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Narrow band imaging could expand endometriosis detection
ORLANDO – Narrow band imaging detects neovascularization associated with endometriosis and can be a useful adjunct to laparoscopic white light evaluation, a prospective cohort trial of 53 women with pelvic pain suggested.
The women in the study had no deep infiltrating endometriosis on preoperative ultrasound. Investigators then conducted a standard laparoscopic survey of the pelvis with white light to identify areas of suspected superficial endometriosis, followed by secondary analysis with narrow band imaging.
In the group of 32 patients, follow-up biopsy results confirmed endometriosis in 24 women, including 7 who also had lesions detected by narrow band imaging. Six of these seven were positive for endometriosis on histology. The women were enrolled in the study from September 2014 to October 2015.
“We found that the [narrow band imaging] is useful in detecting additional areas in patients who had histopathology-proven endometriosis,” said Tony J. Ma, MBBS, a fellow at Mercy Hospital for Women in Melbourne.
In the group of 21 women with no white light lesions, narrow band imaging detected four suspicious lesions. However, these four were not positive for endometriosis.
Narrow band imaging is a mixture of blue and green light, opposite of red color. “It causes blood vessels to be more visually prominent,” Dr. Ma said at the meeting sponsored by AAGL. White light laparoscopy for detection of endometriosis “is the gold standard … but depends on experience of [the] surgeon and severity of the disease.”
These findings support those of a 2008 study that reported a high detection rate of lesions with narrow band imaging, Dr. Ma said. In this earlier prospective cohort study of 20 women, 7 patients with endometriosis who had been ruled out by white light evaluation had a positive histologic finding with narrow band imaging (J Minim Invasive Gynecol. 2008 Sep-Oct;15[5]:636-9).
“Narrow band imaging is a simple, noninvasive adjunct that can assist in the identification of additional sites of endometriosis at laparoscopy,” Dr. Ma said. “The shortened depth of field with narrow band imaging requires the operator to inspect the surface quite closely.”
The study topic is an important one because endometriosis is such a challenge to diagnose and treat, said study discussant Sawsan As-Sanie, MD, a minimally invasive gynecologic surgeon at the University of Michigan, Ann Arbor. She estimated that with the current approach – visualization by white light followed by histopathology – “about 50%-70% of patients we think have endometriosis ultimately do.”
But several unanswered questions remain, Dr. As-Sanie said, such as whether the narrow band imaging findings are clinically relevant and whether they will lead to improved patient outcomes.
“We don’t know the answer yet,” she said. “The end game is really only relevant if we improve patient outcomes.”
Dr. Ma reported having no relevant financial disclosures.
ORLANDO – Narrow band imaging detects neovascularization associated with endometriosis and can be a useful adjunct to laparoscopic white light evaluation, a prospective cohort trial of 53 women with pelvic pain suggested.
The women in the study had no deep infiltrating endometriosis on preoperative ultrasound. Investigators then conducted a standard laparoscopic survey of the pelvis with white light to identify areas of suspected superficial endometriosis, followed by secondary analysis with narrow band imaging.
In the group of 32 patients, follow-up biopsy results confirmed endometriosis in 24 women, including 7 who also had lesions detected by narrow band imaging. Six of these seven were positive for endometriosis on histology. The women were enrolled in the study from September 2014 to October 2015.
“We found that the [narrow band imaging] is useful in detecting additional areas in patients who had histopathology-proven endometriosis,” said Tony J. Ma, MBBS, a fellow at Mercy Hospital for Women in Melbourne.
In the group of 21 women with no white light lesions, narrow band imaging detected four suspicious lesions. However, these four were not positive for endometriosis.
Narrow band imaging is a mixture of blue and green light, opposite of red color. “It causes blood vessels to be more visually prominent,” Dr. Ma said at the meeting sponsored by AAGL. White light laparoscopy for detection of endometriosis “is the gold standard … but depends on experience of [the] surgeon and severity of the disease.”
These findings support those of a 2008 study that reported a high detection rate of lesions with narrow band imaging, Dr. Ma said. In this earlier prospective cohort study of 20 women, 7 patients with endometriosis who had been ruled out by white light evaluation had a positive histologic finding with narrow band imaging (J Minim Invasive Gynecol. 2008 Sep-Oct;15[5]:636-9).
“Narrow band imaging is a simple, noninvasive adjunct that can assist in the identification of additional sites of endometriosis at laparoscopy,” Dr. Ma said. “The shortened depth of field with narrow band imaging requires the operator to inspect the surface quite closely.”
The study topic is an important one because endometriosis is such a challenge to diagnose and treat, said study discussant Sawsan As-Sanie, MD, a minimally invasive gynecologic surgeon at the University of Michigan, Ann Arbor. She estimated that with the current approach – visualization by white light followed by histopathology – “about 50%-70% of patients we think have endometriosis ultimately do.”
But several unanswered questions remain, Dr. As-Sanie said, such as whether the narrow band imaging findings are clinically relevant and whether they will lead to improved patient outcomes.
“We don’t know the answer yet,” she said. “The end game is really only relevant if we improve patient outcomes.”
Dr. Ma reported having no relevant financial disclosures.
ORLANDO – Narrow band imaging detects neovascularization associated with endometriosis and can be a useful adjunct to laparoscopic white light evaluation, a prospective cohort trial of 53 women with pelvic pain suggested.
The women in the study had no deep infiltrating endometriosis on preoperative ultrasound. Investigators then conducted a standard laparoscopic survey of the pelvis with white light to identify areas of suspected superficial endometriosis, followed by secondary analysis with narrow band imaging.
In the group of 32 patients, follow-up biopsy results confirmed endometriosis in 24 women, including 7 who also had lesions detected by narrow band imaging. Six of these seven were positive for endometriosis on histology. The women were enrolled in the study from September 2014 to October 2015.
“We found that the [narrow band imaging] is useful in detecting additional areas in patients who had histopathology-proven endometriosis,” said Tony J. Ma, MBBS, a fellow at Mercy Hospital for Women in Melbourne.
In the group of 21 women with no white light lesions, narrow band imaging detected four suspicious lesions. However, these four were not positive for endometriosis.
Narrow band imaging is a mixture of blue and green light, opposite of red color. “It causes blood vessels to be more visually prominent,” Dr. Ma said at the meeting sponsored by AAGL. White light laparoscopy for detection of endometriosis “is the gold standard … but depends on experience of [the] surgeon and severity of the disease.”
These findings support those of a 2008 study that reported a high detection rate of lesions with narrow band imaging, Dr. Ma said. In this earlier prospective cohort study of 20 women, 7 patients with endometriosis who had been ruled out by white light evaluation had a positive histologic finding with narrow band imaging (J Minim Invasive Gynecol. 2008 Sep-Oct;15[5]:636-9).
“Narrow band imaging is a simple, noninvasive adjunct that can assist in the identification of additional sites of endometriosis at laparoscopy,” Dr. Ma said. “The shortened depth of field with narrow band imaging requires the operator to inspect the surface quite closely.”
The study topic is an important one because endometriosis is such a challenge to diagnose and treat, said study discussant Sawsan As-Sanie, MD, a minimally invasive gynecologic surgeon at the University of Michigan, Ann Arbor. She estimated that with the current approach – visualization by white light followed by histopathology – “about 50%-70% of patients we think have endometriosis ultimately do.”
But several unanswered questions remain, Dr. As-Sanie said, such as whether the narrow band imaging findings are clinically relevant and whether they will lead to improved patient outcomes.
“We don’t know the answer yet,” she said. “The end game is really only relevant if we improve patient outcomes.”
Dr. Ma reported having no relevant financial disclosures.
AT THE AAGL GLOBAL CONGRESS
Only topical lidocaine consistently eased infant vaccine pain
During infant vaccinations, only liposomal lidocaine provided consistent pain relief as part of a pain intervention, based on data from 352 infants.
“There is a dearth of data regarding the relative effects of combined interventions [for infants’ pain during vaccination] and their effectiveness over time,” wrote Anna Taddio, Ph.D., of the University of Toronto and her colleagues.
The researchers randomized 352 infants to one of four pain relief regimens to be used for all vaccinations during the first year of life: placebo control, parent-directed video education about infant soothing, the video plus oral sucrose, and the video plus sucrose plus topical lidocaine. The primary outcome of infant distress was assessed using the Modified Behavioural Pain Scale.
Overall, the mean pain scores were significantly lower in the video/sucrose/lidocaine group, compared with all other groups, and there were no significant differences in scores among the other groups.
“The observed treatment effect, albeit above the a priori threshold value set for clinical significance, may not be sufficiently compelling to clinicians to alter clinical practice, particularly in light of the short-lived nature of the pain,” the researchers said. However, “given that vaccination pain is iatrogenic and most infants were distressed despite the use of cointerventions, consideration should be given to adding lidocaine to reduce the burden of pain.”
Dr. Taddio disclosed a research grant from Pfizer, and materials for the study were supplied by Natus and Ferndale.
The findings were published online Dec. 12 in the Canadian Medical Association Journal (CMAJ 2016. doi: 10.1503/ cmaj.160542). Read the full study here.
During infant vaccinations, only liposomal lidocaine provided consistent pain relief as part of a pain intervention, based on data from 352 infants.
“There is a dearth of data regarding the relative effects of combined interventions [for infants’ pain during vaccination] and their effectiveness over time,” wrote Anna Taddio, Ph.D., of the University of Toronto and her colleagues.
The researchers randomized 352 infants to one of four pain relief regimens to be used for all vaccinations during the first year of life: placebo control, parent-directed video education about infant soothing, the video plus oral sucrose, and the video plus sucrose plus topical lidocaine. The primary outcome of infant distress was assessed using the Modified Behavioural Pain Scale.
Overall, the mean pain scores were significantly lower in the video/sucrose/lidocaine group, compared with all other groups, and there were no significant differences in scores among the other groups.
“The observed treatment effect, albeit above the a priori threshold value set for clinical significance, may not be sufficiently compelling to clinicians to alter clinical practice, particularly in light of the short-lived nature of the pain,” the researchers said. However, “given that vaccination pain is iatrogenic and most infants were distressed despite the use of cointerventions, consideration should be given to adding lidocaine to reduce the burden of pain.”
Dr. Taddio disclosed a research grant from Pfizer, and materials for the study were supplied by Natus and Ferndale.
The findings were published online Dec. 12 in the Canadian Medical Association Journal (CMAJ 2016. doi: 10.1503/ cmaj.160542). Read the full study here.
During infant vaccinations, only liposomal lidocaine provided consistent pain relief as part of a pain intervention, based on data from 352 infants.
“There is a dearth of data regarding the relative effects of combined interventions [for infants’ pain during vaccination] and their effectiveness over time,” wrote Anna Taddio, Ph.D., of the University of Toronto and her colleagues.
The researchers randomized 352 infants to one of four pain relief regimens to be used for all vaccinations during the first year of life: placebo control, parent-directed video education about infant soothing, the video plus oral sucrose, and the video plus sucrose plus topical lidocaine. The primary outcome of infant distress was assessed using the Modified Behavioural Pain Scale.
Overall, the mean pain scores were significantly lower in the video/sucrose/lidocaine group, compared with all other groups, and there were no significant differences in scores among the other groups.
“The observed treatment effect, albeit above the a priori threshold value set for clinical significance, may not be sufficiently compelling to clinicians to alter clinical practice, particularly in light of the short-lived nature of the pain,” the researchers said. However, “given that vaccination pain is iatrogenic and most infants were distressed despite the use of cointerventions, consideration should be given to adding lidocaine to reduce the burden of pain.”
Dr. Taddio disclosed a research grant from Pfizer, and materials for the study were supplied by Natus and Ferndale.
The findings were published online Dec. 12 in the Canadian Medical Association Journal (CMAJ 2016. doi: 10.1503/ cmaj.160542). Read the full study here.
FROM THE CANADIAN MEDICAL ASSOCIATION JOURNAL
Gene therapy to boost levodopa conversion enzyme shows benefit in Parkinson’s
Patients with advanced Parkinson’s disease were able to reduce daily levodopa doses in phase Ib testing of an experimental gene therapy from Voyager Therapeutics of Cambridge, Mass.
The company packed the gene for aromatic L-amino acid decarboxylase (AADC) – the enzyme that converts levodopa to dopamine – into a benign adenovirus capsid, then injected it directly into the putamen of 10 patients under MRI-guidance. The idea was to counter the decline in AADC as Parkinson’s progresses. For now, the name of the AADC vector is VY-AADC01.
Due to symptom improvement, cohort 1 patients were able to reduce daily levodopa and related medications by 14%, and cohort 2 patients by 34%, at 6 months. The “reduction in oral medication was generally maintained at 12 months,” the company said in an announcement. The results have not been published in a peer-reviewed journal.
“VY-AADC01 treatment prolonged the duration and markedly increased the motor symptom response to levodopa measured following a controlled intravenous infusion of levodopa [at] 6 months ... when compared to baseline.” There were no serious treatment-related adverse events, and patients went home within 2 days, Voyager said.
“We are excited about the data,” but “we think we have to be as good [as deep brain stimulation]; ideally, we’d obviously like to be better,” Voyager President and CEO Steven Paul, MD, said in a conference call Dec. 7. “We are optimistic that we can at least be equivalent with a onetime treatment, no indwelling hardware, no stimulators, and possibly even beat [deep brain stimulation], but that’s to be determined.” A placebo-controlled trial is scheduled to begin in late 2017 “so we can establish this really does work well against placebo.”
At 6 months, cohort 1 patients had a 15.6-point, off-medication improvement on the 56-point motor exam section of the Unified Parkinson’s Disease Rating Scale (UPDRS-III), which further improved to 16.4 points over baseline at 12 months. Cohort 2 patient improved 17.8 points at 6 months, but declined to 14.3 points over baseline at 12 months.
On medication, cohort 1 worsened 1.6 points on the UPDRS-III at 6 months, and remained there at month 12. Cohort 2 improved 9.6 points over baseline at 6 months, and kept the gain at 1 year.
Cohort 1 lost 0.3 hours in diary on-time over baseline at 6 months, but gained 1.6 hours at 12 months, a 16% improvement. Cohort 2 had a 2.2-hour increase at 6 months, and a further increase to 4.1 hours at 1 year, a 43% improvement over baseline.
Patients had Parkinson’s for an average of 10 years, after being diagnosed at a mean age of 58 years.
Voyager’s stock jumped more than 20% when the results were announced, but lost much of the gain in subsequent trading; VY-AADC01 is one of several gene therapies under development for Parkinson’s.
Patients with advanced Parkinson’s disease were able to reduce daily levodopa doses in phase Ib testing of an experimental gene therapy from Voyager Therapeutics of Cambridge, Mass.
The company packed the gene for aromatic L-amino acid decarboxylase (AADC) – the enzyme that converts levodopa to dopamine – into a benign adenovirus capsid, then injected it directly into the putamen of 10 patients under MRI-guidance. The idea was to counter the decline in AADC as Parkinson’s progresses. For now, the name of the AADC vector is VY-AADC01.
Due to symptom improvement, cohort 1 patients were able to reduce daily levodopa and related medications by 14%, and cohort 2 patients by 34%, at 6 months. The “reduction in oral medication was generally maintained at 12 months,” the company said in an announcement. The results have not been published in a peer-reviewed journal.
“VY-AADC01 treatment prolonged the duration and markedly increased the motor symptom response to levodopa measured following a controlled intravenous infusion of levodopa [at] 6 months ... when compared to baseline.” There were no serious treatment-related adverse events, and patients went home within 2 days, Voyager said.
“We are excited about the data,” but “we think we have to be as good [as deep brain stimulation]; ideally, we’d obviously like to be better,” Voyager President and CEO Steven Paul, MD, said in a conference call Dec. 7. “We are optimistic that we can at least be equivalent with a onetime treatment, no indwelling hardware, no stimulators, and possibly even beat [deep brain stimulation], but that’s to be determined.” A placebo-controlled trial is scheduled to begin in late 2017 “so we can establish this really does work well against placebo.”
At 6 months, cohort 1 patients had a 15.6-point, off-medication improvement on the 56-point motor exam section of the Unified Parkinson’s Disease Rating Scale (UPDRS-III), which further improved to 16.4 points over baseline at 12 months. Cohort 2 patient improved 17.8 points at 6 months, but declined to 14.3 points over baseline at 12 months.
On medication, cohort 1 worsened 1.6 points on the UPDRS-III at 6 months, and remained there at month 12. Cohort 2 improved 9.6 points over baseline at 6 months, and kept the gain at 1 year.
Cohort 1 lost 0.3 hours in diary on-time over baseline at 6 months, but gained 1.6 hours at 12 months, a 16% improvement. Cohort 2 had a 2.2-hour increase at 6 months, and a further increase to 4.1 hours at 1 year, a 43% improvement over baseline.
Patients had Parkinson’s for an average of 10 years, after being diagnosed at a mean age of 58 years.
Voyager’s stock jumped more than 20% when the results were announced, but lost much of the gain in subsequent trading; VY-AADC01 is one of several gene therapies under development for Parkinson’s.
Patients with advanced Parkinson’s disease were able to reduce daily levodopa doses in phase Ib testing of an experimental gene therapy from Voyager Therapeutics of Cambridge, Mass.
The company packed the gene for aromatic L-amino acid decarboxylase (AADC) – the enzyme that converts levodopa to dopamine – into a benign adenovirus capsid, then injected it directly into the putamen of 10 patients under MRI-guidance. The idea was to counter the decline in AADC as Parkinson’s progresses. For now, the name of the AADC vector is VY-AADC01.
Due to symptom improvement, cohort 1 patients were able to reduce daily levodopa and related medications by 14%, and cohort 2 patients by 34%, at 6 months. The “reduction in oral medication was generally maintained at 12 months,” the company said in an announcement. The results have not been published in a peer-reviewed journal.
“VY-AADC01 treatment prolonged the duration and markedly increased the motor symptom response to levodopa measured following a controlled intravenous infusion of levodopa [at] 6 months ... when compared to baseline.” There were no serious treatment-related adverse events, and patients went home within 2 days, Voyager said.
