LeFevre and his associates said.
On the other side of the benefit-to-harm scale, carotid endarterectomy is associated with a 30-day rate of stroke or mortality of approximately 2.4% overall. However, the rates are as high as 5% in low-volume medical centers and 6% in certain states. The 30-day rate of stroke or mortality associated with CAAS is 3.1%-3.8%. Those risks are far too high to counterbalance the small benefit of screening, the USPSTF reviewers noted.
Other important harms after CEA or CAAS include myocardial infarction, surgical complications, cranial nerve injury, lung embolism, pneumonia, and local hematoma requiring further surgery.
The review and meta-analysis were hampered by a dearth of high-quality data. Specifically, much more data are needed comparing patient outcomes after CEA or CAAS with those after optimal medical therapy. The planned CREST-2 (Carotid Revascularization Endarterectomy vs Stenting Trial 2) will include a comparator group on medical management alone, and should provide important findings in this regard, Dr. LeFevre and his associates said.
They added that the USPSTF recommendation against screening the general population for carotid stenosis agrees with recommendations from the American Heart Association, American Stroke Association, American College of Cardiology, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Society for Vascular Surgery, Society for Vascular Medicine, and the American Academy of Family Physicians.
More information on this recommendation – as well as recommendations for the related issues of hypertension, dyslipidemia, CHD, and diet – is available at the USPSTF website.
The USPSTF is an independent group that makes recommendations about the effectiveness of specific preventive care services and is funded by the Agency for Healthcare Research and Quality.
The available data clearly support the USPSTF’s reaffirmation of its previous recommendation against screening for asymptomatic carotid artery stenosis in the general population, yet "such screenings are offered throughout the country in health fairs and other settings," said Dr. Larry B. Goldstein.
Patients should be aware that such tests are unlikely to prevent them from having a stroke or to otherwise improve their health. The population-attributable risk for stroke related to asymptomatic CAS is only 0.7% – a figure that is dwarfed by such factors as hypertension (population-attributable risk greater than 95%), atrial fibrillation (population-attributable risk as high as 24%, depending on patient age and other factors), cigarette smoking (population-attributable risk of up to 14%), and hyperlipidemia (population-attributable risk of 9%), he noted.
Dr. Goldstein is at Duke University’s Stroke Center and Durham Veterans Affairs Medical Center in Durham, N.C. These remarks were taken from his editorial accompanying Dr. LeFevre’s report.
The available data clearly support the USPSTF’s reaffirmation of its previous recommendation against screening for asymptomatic carotid artery stenosis in the general population, yet "such screenings are offered throughout the country in health fairs and other settings," said Dr. Larry B. Goldstein.
Patients should be aware that such tests are unlikely to prevent them from having a stroke or to otherwise improve their health. The population-attributable risk for stroke related to asymptomatic CAS is only 0.7% – a figure that is dwarfed by such factors as hypertension (population-attributable risk greater than 95%), atrial fibrillation (population-attributable risk as high as 24%, depending on patient age and other factors), cigarette smoking (population-attributable risk of up to 14%), and hyperlipidemia (population-attributable risk of 9%), he noted.
Dr. Goldstein is at Duke University’s Stroke Center and Durham Veterans Affairs Medical Center in Durham, N.C. These remarks were taken from his editorial accompanying Dr. LeFevre’s report.
The available data clearly support the USPSTF’s reaffirmation of its previous recommendation against screening for asymptomatic carotid artery stenosis in the general population, yet "such screenings are offered throughout the country in health fairs and other settings," said Dr. Larry B. Goldstein.
Patients should be aware that such tests are unlikely to prevent them from having a stroke or to otherwise improve their health. The population-attributable risk for stroke related to asymptomatic CAS is only 0.7% – a figure that is dwarfed by such factors as hypertension (population-attributable risk greater than 95%), atrial fibrillation (population-attributable risk as high as 24%, depending on patient age and other factors), cigarette smoking (population-attributable risk of up to 14%), and hyperlipidemia (population-attributable risk of 9%), he noted.
Dr. Goldstein is at Duke University’s Stroke Center and Durham Veterans Affairs Medical Center in Durham, N.C. These remarks were taken from his editorial accompanying Dr. LeFevre’s report.
Asymptomatic adults in the general population who have no history of stroke, transient ischemic attack, or neurologic signs or symptoms should not be screened for carotid artery stenosis, according to a U.S. Preventive Services Task Force recommendation published online July 7 in Annals of Internal Medicine.
All screening strategies, even a noninvasive one that has minimal harmful effects such as ultrasonography, are insufficiently sensitive for detecting the condition. And all of them can lead to unnecessary treatment or can themselves induce serious harms including death, stroke, and myocardial infarction. Therefore, at this time, "the harms of screening for asymptomatic carotid artery stenosis outweigh the benefits," said Dr. Michael L. LeFevre of the University of Missouri, Columbia, and his associates with the USPSTF.
The recommendation is an update of the previous one issued in 2007, which also concluded that screening the general population for carotid stenosis was unwarranted. For this update, the USPSTF performed an exhaustive review and meta-analysis of the data that have accrued since that time, which addressed advances in screening tests, risk stratification tools, both screening and treatment using carotid endarterectomy (CEA) and carotid angioplasty and stenting (CAAS), and optimal medical therapies.
Dr. LeFevre, a cochair of USPSTF, and his colleagues reviewed recent randomized controlled trials, meta-analyses, and cohort studies of these topics. They found that the prevalence of carotid artery stenosis is only 0.5%-1% in the general population of adults. The most feasible screen for the condition is duplex ultrasonography; but in real-world practice, even this screen yields many false-positive results in such patients, and so exposes them to harm.
There also is no evidence that another noninvasive screen for carotid artery stenosis – auscultation of the neck to detect carotid bruits – is accurate or provides any benefit. Only four studies examined this strategy; none of them used angiography as a gold standard for diagnosis, and only two involved patients from the general population.
Moreover, even when screening of asymptomatic patients leads to detection and early intervention, "the magnitude of benefit is small to none." In particular, adding medications to current optimal medical management does not appear to convey any benefit, Dr. LeFevre and his associates said.
On the other side of the benefit-to-harm scale, carotid endarterectomy is associated with a 30-day rate of stroke or mortality of approximately 2.4% overall. However, the rates are as high as 5% in low-volume medical centers and 6% in certain states. The 30-day rate of stroke or mortality associated with CAAS is 3.1%-3.8%. Those risks are far too high to counterbalance the small benefit of screening, the USPSTF reviewers noted.
Other important harms after CEA or CAAS include myocardial infarction, surgical complications, cranial nerve injury, lung embolism, pneumonia, and local hematoma requiring further surgery.
The review and meta-analysis were hampered by a dearth of high-quality data. Specifically, much more data are needed comparing patient outcomes after CEA or CAAS with those after optimal medical therapy. The planned CREST-2 (Carotid Revascularization Endarterectomy vs Stenting Trial 2) will include a comparator group on medical management alone, and should provide important findings in this regard, Dr. LeFevre and his associates said.
They added that the USPSTF recommendation against screening the general population for carotid stenosis agrees with recommendations from the American Heart Association, American Stroke Association, American College of Cardiology, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Society for Vascular Surgery, Society for Vascular Medicine, and the American Academy of Family Physicians.
More information on this recommendation – as well as recommendations for the related issues of hypertension, dyslipidemia, CHD, and diet – is available at the USPSTF website.
The USPSTF is an independent group that makes recommendations about the effectiveness of specific preventive care services and is funded by the Agency for Healthcare Research and Quality.
Asymptomatic adults in the general population who have no history of stroke, transient ischemic attack, or neurologic signs or symptoms should not be screened for carotid artery stenosis, according to a U.S. Preventive Services Task Force recommendation published online July 7 in Annals of Internal Medicine.
All screening strategies, even a noninvasive one that has minimal harmful effects such as ultrasonography, are insufficiently sensitive for detecting the condition. And all of them can lead to unnecessary treatment or can themselves induce serious harms including death, stroke, and myocardial infarction. Therefore, at this time, "the harms of screening for asymptomatic carotid artery stenosis outweigh the benefits," said Dr. Michael L. LeFevre of the University of Missouri, Columbia, and his associates with the USPSTF.
The recommendation is an update of the previous one issued in 2007, which also concluded that screening the general population for carotid stenosis was unwarranted. For this update, the USPSTF performed an exhaustive review and meta-analysis of the data that have accrued since that time, which addressed advances in screening tests, risk stratification tools, both screening and treatment using carotid endarterectomy (CEA) and carotid angioplasty and stenting (CAAS), and optimal medical therapies.
Dr. LeFevre, a cochair of USPSTF, and his colleagues reviewed recent randomized controlled trials, meta-analyses, and cohort studies of these topics. They found that the prevalence of carotid artery stenosis is only 0.5%-1% in the general population of adults. The most feasible screen for the condition is duplex ultrasonography; but in real-world practice, even this screen yields many false-positive results in such patients, and so exposes them to harm.
