Patricia Goodemote, MD

Evidence summary

Upper extremity venous thrombosis (UEVT)—which typically refers to thrombosis of the brachial, axillary, or subclavian veins—accounts for approximately 10% of all cases of venous thromboembolism.¹ UEVT can occur spontaneously (Paget-Schroetter syndrome) or develop as a complication of cancer or in-dwelling medical devices (such as long-term central venous catheters).

Although significant evidence-based data exist on treatment of lower extremity venous thrombosis, no good-quality studies specifically address management of UEVT. Review of the current literature revealed several small studies that compared various treatment strategies.

Thrombolytics may work better than anticoagulants in some patients
A small retrospective study randomized 20 patients with UEVT to either treatment with anticoagulant therapy with heparin and warfarin (n=11) or thrombolytic therapy (n=9).² After a mean follow-up period of 81.7 months for the anticoagulation group and 52.1 months for the thrombolytic group, 4 more patients in the thrombolytic group achieved complete clinical recovery and vein patency than in the anticoagulant group (P=.04). When patients who recovered completely were added to those who showed some clinical improvement, 89% of the thrombolytic therapy group had satisfactory outcomes, compared with 36% of the anticoagulant group (P=.028).

Another small retrospective study looked at 10 consecutive patients with UEVT who were treated with either anticoagulant therapy (n=6) or thrombolytics (n=4).³ Fifty percent of patients treated with anticoagulants experienced partial or complete improvement in symptoms, whereas 100% of patients treated with thrombolytics had partial or complete resolution of both symptoms and thrombi.

Overall, both studies raise the possibility that thrombolytic therapy is more effective than anticoagulation therapy in certain patients. The studies evaluated only active patients, 23 to 58 years of age, who had no contraindications to thrombolytic therapy. Neither study reported data on long-term outcomes such as recurrences, bleeding, or post-thrombotic sequelae.

Surgery may avoid long-term anticoagulation
Two case studies evaluated treatment of UEVT with thrombolytic therapy followed by various surgical interventions (angioplasty, thrombectomy, decompression via first rib resection or anterior scalenectomy, and venous bypass).^4,5 The first study reported that 8 of 9 patients who underwent first-rib resection and 1 of 2 who underwent scalenectomy were free of residual symptoms at follow-up (mean 2 years, range 6 months to 5 years).⁴ All patients were treated with thrombolytics before surgery.

The second study demonstrated that 50% of the patients treated with a surgical intervention without thrombolysis had complete symptom relief, while the remaining 50% reported relief from pain but still had occasional swelling.⁵ Although more invasive, surgery may eliminate the need for long-term anticoagulation therapy and enable a more rapid return to normal activities.

Data on vena cava filters are limited
Data supporting superior vena cava Green-field filters to treat UEVT are extremely limited. Of 6 patients with contraindications to anticoagulation therapy who were treated with a Greenfield filter, none had clinical evidence of pulmonary embolism at 14 months.⁶ The study reported no data regarding long-term sequelae or effects of the UEVT on the patients’ upper extremity.⁶

When in doubt, don’t (necessarily) take it out
For patients with central venous catheter-related deep vein thrombosis, taking out the catheter as part of treatment is controversial and should depend on clinical symptoms, the reason for the catheter, and duration of use, as well as physician judgment.⁷ No RCTs have studied the effects of catheter removal as part of initial treatment. Current guidelines recommend removing the catheter from patients with persistent symptoms who have failed anticoagulant or thrombolytic treatment.¹

Recommendations

The American College of Chest Physicians recommends therapeutic doses of intravenous unfractionated heparin, low-molecular-weight heparin, or fondaparinux for initial treatment of UEVT, followed by at least 3 months of treatment with a vitamin K antagonist.¹ The organization also suggests that surgical thrombectomy, superior vena caval filters, thrombolytic therapy, or catheter extraction may benefit selected patients.

Acknowledgement
The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Upper extremity venous thrombosis (UEVT)—which typically refers to thrombosis of the brachial, axillary, or subclavian veins—accounts for approximately 10% of all cases of venous thromboembolism.¹ UEVT can occur spontaneously (Paget-Schroetter syndrome) or develop as a complication of cancer or in-dwelling medical devices (such as long-term central venous catheters).