“We are excited about the data,” but “we think we have to be as good [as deep brain stimulation]; ideally, we’d obviously like to be better,” Voyager President and CEO Steven Paul, MD, said in a conference call Dec. 7. “We are optimistic that we can at least be equivalent with a onetime treatment, no indwelling hardware, no stimulators, and possibly even beat [deep brain stimulation], but that’s to be determined.” A placebo-controlled trial is scheduled to begin in late 2017 “so we can establish this really does work well against placebo.”
At 6 months, cohort 1 patients had a 15.6-point, off-medication improvement on the 56-point motor exam section of the Unified Parkinson’s Disease Rating Scale (UPDRS-III), which further improved to 16.4 points over baseline at 12 months. Cohort 2 patient improved 17.8 points at 6 months, but declined to 14.3 points over baseline at 12 months.
On medication, cohort 1 worsened 1.6 points on the UPDRS-III at 6 months, and remained there at month 12. Cohort 2 improved 9.6 points over baseline at 6 months, and kept the gain at 1 year.
Cohort 1 lost 0.3 hours in diary on-time over baseline at 6 months, but gained 1.6 hours at 12 months, a 16% improvement. Cohort 2 had a 2.2-hour increase at 6 months, and a further increase to 4.1 hours at 1 year, a 43% improvement over baseline.
Patients had Parkinson’s for an average of 10 years, after being diagnosed at a mean age of 58 years.
Voyager’s stock jumped more than 20% when the results were announced, but lost much of the gain in subsequent trading; VY-AADC01 is one of several gene therapies under development for Parkinson’s.
Key clinical point:
Major finding: Cohort 1 patients were able to reduce daily levodopa and related medications by 14%, and cohort 2 patients by 34%, at 6 months.
Data source: Phase Ib testing in 10 advanced Parkinson’s disease patients.
Disclosures: The study was funded and conducted by Voyager Therapeutics. The company announced the results; they have not been published in a peer-reviewed journal.
Two-test sequence identifies sporadic Creutzfeldt-Jakob with 100% sensitivity, specificity
The sequential use of two diagnostic tests – one assessing cerebrospinal fluid and the other assessing nasal swabs – identifies sporadic Creutzfeldt-Jakob disease with virtually 100% sensitivity and specificity, according to a report published online Dec. 12 in JAMA Neurology.
“Patients with sporadic CJD show great variability in clinical signs and pathologic lesions,” which makes distinguishing the disorder from other neurodegenerative abnormalities challenging. Researchers assessed the performance of two diagnostic tests in a case-control study involving 86 patients referred because of clinical suspicion of CJD, 81 control subjects who had other neurologic disorders, and 23 control subjects who had no neurologic disorders. The final diagnoses of the 86 case patients were established either at postmortem examination or when a definite alternative diagnosis was made, said Matilde Bongianni, PhD, of the department of neurosciences, biomedicine, and movement sciences at the University of Verona (Italy) and associates.
The first diagnostic test was a second-generation real-time quaking-induced conversion (RT-QuIC) assay that detects femtograms of an abnormal CJD-specific prion protein in the cerebrospinal fluid (CSF), which has been reported to have a diagnostic sensitivity of 96%. The second diagnostic test applied the RT-QuIC to brushings from the olfactory mucosa using a soft, flocked nasal swab rather than the more invasive and painful cytobrush, which has been reported to have a diagnostic sensitivity of 97%.
By using these two tests sequentially, the investigators were able to identify all cases of CJD and distinguish affected patients from all the control subjects. Alternative diagnoses were immediately pursued in the 17 case patients in whom CJD was ruled out, and 5 of them were successfully treated for other abnormalities, the investigators said (JAMA Neurol. 2016 Dec 12. doi: 10.1001/jamaneurol.2016.4614).
“Our results suggest that the application of RT-QuIC testing will improve the accuracy and speed of sporadic CJD diagnosis compared with internationally recognized antemortem diagnostic criteria,” Dr. Bongianni and associates wrote.
“A positive RT-QuIC finding in the CSF of patients with progressive neurologic signs should be sufficient to establish a diagnosis of probable CJD and would make olfactory mucosa sampling unnecessary. However, when the RT-QuIC CSF finding is negative or lumbar puncture is not feasible, olfactory mucosa sampling would become necessary to confirm prion disease or to divert to alternative diagnoses,” they added.
The study was supported by the Alliance Biosecure Foundation, the University of Verona, and the National Institute of Allergy and Infectious Diseases. The investigators reported having no relevant financial disclosures.
At last we have a truly practical, inexpensive, and accurate procedure for diagnosing sporadic CJD, thanks to the impeccably conducted and convincing work of Dr. Bongianni and associates.
Testing the CSF and then the olfactory mucosa using the RT-QuIC assay should soon become the standard approach for diagnosing CJD, possibly replacing current CSF tests for 14-3-3 and tau proteins. This assay also could be extended to an even larger patient population if it is included in routine laboratory examinations of all patients who have mental/behavioral or cerebellar signs, regardless of their presumed diagnosis.
Because only four of eight mutation-positive symptomatic patients with genetic forms of prion disease tested positive, there may be some future cases of sporadic CJD with false-negative test results or it may be the case that genetic forms have a different timing and spread of misfolded prion protein through the CSF and nasal mucosa.
Paul Brown, MD, is a retired senior investigator at the Laboratory of Central Nervous System Studies at the National Institutes of Health, Bethesda, Md. He reported having no relevant financial disclosures. Dr. Brown made these remarks in an accompanying editorial (JAMA Neurol. 2016 Dec 12. doi: 10.1001/jamaneurol.2016.4877).
At last we have a truly practical, inexpensive, and accurate procedure for diagnosing sporadic CJD, thanks to the impeccably conducted and convincing work of Dr. Bongianni and associates.
Testing the CSF and then the olfactory mucosa using the RT-QuIC assay should soon become the standard approach for diagnosing CJD, possibly replacing current CSF tests for 14-3-3 and tau proteins. This assay also could be extended to an even larger patient population if it is included in routine laboratory examinations of all patients who have mental/behavioral or cerebellar signs, regardless of their presumed diagnosis.
Because only four of eight mutation-positive symptomatic patients with genetic forms of prion disease tested positive, there may be some future cases of sporadic CJD with false-negative test results or it may be the case that genetic forms have a different timing and spread of misfolded prion protein through the CSF and nasal mucosa.
Paul Brown, MD, is a retired senior investigator at the Laboratory of Central Nervous System Studies at the National Institutes of Health, Bethesda, Md. He reported having no relevant financial disclosures. Dr. Brown made these remarks in an accompanying editorial (JAMA Neurol. 2016 Dec 12. doi: 10.1001/jamaneurol.2016.4877).
At last we have a truly practical, inexpensive, and accurate procedure for diagnosing sporadic CJD, thanks to the impeccably conducted and convincing work of Dr. Bongianni and associates.
Testing the CSF and then the olfactory mucosa using the RT-QuIC assay should soon become the standard approach for diagnosing CJD, possibly replacing current CSF tests for 14-3-3 and tau proteins. This assay also could be extended to an even larger patient population if it is included in routine laboratory examinations of all patients who have mental/behavioral or cerebellar signs, regardless of their presumed diagnosis.
Because only four of eight mutation-positive symptomatic patients with genetic forms of prion disease tested positive, there may be some future cases of sporadic CJD with false-negative test results or it may be the case that genetic forms have a different timing and spread of misfolded prion protein through the CSF and nasal mucosa.
Paul Brown, MD, is a retired senior investigator at the Laboratory of Central Nervous System Studies at the National Institutes of Health, Bethesda, Md. He reported having no relevant financial disclosures. Dr. Brown made these remarks in an accompanying editorial (JAMA Neurol. 2016 Dec 12. doi: 10.1001/jamaneurol.2016.4877).
The sequential use of two diagnostic tests – one assessing cerebrospinal fluid and the other assessing nasal swabs – identifies sporadic Creutzfeldt-Jakob disease with virtually 100% sensitivity and specificity, according to a report published online Dec. 12 in JAMA Neurology.
“Patients with sporadic CJD show great variability in clinical signs and pathologic lesions,” which makes distinguishing the disorder from other neurodegenerative abnormalities challenging. Researchers assessed the performance of two diagnostic tests in a case-control study involving 86 patients referred because of clinical suspicion of CJD, 81 control subjects who had other neurologic disorders, and 23 control subjects who had no neurologic disorders. The final diagnoses of the 86 case patients were established either at postmortem examination or when a definite alternative diagnosis was made, said Matilde Bongianni, PhD, of the department of neurosciences, biomedicine, and movement sciences at the University of Verona (Italy) and associates.
The first diagnostic test was a second-generation real-time quaking-induced conversion (RT-QuIC) assay that detects femtograms of an abnormal CJD-specific prion protein in the cerebrospinal fluid (CSF), which has been reported to have a diagnostic sensitivity of 96%. The second diagnostic test applied the RT-QuIC to brushings from the olfactory mucosa using a soft, flocked nasal swab rather than the more invasive and painful cytobrush, which has been reported to have a diagnostic sensitivity of 97%.
By using these two tests sequentially, the investigators were able to identify all cases of CJD and distinguish affected patients from all the control subjects. Alternative diagnoses were immediately pursued in the 17 case patients in whom CJD was ruled out, and 5 of them were successfully treated for other abnormalities, the investigators said (JAMA Neurol. 2016 Dec 12. doi: 10.1001/jamaneurol.2016.4614).
“Our results suggest that the application of RT-QuIC testing will improve the accuracy and speed of sporadic CJD diagnosis compared with internationally recognized antemortem diagnostic criteria,” Dr. Bongianni and associates wrote.
“A positive RT-QuIC finding in the CSF of patients with progressive neurologic signs should be sufficient to establish a diagnosis of probable CJD and would make olfactory mucosa sampling unnecessary. However, when the RT-QuIC CSF finding is negative or lumbar puncture is not feasible, olfactory mucosa sampling would become necessary to confirm prion disease or to divert to alternative diagnoses,” they added.
The study was supported by the Alliance Biosecure Foundation, the University of Verona, and the National Institute of Allergy and Infectious Diseases. The investigators reported having no relevant financial disclosures.
The sequential use of two diagnostic tests – one assessing cerebrospinal fluid and the other assessing nasal swabs – identifies sporadic Creutzfeldt-Jakob disease with virtually 100% sensitivity and specificity, according to a report published online Dec. 12 in JAMA Neurology.
“Patients with sporadic CJD show great variability in clinical signs and pathologic lesions,” which makes distinguishing the disorder from other neurodegenerative abnormalities challenging. Researchers assessed the performance of two diagnostic tests in a case-control study involving 86 patients referred because of clinical suspicion of CJD, 81 control subjects who had other neurologic disorders, and 23 control subjects who had no neurologic disorders. The final diagnoses of the 86 case patients were established either at postmortem examination or when a definite alternative diagnosis was made, said Matilde Bongianni, PhD, of the department of neurosciences, biomedicine, and movement sciences at the University of Verona (Italy) and associates.
The first diagnostic test was a second-generation real-time quaking-induced conversion (RT-QuIC) assay that detects femtograms of an abnormal CJD-specific prion protein in the cerebrospinal fluid (CSF), which has been reported to have a diagnostic sensitivity of 96%. The second diagnostic test applied the RT-QuIC to brushings from the olfactory mucosa using a soft, flocked nasal swab rather than the more invasive and painful cytobrush, which has been reported to have a diagnostic sensitivity of 97%.
By using these two tests sequentially, the investigators were able to identify all cases of CJD and distinguish affected patients from all the control subjects. Alternative diagnoses were immediately pursued in the 17 case patients in whom CJD was ruled out, and 5 of them were successfully treated for other abnormalities, the investigators said (JAMA Neurol. 2016 Dec 12. doi: 10.1001/jamaneurol.2016.4614).
“Our results suggest that the application of RT-QuIC testing will improve the accuracy and speed of sporadic CJD diagnosis compared with internationally recognized antemortem diagnostic criteria,” Dr. Bongianni and associates wrote.
“A positive RT-QuIC finding in the CSF of patients with progressive neurologic signs should be sufficient to establish a diagnosis of probable CJD and would make olfactory mucosa sampling unnecessary. However, when the RT-QuIC CSF finding is negative or lumbar puncture is not feasible, olfactory mucosa sampling would become necessary to confirm prion disease or to divert to alternative diagnoses,” they added.
The study was supported by the Alliance Biosecure Foundation, the University of Verona, and the National Institute of Allergy and Infectious Diseases. The investigators reported having no relevant financial disclosures.
FROM JAMA NEUROLOGY
Key clinical point:
Major finding: By using the RT-QuIC assay first on cerebrospinal fluid samples and then on olfactory mucosal swabbings, all 69 cases of CJD and prion disease were readily distinguished from all 17 cases of other neurologic disorders and from all 104 control subjects.
Data source: A case-control study involving 86 adults with clinical diagnoses of suspected, possible, or probable sporadic CJD; 81 control subjects with other neurologic disorders; and 23 control subjects with no neurologic disorders.
Disclosures: This study was supported by the Alliance Biosecure Foundation, the University of Verona, and the National Institute of Allergy and Infectious Diseases. Dr. Bongianni and her associates reported having no relevant financial disclosures.
Statins protect against Alzheimer’s in most patients
Statins taken to reduce cholesterol also protect most patients against Alzheimer’s disease, but the decrease in risk varies across different statins and by the patient’s gender and race/ethnicity, according to a report published Dec. 12 in JAMA Neurology.
In particular, none of the statins assessed in this study affected the risk of developing Alzheimer’s disease among black men, said Julie M. Zissimopoulos, PhD, and her associates at the University of Southern California, Los Angeles.
The study population included 310,240 non-Hispanic white people, 32,658 Hispanic people, 32,278 non-Hispanic black people, and 24,803 people of Asian, Native American, other, or unknown race/ethnicity. The investigators confined their analysis to the four most commonly prescribed statins: simvastatin and atorvastatin, which are both lipophilic, and pravastatin and rosuvastatin, which are both hydrophilic. Overall, 1.72% of women and 1.32% of men were diagnosed as having Alzheimer’s disease during each year of follow-up.
Study participants who were exposed to higher statin levels during the 2-year exposure period were 10% less likely to receive an Alzheimer’s diagnosis during follow-up than were those exposed to lower levels of statins, across all four statins. High exposure to statins reduced the risk of Alzheimer’s among women of all races (hazard ratio, 0.85) and men of all races (HR, 0.88), reflecting 15% and 12% decreases, respectively.
This association, however, varied across gender and race/ethnicity. Statins decreased the risk of Alzheimer’s the most among Hispanic men (HR, 0.71), followed by black women (HR, 0.82), white women (HR, 0.86), and white men (HR, 0.89), but they did not decrease the risk of Alzheimer’s among black men, Dr. Zissimopoulos and her associates said (JAMA Neurol. 2016 Dec 12. doi: 10.1001/jamaneurol.2016.3783). Simvastatin significantly decreased the risk of Alzheimer’s among white, Hispanic, and black women, compared with other subgroups, and atorvastatin significantly decreased the risk among white women, Hispanic women, and Hispanic men. Pravastatin and rosuvastatin only decreased the risk of Alzheimer’s significantly among white women.
These findings suggest that “certain patients, facing multiple, otherwise equal statin alternatives for hyperlipidemia treatment, may reduce Alzheimer’s risk by using a particular statin. The right statin type for the right person at the right time may provide a relatively inexpensive means to lessen the burden of Alzheimer’s disease,” the investigators said.
This study was supported by the National Institute on Aging, the University of Southern California Zumberge Research Fund, and the Schaeffer-Amgen Fellowship Program. Dr. Zissimopoulos and her associates reported having no relevant financial disclosures.
Statins taken to reduce cholesterol also protect most patients against Alzheimer’s disease, but the decrease in risk varies across different statins and by the patient’s gender and race/ethnicity, according to a report published Dec. 12 in JAMA Neurology.
In particular, none of the statins assessed in this study affected the risk of developing Alzheimer’s disease among black men, said Julie M. Zissimopoulos, PhD, and her associates at the University of Southern California, Los Angeles.
The study population included 310,240 non-Hispanic white people, 32,658 Hispanic people, 32,278 non-Hispanic black people, and 24,803 people of Asian, Native American, other, or unknown race/ethnicity. The investigators confined their analysis to the four most commonly prescribed statins: simvastatin and atorvastatin, which are both lipophilic, and pravastatin and rosuvastatin, which are both hydrophilic. Overall, 1.72% of women and 1.32% of men were diagnosed as having Alzheimer’s disease during each year of follow-up.
Study participants who were exposed to higher statin levels during the 2-year exposure period were 10% less likely to receive an Alzheimer’s diagnosis during follow-up than were those exposed to lower levels of statins, across all four statins. High exposure to statins reduced the risk of Alzheimer’s among women of all races (hazard ratio, 0.85) and men of all races (HR, 0.88), reflecting 15% and 12% decreases, respectively.
This association, however, varied across gender and race/ethnicity. Statins decreased the risk of Alzheimer’s the most among Hispanic men (HR, 0.71), followed by black women (HR, 0.82), white women (HR, 0.86), and white men (HR, 0.89), but they did not decrease the risk of Alzheimer’s among black men, Dr. Zissimopoulos and her associates said (JAMA Neurol. 2016 Dec 12. doi: 10.1001/jamaneurol.2016.3783). Simvastatin significantly decreased the risk of Alzheimer’s among white, Hispanic, and black women, compared with other subgroups, and atorvastatin significantly decreased the risk among white women, Hispanic women, and Hispanic men. Pravastatin and rosuvastatin only decreased the risk of Alzheimer’s significantly among white women.
These findings suggest that “certain patients, facing multiple, otherwise equal statin alternatives for hyperlipidemia treatment, may reduce Alzheimer’s risk by using a particular statin. The right statin type for the right person at the right time may provide a relatively inexpensive means to lessen the burden of Alzheimer’s disease,” the investigators said.
This study was supported by the National Institute on Aging, the University of Southern California Zumberge Research Fund, and the Schaeffer-Amgen Fellowship Program. Dr. Zissimopoulos and her associates reported having no relevant financial disclosures.