There also is no evidence that another noninvasive screen for carotid artery stenosis – auscultation of the neck to detect carotid bruits – is accurate or provides any benefit. Only four studies examined this strategy; none of them used angiography as a gold standard for diagnosis, and only two involved patients from the general population.
Moreover, even when screening of asymptomatic patients leads to detection and early intervention, "the magnitude of benefit is small to none." In particular, adding medications to current optimal medical management does not appear to convey any benefit, Dr. LeFevre and his associates said.
On the other side of the benefit-to-harm scale, carotid endarterectomy is associated with a 30-day rate of stroke or mortality of approximately 2.4% overall. However, the rates are as high as 5% in low-volume medical centers and 6% in certain states. The 30-day rate of stroke or mortality associated with CAAS is 3.1%-3.8%. Those risks are far too high to counterbalance the small benefit of screening, the USPSTF reviewers noted.
Other important harms after CEA or CAAS include myocardial infarction, surgical complications, cranial nerve injury, lung embolism, pneumonia, and local hematoma requiring further surgery.
The review and meta-analysis were hampered by a dearth of high-quality data. Specifically, much more data are needed comparing patient outcomes after CEA or CAAS with those after optimal medical therapy. The planned CREST-2 (Carotid Revascularization Endarterectomy vs Stenting Trial 2) will include a comparator group on medical management alone, and should provide important findings in this regard, Dr. LeFevre and his associates said.
They added that the USPSTF recommendation against screening the general population for carotid stenosis agrees with recommendations from the American Heart Association, American Stroke Association, American College of Cardiology, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Society for Vascular Surgery, Society for Vascular Medicine, and the American Academy of Family Physicians.
More information on this recommendation – as well as recommendations for the related issues of hypertension, dyslipidemia, CHD, and diet – is available at the USPSTF website.
The USPSTF is an independent group that makes recommendations about the effectiveness of specific preventive care services and is funded by the Agency for Healthcare Research and Quality.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical finding: Don’t screen asymptomatic adults for carotid artery stenosis.
Major finding: The harms of screening asymptomatic adults in the general population for carotid artery stenosis outweigh the benefits, because all currently available screens "have imperfect sensitivity" and can lead to unnecessary treatment that induces serious harms, including death, stroke, myocardial infarction, cranial nerve injury, and embolism.
Data source: A comprehensive review and meta-analysis of data from randomized controlled trials, meta-analyses, and cohort studies performed since 2007 regarding CAS screening tests, risk stratification tools, for both screening and treatment using CEA and CAAS, and optimal medical therapies.
Disclosures: The USPSTF is an independent group that makes recommendations about the effectiveness of specific preventive care services and is funded by the Agency for Healthcare Research and Quality.
Metabolic syndrome, insulin resistance occur frequently in psoriatic arthritis patients
The metabolic syndrome and insulin resistance are not just common among patients with psoriatic arthritis, but both also correlate with the severity of the inflammatory musculoskeletal disease, according to a single-center, cross-sectional cohort study.
In the study of 283 consecutive white patients with longstanding psoriatic arthritis who attended a rheumatology clinic during a 1-year period, 44% were found to have the metabolic syndrome and 16% to have insulin resistance. "Our findings are novel and support our pretest hypothesis that the risk of metabolic syndrome and insulin resistance increases with the severity of underlying psoriatic arthritis, probably reflecting the increasing burden of inflammation," said Dr. Muhammad Haroon of the department of rheumatology and his associates at St. Vincent’s University Hospital, Dublin.
Psoriatic arthritis is known to be associated with heightened cardiovascular risk, and CV diseases are the leading causes of death in patients with psoriatic arthritis. Until now, however, the prevalences of these two major CV risk factors have not been well studied in patients with psoriatic arthritis. "We hypothesized, therefore, that there might be a greater burden of metabolic syndrome and insulin resistance in psoriatic arthritis, and consequently of cardiovascular diseases because of a greater inflammatory load," Dr. Haroon and his colleagues wrote (J. Rheumatol. 2014;41:1357-65).
The patients had psoriatic arthritis for a duration of at least 10 years (mean of 19 years), and just over half of the patients were women. Their mean age was 54.6 years.
A total of 124 patients (44%) were found to have the metabolic syndrome. "Even more alarming was the finding that about 50% of these newly diagnosed patients with metabolic syndrome had a combination of 4 or 5 of these risk features," the investigators said. In particular, elevated blood pressure (74%), greater waist circumference (56%), and elevated triglycerides (44%) were common among these psoriatic arthritis patients.
On multivariate analysis, metabolic syndrome was significantly associated with more severe disease, higher smoking pack-years, and worse EuroQol-5 dimension (EQ-5D). Metabolic syndrome was significantly associated with severe disease, even after adjustment for the presence of insulin resistance.
A total of 41 patients (16%) had insulin resistance of the 263 for whom insulin resistance data were available, which on multivariate analysis was significantly associated more severe disease, older age at the onset of psoriasis, and higher body-mass index, even after adjusting for the presence of metabolic syndrome.
Both the metabolic syndrome and insulin resistance were more frequent among patients with the most severe psoriatic arthritis, as measured by current and previous skin assessments; inflammatory markers; measures of disease activity; the number of deformed joints; and the presence of dactylitis, enthesitis, peripheral joint erosions, osteolysis, and sacroiliitis, the investigators said.
The study findings suggest, but do not establish, that "the higher burden of inflammatory arthritis or the combination of severe psoriatic disease features play major roles in the development of the metabolic syndrome and/or insulin resistance," Dr. Haroon and his associates said.
Their observations "can also help inform risk stratification" of patients with psoriatic arthritis, they added.
No disclosures were provided.
The metabolic syndrome and insulin resistance are not just common among patients with psoriatic arthritis, but both also correlate with the severity of the inflammatory musculoskeletal disease, according to a single-center, cross-sectional cohort study.
In the study of 283 consecutive white patients with longstanding psoriatic arthritis who attended a rheumatology clinic during a 1-year period, 44% were found to have the metabolic syndrome and 16% to have insulin resistance. "Our findings are novel and support our pretest hypothesis that the risk of metabolic syndrome and insulin resistance increases with the severity of underlying psoriatic arthritis, probably reflecting the increasing burden of inflammation," said Dr. Muhammad Haroon of the department of rheumatology and his associates at St. Vincent’s University Hospital, Dublin.
Psoriatic arthritis is known to be associated with heightened cardiovascular risk, and CV diseases are the leading causes of death in patients with psoriatic arthritis. Until now, however, the prevalences of these two major CV risk factors have not been well studied in patients with psoriatic arthritis. "We hypothesized, therefore, that there might be a greater burden of metabolic syndrome and insulin resistance in psoriatic arthritis, and consequently of cardiovascular diseases because of a greater inflammatory load," Dr. Haroon and his colleagues wrote (J. Rheumatol. 2014;41:1357-65).
The patients had psoriatic arthritis for a duration of at least 10 years (mean of 19 years), and just over half of the patients were women. Their mean age was 54.6 years.
A total of 124 patients (44%) were found to have the metabolic syndrome. "Even more alarming was the finding that about 50% of these newly diagnosed patients with metabolic syndrome had a combination of 4 or 5 of these risk features," the investigators said. In particular, elevated blood pressure (74%), greater waist circumference (56%), and elevated triglycerides (44%) were common among these psoriatic arthritis patients.
On multivariate analysis, metabolic syndrome was significantly associated with more severe disease, higher smoking pack-years, and worse EuroQol-5 dimension (EQ-5D). Metabolic syndrome was significantly associated with severe disease, even after adjustment for the presence of insulin resistance.
A total of 41 patients (16%) had insulin resistance of the 263 for whom insulin resistance data were available, which on multivariate analysis was significantly associated more severe disease, older age at the onset of psoriasis, and higher body-mass index, even after adjusting for the presence of metabolic syndrome.
Both the metabolic syndrome and insulin resistance were more frequent among patients with the most severe psoriatic arthritis, as measured by current and previous skin assessments; inflammatory markers; measures of disease activity; the number of deformed joints; and the presence of dactylitis, enthesitis, peripheral joint erosions, osteolysis, and sacroiliitis, the investigators said.
The study findings suggest, but do not establish, that "the higher burden of inflammatory arthritis or the combination of severe psoriatic disease features play major roles in the development of the metabolic syndrome and/or insulin resistance," Dr. Haroon and his associates said.
Their observations "can also help inform risk stratification" of patients with psoriatic arthritis, they added.
No disclosures were provided.
The metabolic syndrome and insulin resistance are not just common among patients with psoriatic arthritis, but both also correlate with the severity of the inflammatory musculoskeletal disease, according to a single-center, cross-sectional cohort study.