Although significant evidence-based data exist on treatment of lower extremity venous thrombosis, no good-quality studies specifically address management of UEVT. Review of the current literature revealed several small studies that compared various treatment strategies.

Thrombolytics may work better than anticoagulants in some patients
A small retrospective study randomized 20 patients with UEVT to either treatment with anticoagulant therapy with heparin and warfarin (n=11) or thrombolytic therapy (n=9).² After a mean follow-up period of 81.7 months for the anticoagulation group and 52.1 months for the thrombolytic group, 4 more patients in the thrombolytic group achieved complete clinical recovery and vein patency than in the anticoagulant group (P=.04). When patients who recovered completely were added to those who showed some clinical improvement, 89% of the thrombolytic therapy group had satisfactory outcomes, compared with 36% of the anticoagulant group (P=.028).

Another small retrospective study looked at 10 consecutive patients with UEVT who were treated with either anticoagulant therapy (n=6) or thrombolytics (n=4).³ Fifty percent of patients treated with anticoagulants experienced partial or complete improvement in symptoms, whereas 100% of patients treated with thrombolytics had partial or complete resolution of both symptoms and thrombi.

Overall, both studies raise the possibility that thrombolytic therapy is more effective than anticoagulation therapy in certain patients. The studies evaluated only active patients, 23 to 58 years of age, who had no contraindications to thrombolytic therapy. Neither study reported data on long-term outcomes such as recurrences, bleeding, or post-thrombotic sequelae.

Surgery may avoid long-term anticoagulation
Two case studies evaluated treatment of UEVT with thrombolytic therapy followed by various surgical interventions (angioplasty, thrombectomy, decompression via first rib resection or anterior scalenectomy, and venous bypass).^4,5 The first study reported that 8 of 9 patients who underwent first-rib resection and 1 of 2 who underwent scalenectomy were free of residual symptoms at follow-up (mean 2 years, range 6 months to 5 years).⁴ All patients were treated with thrombolytics before surgery.

The second study demonstrated that 50% of the patients treated with a surgical intervention without thrombolysis had complete symptom relief, while the remaining 50% reported relief from pain but still had occasional swelling.⁵ Although more invasive, surgery may eliminate the need for long-term anticoagulation therapy and enable a more rapid return to normal activities.

Data on vena cava filters are limited
Data supporting superior vena cava Green-field filters to treat UEVT are extremely limited. Of 6 patients with contraindications to anticoagulation therapy who were treated with a Greenfield filter, none had clinical evidence of pulmonary embolism at 14 months.⁶ The study reported no data regarding long-term sequelae or effects of the UEVT on the patients’ upper extremity.⁶

When in doubt, don’t (necessarily) take it out
For patients with central venous catheter-related deep vein thrombosis, taking out the catheter as part of treatment is controversial and should depend on clinical symptoms, the reason for the catheter, and duration of use, as well as physician judgment.⁷ No RCTs have studied the effects of catheter removal as part of initial treatment. Current guidelines recommend removing the catheter from patients with persistent symptoms who have failed anticoagulant or thrombolytic treatment.¹

Recommendations

The American College of Chest Physicians recommends therapeutic doses of intravenous unfractionated heparin, low-molecular-weight heparin, or fondaparinux for initial treatment of UEVT, followed by at least 3 months of treatment with a vitamin K antagonist.¹ The organization also suggests that surgical thrombectomy, superior vena caval filters, thrombolytic therapy, or catheter extraction may benefit selected patients.

Acknowledgement
The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Upper extremity venous thrombosis (UEVT)—which typically refers to thrombosis of the brachial, axillary, or subclavian veins—accounts for approximately 10% of all cases of venous thromboembolism.¹ UEVT can occur spontaneously (Paget-Schroetter syndrome) or develop as a complication of cancer or in-dwelling medical devices (such as long-term central venous catheters).

Although significant evidence-based data exist on treatment of lower extremity venous thrombosis, no good-quality studies specifically address management of UEVT. Review of the current literature revealed several small studies that compared various treatment strategies.

Thrombolytics may work better than anticoagulants in some patients
A small retrospective study randomized 20 patients with UEVT to either treatment with anticoagulant therapy with heparin and warfarin (n=11) or thrombolytic therapy (n=9).² After a mean follow-up period of 81.7 months for the anticoagulation group and 52.1 months for the thrombolytic group, 4 more patients in the thrombolytic group achieved complete clinical recovery and vein patency than in the anticoagulant group (P=.04). When patients who recovered completely were added to those who showed some clinical improvement, 89% of the thrombolytic therapy group had satisfactory outcomes, compared with 36% of the anticoagulant group (P=.028).