Statins taken to reduce cholesterol also protect most patients against Alzheimer’s disease, but the decrease in risk varies across different statins and by the patient’s gender and race/ethnicity, according to a report published Dec. 12 in JAMA Neurology.
In particular, none of the statins assessed in this study affected the risk of developing Alzheimer’s disease among black men, said Julie M. Zissimopoulos, PhD, and her associates at the University of Southern California, Los Angeles.
The study population included 310,240 non-Hispanic white people, 32,658 Hispanic people, 32,278 non-Hispanic black people, and 24,803 people of Asian, Native American, other, or unknown race/ethnicity. The investigators confined their analysis to the four most commonly prescribed statins: simvastatin and atorvastatin, which are both lipophilic, and pravastatin and rosuvastatin, which are both hydrophilic. Overall, 1.72% of women and 1.32% of men were diagnosed as having Alzheimer’s disease during each year of follow-up.
Study participants who were exposed to higher statin levels during the 2-year exposure period were 10% less likely to receive an Alzheimer’s diagnosis during follow-up than were those exposed to lower levels of statins, across all four statins. High exposure to statins reduced the risk of Alzheimer’s among women of all races (hazard ratio, 0.85) and men of all races (HR, 0.88), reflecting 15% and 12% decreases, respectively.
This association, however, varied across gender and race/ethnicity. Statins decreased the risk of Alzheimer’s the most among Hispanic men (HR, 0.71), followed by black women (HR, 0.82), white women (HR, 0.86), and white men (HR, 0.89), but they did not decrease the risk of Alzheimer’s among black men, Dr. Zissimopoulos and her associates said (JAMA Neurol. 2016 Dec 12. doi: 10.1001/jamaneurol.2016.3783). Simvastatin significantly decreased the risk of Alzheimer’s among white, Hispanic, and black women, compared with other subgroups, and atorvastatin significantly decreased the risk among white women, Hispanic women, and Hispanic men. Pravastatin and rosuvastatin only decreased the risk of Alzheimer’s significantly among white women.
These findings suggest that “certain patients, facing multiple, otherwise equal statin alternatives for hyperlipidemia treatment, may reduce Alzheimer’s risk by using a particular statin. The right statin type for the right person at the right time may provide a relatively inexpensive means to lessen the burden of Alzheimer’s disease,” the investigators said.
This study was supported by the National Institute on Aging, the University of Southern California Zumberge Research Fund, and the Schaeffer-Amgen Fellowship Program. Dr. Zissimopoulos and her associates reported having no relevant financial disclosures.
FROM JAMA NEUROLOGY
Key clinical point: Statins taken to reduce cholesterol also protect most patients against Alzheimer’s disease, but the decrease in risk varies across different statins and according to the patient’s gender and race/ethnicity.
Major finding: Statins decreased the risk of Alzheimer’s the most among Hispanic men (hazard ratio, 0.71), followed by black women (HR, 0.82), white women (HR, 0.86), and white men (HR, 0.89), but they did not decrease the risk of Alzheimer’s among black men.
Data source: A retrospective, longitudinal analysis of medical and pharmacy claims for approximately 400,000 Medicare beneficiaries from 2006 to 2013.
Disclosures: This study was supported by the National Institute on Aging, the University of Southern California Zumberge Research Fund, and the Schaeffer-Amgen Fellowship Program. Dr. Zissimopoulos and her associates reported having no relevant financial disclosures.
Light and heavy mesh deliver similar outcomes and QOL for lap inguinal repair
WASHINGTON – The weight of mesh used in laparoscopic inguinal hernia repairs was not a significant factor in postoperative outcomes and quality of life, in a large, long-term study.
“There are approximately 700,000 inguinal hernia repairs annually,” said Steve Groene, MD, of the Carolinas Medical Center, Charlotte, N.C. “The goal of our study was to utilize a large sample size of long-term follow-up and compare surgical and quality of life outcomes between light-weight and heavy-weight mesh in laparoscopic inguinal hernia repairs.”
The rates of postoperative complications such as surgical infection, urinary retention, and recurrence in the two groups were similar. Although the LW mesh group had a significantly higher rate of hematoma and seroma, that difference vanished with a multivariate analysis that accounted for confounding factors such as smoking, elective vs. emergent surgery, and surgical technique, Dr. Groene said at the annual clinical congress of the American College of Surgeons.
Quality of life (QOL) was measured with the Carolina Comfort Scale before surgery and at the 2-week, 1-month, 6-month, 12-month, 24-month, and 36-month follow-ups. The investigators looked at pain, movement limitation, and mesh sensation for outcomes and symptoms. There were no other statistically significant differences in QOL between the groups at any of the follow-up time points.
When asked during the discussion about the experience of the investigators in getting patients to continue through a 36-month follow-up, Dr. Groene said that “at 1 month, we were about 60%, [and] at 1 year about 40%; having about 40%-42% of people following up at 1 month is very good.”
Dr. Groene concluded that surgeons should continue to use the type of mesh they feel most comfortable with for laparoscopic inguinal hernia repair and expect to have similar outcomes.
He reported having no relevant financial disclosures.
WASHINGTON – The weight of mesh used in laparoscopic inguinal hernia repairs was not a significant factor in postoperative outcomes and quality of life, in a large, long-term study.
“There are approximately 700,000 inguinal hernia repairs annually,” said Steve Groene, MD, of the Carolinas Medical Center, Charlotte, N.C. “The goal of our study was to utilize a large sample size of long-term follow-up and compare surgical and quality of life outcomes between light-weight and heavy-weight mesh in laparoscopic inguinal hernia repairs.”
The rates of postoperative complications such as surgical infection, urinary retention, and recurrence in the two groups were similar. Although the LW mesh group had a significantly higher rate of hematoma and seroma, that difference vanished with a multivariate analysis that accounted for confounding factors such as smoking, elective vs. emergent surgery, and surgical technique, Dr. Groene said at the annual clinical congress of the American College of Surgeons.
Quality of life (QOL) was measured with the Carolina Comfort Scale before surgery and at the 2-week, 1-month, 6-month, 12-month, 24-month, and 36-month follow-ups. The investigators looked at pain, movement limitation, and mesh sensation for outcomes and symptoms. There were no other statistically significant differences in QOL between the groups at any of the follow-up time points.
When asked during the discussion about the experience of the investigators in getting patients to continue through a 36-month follow-up, Dr. Groene said that “at 1 month, we were about 60%, [and] at 1 year about 40%; having about 40%-42% of people following up at 1 month is very good.”
Dr. Groene concluded that surgeons should continue to use the type of mesh they feel most comfortable with for laparoscopic inguinal hernia repair and expect to have similar outcomes.
He reported having no relevant financial disclosures.
WASHINGTON – The weight of mesh used in laparoscopic inguinal hernia repairs was not a significant factor in postoperative outcomes and quality of life, in a large, long-term study.
“There are approximately 700,000 inguinal hernia repairs annually,” said Steve Groene, MD, of the Carolinas Medical Center, Charlotte, N.C. “The goal of our study was to utilize a large sample size of long-term follow-up and compare surgical and quality of life outcomes between light-weight and heavy-weight mesh in laparoscopic inguinal hernia repairs.”
The rates of postoperative complications such as surgical infection, urinary retention, and recurrence in the two groups were similar. Although the LW mesh group had a significantly higher rate of hematoma and seroma, that difference vanished with a multivariate analysis that accounted for confounding factors such as smoking, elective vs. emergent surgery, and surgical technique, Dr. Groene said at the annual clinical congress of the American College of Surgeons.
Quality of life (QOL) was measured with the Carolina Comfort Scale before surgery and at the 2-week, 1-month, 6-month, 12-month, 24-month, and 36-month follow-ups. The investigators looked at pain, movement limitation, and mesh sensation for outcomes and symptoms. There were no other statistically significant differences in QOL between the groups at any of the follow-up time points.
When asked during the discussion about the experience of the investigators in getting patients to continue through a 36-month follow-up, Dr. Groene said that “at 1 month, we were about 60%, [and] at 1 year about 40%; having about 40%-42% of people following up at 1 month is very good.”
Dr. Groene concluded that surgeons should continue to use the type of mesh they feel most comfortable with for laparoscopic inguinal hernia repair and expect to have similar outcomes.
He reported having no relevant financial disclosures.
FROM ACS CLINICAL CONGRESS
Key clinical point:
Major finding: For laparoscopic inguinal hernia repair, mesh weight was not a significant factor in postoperative complications or quality of life, as measured by the Carolinas Comfort Scale.
Data source: A prospective study of 1,270 laparoscopic inguinal hernia repair patients from a hernia-specific database.
Disclosures: Dr. Groene reported having no relevant financial disclosures.
Risk models for hernia recurrence don’t hold up to external validation
Five common variable selection strategies failed to produce a statistical model that accurately predicted ventral hernia recurrence in an investigation published in the Journal of Surgical Research.
The finding matters because those five techniques – expert opinion and various multivariate regression and bootstrapping strategies – have been widely used in previous studies to create risk scores for ventral hernia recurrence. The new study calls the value of existing scoring systems into question (J Surg Res. 2016 Nov;206[1]:159-67. doi: 10.1016/j.jss.2016.07.042).
The lack of external validation in many studies leads to medical findings that often can’t be confirmed by subsequent studies. It’s a problem that has contributed to skepticism about research results in both the medical community and the general public, they said.
“This study demonstrates the importance of true external validation on an external data set. Simply splitting a data set and validating [internally] does not appear to be an adequate assessment of predictive accuracy. … We recommend that future researchers consider using and presenting the results of multiple variable selection strategies [and] focus on presenting predictive accuracy on external data sets to validate their model,” the team concluded.
The original goal of the project was to identify the best predictors of ventral hernia recurrence since suggestions from past studies have varied. The team first used a prospective database of 790 ventral hernia repair patients to identify predictors of recurrence. Of that group, 526 patients – 173 (32.9%) of whom had a recurrence after a median follow-up of 20 months – were used to identify risk variables using expert opinion, selective stepwise regression, liberal stepwise regression, and bootstrapping with both restrictive and liberal internal resampling.
The team used the remaining 264 patients to confirm the findings. As in previous studies, internal validation worked: all five models had a Harrell’s C-statistic of about 0.76, which is considered reasonable, Dr. Holihan and her associates reported.
However, when the investigators applied their models to a second database of 1,225 patients followed for a median of 9 months – with 155 recurrences (12.7%) – they were not much better at predicting recurrence than a coin toss, with C-statistic values of about 0.56.
Some variables made the cut with all five selection techniques, including hernia type, wound class, and albumin levels, which are related to how well the wound heals. Other variables were significant in some selection strategies but not others, including smoking status, open versus laparoscopic approach, and mesh use.
At least for now, clinical intuition remains important for assessing rerupture risk, they said.
The National Institutes of Health funded the work. Author disclosures were not reported.
Five common variable selection strategies failed to produce a statistical model that accurately predicted ventral hernia recurrence in an investigation published in the Journal of Surgical Research.
The finding matters because those five techniques – expert opinion and various multivariate regression and bootstrapping strategies – have been widely used in previous studies to create risk scores for ventral hernia recurrence. The new study calls the value of existing scoring systems into question (J Surg Res. 2016 Nov;206[1]:159-67. doi: 10.1016/j.jss.2016.07.042).
The lack of external validation in many studies leads to medical findings that often can’t be confirmed by subsequent studies. It’s a problem that has contributed to skepticism about research results in both the medical community and the general public, they said.
“This study demonstrates the importance of true external validation on an external data set. Simply splitting a data set and validating [internally] does not appear to be an adequate assessment of predictive accuracy. … We recommend that future researchers consider using and presenting the results of multiple variable selection strategies [and] focus on presenting predictive accuracy on external data sets to validate their model,” the team concluded.
The original goal of the project was to identify the best predictors of ventral hernia recurrence since suggestions from past studies have varied. The team first used a prospective database of 790 ventral hernia repair patients to identify predictors of recurrence. Of that group, 526 patients – 173 (32.9%) of whom had a recurrence after a median follow-up of 20 months – were used to identify risk variables using expert opinion, selective stepwise regression, liberal stepwise regression, and bootstrapping with both restrictive and liberal internal resampling.
The team used the remaining 264 patients to confirm the findings. As in previous studies, internal validation worked: all five models had a Harrell’s C-statistic of about 0.76, which is considered reasonable, Dr. Holihan and her associates reported.
However, when the investigators applied their models to a second database of 1,225 patients followed for a median of 9 months – with 155 recurrences (12.7%) – they were not much better at predicting recurrence than a coin toss, with C-statistic values of about 0.56.
Some variables made the cut with all five selection techniques, including hernia type, wound class, and albumin levels, which are related to how well the wound heals. Other variables were significant in some selection strategies but not others, including smoking status, open versus laparoscopic approach, and mesh use.
At least for now, clinical intuition remains important for assessing rerupture risk, they said.
The National Institutes of Health funded the work. Author disclosures were not reported.
Five common variable selection strategies failed to produce a statistical model that accurately predicted ventral hernia recurrence in an investigation published in the Journal of Surgical Research.
The finding matters because those five techniques – expert opinion and various multivariate regression and bootstrapping strategies – have been widely used in previous studies to create risk scores for ventral hernia recurrence. The new study calls the value of existing scoring systems into question (J Surg Res. 2016 Nov;206[1]:159-67. doi: 10.1016/j.jss.2016.07.042).
The lack of external validation in many studies leads to medical findings that often can’t be confirmed by subsequent studies. It’s a problem that has contributed to skepticism about research results in both the medical community and the general public, they said.
“This study demonstrates the importance of true external validation on an external data set. Simply splitting a data set and validating [internally] does not appear to be an adequate assessment of predictive accuracy. … We recommend that future researchers consider using and presenting the results of multiple variable selection strategies [and] focus on presenting predictive accuracy on external data sets to validate their model,” the team concluded.
The original goal of the project was to identify the best predictors of ventral hernia recurrence since suggestions from past studies have varied. The team first used a prospective database of 790 ventral hernia repair patients to identify predictors of recurrence. Of that group, 526 patients – 173 (32.9%) of whom had a recurrence after a median follow-up of 20 months – were used to identify risk variables using expert opinion, selective stepwise regression, liberal stepwise regression, and bootstrapping with both restrictive and liberal internal resampling.
The team used the remaining 264 patients to confirm the findings. As in previous studies, internal validation worked: all five models had a Harrell’s C-statistic of about 0.76, which is considered reasonable, Dr. Holihan and her associates reported.
However, when the investigators applied their models to a second database of 1,225 patients followed for a median of 9 months – with 155 recurrences (12.7%) – they were not much better at predicting recurrence than a coin toss, with C-statistic values of about 0.56.
Some variables made the cut with all five selection techniques, including hernia type, wound class, and albumin levels, which are related to how well the wound heals. Other variables were significant in some selection strategies but not others, including smoking status, open versus laparoscopic approach, and mesh use.
At least for now, clinical intuition remains important for assessing rerupture risk, they said.
The National Institutes of Health funded the work. Author disclosures were not reported.
FROM THE JOURNAL OF SURGICAL RESEARCH
Key clinical point:
Major finding: Risk models developed from the five strategies weren’t much better at predicting recurrence than a coin toss, with C-statistic values of about 0.56.
Data source: Analysis of two datasets containing a total of 2,015 ventral hernia repair patients.
Disclosures: The National Institutes of Health funded the work. Author disclosures were not reported.
Tenotomy, Tenodesis, Transfer: A Review of Treatment Options for Biceps-Labrum Complex Disease
Pathology of the biceps-labrum complex (BLC) can be an important source of shoulder pain. Discussion of pathoanatomy, imaging, and surgical intervention is facilitated by distinguishing the anatomical zones of the BLC: inside, junction, and bicipital tunnel (extra-articular), parts of which cannot be visualized with standard diagnostic arthroscopy.
The recent literature indicates that bicipital tunnel lesions are common and perhaps overlooked. Systematic reviews suggest improvement in outcomes of BLC operations when the bicipital tunnel is decompressed. Higher-level clinical and basic science studies are needed to fully elucidate the role of the bicipital tunnel, but it is evident that a comprehensive physical examination and an understanding of the limits of advanced imaging are necessary to correctly diagnose and treat BLC-related shoulder pain.
Anatomy of Biceps-Labrum Complex
The long head of the biceps tendon (LHBT) and the glenoid labrum work as an interdependent functional unit, the biceps-labrum complex (BLC). The BLC is divided into 3 distinct anatomical zones: inside, junction, and bicipital tunnel.1,2
Inside
The inside includes the superior labrum and biceps attachment. The LHBT most commonly originates in the superior labrum.3-5 Vangsness and colleagues3 described 4 types of LHBT origins: Type I biceps attaches solely to the posterior labrum, type II predominantly posterior, type III equally to the anterior and posterior labrum, and type IV mostly to the anterior labrum. The LHBT can also originate in the supraglenoid tubercle or the inferior border of the supraspinatus.3,6
Junction
Junction is the intra-articular segment of the LHBT and the biceps pulley. The LHBT traverses the glenohumeral joint en route to the extra-articular bicipital tunnel.2 The LHBT is enveloped in synovium that extends into part of the bicipital tunnel.2 The intra-articular segment of the LHBT is about 25 mm in length7 and has a diameter of 5 mm to 6 mm.8
A cadaveric study found that the average length of the LHBT that can be arthroscopically visualized at rest is 35.6 mm, or only 40% of the total length of the LHBT with respect to the proximal margin of the pectoralis major tendon.1 When the LHBT was pulled into the joint, more tendon (another 14 mm) was visualized.1 Therefore, diagnostic arthroscopy of the glenohumeral joint visualizes about 50% of the LHBT.9The morphology of the LHBT varies by location. The intra-articular portion of the LHBT is wide and flat, whereas the extra-articular portion is round.8 The tendon becomes smoother and more avascular as it exits the joint to promote gliding within its sheath in the bicipital groove.10 The proximal LHBT receives its vascular supply from superior labrum tributaries, and distally the LHBT is supplied by ascending branches of the anterior humeral circumflex artery.4 There is a hypovascular zone, created by this dual blood supply, about 12 mm to 30 mm from the LHBT origin, predisposing the tendon to rupture or fray in this region.11The LHBT makes a 30° turn into the biceps pulley system as it exits the glenohumeral joint. The fibrous pulley system that stabilizes the LHBT in this region has contributions from the coracohumeral ligament, the superior glenohumeral ligament, and the supraspinatus tendon.12-14 
Bicipital Tunnel
The bicipital tunnel, the third portion of the BLC, remains largely hidden from standard diagnostic glenohumeral arthroscopy. The bicipital tunnel is an extra-articular, closed space that constrains the LHBT from the articular margin through the subpectoral region.2 
Zone 1 is the traditional bicipital groove or “bony groove” that extends from the articular margin to the distal margin of the subscapularis tendon. The floor consists of a deep osseous groove covered by a continuation of subscapularis tendon fibers and periosteum.2Zone 2, “no man’s land,” extends from the distal margin of the subscapularis tendon to the proximal margin of the pectoralis major (PMPM). The LHBT in this zone cannot be visualized during a pull test at arthroscopy, yet lesions commonly occur here.1 Zones 1 and 2 have a similar histology and contain synovium.2Zone 3 is the subpectoral region distal to the PMPM. Fibers of the latissimus dorsi form the flat floor of zone 3, and the pectoralis major inserts lateral to the LHBT on the humerus in this zone. The synovium encapsulating the LHBT in zones 1 and 2 rarely extends past the PMPM. Taylor and colleagues2 found a higher percentage of unoccupied tunnel space in zone 3 than in zones 1 and 2, which results in a “functional bottleneck” between zones 2 and 3 represented by the PMPM.