In the study of 283 consecutive white patients with longstanding psoriatic arthritis who attended a rheumatology clinic during a 1-year period, 44% were found to have the metabolic syndrome and 16% to have insulin resistance. "Our findings are novel and support our pretest hypothesis that the risk of metabolic syndrome and insulin resistance increases with the severity of underlying psoriatic arthritis, probably reflecting the increasing burden of inflammation," said Dr. Muhammad Haroon of the department of rheumatology and his associates at St. Vincent’s University Hospital, Dublin.
Psoriatic arthritis is known to be associated with heightened cardiovascular risk, and CV diseases are the leading causes of death in patients with psoriatic arthritis. Until now, however, the prevalences of these two major CV risk factors have not been well studied in patients with psoriatic arthritis. "We hypothesized, therefore, that there might be a greater burden of metabolic syndrome and insulin resistance in psoriatic arthritis, and consequently of cardiovascular diseases because of a greater inflammatory load," Dr. Haroon and his colleagues wrote (J. Rheumatol. 2014;41:1357-65).
The patients had psoriatic arthritis for a duration of at least 10 years (mean of 19 years), and just over half of the patients were women. Their mean age was 54.6 years.
A total of 124 patients (44%) were found to have the metabolic syndrome. "Even more alarming was the finding that about 50% of these newly diagnosed patients with metabolic syndrome had a combination of 4 or 5 of these risk features," the investigators said. In particular, elevated blood pressure (74%), greater waist circumference (56%), and elevated triglycerides (44%) were common among these psoriatic arthritis patients.
On multivariate analysis, metabolic syndrome was significantly associated with more severe disease, higher smoking pack-years, and worse EuroQol-5 dimension (EQ-5D). Metabolic syndrome was significantly associated with severe disease, even after adjustment for the presence of insulin resistance.
A total of 41 patients (16%) had insulin resistance of the 263 for whom insulin resistance data were available, which on multivariate analysis was significantly associated more severe disease, older age at the onset of psoriasis, and higher body-mass index, even after adjusting for the presence of metabolic syndrome.
Both the metabolic syndrome and insulin resistance were more frequent among patients with the most severe psoriatic arthritis, as measured by current and previous skin assessments; inflammatory markers; measures of disease activity; the number of deformed joints; and the presence of dactylitis, enthesitis, peripheral joint erosions, osteolysis, and sacroiliitis, the investigators said.
The study findings suggest, but do not establish, that "the higher burden of inflammatory arthritis or the combination of severe psoriatic disease features play major roles in the development of the metabolic syndrome and/or insulin resistance," Dr. Haroon and his associates said.
Their observations "can also help inform risk stratification" of patients with psoriatic arthritis, they added.
No disclosures were provided.
FROM THE JOURNAL OF RHEUMATOLOGY
Key clinical point: The presence of metabolic syndrome or insulin resistance may be a marker for more severe psoriatic arthritis.
Major finding: 124 patients (44%) with psoriatic arthritis were found to have the metabolic syndrome and 41 (16%) were found to have insulin resistance.
Data source: A cross-sectional cohort study involving 283 consecutive white patients with psoriatic arthritis of at least 10 years’ duration who were treated at a single rheumatology clinic in a 1-year period.
Disclosures: No disclosures were provided.
Glucocorticoid shots ineffective for spinal stenosis
Epidural injections of glucocorticoids plus lidocaine proved ineffective at improving pain or function in older adults with central spinal stenosis in a double-blind, randomized, controlled trial performed at 16 medical centers across the United States.
In the LESS (Lumbar Epidural Steroid Injections for Spinal Stenosis) trial, fluoroscopically guided transforaminal or interlaminar injections of lidocaine plus triamcinolone, betamethasone, dexamethasone, or methylprednisolone failed to reduce back, buttock, and leg pain or to enhance pain-related function any better than injections of lidocaine alone, reported Dr. Janna L. Friedly of the rehabilitation medicine department at the University of Washington, Seattle, and her associates. (Lidocaine alone has never been demonstrated to offer long-term benefit, they noted.)
The use of steroid injections for spinal stenosis has risen nearly 300% over the past 20 years even though "there is little evidence of effectiveness from clinical trials." The few studies that have examined this treatment have been "small, uncontrolled, or conducted without the use of fluoroscopy," the investigators said.
In their study, patients aged 50 years and older (mean age, 68 years) who had MRI- or CT-proven central spinal stenosis were enrolled over a 2-year period and randomly assigned to receive either a lidocaine plus glucocorticoid injection (200 intervention subjects) or a matching lidocaine injection (200 control subjects) under fluoroscopic guidance. All the study participants reported back, buttock, and leg pain scores of 5 or more on a scale of 0-10 (with 10 representing the worst pain imaginable) and disability scores of 7 or higher on the Roland-Morris Disability Questionnaire (RMDQ) scale of 0-24 (with higher scores indicating greater disability).
The patients were allowed to receive a repeat injection after 3 weeks, if they wished, at the discretion of their treating physicians. The physicians also chose whether to use the transforaminal or interlaminar approach, based on a variety of clinical factors.
At 6 weeks of follow-up, patients in both the glucocorticoid-lidocaine and lidocaine-only study groups reported some improvement in pain and function, but there was no significant difference in improvement between the two groups (–4.2 points and –3.1 points, respectively, on the RMDQ). There also were no significant differences across any of the subgroups of patients studied; in particular, steroid injections were no more effective than lidocaine alone according to the duration of spinal stenosis or the type of injection approach (transforaminal or interlaminar), Dr. Friedly and her associates said (N. Engl. J. Med. 2014 July 3 [doi: 10.1056/NEJMoa1313265]).
There were no differences in the percentage of patients in either group who achieved 30% or 50% improvement RMDQ scores at either 3 or 6 weeks, nor were there any differences in "any improvement" on pain scores or in 50% improvement on pain scores at 6 weeks.
There also were no differences between the groups in scores on secondary outcome measures, including the Brief Pain Inventory, which measures pain-related interference with activities; the Swiss Spinal Stenosis Questionnaire (SSSQ), which measures pain, function, and satisfaction with treatment; the EQ-5D, which measures quality of life; or the Generalized Anxiety Disorder-7 scale.
On the Patient Health Questionnaire-8, the glucocorticoid-lidocaine group reported more improvement in depression symptoms, and on one portion of the SSSQ, more patients in the glucocorticoid-lidocaine group (67%) than in the control group (54%) reported satisfaction with treatment. This is consistent with the systemic effects of cortisol suppression and is likely to be transient, the investigators said.
The glucocorticoid plus lidocaine injections were associated with more adverse effects (21.5% of patients) than were the lidocaine-only injections (15.5%), although the difference was not significant. However, the number of adverse events reported per person was significantly higher among patients who received glucocorticoid plus lidocaine injections (0.29 vs. 0.17), they added.
This study was funded by the Agency for Healthcare Research and Quality and received no commercial support. Dr. Friedly reported no potential financial conflicts of interest; her associates reported ties to Johnson & Johnson, ArthroCare, and other companies.
These findings raise serious questions about the benefits of epidural glucocorticoid injections for spinal stenosis. Patients seeking them should be informed that the best available data do not support a clinically significant long-term benefit, and that complications, though rare, are possible, said Dr. Gunnar B.J. Andersson.
Currently, many insurance companies require that epidural injections be performed as part of nonsurgical treatment before surgery will be approved. The study by Dr. Friedly and her colleagues, together with the Food and Drug Administration safety announcement in April of this year regarding possible catastrophic complications, "suggests that this requirement should be reconsidered," he said.
Dr. Gunnar B.J. Andersson is in the department of orthopedic surgery at Rush University Medical Center, Chicago. These remarks were taken from his editorial accompanying Dr. Friedly’s report (N. Engl. J. Med. 2014 July 3 [doi: 10.1056/NEJMe1405475]).
These findings raise serious questions about the benefits of epidural glucocorticoid injections for spinal stenosis. Patients seeking them should be informed that the best available data do not support a clinically significant long-term benefit, and that complications, though rare, are possible, said Dr. Gunnar B.J. Andersson.
Currently, many insurance companies require that epidural injections be performed as part of nonsurgical treatment before surgery will be approved. The study by Dr. Friedly and her colleagues, together with the Food and Drug Administration safety announcement in April of this year regarding possible catastrophic complications, "suggests that this requirement should be reconsidered," he said.
Dr. Gunnar B.J. Andersson is in the department of orthopedic surgery at Rush University Medical Center, Chicago. These remarks were taken from his editorial accompanying Dr. Friedly’s report (N. Engl. J. Med. 2014 July 3 [doi: 10.1056/NEJMe1405475]).
These findings raise serious questions about the benefits of epidural glucocorticoid injections for spinal stenosis. Patients seeking them should be informed that the best available data do not support a clinically significant long-term benefit, and that complications, though rare, are possible, said Dr. Gunnar B.J. Andersson.