Another small retrospective study looked at 10 consecutive patients with UEVT who were treated with either anticoagulant therapy (n=6) or thrombolytics (n=4).³ Fifty percent of patients treated with anticoagulants experienced partial or complete improvement in symptoms, whereas 100% of patients treated with thrombolytics had partial or complete resolution of both symptoms and thrombi.

Overall, both studies raise the possibility that thrombolytic therapy is more effective than anticoagulation therapy in certain patients. The studies evaluated only active patients, 23 to 58 years of age, who had no contraindications to thrombolytic therapy. Neither study reported data on long-term outcomes such as recurrences, bleeding, or post-thrombotic sequelae.

Surgery may avoid long-term anticoagulation
Two case studies evaluated treatment of UEVT with thrombolytic therapy followed by various surgical interventions (angioplasty, thrombectomy, decompression via first rib resection or anterior scalenectomy, and venous bypass).^4,5 The first study reported that 8 of 9 patients who underwent first-rib resection and 1 of 2 who underwent scalenectomy were free of residual symptoms at follow-up (mean 2 years, range 6 months to 5 years).⁴ All patients were treated with thrombolytics before surgery.

The second study demonstrated that 50% of the patients treated with a surgical intervention without thrombolysis had complete symptom relief, while the remaining 50% reported relief from pain but still had occasional swelling.⁵ Although more invasive, surgery may eliminate the need for long-term anticoagulation therapy and enable a more rapid return to normal activities.

Data on vena cava filters are limited
Data supporting superior vena cava Green-field filters to treat UEVT are extremely limited. Of 6 patients with contraindications to anticoagulation therapy who were treated with a Greenfield filter, none had clinical evidence of pulmonary embolism at 14 months.⁶ The study reported no data regarding long-term sequelae or effects of the UEVT on the patients’ upper extremity.⁶

When in doubt, don’t (necessarily) take it out
For patients with central venous catheter-related deep vein thrombosis, taking out the catheter as part of treatment is controversial and should depend on clinical symptoms, the reason for the catheter, and duration of use, as well as physician judgment.⁷ No RCTs have studied the effects of catheter removal as part of initial treatment. Current guidelines recommend removing the catheter from patients with persistent symptoms who have failed anticoagulant or thrombolytic treatment.¹

Recommendations

The American College of Chest Physicians recommends therapeutic doses of intravenous unfractionated heparin, low-molecular-weight heparin, or fondaparinux for initial treatment of UEVT, followed by at least 3 months of treatment with a vitamin K antagonist.¹ The organization also suggests that surgical thrombectomy, superior vena caval filters, thrombolytic therapy, or catheter extraction may benefit selected patients.

Acknowledgement
The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Ligamentous knee injuries from trauma are common. In 2003, patients made about 19.4 million visits to the doctor because of knee problems.¹ The ACL is the most often injured knee ligament. The incidence of ACL injury is approximately 200,000 annually in the United States; 100,000 ACL reconstructions are performed each year.^2,3 A complete tear of the ACL can lead to significant knee instability and, unless repaired, may limit physical activity and quality of life.

In contrast, PCL injuries don’t often cause significant instability and generally respond to nonsurgical treatment; they have less impact on a patient’s quality of life. Surgery for PCL injury is usually reserved for elite athletes and unstable injuries. MCL and LCL injuries also are generally treated nonsurgically with rehabilitation and bracing; they normally don’t require arthroscopic evaluation and repair.

An effective alternative to arthroscopy
Arthroscopy with direct visualization of the ligamentous structures is considered the gold standard for diagnosing intra-articular ligamentous knee injuries, but it’s invasive and costly. Although clinical examination is helpful in identifying injured ligaments, it may lead to unnecessary arthroscopies when used alone because of the high false-positive rate. MRI has been shown to be an effective tool for accurately diagnosing ligamentous knee injury.^2,3

MRI offers high sensitivity for detecting ACL, PCL tears
Several prospective studies have compared MRI with arthroscopy for diagnosing ACL and PCL tears (TABLE).^4-8 All enrolled patients had sustained knee trauma and had had a clinical exam that suggested ligamentous injury. MRI and arthroscopy were performed regardless of MRI findings. The surgeons performing arthroscopy were blinded to the MRI results.