Pathoanatomy
BLC lesions may occur in isolation or concomitantly across multiple anatomical zones. In a series of 277 chronically symptomatic shoulders that underwent transfer of the LHBT to the conjoint tendon with subdeltoid arthroscopy, Taylor and colleagues1 found 47% incidence of bicipital tunnel lesions, 44% incidence of junctional lesions, and 35% incidence of inside lesions. In their series, 37% of patients had concomitant lesions involving more than 1 anatomical zone.
Inside Lesions
Inside lesions involve the superior labrum, the LHBT origin, or both. Superior labrum anterior-posterior (SLAP) tears are included as inside BLC lesions. Snyder and colleagues16 originally identified 4 broad categories of SLAP tears, but Powell and colleagues17 described up to 10 variations. Type II lesions, which are the most common, destabilize the biceps anchor.
Dynamic incarceration of the biceps between the humeral head and the glenoid labrum is another inside lesion that can be identified during routine diagnostic glenohumeral arthroscopy. The arthroscopic active compression test, as described by Verma and colleagues,18 can be used during surgery to demonstrate incarceration of the biceps tendon.
Medial biceps chondromalacia, attritional chondral wear along the anteromedial aspect of the humeral head, occurs secondary to a windshield wiper effect of the LHBT in the setting of an incarcerating LHBT or may be associated with destabilization of the biceps pulley.
Junctional Lesions
Junctional lesions, which include lesions that affect the intra-articular LHBT, can be visualized during routine glenohumeral arthroscopy. They include partial and complete biceps tears, biceps pulley lesions, and junctional biceps chondromalacia.
Biceps pulley injuries and/or tears of the upper subscapularis tendon can destabilize the biceps as it exits the joint, and this destabilization may result in medial subluxation of the tendon and the aforementioned medial biceps chondromalacia.10,19 Junctional biceps chondromalacia is attritional chondral wear of the humeral head from abnormal tracking of the LHBT deep to the LHBT near the articular margin.
Recently elucidated is the limited ability of diagnostic glenohumeral arthroscopy to fully identify the extent of BLC pathology.1,20-22 Gilmer and colleagues20 found that diagnostic arthroscopy identified only 67% of biceps pathology and underestimated its extent in 56% of patients in their series. Similarly, Moon and colleagues21 found that 79% of proximal LHBT tears propagated distally into the bicipital tunnel and were incompletely visualized with standard arthroscopy.
Bicipital Tunnel Lesions
Recent evidence indicates that the bicipital tunnel is a closed space that often conceals space-occupying lesions, including scar, synovitis, loose bodies, and osteophytes, which can become trapped in the tunnel. The functional bottleneck between zones 2 and 3 of the bicipital tunnel explains the aggregation of loose bodies in this region.2 Similarly, as the percentage of free space within the bicipital tunnel increases, space-occupying lesions (eg scar, loose bodies, osteophytes) may exude a compressive and/or abrasive force within zones 1 and 2, but not as commonly within zone 3.2
Physical Examination of Biceps-Labrum Complex
Accurate diagnosis of BLC disease is crucial in selecting an optimal intervention, but challenging. Beyond identifying biceps pathology, specific examination maneuvers may help distinguish between lesions of the intra-articular BLC and lesions of the extra-articular bicipital tunnel.23
Traditional examination maneuvers for biceps-related shoulder pain include the Speed test, the full can test, and the Yergason test.24,25 For the Speed test, the patient forward-flexes the shoulder to 60° to 90°, extends the arm at the elbow, and supinates the forearm. The clinician applies a downward force as the patient resists. The reported sensitivity of the Speed test ranges from 37% to 63%, and specificity is 60% to 88%.25,26 In the full can test, with the patient’s arm in the plane of the scapula, the shoulder abducted to 90°, and the forearm in neutral rotation, a downward force is applied against resistance. Sensitivity of the full can test is 60% to 67%, and specificity is 76% to 84%.24 The Yergason test is performed with the patient’s arm at his or her side, the elbow flexed to 90°, and the forearm pronated. The patient supinates the forearm against the clinician’s resistance. Sensitivity of the Yergason test is 19% to 32%, and specificity is 70% to 100%.25,26 The Yergason test has a positive predictive value of 92% for bicipital tunnel disease.
O’Brien and colleagues23,26 introduced a “3-pack” physical examination designed to elicit BLC symptoms. In this examination, the LHBT is palpated along its course within the bicipital tunnel. Reproduction of the patient’s pain by palpation had a sensitivity of 98% for bicipital tunnel disease but was less specific (70%). Gill and colleagues27 reported low sensitivity (53%) and low specificity (54%) for biceps palpation, and they used arthroscopy as a gold standard. Since then, multiple studies have demonstrated that glenohumeral arthroscopy fails to identify lesions concealed within the bicipital tunnel.20-22The second part of the 3-pack examination is the active compression test. A downward force is applied as the patient resists with his or her arm forward-flexed to 90° and adducted 10° to 15° with the thumb pointing downward.28 This action is repeated with the humerus externally rotated and the forearm supinated. A positive test is indicated by reproduction of symptoms with the thumb down, and elimination or reduction of symptoms with the palm up. Test sensitivity is 88% to 96%, and specificity is 46% to 64% for BLC lesions, but for bicipital tunnel disease sensitivity is higher (96%), and the negative predictive value is 93%.26The third component of the 3-pack examination is the throwing test. A late-cocking throwing position is re-created with the shoulder externally rotated and abducted to 90° and the elbow flexed to 90°. The patient steps forward with the contralateral leg and moves into the acceleration phase of throwing while the clinician provides isometric resistance. If this maneuver reproduces pain, the test is positive. As Taylor and colleagues26 reported, the throwing test has sensitivity of 73% to 77% and specificity of 65% to 79% for BLC pathology. This test has moderate sensitivity and negative predictive value for bicipital tunnel disease but may be the only positive test on physical examination in the setting of LHBT instability.
Imaging of Biceps-Labrum Complex
Plain anteroposterior, lateral, and axillary radiographs of the shoulder should be obtained for all patients having an orthopedic examination for shoulder pain. Magnetic resonance imaging (MRI) and ultrasound are the advanced modalities most commonly used for diagnostic imaging. These modalities should be considered in conjunction with, not in place of, a comprehensive history and physical examination.
MRI has sensitivity of 9% to 89% for LHBT pathology29-37 and 38% to 98% for SLAP pathology.35,38-41 The wide range of reported sensitivity and specificity might be attributed to the varying criteria for what constitutes a BLC lesion. Some authors include biceps chondromalacia, dynamic incarceration of LHBT, and extra-articular bicipital tunnel lesions, while others historically have included only intra-articular LHBT lesions that can be directly visualized arthroscopically.
In their retrospective review of 277 shoulders with chronic refractory BLC symptoms treated with subdeltoid transfer of the LHBT to the conjoint tendon, Taylor and colleagues30 reported MRI was more sensitive for inside BLC lesions than for junctional or bicipital tunnel lesions (77% vs 43% and 50%, respectively).
Treatment Options for Biceps-Labrum Complex Lesions
A diagnosis of BLC disease warrants a trial of conservative (nonoperative) management for at least 3 months. Many patients improve with activity modification, use of oral anti-inflammatory medication, and structured physical therapy focused on dynamic stabilizers and range of motion. If pain persists, local anesthetic and corticosteroid can be injected under ultrasound guidance into the bicipital tunnel; this injection has the advantage of being both diagnostic and therapeutic. Hashiuchi and colleagues42 found ultrasound-guided injections are 87% successful in achieving intra-sheath placement (injections without ultrasound guidance are only 27% successful).
If the 3-month trial of conservative management fails, surgical intervention should be considered. The goal in treating BLC pain is to maximize clinical function and alleviate pain in a predictable manner while minimizing technical demands and morbidity. A singular solution has not been identified. Furthermore, 3 systematic reviews failed to identify a difference between the most commonly used techniques, biceps tenodesis and tenotomy.43-45 These reviews grouped all tenotomy procedures together and compared them with all tenodesis procedures. A limitation of these systematic reviews is that they did not differentiate tenodesis techniques. We prefer to classify techniques according to whether or not they decompress zones 1 and 2 of the bicipital tunnel.
Bicipital Tunnel Nondecompressing Techniques
Release of the biceps tendon, a biceps tenotomy, is a simple procedure that potentially avoids open surgery and provides patients with a quick return to activity. Disadvantages of tenotomy include cosmetic (Popeye) deformity after surgery, potential cramping and fatigue, and biomechanical changes in the humeral head,46-48 particularly among patients younger than 65 years. High rates of revision after tenotomy have been reported.43,49 Incomplete retraction of the LHBT and/or residual synovium may be responsible for refractory pain following biceps tenotomy.49 We hypothesize that failure of tenotomy may be related to unaddressed bicipital tunnel disease.
Proximal nondecompressing tenodesis techniques may be performed either on soft tissue in the interval or rotator cuff or on bone at the articular margin or within zone 1 of the bicipital tunnel.50-52 These techniques can be performed with standard glenohumeral arthroscopy and generally are fast and well tolerated and have limited operative morbidity. Advantages of these techniques over simple tenotomy are lower rates of cosmetic deformity and lower rates of cramping and fatigue pain, likely resulting from maintenance of the muscle tension relationship of the LHBT. Disadvantages of proximal tenodesis techniques include introduction of hardware for bony fixation, longer postoperative rehabilitation to protect repairs, and failure to address hidden bicipital tunnel disease. Furthermore, the rate of stiffness in patients who undergo proximal tenodesis without decompression of the bicipital tunnel may be as high as 18%.53
Bicipital Tunnel Decompressing Techniques
Surgical techniques that decompress the bicipital tunnel include proximal techniques that release the bicipital sheath within zones 1 and 2 of the bicipital tunnel (to the level of the proximal margin of the pectoralis major tendon) and certain arthroscopic suprapectoral techniques,54 open subpectoral tenodeses,55-57 and arthroscopic transfer of the LHBT to the conjoint tendon.58,59
Open subpectoral tenodesis techniques have the advantage of maintaining the length-tension relationship of the LHBT and preventing Popeye deformity. However, these techniques require making an incision near the axilla, which may introduce an unnecessary source of infection. Furthermore, open subpectoral tenodesis requires drilling the humerus and placing a screw for bony fixation of the LHBT, which can create a risk of neurovascular injury, given the proximity of neurovascular structures,60-62 and humeral shaft fracture, particularly in athletes.63,64Our preferred method is transfer of the LHBT to the conjoint tendon (Figure 3).59 
Am J Orthop. 2016;45(7):E503-E511. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.
1. Taylor SA, Khair MM, Gulotta LV, et al. Diagnostic glenohumeral arthroscopy fails to fully evaluate the biceps-labral complex. Arthroscopy. 2015;31(2):215-224.
2. Taylor SA, Fabricant PD, Bansal M, et al. The anatomy and histology of the bicipital tunnel of the shoulder. J Shoulder Elbow Surg. 2015;24(4):511-519.
3. Vangsness CT Jr, Jorgenson SS, Watson T, Johnson DL. The origin of the long head of the biceps from the scapula and glenoid labrum. An anatomical study of 100 shoulders. J Bone Joint Surg Br. 1994;76(6):951-954.
4. Cooper DE, Arnoczky SP, O’Brien SJ, Warren RF, DiCarlo E, Allen AA. Anatomy, histology, and vascularity of the glenoid labrum. an anatomical study. J Bone Joint Surg Am. 1992;74(1):46-52.
5. Tuoheti Y, Itoi E, Minagawa H, et al. Attachment types of the long head of the biceps tendon to the glenoid labrum and their relationships with the glenohumeral ligaments. Arthroscopy. 2005;21(10):1242-1249.
6. Dierickx C, Ceccarelli E, Conti M, Vanlommel J, Castagna A. Variations of the intra-articular portion of the long head of the biceps tendon: a classification of embryologically explained variations. J Shoulder Elbow Surg. 2009;18(4):556-565.
7. Denard PJ, Dai X, Hanypsiak BT, Burkhart SS. Anatomy of the biceps tendon: implications for restoring physiological length-tension relation during biceps tenodesis with interference screw fixation. Arthroscopy. 2012;28(10):1352-1358.
8. Ahrens PM, Boileau P. The long head of biceps and associated tendinopathy. J Bone Joint Surg Br. 2007;89(8):1001-1009.
9. Hart ND, Golish SR, Dragoo JL. Effects of arm position on maximizing intra-articular visualization of the biceps tendon: a cadaveric study. Arthroscopy. 2012;28(4):481-485.
10. Elser F, Braun S, Dewing CB, Giphart JE, Millett PJ. Anatomy, function, injuries, and treatment of the long head of the biceps brachii tendon. Arthroscopy. 2011;27(4):581-592.
11. Cheng NM, Pan WR, Vally F, Le Roux CM, Richardson MD. The arterial supply of the long head of biceps tendon: anatomical study with implications for tendon rupture. Clin Anat. 2010;23(6):683-692.
12. Habermeyer P, Magosch P, Pritsch M, Scheibel MT, Lichtenberg S. Anterosuperior impingement of the shoulder as a result of pulley lesions: a prospective arthroscopic study. J Shoulder Elbow Surg. 2004;13(1):5-12.
13. Gohlke F, Daum P, Bushe C. The stabilizing function of the glenohumeral joint capsule. Current aspects of the biomechanics of instability [in German]. Z Orthop Ihre Grenzgeb. 1994;132(2):112-119.
14. Arai R, Mochizuki T, Yamaguchi K, et al. Functional anatomy of the superior glenohumeral and coracohumeral ligaments and the subscapularis tendon in view of stabilization of the long head of the biceps tendon. J Shoulder Elbow Surg. 2010;19(1):58-64.
15. Busconi BB, DeAngelis N, Guerrero PE. The proximal biceps tendon: tricks and pearls. Sports Med Arthrosc. 2008;16(3):187-194.
16. Snyder SJ, Karzel RP, Del Pizzo W, Ferkel RD, Friedman MJ. SLAP lesions of the shoulder. Arthroscopy. 1990;6(4):274-279.
17. Powell SE, Nord KD, Ryu RKN. The diagnosis, classification, and treatment of SLAP lesions. Oper Tech Sports Med. 2004;12(2):99-110.
18. Verma NN, Drakos M, O’Brien SJ. The arthroscopic active compression test. Arthroscopy. 2005;21(5):634.
19. Walch G, Nove-Josserand L, Levigne C, Renaud E. Tears of the supraspinatus tendon associated with “hidden” lesions of the rotator interval. J Shoulder Elbow Surg. 1994;3(6):353-360.
20. Gilmer BB, DeMers AM, Guerrero D, Reid JB 3rd, Lubowitz JH, Guttmann D. Arthroscopic versus open comparison of long head of biceps tendon visualization and pathology in patients requiring tenodesis. Arthroscopy. 2015;31(1):29-34.
21. Moon SC, Cho NS, Rhee YG. Analysis of “hidden lesions” of the extra-articular biceps after subpectoral biceps tenodesis: the subpectoral portion as the optimal tenodesis site. Am J Sports Med. 2015;43(1):63-68.
22. Festa A, Allert J, Issa K, Tasto JP, Myer JJ. Visualization of the extra-articular portion of the long head of the biceps tendon during intra-articular shoulder arthroscopy. Arthroscopy. 2014;30(11):1413-1417.
23. O’Brien SJ, Newman AM, Taylor SA, et al. The accurate diagnosis of biceps-labral complex lesions with MRI and “3-pack” physical examination: a retrospective analysis with prospective validation. Orthop J Sports Med. 2013;1(4 suppl). doi:10.1177/2325967113S00018.
24. Hegedus EJ, Goode AP, Cook CE, et al. Which physical examination tests provide clinicians with the most value when examining the shoulder? Update of a systematic review with meta-analysis of individual tests. Br J Sports Med. 2012;46(14):964-978.
25. Chen HS, Lin SH, Hsu YH, Chen SC, Kang JH. A comparison of physical examinations with musculoskeletal ultrasound in the diagnosis of biceps long head tendinitis. Ultrasound Med Biol. 2011;37(9):1392-1398.
26. Taylor SA, Newman AM, Dawson C, et al. The “3-Pack” examination is critical for comprehensive evaluation of the biceps-labrum complex and the bicipital tunnel: a prospective study. Arthroscopy. 2016 Jul 20. [Epub ahead of print]
27. Gill HS, El Rassi G, Bahk MS, Castillo RC, McFarland EG. Physical examination for partial tears of the biceps tendon. Am J Sports Med. 2007;35(8):1334-1340.