Currently, many insurance companies require that epidural injections be performed as part of nonsurgical treatment before surgery will be approved. The study by Dr. Friedly and her colleagues, together with the Food and Drug Administration safety announcement in April of this year regarding possible catastrophic complications, "suggests that this requirement should be reconsidered," he said.
Dr. Gunnar B.J. Andersson is in the department of orthopedic surgery at Rush University Medical Center, Chicago. These remarks were taken from his editorial accompanying Dr. Friedly’s report (N. Engl. J. Med. 2014 July 3 [doi: 10.1056/NEJMe1405475]).
Epidural injections of glucocorticoids plus lidocaine proved ineffective at improving pain or function in older adults with central spinal stenosis in a double-blind, randomized, controlled trial performed at 16 medical centers across the United States.
In the LESS (Lumbar Epidural Steroid Injections for Spinal Stenosis) trial, fluoroscopically guided transforaminal or interlaminar injections of lidocaine plus triamcinolone, betamethasone, dexamethasone, or methylprednisolone failed to reduce back, buttock, and leg pain or to enhance pain-related function any better than injections of lidocaine alone, reported Dr. Janna L. Friedly of the rehabilitation medicine department at the University of Washington, Seattle, and her associates. (Lidocaine alone has never been demonstrated to offer long-term benefit, they noted.)
The use of steroid injections for spinal stenosis has risen nearly 300% over the past 20 years even though "there is little evidence of effectiveness from clinical trials." The few studies that have examined this treatment have been "small, uncontrolled, or conducted without the use of fluoroscopy," the investigators said.
In their study, patients aged 50 years and older (mean age, 68 years) who had MRI- or CT-proven central spinal stenosis were enrolled over a 2-year period and randomly assigned to receive either a lidocaine plus glucocorticoid injection (200 intervention subjects) or a matching lidocaine injection (200 control subjects) under fluoroscopic guidance. All the study participants reported back, buttock, and leg pain scores of 5 or more on a scale of 0-10 (with 10 representing the worst pain imaginable) and disability scores of 7 or higher on the Roland-Morris Disability Questionnaire (RMDQ) scale of 0-24 (with higher scores indicating greater disability).
The patients were allowed to receive a repeat injection after 3 weeks, if they wished, at the discretion of their treating physicians. The physicians also chose whether to use the transforaminal or interlaminar approach, based on a variety of clinical factors.
At 6 weeks of follow-up, patients in both the glucocorticoid-lidocaine and lidocaine-only study groups reported some improvement in pain and function, but there was no significant difference in improvement between the two groups (–4.2 points and –3.1 points, respectively, on the RMDQ). There also were no significant differences across any of the subgroups of patients studied; in particular, steroid injections were no more effective than lidocaine alone according to the duration of spinal stenosis or the type of injection approach (transforaminal or interlaminar), Dr. Friedly and her associates said (N. Engl. J. Med. 2014 July 3 [doi: 10.1056/NEJMoa1313265]).
There were no differences in the percentage of patients in either group who achieved 30% or 50% improvement RMDQ scores at either 3 or 6 weeks, nor were there any differences in "any improvement" on pain scores or in 50% improvement on pain scores at 6 weeks.
There also were no differences between the groups in scores on secondary outcome measures, including the Brief Pain Inventory, which measures pain-related interference with activities; the Swiss Spinal Stenosis Questionnaire (SSSQ), which measures pain, function, and satisfaction with treatment; the EQ-5D, which measures quality of life; or the Generalized Anxiety Disorder-7 scale.
On the Patient Health Questionnaire-8, the glucocorticoid-lidocaine group reported more improvement in depression symptoms, and on one portion of the SSSQ, more patients in the glucocorticoid-lidocaine group (67%) than in the control group (54%) reported satisfaction with treatment. This is consistent with the systemic effects of cortisol suppression and is likely to be transient, the investigators said.
The glucocorticoid plus lidocaine injections were associated with more adverse effects (21.5% of patients) than were the lidocaine-only injections (15.5%), although the difference was not significant. However, the number of adverse events reported per person was significantly higher among patients who received glucocorticoid plus lidocaine injections (0.29 vs. 0.17), they added.
This study was funded by the Agency for Healthcare Research and Quality and received no commercial support. Dr. Friedly reported no potential financial conflicts of interest; her associates reported ties to Johnson & Johnson, ArthroCare, and other companies.
Epidural injections of glucocorticoids plus lidocaine proved ineffective at improving pain or function in older adults with central spinal stenosis in a double-blind, randomized, controlled trial performed at 16 medical centers across the United States.
In the LESS (Lumbar Epidural Steroid Injections for Spinal Stenosis) trial, fluoroscopically guided transforaminal or interlaminar injections of lidocaine plus triamcinolone, betamethasone, dexamethasone, or methylprednisolone failed to reduce back, buttock, and leg pain or to enhance pain-related function any better than injections of lidocaine alone, reported Dr. Janna L. Friedly of the rehabilitation medicine department at the University of Washington, Seattle, and her associates. (Lidocaine alone has never been demonstrated to offer long-term benefit, they noted.)
The use of steroid injections for spinal stenosis has risen nearly 300% over the past 20 years even though "there is little evidence of effectiveness from clinical trials." The few studies that have examined this treatment have been "small, uncontrolled, or conducted without the use of fluoroscopy," the investigators said.
In their study, patients aged 50 years and older (mean age, 68 years) who had MRI- or CT-proven central spinal stenosis were enrolled over a 2-year period and randomly assigned to receive either a lidocaine plus glucocorticoid injection (200 intervention subjects) or a matching lidocaine injection (200 control subjects) under fluoroscopic guidance. All the study participants reported back, buttock, and leg pain scores of 5 or more on a scale of 0-10 (with 10 representing the worst pain imaginable) and disability scores of 7 or higher on the Roland-Morris Disability Questionnaire (RMDQ) scale of 0-24 (with higher scores indicating greater disability).
The patients were allowed to receive a repeat injection after 3 weeks, if they wished, at the discretion of their treating physicians. The physicians also chose whether to use the transforaminal or interlaminar approach, based on a variety of clinical factors.
At 6 weeks of follow-up, patients in both the glucocorticoid-lidocaine and lidocaine-only study groups reported some improvement in pain and function, but there was no significant difference in improvement between the two groups (–4.2 points and –3.1 points, respectively, on the RMDQ). There also were no significant differences across any of the subgroups of patients studied; in particular, steroid injections were no more effective than lidocaine alone according to the duration of spinal stenosis or the type of injection approach (transforaminal or interlaminar), Dr. Friedly and her associates said (N. Engl. J. Med. 2014 July 3 [doi: 10.1056/NEJMoa1313265]).
There were no differences in the percentage of patients in either group who achieved 30% or 50% improvement RMDQ scores at either 3 or 6 weeks, nor were there any differences in "any improvement" on pain scores or in 50% improvement on pain scores at 6 weeks.
There also were no differences between the groups in scores on secondary outcome measures, including the Brief Pain Inventory, which measures pain-related interference with activities; the Swiss Spinal Stenosis Questionnaire (SSSQ), which measures pain, function, and satisfaction with treatment; the EQ-5D, which measures quality of life; or the Generalized Anxiety Disorder-7 scale.
On the Patient Health Questionnaire-8, the glucocorticoid-lidocaine group reported more improvement in depression symptoms, and on one portion of the SSSQ, more patients in the glucocorticoid-lidocaine group (67%) than in the control group (54%) reported satisfaction with treatment. This is consistent with the systemic effects of cortisol suppression and is likely to be transient, the investigators said.
The glucocorticoid plus lidocaine injections were associated with more adverse effects (21.5% of patients) than were the lidocaine-only injections (15.5%), although the difference was not significant. However, the number of adverse events reported per person was significantly higher among patients who received glucocorticoid plus lidocaine injections (0.29 vs. 0.17), they added.
This study was funded by the Agency for Healthcare Research and Quality and received no commercial support. Dr. Friedly reported no potential financial conflicts of interest; her associates reported ties to Johnson & Johnson, ArthroCare, and other companies.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: There is no evidence of a treatment effect at 6 weeks with fluoroscopically guided epidural injections of glucocorticoids plus lidocaine.
Major finding: At 6 weeks of follow-up, patients in both the glucocorticoid-lidocaine and lidocaine-only study groups reported some improvement in pain and function, but there was no significant difference in improvement between the two groups (–4.2 points and –3.1 points, respectively, on the RMDQ).
Data source: A multicenter, double-blind, randomized, controlled trial involving 400 patients aged 50 years and older with central spinal stenosis who received epidural injections of either glucocorticoids plus lidocaine or lidocaine alone and were followed for 6 weeks.