Although MRI equipment and techniques varied in all the studies, the sensitivity and specificity remained consistently high for detecting ACL injuries. Thin-slice views, special oblique views, and a fast spin-echo technique didn’t improve either the sensitivity or specificity compared with conventional techniques or views, nor did decreasing the time interval from injury to imaging.^5,9,10 Prospective studies of PCL injuries also revealed high sensitivity and specificity with MRI.

No data on MRI for MCL and LCL injuries
No prospective studies are available to assess the accuracy of MRI for suspected MCL and LCL injuries; however, MRI would likely not affect treatment or clinical outcomes, as both of these injuries are typically treated nonsurgically.

Recommendations

The American Academy of Orthopaedic Surgeons supports MRI as an effective tool for evaluating knee injury,¹ and offers recommendations and guidelines for treating ligamentous knee injury based on the findings of clinical examination and MRI. The Academy states that MRI is invaluable in preventing unnecessary surgery, and recommends it whenever ligamentous injury is suspected.

Acknowledgements 

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Air Force medical Service or the US Air Force at large.

Evidence summary

Ligamentous knee injuries from trauma are common. In 2003, patients made about 19.4 million visits to the doctor because of knee problems.¹ The ACL is the most often injured knee ligament. The incidence of ACL injury is approximately 200,000 annually in the United States; 100,000 ACL reconstructions are performed each year.^2,3 A complete tear of the ACL can lead to significant knee instability and, unless repaired, may limit physical activity and quality of life.

In contrast, PCL injuries don’t often cause significant instability and generally respond to nonsurgical treatment; they have less impact on a patient’s quality of life. Surgery for PCL injury is usually reserved for elite athletes and unstable injuries. MCL and LCL injuries also are generally treated nonsurgically with rehabilitation and bracing; they normally don’t require arthroscopic evaluation and repair.

An effective alternative to arthroscopy
Arthroscopy with direct visualization of the ligamentous structures is considered the gold standard for diagnosing intra-articular ligamentous knee injuries, but it’s invasive and costly. Although clinical examination is helpful in identifying injured ligaments, it may lead to unnecessary arthroscopies when used alone because of the high false-positive rate. MRI has been shown to be an effective tool for accurately diagnosing ligamentous knee injury.^2,3

MRI offers high sensitivity for detecting ACL, PCL tears
Several prospective studies have compared MRI with arthroscopy for diagnosing ACL and PCL tears (TABLE).^4-8 All enrolled patients had sustained knee trauma and had had a clinical exam that suggested ligamentous injury. MRI and arthroscopy were performed regardless of MRI findings. The surgeons performing arthroscopy were blinded to the MRI results.

Although MRI equipment and techniques varied in all the studies, the sensitivity and specificity remained consistently high for detecting ACL injuries. Thin-slice views, special oblique views, and a fast spin-echo technique didn’t improve either the sensitivity or specificity compared with conventional techniques or views, nor did decreasing the time interval from injury to imaging.^5,9,10 Prospective studies of PCL injuries also revealed high sensitivity and specificity with MRI.

No data on MRI for MCL and LCL injuries
No prospective studies are available to assess the accuracy of MRI for suspected MCL and LCL injuries; however, MRI would likely not affect treatment or clinical outcomes, as both of these injuries are typically treated nonsurgically.

Recommendations

The American Academy of Orthopaedic Surgeons supports MRI as an effective tool for evaluating knee injury,¹ and offers recommendations and guidelines for treating ligamentous knee injury based on the findings of clinical examination and MRI. The Academy states that MRI is invaluable in preventing unnecessary surgery, and recommends it whenever ligamentous injury is suspected.

Acknowledgements 

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Air Force medical Service or the US Air Force at large.

Evidence summary

Ligamentous knee injuries from trauma are common. In 2003, patients made about 19.4 million visits to the doctor because of knee problems.¹ The ACL is the most often injured knee ligament. The incidence of ACL injury is approximately 200,000 annually in the United States; 100,000 ACL reconstructions are performed each year.^2,3 A complete tear of the ACL can lead to significant knee instability and, unless repaired, may limit physical activity and quality of life.