28. O’Brien SJ, Pagnani MJ, Fealy S, McGlynn SR, Wilson JB. The active compression test: a new and effective test for diagnosing labral tears and acromioclavicular joint abnormality. Am J Sports Med. 1998;26(5):610-613.
29. Zanetti M, Weishaupt D, Gerber C, Hodler J. Tendinopathy and rupture of the tendon of the long head of the biceps brachii muscle: evaluation with MR arthrography. AJR Am J Roentgenol. 1998;170(6):1557-1561.
30. Taylor SA, Newman AM, Nguyen J, et al. Magnetic resonance imaging currently fails to fully evaluate the biceps-labrum complex and bicipital tunnel. Arthroscopy. 2016;32(2):238-244.
31. Malavolta EA, Assunção JH, Guglielmetti CL, de Souza FF, Gracitelli ME, Ferreira Neto AA. Accuracy of preoperative MRI in the diagnosis of disorders of the long head of the biceps tendon. Eur J Radiol. 2015;84(11):2250-2254.
32. Dubrow SA, Streit JJ, Shishani Y, Robbin MR, Gobezie R. Diagnostic accuracy in detecting tears in the proximal biceps tendon using standard nonenhancing shoulder MRI. Open Access J Sports Med. 2014;5:81-87.
33. Nourissat G, Tribot-Laspiere Q, Aim F, Radier C. Contribution of MRI and CT arthrography to the diagnosis of intra-articular tendinopathy of the long head of the biceps. Orthop Traumatol Surg Res. 2014;100(8 suppl):S391-S394.
34. De Maeseneer M, Boulet C, Pouliart N, et al. Assessment of the long head of the biceps tendon of the shoulder with 3T magnetic resonance arthrography and CT arthrography. Eur J Radiol. 2012;81(5):934-939.
35. Houtz CG, Schwartzberg RS, Barry JA, Reuss BL, Papa L. Shoulder MRI accuracy in the community setting. J Shoulder Elbow Surg. 2011;20(4):537-542.
36. Buck FM, Grehn H, Hilbe M, Pfirrmann CW, Manzanell S, Hodler J. Degeneration of the long biceps tendon: comparison of MRI with gross anatomy and histology. AJR Am J Roentgenol. 2009;193(5):1367-1375.
37. Mohtadi NG, Vellet AD, Clark ML, et al. A prospective, double-blind comparison of magnetic resonance imaging and arthroscopy in the evaluation of patients presenting with shoulder pain. J Shoulder Elbow Surg. 2004;13(3):258-265.
38. Sheridan K, Kreulen C, Kim S, Mak W, Lewis K, Marder R. Accuracy of magnetic resonance imaging to diagnose superior labrum anterior-posterior tears. Knee Surg Sports Traumatol Arthrosc. 2015;23(9):2645-2650.
39. Connolly KP, Schwartzberg RS, Reuss B, Crumbie D Jr, Homan BM. Sensitivity and specificity of noncontrast magnetic resonance imaging reports in the diagnosis of type-II superior labral anterior-posterior lesions in the community setting. J Bone Joint Surg Am. 2013;95(4):308-313.
40. Reuss BL, Schwartzberg R, Zlatkin MB, Cooperman A, Dixon JR. Magnetic resonance imaging accuracy for the diagnosis of superior labrum anterior-posterior lesions in the community setting: eighty-three arthroscopically confirmed cases. J Shoulder Elbow Surg. 2006;15(5):580-585.
41. Connell DA, Potter HG, Wickiewicz TL, Altchek DW, Warren RF. Noncontrast magnetic resonance imaging of superior labral lesions. 102 cases confirmed at arthroscopic surgery. Am J Sports Med. 1999;27(2):208-213.
42. Hashiuchi T, Sakurai G, Morimoto M, Komei T, Takakura Y, Tanaka Y. Accuracy of the biceps tendon sheath injection: ultrasound-guided or unguided injection? A randomized controlled trial. J Shoulder Elbow Surg. 2011;20(7):1069-1073.
43. Hsu AR, Ghodadra NS, Provencher MT, Lewis PB, Bach BR. Biceps tenotomy versus tenodesis: a review of clinical outcomes and biomechanical results. J Shoulder Elbow Surg. 2011;20(2):326-332.
44. Slenker NR, Lawson K, Ciccotti MG, Dodson CC, Cohen SB. Biceps tenotomy versus tenodesis: clinical outcomes. Arthroscopy. 2012;28(4):576-582.
45. Frost A, Zafar MS, Maffulli N. Tenotomy versus tenodesis in the management of pathologic lesions of the tendon of the long head of the biceps brachii. Am J Sports Med. 2009;37(4):828-833.
46. Kelly AM, Drakos MC, Fealy S, Taylor SA, O’Brien SJ. Arthroscopic release of the long head of the biceps tendon: functional outcome and clinical results. Am J Sports Med. 2005;33(2):208-213.
47. Berlemann U, Bayley I. Tenodesis of the long head of biceps brachii in the painful shoulder: improving results in the long term. J Shoulder Elbow Surg. 1995;4(6):429-435.
48. Gill TJ, McIrvin E, Mair SD, Hawkins RJ. Results of biceps tenotomy for treatment of pathology of the long head of the biceps brachii. J Shoulder Elbow Surg. 2001;10(3):247-249.
49. Sanders B, Lavery KP, Pennington S, Warner JJ. Clinical success of biceps tenodesis with and without release of the transverse humeral ligament. J Shoulder Elbow Surg. 2012;21(1):66-71.
50. Gartsman GM, Hammerman SM. Arthroscopic biceps tenodesis: operative technique. Arthroscopy. 2000;16(5):550-552.
51. Richards DP, Burkhart SS. Arthroscopic-assisted biceps tenodesis for ruptures of the long head of biceps brachii: the cobra procedure. Arthroscopy. 2004;20(suppl 2):201-207.
52. Klepps S, Hazrati Y, Flatow E. Arthroscopic biceps tenodesis. Arthroscopy. 2002;18(9):1040-1045.
53. Werner BC, Pehlivan HC, Hart JM, et al. Increased incidence of postoperative stiffness after arthroscopic compared with open biceps tenodesis. Arthroscopy. 2014;30(9):1075-1084.54. Werner BC, Lyons ML, Evans CL, et al. Arthroscopic suprapectoral and open subpectoral biceps tenodesis: a comparison of restoration of length-tension and mechanical strength between techniques. Arthroscopy. 2015;31(4):620-627.
55. Nho SJ, Reiff SN, Verma NN, Slabaugh MA, Mazzocca AD, Romeo AA. Complications associated with subpectoral biceps tenodesis: low rates of incidence following surgery. J Shoulder Elbow Surg. 2010;19(5):764-768.
56. Mazzocca AD, Cote MP, Arciero CL, Romeo AA, Arciero RA. Clinical outcomes after subpectoral biceps tenodesis with an interference screw. Am J Sports Med. 2008;36(10):1922-1929.
57. Provencher MT, LeClere LE, Romeo AA. Subpectoral biceps tenodesis. Sports Med Arthrosc. 2008;16(3):170-176.
58. Taylor SA, Fabricant PD, Baret NJ, et al. Midterm clinical outcomes for arthroscopic subdeltoid transfer of the long head of the biceps tendon to the conjoint tendon. Arthroscopy. 2014;30(12):1574-1581.
59. Drakos MC, Verma NN, Gulotta LV, et al. Arthroscopic transfer of the long head of the biceps tendon: functional outcome and clinical results. Arthroscopy. 2008;24(2):217-223.
60. Ding DY, Gupta A, Snir N, Wolfson T, Meislin RJ. Nerve proximity during bicortical drilling for subpectoral biceps tenodesis: a cadaveric study. Arthroscopy. 2014;30(8):942-946.
61. Dickens JF, Kilcoyne KG, Tintle SM, Giuliani J, Schaefer RA, Rue JP. Subpectoral biceps tenodesis: an anatomic study and evaluation of at-risk structures. Am J Sports Med. 2012;40(10):2337-2341.
62. Ma H, Van Heest A, Glisson C, Patel S. Musculocutaneous nerve entrapment: an unusual complication after biceps tenodesis. Am J Sports Med. 2009;37(12):2467-2469.
63. Dein EJ, Huri G, Gordon JC, McFarland EG. A humerus fracture in a baseball pitcher after biceps tenodesis. Am J Sports Med. 2014;42(4):877-879.
64. Sears BW, Spencer EE, Getz CL. Humeral fracture following subpectoral biceps tenodesis in 2 active, healthy patients. J Shoulder Elbow Surg. 2011;20(6):e7-e11.
65. O’Brien SJ, Taylor SA, DiPietro JR, Newman AM, Drakos MC, Voos JE. The arthroscopic “subdeltoid approach” to the anterior shoulder. J Shoulder Elbow Surg. 2013;22(4):e6-e10.
66. Urch E, Taylor SA, Ramkumar PN, et al. Biceps tenodesis: a comparison of tendon-to-bone and tendon-to-tendon healing in a rat model. Paper presented at: Closed Meeting of the American Shoulder and Elbow Surgeons; October 10, 2015; Asheville, NC. Paper 26.
67. Taylor SA, Ramkumar PN, Fabricant PD, et al. The clinical impact of bicipital tunnel decompression during long head of the biceps tendon surgery: a systematic review and meta-analysis. Arthroscopy. 2016;32(6):1155-1164.
Pathology of the biceps-labrum complex (BLC) can be an important source of shoulder pain. Discussion of pathoanatomy, imaging, and surgical intervention is facilitated by distinguishing the anatomical zones of the BLC: inside, junction, and bicipital tunnel (extra-articular), parts of which cannot be visualized with standard diagnostic arthroscopy.
The recent literature indicates that bicipital tunnel lesions are common and perhaps overlooked. Systematic reviews suggest improvement in outcomes of BLC operations when the bicipital tunnel is decompressed. Higher-level clinical and basic science studies are needed to fully elucidate the role of the bicipital tunnel, but it is evident that a comprehensive physical examination and an understanding of the limits of advanced imaging are necessary to correctly diagnose and treat BLC-related shoulder pain.
Anatomy of Biceps-Labrum Complex
The long head of the biceps tendon (LHBT) and the glenoid labrum work as an interdependent functional unit, the biceps-labrum complex (BLC). The BLC is divided into 3 distinct anatomical zones: inside, junction, and bicipital tunnel.1,2
Inside
The inside includes the superior labrum and biceps attachment. The LHBT most commonly originates in the superior labrum.3-5 Vangsness and colleagues3 described 4 types of LHBT origins: Type I biceps attaches solely to the posterior labrum, type II predominantly posterior, type III equally to the anterior and posterior labrum, and type IV mostly to the anterior labrum. The LHBT can also originate in the supraglenoid tubercle or the inferior border of the supraspinatus.3,6
Junction
Junction is the intra-articular segment of the LHBT and the biceps pulley. The LHBT traverses the glenohumeral joint en route to the extra-articular bicipital tunnel.2 The LHBT is enveloped in synovium that extends into part of the bicipital tunnel.2 The intra-articular segment of the LHBT is about 25 mm in length7 and has a diameter of 5 mm to 6 mm.8
A cadaveric study found that the average length of the LHBT that can be arthroscopically visualized at rest is 35.6 mm, or only 40% of the total length of the LHBT with respect to the proximal margin of the pectoralis major tendon.1 When the LHBT was pulled into the joint, more tendon (another 14 mm) was visualized.1 Therefore, diagnostic arthroscopy of the glenohumeral joint visualizes about 50% of the LHBT.9The morphology of the LHBT varies by location. The intra-articular portion of the LHBT is wide and flat, whereas the extra-articular portion is round.8 The tendon becomes smoother and more avascular as it exits the joint to promote gliding within its sheath in the bicipital groove.10 The proximal LHBT receives its vascular supply from superior labrum tributaries, and distally the LHBT is supplied by ascending branches of the anterior humeral circumflex artery.4 There is a hypovascular zone, created by this dual blood supply, about 12 mm to 30 mm from the LHBT origin, predisposing the tendon to rupture or fray in this region.11The LHBT makes a 30° turn into the biceps pulley system as it exits the glenohumeral joint. The fibrous pulley system that stabilizes the LHBT in this region has contributions from the coracohumeral ligament, the superior glenohumeral ligament, and the supraspinatus tendon.12-14
Bicipital Tunnel
The bicipital tunnel, the third portion of the BLC, remains largely hidden from standard diagnostic glenohumeral arthroscopy. The bicipital tunnel is an extra-articular, closed space that constrains the LHBT from the articular margin through the subpectoral region.2
Zone 1 is the traditional bicipital groove or “bony groove” that extends from the articular margin to the distal margin of the subscapularis tendon. The floor consists of a deep osseous groove covered by a continuation of subscapularis tendon fibers and periosteum.2Zone 2, “no man’s land,” extends from the distal margin of the subscapularis tendon to the proximal margin of the pectoralis major (PMPM). The LHBT in this zone cannot be visualized during a pull test at arthroscopy, yet lesions commonly occur here.1 Zones 1 and 2 have a similar histology and contain synovium.2Zone 3 is the subpectoral region distal to the PMPM. Fibers of the latissimus dorsi form the flat floor of zone 3, and the pectoralis major inserts lateral to the LHBT on the humerus in this zone. The synovium encapsulating the LHBT in zones 1 and 2 rarely extends past the PMPM. Taylor and colleagues2 found a higher percentage of unoccupied tunnel space in zone 3 than in zones 1 and 2, which results in a “functional bottleneck” between zones 2 and 3 represented by the PMPM.
Pathoanatomy
BLC lesions may occur in isolation or concomitantly across multiple anatomical zones. In a series of 277 chronically symptomatic shoulders that underwent transfer of the LHBT to the conjoint tendon with subdeltoid arthroscopy, Taylor and colleagues1 found 47% incidence of bicipital tunnel lesions, 44% incidence of junctional lesions, and 35% incidence of inside lesions. In their series, 37% of patients had concomitant lesions involving more than 1 anatomical zone.
Inside Lesions
Inside lesions involve the superior labrum, the LHBT origin, or both. Superior labrum anterior-posterior (SLAP) tears are included as inside BLC lesions. Snyder and colleagues16 originally identified 4 broad categories of SLAP tears, but Powell and colleagues17 described up to 10 variations. Type II lesions, which are the most common, destabilize the biceps anchor.
Dynamic incarceration of the biceps between the humeral head and the glenoid labrum is another inside lesion that can be identified during routine diagnostic glenohumeral arthroscopy. The arthroscopic active compression test, as described by Verma and colleagues,18 can be used during surgery to demonstrate incarceration of the biceps tendon.
Medial biceps chondromalacia, attritional chondral wear along the anteromedial aspect of the humeral head, occurs secondary to a windshield wiper effect of the LHBT in the setting of an incarcerating LHBT or may be associated with destabilization of the biceps pulley.
Junctional Lesions
Junctional lesions, which include lesions that affect the intra-articular LHBT, can be visualized during routine glenohumeral arthroscopy. They include partial and complete biceps tears, biceps pulley lesions, and junctional biceps chondromalacia.
Biceps pulley injuries and/or tears of the upper subscapularis tendon can destabilize the biceps as it exits the joint, and this destabilization may result in medial subluxation of the tendon and the aforementioned medial biceps chondromalacia.10,19 Junctional biceps chondromalacia is attritional chondral wear of the humeral head from abnormal tracking of the LHBT deep to the LHBT near the articular margin.
Recently elucidated is the limited ability of diagnostic glenohumeral arthroscopy to fully identify the extent of BLC pathology.1,20-22 Gilmer and colleagues20 found that diagnostic arthroscopy identified only 67% of biceps pathology and underestimated its extent in 56% of patients in their series. Similarly, Moon and colleagues21 found that 79% of proximal LHBT tears propagated distally into the bicipital tunnel and were incompletely visualized with standard arthroscopy.
Bicipital Tunnel Lesions
Recent evidence indicates that the bicipital tunnel is a closed space that often conceals space-occupying lesions, including scar, synovitis, loose bodies, and osteophytes, which can become trapped in the tunnel. The functional bottleneck between zones 2 and 3 of the bicipital tunnel explains the aggregation of loose bodies in this region.2 Similarly, as the percentage of free space within the bicipital tunnel increases, space-occupying lesions (eg scar, loose bodies, osteophytes) may exude a compressive and/or abrasive force within zones 1 and 2, but not as commonly within zone 3.2
Physical Examination of Biceps-Labrum Complex
Accurate diagnosis of BLC disease is crucial in selecting an optimal intervention, but challenging. Beyond identifying biceps pathology, specific examination maneuvers may help distinguish between lesions of the intra-articular BLC and lesions of the extra-articular bicipital tunnel.23
Traditional examination maneuvers for biceps-related shoulder pain include the Speed test, the full can test, and the Yergason test.24,25 For the Speed test, the patient forward-flexes the shoulder to 60° to 90°, extends the arm at the elbow, and supinates the forearm. The clinician applies a downward force as the patient resists. The reported sensitivity of the Speed test ranges from 37% to 63%, and specificity is 60% to 88%.25,26 In the full can test, with the patient’s arm in the plane of the scapula, the shoulder abducted to 90°, and the forearm in neutral rotation, a downward force is applied against resistance. Sensitivity of the full can test is 60% to 67%, and specificity is 76% to 84%.24 The Yergason test is performed with the patient’s arm at his or her side, the elbow flexed to 90°, and the forearm pronated. The patient supinates the forearm against the clinician’s resistance. Sensitivity of the Yergason test is 19% to 32%, and specificity is 70% to 100%.25,26 The Yergason test has a positive predictive value of 92% for bicipital tunnel disease.