Disclosures: This study was funded by the Agency for Healthcare Research and Quality and received no commercial support. Dr. Friedly reported no potential financial conflicts of interest; her associates reported ties to Johnson & Johnson, ArthroCare, and other companies.
Everolimus fails to improve HCC survival
Everolimus failed to improve overall survival among patients with advanced hepatocellular carcinoma in a large international phase III clinical trial, according to a report published online July 1 in JAMA.
Everolimus – which targets the mTOR pathway that is a key regulator of cellular growth, proliferation, angiogenesis, and survival – had shown promise in numerous preclinical, phase I, and phase II studies. So the Everolimus for Liver Cancer Evaluation (EVOLVE-1) trial was designed to compare the drug’s efficacy and safety against that of a matching placebo in patients whose HCC was refractory to, or who were intolerant of, sorafenib, said Dr. Andrew X. Zhu of Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, and his associates.
Sorafenib is the only systemic therapy shown to improve survival in advanced HCC, but its benefits are "transient and modest," and it produces significant adverse events, according to the researchers. In this study, sorafenib was discontinued because of disease progression in 81% of patients and because of intolerance in 19%, they noted.
In EVOLVE-1, 546 patients were enrolled during a 2-year period at 111 medical centers in 17 countries, randomly assigned in a double-blind fashion to receive either 7.5 mg oral everolimus (362 subjects) or placebo (184 subjects) daily, and followed for a median of 2.5 years (range, 14.8-36.6 months). The trial was sponsored by Novartis, maker of everolimus.
HCC was associated with hepatitis B virus in 26.2% of the patients, hepatitis C virus in 25.1%, and alcohol abuse in 20.0%. There were 303 deaths (83.7%) in the active-treatment group and 151 (82.1%) in the placebo group.
At 5 months, the primary endpoint of estimated overall survival was not significantly different between patients taking everolimus (67.0%) and those taking placebo (65.6%); the rates also were not significantly different at 7 months (53.4% and 51.4%, respectively). Median overall survival time was 7.6 months for everolimus and 7.3 months with placebo, also a nonsignificant difference, Dr. Zhu and his associates said (JAMA 2014 July 1 [doi:10.1001/jama.2014.7189]).
These findings were consistent across all but one subgroup of patients. Secondary endpoints, including time to disease progression, rate of complete response (0% in both groups), and time to deterioration in quality of life, also were not significantly different between the two study groups.
Serious adverse events, including adverse events leading to treatment discontinuation, were more common with everolimus than with placebo. These included asthenia, anemia, decreased appetite, resurgence of HBV, ascites, and thrombocytopenia.
Thus, "despite the strong scientific rationale and preclinical data," everolimus failed to improve outcomes in advanced HCC, the investigators said.
However, "given the immunosuppressive and antitumor effects of mTOR inhibitors, the potential benefits of this class of agents in the adjuvant setting are being assessed in a phase-III trial of sirolimus for patients with HCC after liver transplantation," they added.
Everolimus failed to improve overall survival among patients with advanced hepatocellular carcinoma in a large international phase III clinical trial, according to a report published online July 1 in JAMA.
Everolimus – which targets the mTOR pathway that is a key regulator of cellular growth, proliferation, angiogenesis, and survival – had shown promise in numerous preclinical, phase I, and phase II studies. So the Everolimus for Liver Cancer Evaluation (EVOLVE-1) trial was designed to compare the drug’s efficacy and safety against that of a matching placebo in patients whose HCC was refractory to, or who were intolerant of, sorafenib, said Dr. Andrew X. Zhu of Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, and his associates.
Sorafenib is the only systemic therapy shown to improve survival in advanced HCC, but its benefits are "transient and modest," and it produces significant adverse events, according to the researchers. In this study, sorafenib was discontinued because of disease progression in 81% of patients and because of intolerance in 19%, they noted.
In EVOLVE-1, 546 patients were enrolled during a 2-year period at 111 medical centers in 17 countries, randomly assigned in a double-blind fashion to receive either 7.5 mg oral everolimus (362 subjects) or placebo (184 subjects) daily, and followed for a median of 2.5 years (range, 14.8-36.6 months). The trial was sponsored by Novartis, maker of everolimus.
HCC was associated with hepatitis B virus in 26.2% of the patients, hepatitis C virus in 25.1%, and alcohol abuse in 20.0%. There were 303 deaths (83.7%) in the active-treatment group and 151 (82.1%) in the placebo group.
At 5 months, the primary endpoint of estimated overall survival was not significantly different between patients taking everolimus (67.0%) and those taking placebo (65.6%); the rates also were not significantly different at 7 months (53.4% and 51.4%, respectively). Median overall survival time was 7.6 months for everolimus and 7.3 months with placebo, also a nonsignificant difference, Dr. Zhu and his associates said (JAMA 2014 July 1 [doi:10.1001/jama.2014.7189]).
These findings were consistent across all but one subgroup of patients. Secondary endpoints, including time to disease progression, rate of complete response (0% in both groups), and time to deterioration in quality of life, also were not significantly different between the two study groups.
Serious adverse events, including adverse events leading to treatment discontinuation, were more common with everolimus than with placebo. These included asthenia, anemia, decreased appetite, resurgence of HBV, ascites, and thrombocytopenia.
Thus, "despite the strong scientific rationale and preclinical data," everolimus failed to improve outcomes in advanced HCC, the investigators said.
However, "given the immunosuppressive and antitumor effects of mTOR inhibitors, the potential benefits of this class of agents in the adjuvant setting are being assessed in a phase-III trial of sirolimus for patients with HCC after liver transplantation," they added.
Everolimus failed to improve overall survival among patients with advanced hepatocellular carcinoma in a large international phase III clinical trial, according to a report published online July 1 in JAMA.
Everolimus – which targets the mTOR pathway that is a key regulator of cellular growth, proliferation, angiogenesis, and survival – had shown promise in numerous preclinical, phase I, and phase II studies. So the Everolimus for Liver Cancer Evaluation (EVOLVE-1) trial was designed to compare the drug’s efficacy and safety against that of a matching placebo in patients whose HCC was refractory to, or who were intolerant of, sorafenib, said Dr. Andrew X. Zhu of Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, and his associates.
Sorafenib is the only systemic therapy shown to improve survival in advanced HCC, but its benefits are "transient and modest," and it produces significant adverse events, according to the researchers. In this study, sorafenib was discontinued because of disease progression in 81% of patients and because of intolerance in 19%, they noted.
In EVOLVE-1, 546 patients were enrolled during a 2-year period at 111 medical centers in 17 countries, randomly assigned in a double-blind fashion to receive either 7.5 mg oral everolimus (362 subjects) or placebo (184 subjects) daily, and followed for a median of 2.5 years (range, 14.8-36.6 months). The trial was sponsored by Novartis, maker of everolimus.
HCC was associated with hepatitis B virus in 26.2% of the patients, hepatitis C virus in 25.1%, and alcohol abuse in 20.0%. There were 303 deaths (83.7%) in the active-treatment group and 151 (82.1%) in the placebo group.
At 5 months, the primary endpoint of estimated overall survival was not significantly different between patients taking everolimus (67.0%) and those taking placebo (65.6%); the rates also were not significantly different at 7 months (53.4% and 51.4%, respectively). Median overall survival time was 7.6 months for everolimus and 7.3 months with placebo, also a nonsignificant difference, Dr. Zhu and his associates said (JAMA 2014 July 1 [doi:10.1001/jama.2014.7189]).
These findings were consistent across all but one subgroup of patients. Secondary endpoints, including time to disease progression, rate of complete response (0% in both groups), and time to deterioration in quality of life, also were not significantly different between the two study groups.
Serious adverse events, including adverse events leading to treatment discontinuation, were more common with everolimus than with placebo. These included asthenia, anemia, decreased appetite, resurgence of HBV, ascites, and thrombocytopenia.
Thus, "despite the strong scientific rationale and preclinical data," everolimus failed to improve outcomes in advanced HCC, the investigators said.
However, "given the immunosuppressive and antitumor effects of mTOR inhibitors, the potential benefits of this class of agents in the adjuvant setting are being assessed in a phase-III trial of sirolimus for patients with HCC after liver transplantation," they added.
FROM JAMA
Key clinical point: Despite the "strong scientific rationale and preclinical data," everolimus failed to improve outcomes in advanced HCC.
Major finding: At 5 months, the primary endpoint of estimated overall survival was not significantly different between patients taking everolimus (67.0%) and those taking placebo (65.6%); the rates also were not significantly different at 7 months (53.4% and 51.4%, respectively).
Data source: An international prospective, double-blind placebo-controlled phase III clinical trial of 546 patients with advanced hepatocellular carcinoma who were followed for a median of 2.5 years.
Disclosures: EVOLVE-1 was sponsored by Novartis. Dr. Zhu reported serving as a consultant to Sanofi-Aventis, Exelixis, Eisai, and Daiichi Sankyo; his associates reported ties to numerous industry sources.