In contrast, PCL injuries don’t often cause significant instability and generally respond to nonsurgical treatment; they have less impact on a patient’s quality of life. Surgery for PCL injury is usually reserved for elite athletes and unstable injuries. MCL and LCL injuries also are generally treated nonsurgically with rehabilitation and bracing; they normally don’t require arthroscopic evaluation and repair.

An effective alternative to arthroscopy
Arthroscopy with direct visualization of the ligamentous structures is considered the gold standard for diagnosing intra-articular ligamentous knee injuries, but it’s invasive and costly. Although clinical examination is helpful in identifying injured ligaments, it may lead to unnecessary arthroscopies when used alone because of the high false-positive rate. MRI has been shown to be an effective tool for accurately diagnosing ligamentous knee injury.^2,3

MRI offers high sensitivity for detecting ACL, PCL tears
Several prospective studies have compared MRI with arthroscopy for diagnosing ACL and PCL tears (TABLE).^4-8 All enrolled patients had sustained knee trauma and had had a clinical exam that suggested ligamentous injury. MRI and arthroscopy were performed regardless of MRI findings. The surgeons performing arthroscopy were blinded to the MRI results.

Although MRI equipment and techniques varied in all the studies, the sensitivity and specificity remained consistently high for detecting ACL injuries. Thin-slice views, special oblique views, and a fast spin-echo technique didn’t improve either the sensitivity or specificity compared with conventional techniques or views, nor did decreasing the time interval from injury to imaging.^5,9,10 Prospective studies of PCL injuries also revealed high sensitivity and specificity with MRI.

No data on MRI for MCL and LCL injuries
No prospective studies are available to assess the accuracy of MRI for suspected MCL and LCL injuries; however, MRI would likely not affect treatment or clinical outcomes, as both of these injuries are typically treated nonsurgically.

Recommendations

The American Academy of Orthopaedic Surgeons supports MRI as an effective tool for evaluating knee injury,¹ and offers recommendations and guidelines for treating ligamentous knee injury based on the findings of clinical examination and MRI. The Academy states that MRI is invaluable in preventing unnecessary surgery, and recommends it whenever ligamentous injury is suspected.

Acknowledgements 

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Air Force medical Service or the US Air Force at large.

Evidence summary

Breast augmentation is one of the most popular plastic surgeries in the United States; an estimated 291,350 such procedures were performed in 2005.¹ Breast cancer occurs in 1 of every 8 women; a projected 32,000 women who received breast implants in 2003 will develop cancer.¹ Available research has focused on retrospective and prospective designs because of the ethical limitations of experimental designs. No US studies directly compare mammography with alternate screening methods, such as sonography or magnetic resonance imaging.

With implants: Lower screening sensitivity but similar prognosis

Studies show that augmentation decreases the sensitivity of screening mammography but doesn’t affect breast cancer prognosis.² A 2004 prospective cohort study of 986,270 women found that, among asymptomatic women diagnosed with breast cancer (40 augmented, 238 nonaugmented), the sensitivity of screening mammograms was lower in women with breast implants (45%; 95% confidence interval [CI], 29.3%–61.5%) than those without (66.8%; 95% CI, 60.4%–72.8%); P=.008).² Similarly, in symptomatic women diagnosed with breast cancer (41 augmented, 145 nonaugmented), screening sensitivity was lower in the augmented women (73.2%) than the nonaugmented women (81.4%)—although the results weren’t significant (P=.25).

Despite lower screening sensitivity, breast tumors in asymptomatic women, whether augmented or not, had similar characteristics, except for larger tumor size (3 mm) at diagnosis in augmented women. Symptomatic women with breast implants had cancers that were smaller, lower-grade, and more likely to be estrogen receptor dependent and invasive (P=.052) compared with nonaugmented women. The authors concluded that augmentation doesn’t influence the prognostic characteristics of tumors, and they recommended screening mammography at appropriate intervals.

Two other prospective cohort studies produced similar findings. A 2006 study of 4082 breast cancer patients concluded that mammography yielded a false-negative rate of 41.4% in augmented patients compared with 8.8% in nonaugmented patients (P<.0001).³ However, both augmented (n=129) and nonaugmented (n=3953) women had a comparable prognosis at diagnosis. The authors of the studies suggested diagnostic mammography for augmented patients and correlation with physical exam findings.