O’Brien and colleagues23,26 introduced a “3-pack” physical examination designed to elicit BLC symptoms. In this examination, the LHBT is palpated along its course within the bicipital tunnel. Reproduction of the patient’s pain by palpation had a sensitivity of 98% for bicipital tunnel disease but was less specific (70%). Gill and colleagues27 reported low sensitivity (53%) and low specificity (54%) for biceps palpation, and they used arthroscopy as a gold standard. Since then, multiple studies have demonstrated that glenohumeral arthroscopy fails to identify lesions concealed within the bicipital tunnel.20-22The second part of the 3-pack examination is the active compression test. A downward force is applied as the patient resists with his or her arm forward-flexed to 90° and adducted 10° to 15° with the thumb pointing downward.28 This action is repeated with the humerus externally rotated and the forearm supinated. A positive test is indicated by reproduction of symptoms with the thumb down, and elimination or reduction of symptoms with the palm up. Test sensitivity is 88% to 96%, and specificity is 46% to 64% for BLC lesions, but for bicipital tunnel disease sensitivity is higher (96%), and the negative predictive value is 93%.26The third component of the 3-pack examination is the throwing test. A late-cocking throwing position is re-created with the shoulder externally rotated and abducted to 90° and the elbow flexed to 90°. The patient steps forward with the contralateral leg and moves into the acceleration phase of throwing while the clinician provides isometric resistance. If this maneuver reproduces pain, the test is positive. As Taylor and colleagues26 reported, the throwing test has sensitivity of 73% to 77% and specificity of 65% to 79% for BLC pathology. This test has moderate sensitivity and negative predictive value for bicipital tunnel disease but may be the only positive test on physical examination in the setting of LHBT instability.
Imaging of Biceps-Labrum Complex
Plain anteroposterior, lateral, and axillary radiographs of the shoulder should be obtained for all patients having an orthopedic examination for shoulder pain. Magnetic resonance imaging (MRI) and ultrasound are the advanced modalities most commonly used for diagnostic imaging. These modalities should be considered in conjunction with, not in place of, a comprehensive history and physical examination.
MRI has sensitivity of 9% to 89% for LHBT pathology29-37 and 38% to 98% for SLAP pathology.35,38-41 The wide range of reported sensitivity and specificity might be attributed to the varying criteria for what constitutes a BLC lesion. Some authors include biceps chondromalacia, dynamic incarceration of LHBT, and extra-articular bicipital tunnel lesions, while others historically have included only intra-articular LHBT lesions that can be directly visualized arthroscopically.
In their retrospective review of 277 shoulders with chronic refractory BLC symptoms treated with subdeltoid transfer of the LHBT to the conjoint tendon, Taylor and colleagues30 reported MRI was more sensitive for inside BLC lesions than for junctional or bicipital tunnel lesions (77% vs 43% and 50%, respectively).
Treatment Options for Biceps-Labrum Complex Lesions
A diagnosis of BLC disease warrants a trial of conservative (nonoperative) management for at least 3 months. Many patients improve with activity modification, use of oral anti-inflammatory medication, and structured physical therapy focused on dynamic stabilizers and range of motion. If pain persists, local anesthetic and corticosteroid can be injected under ultrasound guidance into the bicipital tunnel; this injection has the advantage of being both diagnostic and therapeutic. Hashiuchi and colleagues42 found ultrasound-guided injections are 87% successful in achieving intra-sheath placement (injections without ultrasound guidance are only 27% successful).
If the 3-month trial of conservative management fails, surgical intervention should be considered. The goal in treating BLC pain is to maximize clinical function and alleviate pain in a predictable manner while minimizing technical demands and morbidity. A singular solution has not been identified. Furthermore, 3 systematic reviews failed to identify a difference between the most commonly used techniques, biceps tenodesis and tenotomy.43-45 These reviews grouped all tenotomy procedures together and compared them with all tenodesis procedures. A limitation of these systematic reviews is that they did not differentiate tenodesis techniques. We prefer to classify techniques according to whether or not they decompress zones 1 and 2 of the bicipital tunnel.
Bicipital Tunnel Nondecompressing Techniques
Release of the biceps tendon, a biceps tenotomy, is a simple procedure that potentially avoids open surgery and provides patients with a quick return to activity. Disadvantages of tenotomy include cosmetic (Popeye) deformity after surgery, potential cramping and fatigue, and biomechanical changes in the humeral head,46-48 particularly among patients younger than 65 years. High rates of revision after tenotomy have been reported.43,49 Incomplete retraction of the LHBT and/or residual synovium may be responsible for refractory pain following biceps tenotomy.49 We hypothesize that failure of tenotomy may be related to unaddressed bicipital tunnel disease.
Proximal nondecompressing tenodesis techniques may be performed either on soft tissue in the interval or rotator cuff or on bone at the articular margin or within zone 1 of the bicipital tunnel.50-52 These techniques can be performed with standard glenohumeral arthroscopy and generally are fast and well tolerated and have limited operative morbidity. Advantages of these techniques over simple tenotomy are lower rates of cosmetic deformity and lower rates of cramping and fatigue pain, likely resulting from maintenance of the muscle tension relationship of the LHBT. Disadvantages of proximal tenodesis techniques include introduction of hardware for bony fixation, longer postoperative rehabilitation to protect repairs, and failure to address hidden bicipital tunnel disease. Furthermore, the rate of stiffness in patients who undergo proximal tenodesis without decompression of the bicipital tunnel may be as high as 18%.53
Bicipital Tunnel Decompressing Techniques
Surgical techniques that decompress the bicipital tunnel include proximal techniques that release the bicipital sheath within zones 1 and 2 of the bicipital tunnel (to the level of the proximal margin of the pectoralis major tendon) and certain arthroscopic suprapectoral techniques,54 open subpectoral tenodeses,55-57 and arthroscopic transfer of the LHBT to the conjoint tendon.58,59
Open subpectoral tenodesis techniques have the advantage of maintaining the length-tension relationship of the LHBT and preventing Popeye deformity. However, these techniques require making an incision near the axilla, which may introduce an unnecessary source of infection. Furthermore, open subpectoral tenodesis requires drilling the humerus and placing a screw for bony fixation of the LHBT, which can create a risk of neurovascular injury, given the proximity of neurovascular structures,60-62 and humeral shaft fracture, particularly in athletes.63,64Our preferred method is transfer of the LHBT to the conjoint tendon (Figure 3).59
Am J Orthop. 2016;45(7):E503-E511. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.
Pathology of the biceps-labrum complex (BLC) can be an important source of shoulder pain. Discussion of pathoanatomy, imaging, and surgical intervention is facilitated by distinguishing the anatomical zones of the BLC: inside, junction, and bicipital tunnel (extra-articular), parts of which cannot be visualized with standard diagnostic arthroscopy.
The recent literature indicates that bicipital tunnel lesions are common and perhaps overlooked. Systematic reviews suggest improvement in outcomes of BLC operations when the bicipital tunnel is decompressed. Higher-level clinical and basic science studies are needed to fully elucidate the role of the bicipital tunnel, but it is evident that a comprehensive physical examination and an understanding of the limits of advanced imaging are necessary to correctly diagnose and treat BLC-related shoulder pain.
Anatomy of Biceps-Labrum Complex
The long head of the biceps tendon (LHBT) and the glenoid labrum work as an interdependent functional unit, the biceps-labrum complex (BLC). The BLC is divided into 3 distinct anatomical zones: inside, junction, and bicipital tunnel.1,2
Inside
The inside includes the superior labrum and biceps attachment. The LHBT most commonly originates in the superior labrum.3-5 Vangsness and colleagues3 described 4 types of LHBT origins: Type I biceps attaches solely to the posterior labrum, type II predominantly posterior, type III equally to the anterior and posterior labrum, and type IV mostly to the anterior labrum. The LHBT can also originate in the supraglenoid tubercle or the inferior border of the supraspinatus.3,6
Junction
Junction is the intra-articular segment of the LHBT and the biceps pulley. The LHBT traverses the glenohumeral joint en route to the extra-articular bicipital tunnel.2 The LHBT is enveloped in synovium that extends into part of the bicipital tunnel.2 The intra-articular segment of the LHBT is about 25 mm in length7 and has a diameter of 5 mm to 6 mm.8
A cadaveric study found that the average length of the LHBT that can be arthroscopically visualized at rest is 35.6 mm, or only 40% of the total length of the LHBT with respect to the proximal margin of the pectoralis major tendon.1 When the LHBT was pulled into the joint, more tendon (another 14 mm) was visualized.1 Therefore, diagnostic arthroscopy of the glenohumeral joint visualizes about 50% of the LHBT.9The morphology of the LHBT varies by location. The intra-articular portion of the LHBT is wide and flat, whereas the extra-articular portion is round.8 The tendon becomes smoother and more avascular as it exits the joint to promote gliding within its sheath in the bicipital groove.10 The proximal LHBT receives its vascular supply from superior labrum tributaries, and distally the LHBT is supplied by ascending branches of the anterior humeral circumflex artery.4 There is a hypovascular zone, created by this dual blood supply, about 12 mm to 30 mm from the LHBT origin, predisposing the tendon to rupture or fray in this region.11The LHBT makes a 30° turn into the biceps pulley system as it exits the glenohumeral joint. The fibrous pulley system that stabilizes the LHBT in this region has contributions from the coracohumeral ligament, the superior glenohumeral ligament, and the supraspinatus tendon.12-14
Bicipital Tunnel
The bicipital tunnel, the third portion of the BLC, remains largely hidden from standard diagnostic glenohumeral arthroscopy. The bicipital tunnel is an extra-articular, closed space that constrains the LHBT from the articular margin through the subpectoral region.2
Zone 1 is the traditional bicipital groove or “bony groove” that extends from the articular margin to the distal margin of the subscapularis tendon. The floor consists of a deep osseous groove covered by a continuation of subscapularis tendon fibers and periosteum.2Zone 2, “no man’s land,” extends from the distal margin of the subscapularis tendon to the proximal margin of the pectoralis major (PMPM). The LHBT in this zone cannot be visualized during a pull test at arthroscopy, yet lesions commonly occur here.1 Zones 1 and 2 have a similar histology and contain synovium.2Zone 3 is the subpectoral region distal to the PMPM. Fibers of the latissimus dorsi form the flat floor of zone 3, and the pectoralis major inserts lateral to the LHBT on the humerus in this zone. The synovium encapsulating the LHBT in zones 1 and 2 rarely extends past the PMPM. Taylor and colleagues2 found a higher percentage of unoccupied tunnel space in zone 3 than in zones 1 and 2, which results in a “functional bottleneck” between zones 2 and 3 represented by the PMPM.
Pathoanatomy
BLC lesions may occur in isolation or concomitantly across multiple anatomical zones. In a series of 277 chronically symptomatic shoulders that underwent transfer of the LHBT to the conjoint tendon with subdeltoid arthroscopy, Taylor and colleagues1 found 47% incidence of bicipital tunnel lesions, 44% incidence of junctional lesions, and 35% incidence of inside lesions. In their series, 37% of patients had concomitant lesions involving more than 1 anatomical zone.
Inside Lesions
Inside lesions involve the superior labrum, the LHBT origin, or both. Superior labrum anterior-posterior (SLAP) tears are included as inside BLC lesions. Snyder and colleagues16 originally identified 4 broad categories of SLAP tears, but Powell and colleagues17 described up to 10 variations. Type II lesions, which are the most common, destabilize the biceps anchor.
Dynamic incarceration of the biceps between the humeral head and the glenoid labrum is another inside lesion that can be identified during routine diagnostic glenohumeral arthroscopy. The arthroscopic active compression test, as described by Verma and colleagues,18 can be used during surgery to demonstrate incarceration of the biceps tendon.
Medial biceps chondromalacia, attritional chondral wear along the anteromedial aspect of the humeral head, occurs secondary to a windshield wiper effect of the LHBT in the setting of an incarcerating LHBT or may be associated with destabilization of the biceps pulley.
Junctional Lesions
Junctional lesions, which include lesions that affect the intra-articular LHBT, can be visualized during routine glenohumeral arthroscopy. They include partial and complete biceps tears, biceps pulley lesions, and junctional biceps chondromalacia.
Biceps pulley injuries and/or tears of the upper subscapularis tendon can destabilize the biceps as it exits the joint, and this destabilization may result in medial subluxation of the tendon and the aforementioned medial biceps chondromalacia.10,19 Junctional biceps chondromalacia is attritional chondral wear of the humeral head from abnormal tracking of the LHBT deep to the LHBT near the articular margin.
Recently elucidated is the limited ability of diagnostic glenohumeral arthroscopy to fully identify the extent of BLC pathology.1,20-22 Gilmer and colleagues20 found that diagnostic arthroscopy identified only 67% of biceps pathology and underestimated its extent in 56% of patients in their series. Similarly, Moon and colleagues21 found that 79% of proximal LHBT tears propagated distally into the bicipital tunnel and were incompletely visualized with standard arthroscopy.
Bicipital Tunnel Lesions
Recent evidence indicates that the bicipital tunnel is a closed space that often conceals space-occupying lesions, including scar, synovitis, loose bodies, and osteophytes, which can become trapped in the tunnel. The functional bottleneck between zones 2 and 3 of the bicipital tunnel explains the aggregation of loose bodies in this region.2 Similarly, as the percentage of free space within the bicipital tunnel increases, space-occupying lesions (eg scar, loose bodies, osteophytes) may exude a compressive and/or abrasive force within zones 1 and 2, but not as commonly within zone 3.2
Physical Examination of Biceps-Labrum Complex
Accurate diagnosis of BLC disease is crucial in selecting an optimal intervention, but challenging. Beyond identifying biceps pathology, specific examination maneuvers may help distinguish between lesions of the intra-articular BLC and lesions of the extra-articular bicipital tunnel.23
Traditional examination maneuvers for biceps-related shoulder pain include the Speed test, the full can test, and the Yergason test.24,25 For the Speed test, the patient forward-flexes the shoulder to 60° to 90°, extends the arm at the elbow, and supinates the forearm. The clinician applies a downward force as the patient resists. The reported sensitivity of the Speed test ranges from 37% to 63%, and specificity is 60% to 88%.25,26 In the full can test, with the patient’s arm in the plane of the scapula, the shoulder abducted to 90°, and the forearm in neutral rotation, a downward force is applied against resistance. Sensitivity of the full can test is 60% to 67%, and specificity is 76% to 84%.24 The Yergason test is performed with the patient’s arm at his or her side, the elbow flexed to 90°, and the forearm pronated. The patient supinates the forearm against the clinician’s resistance. Sensitivity of the Yergason test is 19% to 32%, and specificity is 70% to 100%.25,26 The Yergason test has a positive predictive value of 92% for bicipital tunnel disease.
O’Brien and colleagues23,26 introduced a “3-pack” physical examination designed to elicit BLC symptoms. In this examination, the LHBT is palpated along its course within the bicipital tunnel. Reproduction of the patient’s pain by palpation had a sensitivity of 98% for bicipital tunnel disease but was less specific (70%). Gill and colleagues27 reported low sensitivity (53%) and low specificity (54%) for biceps palpation, and they used arthroscopy as a gold standard. Since then, multiple studies have demonstrated that glenohumeral arthroscopy fails to identify lesions concealed within the bicipital tunnel.20-22The second part of the 3-pack examination is the active compression test. A downward force is applied as the patient resists with his or her arm forward-flexed to 90° and adducted 10° to 15° with the thumb pointing downward.28 This action is repeated with the humerus externally rotated and the forearm supinated. A positive test is indicated by reproduction of symptoms with the thumb down, and elimination or reduction of symptoms with the palm up. Test sensitivity is 88% to 96%, and specificity is 46% to 64% for BLC lesions, but for bicipital tunnel disease sensitivity is higher (96%), and the negative predictive value is 93%.26The third component of the 3-pack examination is the throwing test. A late-cocking throwing position is re-created with the shoulder externally rotated and abducted to 90° and the elbow flexed to 90°. The patient steps forward with the contralateral leg and moves into the acceleration phase of throwing while the clinician provides isometric resistance. If this maneuver reproduces pain, the test is positive. As Taylor and colleagues26 reported, the throwing test has sensitivity of 73% to 77% and specificity of 65% to 79% for BLC pathology. This test has moderate sensitivity and negative predictive value for bicipital tunnel disease but may be the only positive test on physical examination in the setting of LHBT instability.
Imaging of Biceps-Labrum Complex
Plain anteroposterior, lateral, and axillary radiographs of the shoulder should be obtained for all patients having an orthopedic examination for shoulder pain. Magnetic resonance imaging (MRI) and ultrasound are the advanced modalities most commonly used for diagnostic imaging. These modalities should be considered in conjunction with, not in place of, a comprehensive history and physical examination.
MRI has sensitivity of 9% to 89% for LHBT pathology29-37 and 38% to 98% for SLAP pathology.35,38-41 The wide range of reported sensitivity and specificity might be attributed to the varying criteria for what constitutes a BLC lesion. Some authors include biceps chondromalacia, dynamic incarceration of LHBT, and extra-articular bicipital tunnel lesions, while others historically have included only intra-articular LHBT lesions that can be directly visualized arthroscopically.
In their retrospective review of 277 shoulders with chronic refractory BLC symptoms treated with subdeltoid transfer of the LHBT to the conjoint tendon, Taylor and colleagues30 reported MRI was more sensitive for inside BLC lesions than for junctional or bicipital tunnel lesions (77% vs 43% and 50%, respectively).
Treatment Options for Biceps-Labrum Complex Lesions
A diagnosis of BLC disease warrants a trial of conservative (nonoperative) management for at least 3 months. Many patients improve with activity modification, use of oral anti-inflammatory medication, and structured physical therapy focused on dynamic stabilizers and range of motion. If pain persists, local anesthetic and corticosteroid can be injected under ultrasound guidance into the bicipital tunnel; this injection has the advantage of being both diagnostic and therapeutic. Hashiuchi and colleagues42 found ultrasound-guided injections are 87% successful in achieving intra-sheath placement (injections without ultrasound guidance are only 27% successful).
If the 3-month trial of conservative management fails, surgical intervention should be considered. The goal in treating BLC pain is to maximize clinical function and alleviate pain in a predictable manner while minimizing technical demands and morbidity. A singular solution has not been identified. Furthermore, 3 systematic reviews failed to identify a difference between the most commonly used techniques, biceps tenodesis and tenotomy.43-45 These reviews grouped all tenotomy procedures together and compared them with all tenodesis procedures. A limitation of these systematic reviews is that they did not differentiate tenodesis techniques. We prefer to classify techniques according to whether or not they decompress zones 1 and 2 of the bicipital tunnel.