Neoadjuvant chemoradiotherapy fails to boost survival
For patients with early-stage esophageal cancer, undergoing chemotherapy and radiotherapy before surgical excision failed to improve the rate of curative resection and, most importantly, failed to boost survival in a phase III clinical trial, according to a report published online June 30 in the Journal of Clinical Oncology.
Unfortunately this treatment strategy also tripled postoperative mortality, making the risk-benefit ratio even more lopsided for this patient population, said Dr. Christophe Mariette of the department of digestive and oncologic surgery, University Hospital Claude Huriez-Regional University Hospital Center, Lille (France), and his associates.
Clinical trials examining neoadjuvant chemoradiotherapy for esophageal cancer have produced conflicting results, with some showing that the approach is effective, in some cases doubling median survival, while others showed no benefit. Most such studies have been limited by small sample sizes, heterogeneity of tumor types, variations in radiation doses and chemotherapy regiments, and differences in preoperative staging techniques and the adequacy of surgical resections. Moreover, the number of study participants with early-stage esophageal cancer has been very small because most patients already have more advanced disease at presentation, the investigators noted.
For their study, Dr. Mariette and his associates confined the cohort to patients younger than 75 years with treatment-naive esophageal adenocarcinoma or squamous-cell carcinoma judged to be stage I or II using thoracoabdominal CT and endoscopic ultrasound; additional preoperative assessments using PET scanning, cervical ultrasound, or radionuclide bone scanning were optional. It required 9 years to enroll 195 patients at 30 French medical centers. These study participants were randomly assigned to receive either neoadjuvant chemotherapy plus radiotherapy before potentially curative surgery (98 subjects) or potentially curative surgery alone (97 subjects).
In the intervention group, radiotherapy involved a total dose of 45 Gy delivered in 25 fractions over the course of 5 weeks. Chemotherapy was administered during the same time period and involved two cycles of fluorouracil and cisplatin infusions. All patients in this group were clinically reevaluated 2-4 weeks after completing this regimen, and surgery was performed soon afterward.
Surgery comprised a transthoracic esophagectomy with extended two-field lymphadenectomy and either high intrathoracic anastomosis (for tumors with an infracarinal proximal margin) or cervical anastomosis (for tumors with a proximal margin above the carina).
Median follow-up was 7.8 years. There were 125 deaths: 62.4% of the intervention group died, as did 66% of the surgery-only group, a nonsignificant difference, the investigators said (J. Clin. Oncol. 2014 June 30 [doi:10.1200/JCO.2013.53.6532]).
Median overall survival was 31.8 months in the intervention group and 41.2 months in the surgery-only group, a nonsignificant difference. Similarly, 3-year overall survival was 47.5% and 5-year overall survival was 41.1% in the intervention group, compared with 53% and 33.8%, respectively, in the surgery-only group, which were also nonsignificant differences.
The rate of curative resection also was not significantly different between the intervention group (93.8%) and the surgery-only group (92.1%), indicating that reducing the tumor with chemotherapy and radiotherapy had no beneficial effect in these early-stage cancers. Previous studies have demonstrated that such downsizing is effective in more advanced esophageal cancers, Dr. Mariette and his associates noted.
Postoperative mortality was more than threefold higher among patients who underwent preoperative chemoradiotherapy (11.1%) than in the surgery-only group (3.4%). The causes of postoperative death included aortic rupture, uncontrollable chylothorax, anastomotic leak, gastric conduit necrosis, mesenteric and lower limb ischemia, and acute RDS in the intervention group, compared with pneumonia and acute RDS in the surgery-only group.
These findings suggest that preoperative chemoradiotherapy "is not the appropriate neoadjuvant therapeutic strategy for stage I or II esophageal cancer," the investigators said.
Since patients with early-stage esophageal cancer don’t appear to benefit from preoperative neoadjuvant chemoradiotherapy, perhaps it is time to consider a different approach: definitive rather than neoadjuvant chemoradiotherapy as the first-line treatment, said Dr. Brian G. Czito, Dr. Manisha Palta, and Dr. Christopher G. Willett.
Some medical centers have already adopted this approach for patients with potentially curable esophageal cancer, reserving surgery as salvage treatment. Compared with surgery as first-line treatment, definitive chemoradiotherapy is associated with a lower rate of treatment-related mortality and similar survival outcomes, they noted.
Dr. Czito, Dr. Palta, and Dr. Willett are in the department of radiation oncology at Duke Cancer Institute, Durham, N.C. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Mariette’s report (J. Clin. Oncol. 2014 June 30 [doi:10.1200/JCO.2013.53.6532]).
Since patients with early-stage esophageal cancer don’t appear to benefit from preoperative neoadjuvant chemoradiotherapy, perhaps it is time to consider a different approach: definitive rather than neoadjuvant chemoradiotherapy as the first-line treatment, said Dr. Brian G. Czito, Dr. Manisha Palta, and Dr. Christopher G. Willett.
Some medical centers have already adopted this approach for patients with potentially curable esophageal cancer, reserving surgery as salvage treatment. Compared with surgery as first-line treatment, definitive chemoradiotherapy is associated with a lower rate of treatment-related mortality and similar survival outcomes, they noted.
Dr. Czito, Dr. Palta, and Dr. Willett are in the department of radiation oncology at Duke Cancer Institute, Durham, N.C. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Mariette’s report (J. Clin. Oncol. 2014 June 30 [doi:10.1200/JCO.2013.53.6532]).
Since patients with early-stage esophageal cancer don’t appear to benefit from preoperative neoadjuvant chemoradiotherapy, perhaps it is time to consider a different approach: definitive rather than neoadjuvant chemoradiotherapy as the first-line treatment, said Dr. Brian G. Czito, Dr. Manisha Palta, and Dr. Christopher G. Willett.
Some medical centers have already adopted this approach for patients with potentially curable esophageal cancer, reserving surgery as salvage treatment. Compared with surgery as first-line treatment, definitive chemoradiotherapy is associated with a lower rate of treatment-related mortality and similar survival outcomes, they noted.
Dr. Czito, Dr. Palta, and Dr. Willett are in the department of radiation oncology at Duke Cancer Institute, Durham, N.C. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Mariette’s report (J. Clin. Oncol. 2014 June 30 [doi:10.1200/JCO.2013.53.6532]).
For patients with early-stage esophageal cancer, undergoing chemotherapy and radiotherapy before surgical excision failed to improve the rate of curative resection and, most importantly, failed to boost survival in a phase III clinical trial, according to a report published online June 30 in the Journal of Clinical Oncology.
Unfortunately this treatment strategy also tripled postoperative mortality, making the risk-benefit ratio even more lopsided for this patient population, said Dr. Christophe Mariette of the department of digestive and oncologic surgery, University Hospital Claude Huriez-Regional University Hospital Center, Lille (France), and his associates.
Clinical trials examining neoadjuvant chemoradiotherapy for esophageal cancer have produced conflicting results, with some showing that the approach is effective, in some cases doubling median survival, while others showed no benefit. Most such studies have been limited by small sample sizes, heterogeneity of tumor types, variations in radiation doses and chemotherapy regiments, and differences in preoperative staging techniques and the adequacy of surgical resections. Moreover, the number of study participants with early-stage esophageal cancer has been very small because most patients already have more advanced disease at presentation, the investigators noted.
For their study, Dr. Mariette and his associates confined the cohort to patients younger than 75 years with treatment-naive esophageal adenocarcinoma or squamous-cell carcinoma judged to be stage I or II using thoracoabdominal CT and endoscopic ultrasound; additional preoperative assessments using PET scanning, cervical ultrasound, or radionuclide bone scanning were optional. It required 9 years to enroll 195 patients at 30 French medical centers. These study participants were randomly assigned to receive either neoadjuvant chemotherapy plus radiotherapy before potentially curative surgery (98 subjects) or potentially curative surgery alone (97 subjects).
In the intervention group, radiotherapy involved a total dose of 45 Gy delivered in 25 fractions over the course of 5 weeks. Chemotherapy was administered during the same time period and involved two cycles of fluorouracil and cisplatin infusions. All patients in this group were clinically reevaluated 2-4 weeks after completing this regimen, and surgery was performed soon afterward.
Surgery comprised a transthoracic esophagectomy with extended two-field lymphadenectomy and either high intrathoracic anastomosis (for tumors with an infracarinal proximal margin) or cervical anastomosis (for tumors with a proximal margin above the carina).
Median follow-up was 7.8 years. There were 125 deaths: 62.4% of the intervention group died, as did 66% of the surgery-only group, a nonsignificant difference, the investigators said (J. Clin. Oncol. 2014 June 30 [doi:10.1200/JCO.2013.53.6532]).