An earlier study of 2956 cancer patients found that mammography detected an abnormal breast mass in 66.3% of augmented women compared with 94.6% of nonaugmented women (P=.001).⁴ No significant differences were noted in cancer characteristics at diagnosis or survival rates (P=.78). The authors of this study concluded that mammography should be used for augmented women until a more effective screening tool is found.

Sonography vs mammography: The jury is still out

Although studies comparing screening methods have not been performed in the United States, a small Taiwanese study directly compared ultrasound to mammography in 105 women without breast implants. This retrospective cohort study found sonography to be a more useful diagnostic tool than mammography in Taiwanese women.⁵ Sonography had the highest sensitivity (87.5%) compared to physical examination (50.0%) and mammography (25.5%).

Sonography was recommended as the imaging tool for Asian women with smaller, denser breasts. However, it is unclear whether this result applies to US women or women who have undergone breast augmentation surgery.

Training in implant imaging is needed

Mammography appears to be the most effective screening method for women with breast implants. Despite the small differences in cancer characteristics at diagnosis between augmented and nonaugmented women, overall prognosis and survival rates are no different.^1-3,6 This is true whether a screening mammogram or diagnostic mammogram is used. In any case, all available findings suggest that clinicians who perform mammography should be trained in imaging the augmented breast.^6-8

Recommendations

The National Cancer Institute indicates that the best screening method for augmented women is mammography performed at a facility with employees trained in implant imaging.⁷ The American College of Radiology’s practice guidelines affirm that mammography is the best imaging tool available.⁸ The American College of Obstetrics and Gynecology and the US Preventive Services Task Force don’t comment on screening augmented women.

Acknowledgments

The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Breast augmentation is one of the most popular plastic surgeries in the United States; an estimated 291,350 such procedures were performed in 2005.¹ Breast cancer occurs in 1 of every 8 women; a projected 32,000 women who received breast implants in 2003 will develop cancer.¹ Available research has focused on retrospective and prospective designs because of the ethical limitations of experimental designs. No US studies directly compare mammography with alternate screening methods, such as sonography or magnetic resonance imaging.

With implants: Lower screening sensitivity but similar prognosis

Studies show that augmentation decreases the sensitivity of screening mammography but doesn’t affect breast cancer prognosis.² A 2004 prospective cohort study of 986,270 women found that, among asymptomatic women diagnosed with breast cancer (40 augmented, 238 nonaugmented), the sensitivity of screening mammograms was lower in women with breast implants (45%; 95% confidence interval [CI], 29.3%–61.5%) than those without (66.8%; 95% CI, 60.4%–72.8%); P=.008).² Similarly, in symptomatic women diagnosed with breast cancer (41 augmented, 145 nonaugmented), screening sensitivity was lower in the augmented women (73.2%) than the nonaugmented women (81.4%)—although the results weren’t significant (P=.25).

Despite lower screening sensitivity, breast tumors in asymptomatic women, whether augmented or not, had similar characteristics, except for larger tumor size (3 mm) at diagnosis in augmented women. Symptomatic women with breast implants had cancers that were smaller, lower-grade, and more likely to be estrogen receptor dependent and invasive (P=.052) compared with nonaugmented women. The authors concluded that augmentation doesn’t influence the prognostic characteristics of tumors, and they recommended screening mammography at appropriate intervals.

Two other prospective cohort studies produced similar findings. A 2006 study of 4082 breast cancer patients concluded that mammography yielded a false-negative rate of 41.4% in augmented patients compared with 8.8% in nonaugmented patients (P<.0001).³ However, both augmented (n=129) and nonaugmented (n=3953) women had a comparable prognosis at diagnosis. The authors of the studies suggested diagnostic mammography for augmented patients and correlation with physical exam findings.

An earlier study of 2956 cancer patients found that mammography detected an abnormal breast mass in 66.3% of augmented women compared with 94.6% of nonaugmented women (P=.001).⁴ No significant differences were noted in cancer characteristics at diagnosis or survival rates (P=.78). The authors of this study concluded that mammography should be used for augmented women until a more effective screening tool is found.