Bicipital Tunnel Nondecompressing Techniques
Release of the biceps tendon, a biceps tenotomy, is a simple procedure that potentially avoids open surgery and provides patients with a quick return to activity. Disadvantages of tenotomy include cosmetic (Popeye) deformity after surgery, potential cramping and fatigue, and biomechanical changes in the humeral head,46-48 particularly among patients younger than 65 years. High rates of revision after tenotomy have been reported.43,49 Incomplete retraction of the LHBT and/or residual synovium may be responsible for refractory pain following biceps tenotomy.49 We hypothesize that failure of tenotomy may be related to unaddressed bicipital tunnel disease.
Proximal nondecompressing tenodesis techniques may be performed either on soft tissue in the interval or rotator cuff or on bone at the articular margin or within zone 1 of the bicipital tunnel.50-52 These techniques can be performed with standard glenohumeral arthroscopy and generally are fast and well tolerated and have limited operative morbidity. Advantages of these techniques over simple tenotomy are lower rates of cosmetic deformity and lower rates of cramping and fatigue pain, likely resulting from maintenance of the muscle tension relationship of the LHBT. Disadvantages of proximal tenodesis techniques include introduction of hardware for bony fixation, longer postoperative rehabilitation to protect repairs, and failure to address hidden bicipital tunnel disease. Furthermore, the rate of stiffness in patients who undergo proximal tenodesis without decompression of the bicipital tunnel may be as high as 18%.53
Bicipital Tunnel Decompressing Techniques
Surgical techniques that decompress the bicipital tunnel include proximal techniques that release the bicipital sheath within zones 1 and 2 of the bicipital tunnel (to the level of the proximal margin of the pectoralis major tendon) and certain arthroscopic suprapectoral techniques,54 open subpectoral tenodeses,55-57 and arthroscopic transfer of the LHBT to the conjoint tendon.58,59
Open subpectoral tenodesis techniques have the advantage of maintaining the length-tension relationship of the LHBT and preventing Popeye deformity. However, these techniques require making an incision near the axilla, which may introduce an unnecessary source of infection. Furthermore, open subpectoral tenodesis requires drilling the humerus and placing a screw for bony fixation of the LHBT, which can create a risk of neurovascular injury, given the proximity of neurovascular structures,60-62 and humeral shaft fracture, particularly in athletes.63,64Our preferred method is transfer of the LHBT to the conjoint tendon (Figure 3).59
Am J Orthop. 2016;45(7):E503-E511. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.
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53. Werner BC, Pehlivan HC, Hart JM, et al. Increased incidence of postoperative stiffness after arthroscopic compared with open biceps tenodesis. Arthroscopy. 2014;30(9):1075-1084.54. Werner BC, Lyons ML, Evans CL, et al. Arthroscopic suprapectoral and open subpectoral biceps tenodesis: a comparison of restoration of length-tension and mechanical strength between techniques. Arthroscopy. 2015;31(4):620-627.
55. Nho SJ, Reiff SN, Verma NN, Slabaugh MA, Mazzocca AD, Romeo AA. Complications associated with subpectoral biceps tenodesis: low rates of incidence following surgery. J Shoulder Elbow Surg. 2010;19(5):764-768.
56. Mazzocca AD, Cote MP, Arciero CL, Romeo AA, Arciero RA. Clinical outcomes after subpectoral biceps tenodesis with an interference screw. Am J Sports Med. 2008;36(10):1922-1929.
57. Provencher MT, LeClere LE, Romeo AA. Subpectoral biceps tenodesis. Sports Med Arthrosc. 2008;16(3):170-176.
58. Taylor SA, Fabricant PD, Baret NJ, et al. Midterm clinical outcomes for arthroscopic subdeltoid transfer of the long head of the biceps tendon to the conjoint tendon. Arthroscopy. 2014;30(12):1574-1581.
59. Drakos MC, Verma NN, Gulotta LV, et al. Arthroscopic transfer of the long head of the biceps tendon: functional outcome and clinical results. Arthroscopy. 2008;24(2):217-223.
60. Ding DY, Gupta A, Snir N, Wolfson T, Meislin RJ. Nerve proximity during bicortical drilling for subpectoral biceps tenodesis: a cadaveric study. Arthroscopy. 2014;30(8):942-946.
61. Dickens JF, Kilcoyne KG, Tintle SM, Giuliani J, Schaefer RA, Rue JP. Subpectoral biceps tenodesis: an anatomic study and evaluation of at-risk structures. Am J Sports Med. 2012;40(10):2337-2341.
62. Ma H, Van Heest A, Glisson C, Patel S. Musculocutaneous nerve entrapment: an unusual complication after biceps tenodesis. Am J Sports Med. 2009;37(12):2467-2469.
63. Dein EJ, Huri G, Gordon JC, McFarland EG. A humerus fracture in a baseball pitcher after biceps tenodesis. Am J Sports Med. 2014;42(4):877-879.
64. Sears BW, Spencer EE, Getz CL. Humeral fracture following subpectoral biceps tenodesis in 2 active, healthy patients. J Shoulder Elbow Surg. 2011;20(6):e7-e11.
65. O’Brien SJ, Taylor SA, DiPietro JR, Newman AM, Drakos MC, Voos JE. The arthroscopic “subdeltoid approach” to the anterior shoulder. J Shoulder Elbow Surg. 2013;22(4):e6-e10.
66. Urch E, Taylor SA, Ramkumar PN, et al. Biceps tenodesis: a comparison of tendon-to-bone and tendon-to-tendon healing in a rat model. Paper presented at: Closed Meeting of the American Shoulder and Elbow Surgeons; October 10, 2015; Asheville, NC. Paper 26.
67. Taylor SA, Ramkumar PN, Fabricant PD, et al. The clinical impact of bicipital tunnel decompression during long head of the biceps tendon surgery: a systematic review and meta-analysis. Arthroscopy. 2016;32(6):1155-1164.
1. Taylor SA, Khair MM, Gulotta LV, et al. Diagnostic glenohumeral arthroscopy fails to fully evaluate the biceps-labral complex. Arthroscopy. 2015;31(2):215-224.
2. Taylor SA, Fabricant PD, Bansal M, et al. The anatomy and histology of the bicipital tunnel of the shoulder. J Shoulder Elbow Surg. 2015;24(4):511-519.
3. Vangsness CT Jr, Jorgenson SS, Watson T, Johnson DL. The origin of the long head of the biceps from the scapula and glenoid labrum. An anatomical study of 100 shoulders. J Bone Joint Surg Br. 1994;76(6):951-954.
4. Cooper DE, Arnoczky SP, O’Brien SJ, Warren RF, DiCarlo E, Allen AA. Anatomy, histology, and vascularity of the glenoid labrum. an anatomical study. J Bone Joint Surg Am. 1992;74(1):46-52.
5. Tuoheti Y, Itoi E, Minagawa H, et al. Attachment types of the long head of the biceps tendon to the glenoid labrum and their relationships with the glenohumeral ligaments. Arthroscopy. 2005;21(10):1242-1249.
6. Dierickx C, Ceccarelli E, Conti M, Vanlommel J, Castagna A. Variations of the intra-articular portion of the long head of the biceps tendon: a classification of embryologically explained variations. J Shoulder Elbow Surg. 2009;18(4):556-565.
7. Denard PJ, Dai X, Hanypsiak BT, Burkhart SS. Anatomy of the biceps tendon: implications for restoring physiological length-tension relation during biceps tenodesis with interference screw fixation. Arthroscopy. 2012;28(10):1352-1358.
8. Ahrens PM, Boileau P. The long head of biceps and associated tendinopathy. J Bone Joint Surg Br. 2007;89(8):1001-1009.
9. Hart ND, Golish SR, Dragoo JL. Effects of arm position on maximizing intra-articular visualization of the biceps tendon: a cadaveric study. Arthroscopy. 2012;28(4):481-485.
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11. Cheng NM, Pan WR, Vally F, Le Roux CM, Richardson MD. The arterial supply of the long head of biceps tendon: anatomical study with implications for tendon rupture. Clin Anat. 2010;23(6):683-692.
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14. Arai R, Mochizuki T, Yamaguchi K, et al. Functional anatomy of the superior glenohumeral and coracohumeral ligaments and the subscapularis tendon in view of stabilization of the long head of the biceps tendon. J Shoulder Elbow Surg. 2010;19(1):58-64.
15. Busconi BB, DeAngelis N, Guerrero PE. The proximal biceps tendon: tricks and pearls. Sports Med Arthrosc. 2008;16(3):187-194.
16. Snyder SJ, Karzel RP, Del Pizzo W, Ferkel RD, Friedman MJ. SLAP lesions of the shoulder. Arthroscopy. 1990;6(4):274-279.
17. Powell SE, Nord KD, Ryu RKN. The diagnosis, classification, and treatment of SLAP lesions. Oper Tech Sports Med. 2004;12(2):99-110.
18. Verma NN, Drakos M, O’Brien SJ. The arthroscopic active compression test. Arthroscopy. 2005;21(5):634.
19. Walch G, Nove-Josserand L, Levigne C, Renaud E. Tears of the supraspinatus tendon associated with “hidden” lesions of the rotator interval. J Shoulder Elbow Surg. 1994;3(6):353-360.
20. Gilmer BB, DeMers AM, Guerrero D, Reid JB 3rd, Lubowitz JH, Guttmann D. Arthroscopic versus open comparison of long head of biceps tendon visualization and pathology in patients requiring tenodesis. Arthroscopy. 2015;31(1):29-34.
21. Moon SC, Cho NS, Rhee YG. Analysis of “hidden lesions” of the extra-articular biceps after subpectoral biceps tenodesis: the subpectoral portion as the optimal tenodesis site. Am J Sports Med. 2015;43(1):63-68.
22. Festa A, Allert J, Issa K, Tasto JP, Myer JJ. Visualization of the extra-articular portion of the long head of the biceps tendon during intra-articular shoulder arthroscopy. Arthroscopy. 2014;30(11):1413-1417.
23. O’Brien SJ, Newman AM, Taylor SA, et al. The accurate diagnosis of biceps-labral complex lesions with MRI and “3-pack” physical examination: a retrospective analysis with prospective validation. Orthop J Sports Med. 2013;1(4 suppl). doi:10.1177/2325967113S00018.
24. Hegedus EJ, Goode AP, Cook CE, et al. Which physical examination tests provide clinicians with the most value when examining the shoulder? Update of a systematic review with meta-analysis of individual tests. Br J Sports Med. 2012;46(14):964-978.
25. Chen HS, Lin SH, Hsu YH, Chen SC, Kang JH. A comparison of physical examinations with musculoskeletal ultrasound in the diagnosis of biceps long head tendinitis. Ultrasound Med Biol. 2011;37(9):1392-1398.
26. Taylor SA, Newman AM, Dawson C, et al. The “3-Pack” examination is critical for comprehensive evaluation of the biceps-labrum complex and the bicipital tunnel: a prospective study. Arthroscopy. 2016 Jul 20. [Epub ahead of print]
27. Gill HS, El Rassi G, Bahk MS, Castillo RC, McFarland EG. Physical examination for partial tears of the biceps tendon. Am J Sports Med. 2007;35(8):1334-1340.
28. O’Brien SJ, Pagnani MJ, Fealy S, McGlynn SR, Wilson JB. The active compression test: a new and effective test for diagnosing labral tears and acromioclavicular joint abnormality. Am J Sports Med. 1998;26(5):610-613.
29. Zanetti M, Weishaupt D, Gerber C, Hodler J. Tendinopathy and rupture of the tendon of the long head of the biceps brachii muscle: evaluation with MR arthrography. AJR Am J Roentgenol. 1998;170(6):1557-1561.
30. Taylor SA, Newman AM, Nguyen J, et al. Magnetic resonance imaging currently fails to fully evaluate the biceps-labrum complex and bicipital tunnel. Arthroscopy. 2016;32(2):238-244.
31. Malavolta EA, Assunção JH, Guglielmetti CL, de Souza FF, Gracitelli ME, Ferreira Neto AA. Accuracy of preoperative MRI in the diagnosis of disorders of the long head of the biceps tendon. Eur J Radiol. 2015;84(11):2250-2254.
32. Dubrow SA, Streit JJ, Shishani Y, Robbin MR, Gobezie R. Diagnostic accuracy in detecting tears in the proximal biceps tendon using standard nonenhancing shoulder MRI. Open Access J Sports Med. 2014;5:81-87.
33. Nourissat G, Tribot-Laspiere Q, Aim F, Radier C. Contribution of MRI and CT arthrography to the diagnosis of intra-articular tendinopathy of the long head of the biceps. Orthop Traumatol Surg Res. 2014;100(8 suppl):S391-S394.
34. De Maeseneer M, Boulet C, Pouliart N, et al. Assessment of the long head of the biceps tendon of the shoulder with 3T magnetic resonance arthrography and CT arthrography. Eur J Radiol. 2012;81(5):934-939.
35. Houtz CG, Schwartzberg RS, Barry JA, Reuss BL, Papa L. Shoulder MRI accuracy in the community setting. J Shoulder Elbow Surg. 2011;20(4):537-542.
36. Buck FM, Grehn H, Hilbe M, Pfirrmann CW, Manzanell S, Hodler J. Degeneration of the long biceps tendon: comparison of MRI with gross anatomy and histology. AJR Am J Roentgenol. 2009;193(5):1367-1375.
37. Mohtadi NG, Vellet AD, Clark ML, et al. A prospective, double-blind comparison of magnetic resonance imaging and arthroscopy in the evaluation of patients presenting with shoulder pain. J Shoulder Elbow Surg. 2004;13(3):258-265.
38. Sheridan K, Kreulen C, Kim S, Mak W, Lewis K, Marder R. Accuracy of magnetic resonance imaging to diagnose superior labrum anterior-posterior tears. Knee Surg Sports Traumatol Arthrosc. 2015;23(9):2645-2650.
39. Connolly KP, Schwartzberg RS, Reuss B, Crumbie D Jr, Homan BM. Sensitivity and specificity of noncontrast magnetic resonance imaging reports in the diagnosis of type-II superior labral anterior-posterior lesions in the community setting. J Bone Joint Surg Am. 2013;95(4):308-313.
40. Reuss BL, Schwartzberg R, Zlatkin MB, Cooperman A, Dixon JR. Magnetic resonance imaging accuracy for the diagnosis of superior labrum anterior-posterior lesions in the community setting: eighty-three arthroscopically confirmed cases. J Shoulder Elbow Surg. 2006;15(5):580-585.
41. Connell DA, Potter HG, Wickiewicz TL, Altchek DW, Warren RF. Noncontrast magnetic resonance imaging of superior labral lesions. 102 cases confirmed at arthroscopic surgery. Am J Sports Med. 1999;27(2):208-213.
42. Hashiuchi T, Sakurai G, Morimoto M, Komei T, Takakura Y, Tanaka Y. Accuracy of the biceps tendon sheath injection: ultrasound-guided or unguided injection? A randomized controlled trial. J Shoulder Elbow Surg. 2011;20(7):1069-1073.
43. Hsu AR, Ghodadra NS, Provencher MT, Lewis PB, Bach BR. Biceps tenotomy versus tenodesis: a review of clinical outcomes and biomechanical results. J Shoulder Elbow Surg. 2011;20(2):326-332.
44. Slenker NR, Lawson K, Ciccotti MG, Dodson CC, Cohen SB. Biceps tenotomy versus tenodesis: clinical outcomes. Arthroscopy. 2012;28(4):576-582.
45. Frost A, Zafar MS, Maffulli N. Tenotomy versus tenodesis in the management of pathologic lesions of the tendon of the long head of the biceps brachii. Am J Sports Med. 2009;37(4):828-833.
46. Kelly AM, Drakos MC, Fealy S, Taylor SA, O’Brien SJ. Arthroscopic release of the long head of the biceps tendon: functional outcome and clinical results. Am J Sports Med. 2005;33(2):208-213.
47. Berlemann U, Bayley I. Tenodesis of the long head of biceps brachii in the painful shoulder: improving results in the long term. J Shoulder Elbow Surg. 1995;4(6):429-435.
48. Gill TJ, McIrvin E, Mair SD, Hawkins RJ. Results of biceps tenotomy for treatment of pathology of the long head of the biceps brachii. J Shoulder Elbow Surg. 2001;10(3):247-249.
49. Sanders B, Lavery KP, Pennington S, Warner JJ. Clinical success of biceps tenodesis with and without release of the transverse humeral ligament. J Shoulder Elbow Surg. 2012;21(1):66-71.
50. Gartsman GM, Hammerman SM. Arthroscopic biceps tenodesis: operative technique. Arthroscopy. 2000;16(5):550-552.
51. Richards DP, Burkhart SS. Arthroscopic-assisted biceps tenodesis for ruptures of the long head of biceps brachii: the cobra procedure. Arthroscopy. 2004;20(suppl 2):201-207.
52. Klepps S, Hazrati Y, Flatow E. Arthroscopic biceps tenodesis. Arthroscopy. 2002;18(9):1040-1045.
53. Werner BC, Pehlivan HC, Hart JM, et al. Increased incidence of postoperative stiffness after arthroscopic compared with open biceps tenodesis. Arthroscopy. 2014;30(9):1075-1084.54. Werner BC, Lyons ML, Evans CL, et al. Arthroscopic suprapectoral and open subpectoral biceps tenodesis: a comparison of restoration of length-tension and mechanical strength between techniques. Arthroscopy. 2015;31(4):620-627.
55. Nho SJ, Reiff SN, Verma NN, Slabaugh MA, Mazzocca AD, Romeo AA. Complications associated with subpectoral biceps tenodesis: low rates of incidence following surgery. J Shoulder Elbow Surg. 2010;19(5):764-768.
56. Mazzocca AD, Cote MP, Arciero CL, Romeo AA, Arciero RA. Clinical outcomes after subpectoral biceps tenodesis with an interference screw. Am J Sports Med. 2008;36(10):1922-1929.