Median overall survival was 31.8 months in the intervention group and 41.2 months in the surgery-only group, a nonsignificant difference. Similarly, 3-year overall survival was 47.5% and 5-year overall survival was 41.1% in the intervention group, compared with 53% and 33.8%, respectively, in the surgery-only group, which were also nonsignificant differences.
The rate of curative resection also was not significantly different between the intervention group (93.8%) and the surgery-only group (92.1%), indicating that reducing the tumor with chemotherapy and radiotherapy had no beneficial effect in these early-stage cancers. Previous studies have demonstrated that such downsizing is effective in more advanced esophageal cancers, Dr. Mariette and his associates noted.
Postoperative mortality was more than threefold higher among patients who underwent preoperative chemoradiotherapy (11.1%) than in the surgery-only group (3.4%). The causes of postoperative death included aortic rupture, uncontrollable chylothorax, anastomotic leak, gastric conduit necrosis, mesenteric and lower limb ischemia, and acute RDS in the intervention group, compared with pneumonia and acute RDS in the surgery-only group.
These findings suggest that preoperative chemoradiotherapy "is not the appropriate neoadjuvant therapeutic strategy for stage I or II esophageal cancer," the investigators said.
For patients with early-stage esophageal cancer, undergoing chemotherapy and radiotherapy before surgical excision failed to improve the rate of curative resection and, most importantly, failed to boost survival in a phase III clinical trial, according to a report published online June 30 in the Journal of Clinical Oncology.
Unfortunately this treatment strategy also tripled postoperative mortality, making the risk-benefit ratio even more lopsided for this patient population, said Dr. Christophe Mariette of the department of digestive and oncologic surgery, University Hospital Claude Huriez-Regional University Hospital Center, Lille (France), and his associates.
Clinical trials examining neoadjuvant chemoradiotherapy for esophageal cancer have produced conflicting results, with some showing that the approach is effective, in some cases doubling median survival, while others showed no benefit. Most such studies have been limited by small sample sizes, heterogeneity of tumor types, variations in radiation doses and chemotherapy regiments, and differences in preoperative staging techniques and the adequacy of surgical resections. Moreover, the number of study participants with early-stage esophageal cancer has been very small because most patients already have more advanced disease at presentation, the investigators noted.
For their study, Dr. Mariette and his associates confined the cohort to patients younger than 75 years with treatment-naive esophageal adenocarcinoma or squamous-cell carcinoma judged to be stage I or II using thoracoabdominal CT and endoscopic ultrasound; additional preoperative assessments using PET scanning, cervical ultrasound, or radionuclide bone scanning were optional. It required 9 years to enroll 195 patients at 30 French medical centers. These study participants were randomly assigned to receive either neoadjuvant chemotherapy plus radiotherapy before potentially curative surgery (98 subjects) or potentially curative surgery alone (97 subjects).
In the intervention group, radiotherapy involved a total dose of 45 Gy delivered in 25 fractions over the course of 5 weeks. Chemotherapy was administered during the same time period and involved two cycles of fluorouracil and cisplatin infusions. All patients in this group were clinically reevaluated 2-4 weeks after completing this regimen, and surgery was performed soon afterward.
Surgery comprised a transthoracic esophagectomy with extended two-field lymphadenectomy and either high intrathoracic anastomosis (for tumors with an infracarinal proximal margin) or cervical anastomosis (for tumors with a proximal margin above the carina).
Median follow-up was 7.8 years. There were 125 deaths: 62.4% of the intervention group died, as did 66% of the surgery-only group, a nonsignificant difference, the investigators said (J. Clin. Oncol. 2014 June 30 [doi:10.1200/JCO.2013.53.6532]).
Median overall survival was 31.8 months in the intervention group and 41.2 months in the surgery-only group, a nonsignificant difference. Similarly, 3-year overall survival was 47.5% and 5-year overall survival was 41.1% in the intervention group, compared with 53% and 33.8%, respectively, in the surgery-only group, which were also nonsignificant differences.
The rate of curative resection also was not significantly different between the intervention group (93.8%) and the surgery-only group (92.1%), indicating that reducing the tumor with chemotherapy and radiotherapy had no beneficial effect in these early-stage cancers. Previous studies have demonstrated that such downsizing is effective in more advanced esophageal cancers, Dr. Mariette and his associates noted.
Postoperative mortality was more than threefold higher among patients who underwent preoperative chemoradiotherapy (11.1%) than in the surgery-only group (3.4%). The causes of postoperative death included aortic rupture, uncontrollable chylothorax, anastomotic leak, gastric conduit necrosis, mesenteric and lower limb ischemia, and acute RDS in the intervention group, compared with pneumonia and acute RDS in the surgery-only group.
These findings suggest that preoperative chemoradiotherapy "is not the appropriate neoadjuvant therapeutic strategy for stage I or II esophageal cancer," the investigators said.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Don’t postpone surgery for esophageal cancer to perform chemoradiotherapy.
Major finding: Median overall survival was 31.8 months in the intervention group and 41.2 months in the surgery-only group; 3-year overall survival was 47.5% and 5-year overall survival was 41.1% in the intervention group, compared with 53% and 33.8%, respectively, in the surgery-only group. All these differences are nonsignificant.
Data source: A multicenter randomized phase III clinical trial involving 98 patients treated with neoadjuvant chemoradiotherapy and 97 treated with surgery alone for early-stage esophageal cancer, who were followed for a median of approximately 8 years.
Disclosures: This study was supported by the French National Cancer Institute’s Programme Hospitalier pour la Recherche Clinque and Lille University Hospital; it received no commercial support. Dr. Mariette reported no financial conflicts of interest; one of his associates reported ties to Roche and Merck.
Anatomic segmentectomy as good as lobectomy
Patients with stage I non–small cell lung cancer who underwent anatomic segmentectomy had similar outcomes to those who underwent lobectomy in a large propensity-matched trial comparing the two approaches, which was reported online June 30 in the Journal of Clinical Oncology.
Long-term survival and recurrence rates, as well as perioperative morbidity and mortality, were not significantly different between the two groups of patients, even though lobectomy is considered the gold standard of treatment for early-stage non–small cell lung cancer (NSCLC), said Dr. Rodney J. Landreneau of the department of cardiothoracic surgery, University of Pittsburgh Medical Center, and his associates.
If the results of this retrospective single-center study are validated in future prospective, multicenter, randomized controlled trials, "anatomic segmentectomy should be considered as a valid alternative to lobectomy in properly selected patients," the investigators noted.
Interest in using the less radical segmentectomy approach is being driven by earlier detection of smaller lesions using computed tomography imaging, a new understanding of lesion pathology, and the fact that the randomized controlled trial that established lobectomy as the gold standard occurred more than 20 years ago, said Dr. Hisao Asamura, in his editorial commentary on the study.
The investigators identified 392 patients in their center’s lung cancer database who had anatomic segmentectomy and 800 who had lobectomy, then performed propensity matching to account for the confounding effects of patient age, sex, smoking status, and forced expiratory volume in 1 second (FEV1) level; tumor size; and patient history of hypertension, chronic obstructive pulmonary disease, diabetes, gastroesophageal reflux, coronary artery disease, and other types of cancer. They then assessed outcomes in 624 propensity-matched patients: 312 who had segmentectomies (cases) and 312 who had lobectomies (controls).
Approximately 93% of the study cohort were current or former smokers. The mean patient age was 68.5 years at baseline. The mean tumor size was 2.2 cm. The participants were followed for a median of 5.4 years.
Overall survival was 54% for cases and 60% for controls, a nonsignificant difference. Both locoregional recurrence rates (5.5% and 5.1%, respectively) and distant recurrence rates (14.8% and 11.6%) also showed no significant difference by treatment type. Perioperative morbidity (1.2% and 2.5%) and mortality (2.6% and 4.8%) slightly favored anatomic segmentectomy, but not significantly so, Dr. Landreneau and his associates reported (J. Clin. Oncol. 2014 June 30 [doi:10.1200/JCO.2013.50.8762]).
Further analyses demonstrated that anatomic segmentectomy was not a predictor of recurrence or of survival.
Surgeons excised a greater number of lymph nodes with lobectomy (median, 12 nodes) than with anatomic segmentectomy (median, 6 nodes). However, the number of lymph node stations assessed was the same in both groups (a median of three in each), and the proportion of cancers that required upstaging at surgery was not significantly different between cases (29.5%) and controls (36.5%).
Multicenter prospective randomized trials comparing the two approaches are needed to confirm these findings. Two such trials are currently underway, the researchers said.
This study was supported in part by the National Heart, Lung, and Blood Institute; the Thoracic Surgery Foundation for Research and Education; and the National Cancer Institute. Dr. Landreneau reported no potential financial conflicts of interest; two of his associates reported ties to Varian and Accuray.
Even though these findings are promising, several more years of study are required "before we will reach a definitive conclusion regarding the appropriateness of sublobar resection for early-stage lung cancer," said Dr. Hisao Asamura.