Sonography vs mammography: The jury is still out

Although studies comparing screening methods have not been performed in the United States, a small Taiwanese study directly compared ultrasound to mammography in 105 women without breast implants. This retrospective cohort study found sonography to be a more useful diagnostic tool than mammography in Taiwanese women.⁵ Sonography had the highest sensitivity (87.5%) compared to physical examination (50.0%) and mammography (25.5%).

Sonography was recommended as the imaging tool for Asian women with smaller, denser breasts. However, it is unclear whether this result applies to US women or women who have undergone breast augmentation surgery.

Training in implant imaging is needed

Mammography appears to be the most effective screening method for women with breast implants. Despite the small differences in cancer characteristics at diagnosis between augmented and nonaugmented women, overall prognosis and survival rates are no different.^1-3,6 This is true whether a screening mammogram or diagnostic mammogram is used. In any case, all available findings suggest that clinicians who perform mammography should be trained in imaging the augmented breast.^6-8

Recommendations

The National Cancer Institute indicates that the best screening method for augmented women is mammography performed at a facility with employees trained in implant imaging.⁷ The American College of Radiology’s practice guidelines affirm that mammography is the best imaging tool available.⁸ The American College of Obstetrics and Gynecology and the US Preventive Services Task Force don’t comment on screening augmented women.

Acknowledgments

The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Breast augmentation is one of the most popular plastic surgeries in the United States; an estimated 291,350 such procedures were performed in 2005.¹ Breast cancer occurs in 1 of every 8 women; a projected 32,000 women who received breast implants in 2003 will develop cancer.¹ Available research has focused on retrospective and prospective designs because of the ethical limitations of experimental designs. No US studies directly compare mammography with alternate screening methods, such as sonography or magnetic resonance imaging.

With implants: Lower screening sensitivity but similar prognosis

Studies show that augmentation decreases the sensitivity of screening mammography but doesn’t affect breast cancer prognosis.² A 2004 prospective cohort study of 986,270 women found that, among asymptomatic women diagnosed with breast cancer (40 augmented, 238 nonaugmented), the sensitivity of screening mammograms was lower in women with breast implants (45%; 95% confidence interval [CI], 29.3%–61.5%) than those without (66.8%; 95% CI, 60.4%–72.8%); P=.008).² Similarly, in symptomatic women diagnosed with breast cancer (41 augmented, 145 nonaugmented), screening sensitivity was lower in the augmented women (73.2%) than the nonaugmented women (81.4%)—although the results weren’t significant (P=.25).

Despite lower screening sensitivity, breast tumors in asymptomatic women, whether augmented or not, had similar characteristics, except for larger tumor size (3 mm) at diagnosis in augmented women. Symptomatic women with breast implants had cancers that were smaller, lower-grade, and more likely to be estrogen receptor dependent and invasive (P=.052) compared with nonaugmented women. The authors concluded that augmentation doesn’t influence the prognostic characteristics of tumors, and they recommended screening mammography at appropriate intervals.

Two other prospective cohort studies produced similar findings. A 2006 study of 4082 breast cancer patients concluded that mammography yielded a false-negative rate of 41.4% in augmented patients compared with 8.8% in nonaugmented patients (P<.0001).³ However, both augmented (n=129) and nonaugmented (n=3953) women had a comparable prognosis at diagnosis. The authors of the studies suggested diagnostic mammography for augmented patients and correlation with physical exam findings.

An earlier study of 2956 cancer patients found that mammography detected an abnormal breast mass in 66.3% of augmented women compared with 94.6% of nonaugmented women (P=.001).⁴ No significant differences were noted in cancer characteristics at diagnosis or survival rates (P=.78). The authors of this study concluded that mammography should be used for augmented women until a more effective screening tool is found.

Sonography vs mammography: The jury is still out

Although studies comparing screening methods have not been performed in the United States, a small Taiwanese study directly compared ultrasound to mammography in 105 women without breast implants. This retrospective cohort study found sonography to be a more useful diagnostic tool than mammography in Taiwanese women.⁵ Sonography had the highest sensitivity (87.5%) compared to physical examination (50.0%) and mammography (25.5%).

Sonography was recommended as the imaging tool for Asian women with smaller, denser breasts. However, it is unclear whether this result applies to US women or women who have undergone breast augmentation surgery.