57. Provencher MT, LeClere LE, Romeo AA. Subpectoral biceps tenodesis. Sports Med Arthrosc. 2008;16(3):170-176.
58. Taylor SA, Fabricant PD, Baret NJ, et al. Midterm clinical outcomes for arthroscopic subdeltoid transfer of the long head of the biceps tendon to the conjoint tendon. Arthroscopy. 2014;30(12):1574-1581.
59. Drakos MC, Verma NN, Gulotta LV, et al. Arthroscopic transfer of the long head of the biceps tendon: functional outcome and clinical results. Arthroscopy. 2008;24(2):217-223.
60. Ding DY, Gupta A, Snir N, Wolfson T, Meislin RJ. Nerve proximity during bicortical drilling for subpectoral biceps tenodesis: a cadaveric study. Arthroscopy. 2014;30(8):942-946.
61. Dickens JF, Kilcoyne KG, Tintle SM, Giuliani J, Schaefer RA, Rue JP. Subpectoral biceps tenodesis: an anatomic study and evaluation of at-risk structures. Am J Sports Med. 2012;40(10):2337-2341.
62. Ma H, Van Heest A, Glisson C, Patel S. Musculocutaneous nerve entrapment: an unusual complication after biceps tenodesis. Am J Sports Med. 2009;37(12):2467-2469.
63. Dein EJ, Huri G, Gordon JC, McFarland EG. A humerus fracture in a baseball pitcher after biceps tenodesis. Am J Sports Med. 2014;42(4):877-879.
64. Sears BW, Spencer EE, Getz CL. Humeral fracture following subpectoral biceps tenodesis in 2 active, healthy patients. J Shoulder Elbow Surg. 2011;20(6):e7-e11.
65. O’Brien SJ, Taylor SA, DiPietro JR, Newman AM, Drakos MC, Voos JE. The arthroscopic “subdeltoid approach” to the anterior shoulder. J Shoulder Elbow Surg. 2013;22(4):e6-e10.
66. Urch E, Taylor SA, Ramkumar PN, et al. Biceps tenodesis: a comparison of tendon-to-bone and tendon-to-tendon healing in a rat model. Paper presented at: Closed Meeting of the American Shoulder and Elbow Surgeons; October 10, 2015; Asheville, NC. Paper 26.
67. Taylor SA, Ramkumar PN, Fabricant PD, et al. The clinical impact of bicipital tunnel decompression during long head of the biceps tendon surgery: a systematic review and meta-analysis. Arthroscopy. 2016;32(6):1155-1164.
The Role of Hysteroscopy in Minimally Invasive Management of Intrauterine Health
Faculty/Faculty Disclosure
Linda D. Bradley, MD
Obstetrics, Gynecology and Women’s
Health Institute,
Cleveland Clinic,
Cleveland, Ohio, USA
Competing Interest and Financial Disclosures: Dr. Bradley reports that she has received grant/research/clinical trial support from Bayer Healthcare Pharmaceuticals Inc. She is a consultant and on the advisory board for Bayer Healthcare Pharmaceuticals Inc., Boston Scientific Corporation, and Smith & Nephew; she is on the advisory board for Patient-Centered Outcomes Research Institute; she is on the speakers' bureau for Smith & Nephew (Medtronic); she is on the scientific advisory panel for Karl Storz; and she is on the data safety and monitoring board for Gynesonics.
Faculty/Faculty Disclosure
Linda D. Bradley, MD
Obstetrics, Gynecology and Women’s
Health Institute,
Cleveland Clinic,
Cleveland, Ohio, USA
Competing Interest and Financial Disclosures: Dr. Bradley reports that she has received grant/research/clinical trial support from Bayer Healthcare Pharmaceuticals Inc. She is a consultant and on the advisory board for Bayer Healthcare Pharmaceuticals Inc., Boston Scientific Corporation, and Smith & Nephew; she is on the advisory board for Patient-Centered Outcomes Research Institute; she is on the speakers' bureau for Smith & Nephew (Medtronic); she is on the scientific advisory panel for Karl Storz; and she is on the data safety and monitoring board for Gynesonics.
Faculty/Faculty Disclosure
Linda D. Bradley, MD
Obstetrics, Gynecology and Women’s
Health Institute,
Cleveland Clinic,
Cleveland, Ohio, USA
Competing Interest and Financial Disclosures: Dr. Bradley reports that she has received grant/research/clinical trial support from Bayer Healthcare Pharmaceuticals Inc. She is a consultant and on the advisory board for Bayer Healthcare Pharmaceuticals Inc., Boston Scientific Corporation, and Smith & Nephew; she is on the advisory board for Patient-Centered Outcomes Research Institute; she is on the speakers' bureau for Smith & Nephew (Medtronic); she is on the scientific advisory panel for Karl Storz; and she is on the data safety and monitoring board for Gynesonics.
c-Myc could be key to alisertib potential in small-cell lung cancer
VIENNA – The investigational agent alisertib plus paclitaxel improved progression-free survival (PFS), compared with paclitaxel plus placebo, in a randomized, double-blind, phase II study of patients with relapsed or refractory small-cell lung cancer (SCLC).
The median PFS was 3.32 months with alisertib/paclitaxel and 2.17 months with paclitaxel/placebo, giving an overall 30% improvement with the combination (hazard ratio, 0.71; 95% confidence interval, 0.509-0.985; P = .038).
“c-Myc protein expression showed a strong association with improved PFS, despite the small number of evaluable patients,” study investigator Taofeek Owonikoko, MD, of Emory University, Atlanta, said at the World Conference on Lung Cancer.
Amplification and overexpression of c-Myc is a strong oncogenic driver in many cancers, he explained. Around 18%-31% of SCLCs overexpress the protein, and it is often found in patients with chemorefractory disease, he said.
In the study, longer PFS was achieved in patients treated with alisertib/paclitaxel than in those given placebo/paclitaxel if they were c-Myc positive (4.64 vs. 2.27 months; HR, 0.29). Conversely, patients who were c-Myc negative had a shorter PFS with the combination (3.32 vs. 5.16 months; HR, 11.8).
“A prospective study is needed to further validate the predictive value of c-Myc in the clinic,” Dr. Owonikoko said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
Alisertib is an aurora A kinase inhibitor that has already been shown to have antitumor activity in patients with solid tumors, including those with SCLC (Lancet Oncol. 2015;16[4]:395-405).
The current phase II study was designed to evaluate the efficacy and safety of alisertib in combination with paclitaxel, compared with placebo plus paclitaxel, in a larger population of patients with SCLC who had relapsed within 6 months or did not respond to standard first-line, platinum-based chemotherapy.
Treatment was given in 28-day cycles, with patients randomized to the combination receiving alisertib at an oral, 40-mg, twice-daily dose on days 1-3, 8-10, and 15-17 and paclitaxel administered intravenously at a dose of 60 mg/m2 IV on days 1, 8, 15. Patients randomized to the control arm received a matched placebo plus paclitaxel given on the same days but at a dose of 80 mg/m2.
Overall, 178 patients were randomized, with a mean age of 62 years, and just over half (57%) were men.
Numerically higher objective response rates (22% vs. 18%), disease control rates (77 vs. 67%), and overall survival (6.87 vs. 5.58 months) also were seen with the combination over paclitaxel alone, although they did not achieve statistical significance.
Additional toxicities were observed with the combination treatment versus paclitaxel. Many of these were to be expected, Dr. Owonikoko said. Almost all (99% vs. 96%) of patients reported some type of adverse event, of which 75% and 51% were grade 3 or higher, respectively. Common any-grade adverse effects were diarrhea (59% vs. 20%), neutropenia (49% vs. 8%), anemia (44% vs. 20%), and fatigue (44% vs. 33%).
These toxicities, however, did not appear to affect patients’ quality of life, Dr. Owonikoko said, as comparable changes in quality-of-life scores using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 instrument were observed. There was even an indication that patients taking alisertib/paclitaxel might have improved lung-related symptoms, such as shortness of breath and worsening cough.
The treatment of SCLC, particularly in the second-line setting, remains challenging, observed the invited discussant for the trial Jens Benn Sørensen, MD, of the Finsen Centre at Rigshospitalet, Copenhagen.
“There have been no major improvements in the last decade and there are no targeted agents approved for use,” Dr. Sørensen said. Although that is not for lack of trying, he qualified.
When first-line therapies fail, the guideline-recommended option is to put patients back on platinum-based chemotherapy if they were sensitive to such chemotherapy. If not, then topotecan is often an appropriate, reasonably tolerated option.
“The clinical relevance of second-line paclitaxel/alisertib in all comers is questionable,” he said. The PFS improvement of 1.2 months in this phase II study seems “mostly at the same level” when comparing trials of second-line, single-agent topotecan.
“However, the use of c-Myc as a predictor for efficacy seems very promising and should clearly be explored,” Dr. Sørensen noted.
He also suggested that it might be interesting to look into the combination of topotecan and alisertib versus topotecan alone in c-Myc-positive patients.
The study was funded by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company. Dr. Owonikoko disclosed consulting for Takeda and several other pharmaceutical companies. Dr. Sørensen did not have disclosures.
VIENNA – The investigational agent alisertib plus paclitaxel improved progression-free survival (PFS), compared with paclitaxel plus placebo, in a randomized, double-blind, phase II study of patients with relapsed or refractory small-cell lung cancer (SCLC).
The median PFS was 3.32 months with alisertib/paclitaxel and 2.17 months with paclitaxel/placebo, giving an overall 30% improvement with the combination (hazard ratio, 0.71; 95% confidence interval, 0.509-0.985; P = .038).
“c-Myc protein expression showed a strong association with improved PFS, despite the small number of evaluable patients,” study investigator Taofeek Owonikoko, MD, of Emory University, Atlanta, said at the World Conference on Lung Cancer.
Amplification and overexpression of c-Myc is a strong oncogenic driver in many cancers, he explained. Around 18%-31% of SCLCs overexpress the protein, and it is often found in patients with chemorefractory disease, he said.
In the study, longer PFS was achieved in patients treated with alisertib/paclitaxel than in those given placebo/paclitaxel if they were c-Myc positive (4.64 vs. 2.27 months; HR, 0.29). Conversely, patients who were c-Myc negative had a shorter PFS with the combination (3.32 vs. 5.16 months; HR, 11.8).
“A prospective study is needed to further validate the predictive value of c-Myc in the clinic,” Dr. Owonikoko said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
Alisertib is an aurora A kinase inhibitor that has already been shown to have antitumor activity in patients with solid tumors, including those with SCLC (Lancet Oncol. 2015;16[4]:395-405).
The current phase II study was designed to evaluate the efficacy and safety of alisertib in combination with paclitaxel, compared with placebo plus paclitaxel, in a larger population of patients with SCLC who had relapsed within 6 months or did not respond to standard first-line, platinum-based chemotherapy.
Treatment was given in 28-day cycles, with patients randomized to the combination receiving alisertib at an oral, 40-mg, twice-daily dose on days 1-3, 8-10, and 15-17 and paclitaxel administered intravenously at a dose of 60 mg/m2 IV on days 1, 8, 15. Patients randomized to the control arm received a matched placebo plus paclitaxel given on the same days but at a dose of 80 mg/m2.
Overall, 178 patients were randomized, with a mean age of 62 years, and just over half (57%) were men.
Numerically higher objective response rates (22% vs. 18%), disease control rates (77 vs. 67%), and overall survival (6.87 vs. 5.58 months) also were seen with the combination over paclitaxel alone, although they did not achieve statistical significance.
Additional toxicities were observed with the combination treatment versus paclitaxel. Many of these were to be expected, Dr. Owonikoko said. Almost all (99% vs. 96%) of patients reported some type of adverse event, of which 75% and 51% were grade 3 or higher, respectively. Common any-grade adverse effects were diarrhea (59% vs. 20%), neutropenia (49% vs. 8%), anemia (44% vs. 20%), and fatigue (44% vs. 33%).
These toxicities, however, did not appear to affect patients’ quality of life, Dr. Owonikoko said, as comparable changes in quality-of-life scores using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 instrument were observed. There was even an indication that patients taking alisertib/paclitaxel might have improved lung-related symptoms, such as shortness of breath and worsening cough.
The treatment of SCLC, particularly in the second-line setting, remains challenging, observed the invited discussant for the trial Jens Benn Sørensen, MD, of the Finsen Centre at Rigshospitalet, Copenhagen.
“There have been no major improvements in the last decade and there are no targeted agents approved for use,” Dr. Sørensen said. Although that is not for lack of trying, he qualified.
When first-line therapies fail, the guideline-recommended option is to put patients back on platinum-based chemotherapy if they were sensitive to such chemotherapy. If not, then topotecan is often an appropriate, reasonably tolerated option.
“The clinical relevance of second-line paclitaxel/alisertib in all comers is questionable,” he said. The PFS improvement of 1.2 months in this phase II study seems “mostly at the same level” when comparing trials of second-line, single-agent topotecan.
“However, the use of c-Myc as a predictor for efficacy seems very promising and should clearly be explored,” Dr. Sørensen noted.
He also suggested that it might be interesting to look into the combination of topotecan and alisertib versus topotecan alone in c-Myc-positive patients.
The study was funded by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company. Dr. Owonikoko disclosed consulting for Takeda and several other pharmaceutical companies. Dr. Sørensen did not have disclosures.
VIENNA – The investigational agent alisertib plus paclitaxel improved progression-free survival (PFS), compared with paclitaxel plus placebo, in a randomized, double-blind, phase II study of patients with relapsed or refractory small-cell lung cancer (SCLC).
The median PFS was 3.32 months with alisertib/paclitaxel and 2.17 months with paclitaxel/placebo, giving an overall 30% improvement with the combination (hazard ratio, 0.71; 95% confidence interval, 0.509-0.985; P = .038).
“c-Myc protein expression showed a strong association with improved PFS, despite the small number of evaluable patients,” study investigator Taofeek Owonikoko, MD, of Emory University, Atlanta, said at the World Conference on Lung Cancer.
Amplification and overexpression of c-Myc is a strong oncogenic driver in many cancers, he explained. Around 18%-31% of SCLCs overexpress the protein, and it is often found in patients with chemorefractory disease, he said.
In the study, longer PFS was achieved in patients treated with alisertib/paclitaxel than in those given placebo/paclitaxel if they were c-Myc positive (4.64 vs. 2.27 months; HR, 0.29). Conversely, patients who were c-Myc negative had a shorter PFS with the combination (3.32 vs. 5.16 months; HR, 11.8).
“A prospective study is needed to further validate the predictive value of c-Myc in the clinic,” Dr. Owonikoko said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.
Alisertib is an aurora A kinase inhibitor that has already been shown to have antitumor activity in patients with solid tumors, including those with SCLC (Lancet Oncol. 2015;16[4]:395-405).
The current phase II study was designed to evaluate the efficacy and safety of alisertib in combination with paclitaxel, compared with placebo plus paclitaxel, in a larger population of patients with SCLC who had relapsed within 6 months or did not respond to standard first-line, platinum-based chemotherapy.
Treatment was given in 28-day cycles, with patients randomized to the combination receiving alisertib at an oral, 40-mg, twice-daily dose on days 1-3, 8-10, and 15-17 and paclitaxel administered intravenously at a dose of 60 mg/m2 IV on days 1, 8, 15. Patients randomized to the control arm received a matched placebo plus paclitaxel given on the same days but at a dose of 80 mg/m2.
Overall, 178 patients were randomized, with a mean age of 62 years, and just over half (57%) were men.
Numerically higher objective response rates (22% vs. 18%), disease control rates (77 vs. 67%), and overall survival (6.87 vs. 5.58 months) also were seen with the combination over paclitaxel alone, although they did not achieve statistical significance.
Additional toxicities were observed with the combination treatment versus paclitaxel. Many of these were to be expected, Dr. Owonikoko said. Almost all (99% vs. 96%) of patients reported some type of adverse event, of which 75% and 51% were grade 3 or higher, respectively. Common any-grade adverse effects were diarrhea (59% vs. 20%), neutropenia (49% vs. 8%), anemia (44% vs. 20%), and fatigue (44% vs. 33%).
These toxicities, however, did not appear to affect patients’ quality of life, Dr. Owonikoko said, as comparable changes in quality-of-life scores using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 instrument were observed. There was even an indication that patients taking alisertib/paclitaxel might have improved lung-related symptoms, such as shortness of breath and worsening cough.
The treatment of SCLC, particularly in the second-line setting, remains challenging, observed the invited discussant for the trial Jens Benn Sørensen, MD, of the Finsen Centre at Rigshospitalet, Copenhagen.
“There have been no major improvements in the last decade and there are no targeted agents approved for use,” Dr. Sørensen said. Although that is not for lack of trying, he qualified.
When first-line therapies fail, the guideline-recommended option is to put patients back on platinum-based chemotherapy if they were sensitive to such chemotherapy. If not, then topotecan is often an appropriate, reasonably tolerated option.
“The clinical relevance of second-line paclitaxel/alisertib in all comers is questionable,” he said. The PFS improvement of 1.2 months in this phase II study seems “mostly at the same level” when comparing trials of second-line, single-agent topotecan.
“However, the use of c-Myc as a predictor for efficacy seems very promising and should clearly be explored,” Dr. Sørensen noted.
He also suggested that it might be interesting to look into the combination of topotecan and alisertib versus topotecan alone in c-Myc-positive patients.
The study was funded by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company. Dr. Owonikoko disclosed consulting for Takeda and several other pharmaceutical companies. Dr. Sørensen did not have disclosures.
AT WCLC 2016
Key clinical point: Alisertib/paclitaxel is an investigational combination that was tested for the treatment of relapsed or refractory small-cell lung cancer (SCLC).
Major finding: Improved progression-free survival was seen with the combination versus paclitaxel alone (3.2 vs. 2.17 months, P less than .038).
Data source: Randomized, double-blind, multicenter, phase II study of alisertib/paclitaxel versus placebo/paclitaxel in 178 patients with relapsed or refractory SCLC.
Disclosures: The study was funded by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company. Dr. Owonikoko disclosed consulting for Takeda and several other pharmaceutical companies. Dr. Sørensen had no conflicts of interest to disclose.