Until then, choosing the surgical mode for such cases "should be based on solid data that demonstrate a clear advantage over the standard mode of resection (lobectomy)," he noted.
Dr. Asamura is in the division of thoracic surgery at the National Cancer Center Hospital, Tokyo. He reported receiving honoraria from Johnson & Johnson and Covidien Japan. These remarks were taken from his editorial accompanying Dr. Landreneau’s report (J. Clin. Oncol. 2014 June 30 [doi:10.1200/JCO.2014.56.4203]).
Even though these findings are promising, several more years of study are required "before we will reach a definitive conclusion regarding the appropriateness of sublobar resection for early-stage lung cancer," said Dr. Hisao Asamura.
Until then, choosing the surgical mode for such cases "should be based on solid data that demonstrate a clear advantage over the standard mode of resection (lobectomy)," he noted.
Dr. Asamura is in the division of thoracic surgery at the National Cancer Center Hospital, Tokyo. He reported receiving honoraria from Johnson & Johnson and Covidien Japan. These remarks were taken from his editorial accompanying Dr. Landreneau’s report (J. Clin. Oncol. 2014 June 30 [doi:10.1200/JCO.2014.56.4203]).
Even though these findings are promising, several more years of study are required "before we will reach a definitive conclusion regarding the appropriateness of sublobar resection for early-stage lung cancer," said Dr. Hisao Asamura.
Until then, choosing the surgical mode for such cases "should be based on solid data that demonstrate a clear advantage over the standard mode of resection (lobectomy)," he noted.
Dr. Asamura is in the division of thoracic surgery at the National Cancer Center Hospital, Tokyo. He reported receiving honoraria from Johnson & Johnson and Covidien Japan. These remarks were taken from his editorial accompanying Dr. Landreneau’s report (J. Clin. Oncol. 2014 June 30 [doi:10.1200/JCO.2014.56.4203]).
Patients with stage I non–small cell lung cancer who underwent anatomic segmentectomy had similar outcomes to those who underwent lobectomy in a large propensity-matched trial comparing the two approaches, which was reported online June 30 in the Journal of Clinical Oncology.
Long-term survival and recurrence rates, as well as perioperative morbidity and mortality, were not significantly different between the two groups of patients, even though lobectomy is considered the gold standard of treatment for early-stage non–small cell lung cancer (NSCLC), said Dr. Rodney J. Landreneau of the department of cardiothoracic surgery, University of Pittsburgh Medical Center, and his associates.
If the results of this retrospective single-center study are validated in future prospective, multicenter, randomized controlled trials, "anatomic segmentectomy should be considered as a valid alternative to lobectomy in properly selected patients," the investigators noted.
Interest in using the less radical segmentectomy approach is being driven by earlier detection of smaller lesions using computed tomography imaging, a new understanding of lesion pathology, and the fact that the randomized controlled trial that established lobectomy as the gold standard occurred more than 20 years ago, said Dr. Hisao Asamura, in his editorial commentary on the study.
The investigators identified 392 patients in their center’s lung cancer database who had anatomic segmentectomy and 800 who had lobectomy, then performed propensity matching to account for the confounding effects of patient age, sex, smoking status, and forced expiratory volume in 1 second (FEV1) level; tumor size; and patient history of hypertension, chronic obstructive pulmonary disease, diabetes, gastroesophageal reflux, coronary artery disease, and other types of cancer. They then assessed outcomes in 624 propensity-matched patients: 312 who had segmentectomies (cases) and 312 who had lobectomies (controls).
Approximately 93% of the study cohort were current or former smokers. The mean patient age was 68.5 years at baseline. The mean tumor size was 2.2 cm. The participants were followed for a median of 5.4 years.
Overall survival was 54% for cases and 60% for controls, a nonsignificant difference. Both locoregional recurrence rates (5.5% and 5.1%, respectively) and distant recurrence rates (14.8% and 11.6%) also showed no significant difference by treatment type. Perioperative morbidity (1.2% and 2.5%) and mortality (2.6% and 4.8%) slightly favored anatomic segmentectomy, but not significantly so, Dr. Landreneau and his associates reported (J. Clin. Oncol. 2014 June 30 [doi:10.1200/JCO.2013.50.8762]).
Further analyses demonstrated that anatomic segmentectomy was not a predictor of recurrence or of survival.
Surgeons excised a greater number of lymph nodes with lobectomy (median, 12 nodes) than with anatomic segmentectomy (median, 6 nodes). However, the number of lymph node stations assessed was the same in both groups (a median of three in each), and the proportion of cancers that required upstaging at surgery was not significantly different between cases (29.5%) and controls (36.5%).
Multicenter prospective randomized trials comparing the two approaches are needed to confirm these findings. Two such trials are currently underway, the researchers said.
This study was supported in part by the National Heart, Lung, and Blood Institute; the Thoracic Surgery Foundation for Research and Education; and the National Cancer Institute. Dr. Landreneau reported no potential financial conflicts of interest; two of his associates reported ties to Varian and Accuray.
Patients with stage I non–small cell lung cancer who underwent anatomic segmentectomy had similar outcomes to those who underwent lobectomy in a large propensity-matched trial comparing the two approaches, which was reported online June 30 in the Journal of Clinical Oncology.
Long-term survival and recurrence rates, as well as perioperative morbidity and mortality, were not significantly different between the two groups of patients, even though lobectomy is considered the gold standard of treatment for early-stage non–small cell lung cancer (NSCLC), said Dr. Rodney J. Landreneau of the department of cardiothoracic surgery, University of Pittsburgh Medical Center, and his associates.
If the results of this retrospective single-center study are validated in future prospective, multicenter, randomized controlled trials, "anatomic segmentectomy should be considered as a valid alternative to lobectomy in properly selected patients," the investigators noted.
Interest in using the less radical segmentectomy approach is being driven by earlier detection of smaller lesions using computed tomography imaging, a new understanding of lesion pathology, and the fact that the randomized controlled trial that established lobectomy as the gold standard occurred more than 20 years ago, said Dr. Hisao Asamura, in his editorial commentary on the study.
The investigators identified 392 patients in their center’s lung cancer database who had anatomic segmentectomy and 800 who had lobectomy, then performed propensity matching to account for the confounding effects of patient age, sex, smoking status, and forced expiratory volume in 1 second (FEV1) level; tumor size; and patient history of hypertension, chronic obstructive pulmonary disease, diabetes, gastroesophageal reflux, coronary artery disease, and other types of cancer. They then assessed outcomes in 624 propensity-matched patients: 312 who had segmentectomies (cases) and 312 who had lobectomies (controls).
Approximately 93% of the study cohort were current or former smokers. The mean patient age was 68.5 years at baseline. The mean tumor size was 2.2 cm. The participants were followed for a median of 5.4 years.
Overall survival was 54% for cases and 60% for controls, a nonsignificant difference. Both locoregional recurrence rates (5.5% and 5.1%, respectively) and distant recurrence rates (14.8% and 11.6%) also showed no significant difference by treatment type. Perioperative morbidity (1.2% and 2.5%) and mortality (2.6% and 4.8%) slightly favored anatomic segmentectomy, but not significantly so, Dr. Landreneau and his associates reported (J. Clin. Oncol. 2014 June 30 [doi:10.1200/JCO.2013.50.8762]).
Further analyses demonstrated that anatomic segmentectomy was not a predictor of recurrence or of survival.
Surgeons excised a greater number of lymph nodes with lobectomy (median, 12 nodes) than with anatomic segmentectomy (median, 6 nodes). However, the number of lymph node stations assessed was the same in both groups (a median of three in each), and the proportion of cancers that required upstaging at surgery was not significantly different between cases (29.5%) and controls (36.5%).
Multicenter prospective randomized trials comparing the two approaches are needed to confirm these findings. Two such trials are currently underway, the researchers said.
This study was supported in part by the National Heart, Lung, and Blood Institute; the Thoracic Surgery Foundation for Research and Education; and the National Cancer Institute. Dr. Landreneau reported no potential financial conflicts of interest; two of his associates reported ties to Varian and Accuray.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Major finding: Overall survival was 54% for anatomic segmentectomy and 60% for lobectomy, a nonsignificant difference; both locoregional recurrence rates (5.5% and 5.1%, respectively) and distant recurrence rates (14.8% and 11.6%) also showed no significant difference by surgery type.
Data source: A retrospective single-center propensity-matched analysis of short- and long-term outcomes in 624 patients with stage I NSCLC who underwent either anatomic segmentectomy or lobectomy and were followed for 5 years.
Disclosures: This study was supported in part by the National Heart, Lung, and Blood Institute; the Thoracic Surgery Foundation for Research and Education; and the National Cancer Institute. Dr. Landreneau reported no potential financial conflicts of interest; two of his associates reported ties to Varian and Accuray.