Training in implant imaging is needed

Mammography appears to be the most effective screening method for women with breast implants. Despite the small differences in cancer characteristics at diagnosis between augmented and nonaugmented women, overall prognosis and survival rates are no different.^1-3,6 This is true whether a screening mammogram or diagnostic mammogram is used. In any case, all available findings suggest that clinicians who perform mammography should be trained in imaging the augmented breast.^6-8

Recommendations

The National Cancer Institute indicates that the best screening method for augmented women is mammography performed at a facility with employees trained in implant imaging.⁷ The American College of Radiology’s practice guidelines affirm that mammography is the best imaging tool available.⁸ The American College of Obstetrics and Gynecology and the US Preventive Services Task Force don’t comment on screening augmented women.

Acknowledgments

The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

The use of DMARDs has become standard of care for rheumatoid arthritis, for both therapy and prevention of progression of this debilitating disease. However, the use of DMARDs in nonrheumatoid rheumatologic disease is still under investigation, and at this point, the use of DMARDs as first-line therapy is not recommended; however, second-line therapy with DMARDs is common.

For psoriatic arthritis, DMARDs are beneficial as a second-line therapy

A Cochrane systematic review identified 13 randomized controlled trials enrolling a combined 1022 patients with psoriatic arthritis randomly assigned to receive a DMARD—methotrexate, sulfasalazine (Azulfidine), azathioprine (Imuran/ Azasan), or etretinate (Tegison; no longer available in the US)—compared with placebo.² All agents were better than placebo; however, only 2 agents (parenteral high-dose methotrexate and sulfasalazine) had clinically important benefits for more than half the patients. The studies were too small to establish toxicity or to evaluate the other agents.

NSAIDs are still the preferred first-line therapy, concluded a recent publication on the treatment of psoriatic arthritis, which looked at 54 different studies; however, second-line therapy could include methotrexate, sulfasalazine, etanercept (Enbrel), infliximab (Remicade), cyclosporine, or combination therapy.³ Sulfasalazine appeared to be clinically beneficial for peripheral psoriatic arthritis.

Etanercept vs placebo. An initial study (60 patients) of etanercept vs placebo among patients who were permitted to stay on methotrexate or prednisone showed a response rate of 87% vs 23% (P<.0001; number needed to treat [NNT]=1.56).⁴

Infliximab vs placebo. A study of infliximab vs placebo involving 104 patients had similar results, with good response in 65% vs 10% (NNT=1.81) at 16 weeks; infliximab also inhibited radiographic progression by 22%.⁵

Cyclosporine. Although it is effective, reserve cyclosporine for patients who do not improve on other regimens, because of its nephrotoxicity.³

DMARDs show some benefit in treating ankylosing spondylitis

Two recent Cochrane systematic reviews on ankylosing spondylitis examined the use of sulfasalazine and methotrexate as second-line agents.^6,7 Eleven trials were included in the sulfasalazine analysis, with a total of 895 patients. Sulfasalazine demonstrated some benefit in reducing erythrocyte sedimentation rates (ESRs) and morning stiffness, but there was no evidence that the drug reduced pain or improved physical function, spinal mobility, or rate of enthesitis. Sulfasalazine was well tolerated and may be useful in early mild disease for patients with peripheral arthritis and high ESRs. On the other hand, evidence was insufficient to determine whether methotrexate benefited patients with ankylosing spondylitis.

In other trials, infliximab and etanercept showed good potential for benefit in treating ankylosing spondylitis.

One study of infliximab vs placebo showed 61.2% vs 19.2% patients with good clinical benefit at 24 weeks and only mild or moderate adverse events (P<.001; NNT=2.38).⁸

Similarly, a smaller study (84 patients) showed that 60% of patients on etanercept vs 20% on placebo had good clinical benefit at only 12 weeks (P<.001, NNT=2.5).⁹

For other rheumatic diseases, studies are mixed

Due to cyclosporine’s toxicity, less toxic DMARDs are being evaluated to replace it for treatment of other rheumatic diseases. A recent randomized controlled trial of 100 patients with antineutrophil cytoplasmic antibody–associated systemic vasculitis showed methotrexate may be able to replace cyclosporine for both induction of remission (methotrexate=89.8% vs cyclosporine=93.5%; P=.041) and maintenance of remission (69.5% vs 46.5% at 18 months; P=.023).¹⁰

Initial trials on other rheumatic diseases have been small and have had varied results. There are mixed studies on the effectiveness of adding methotrexate to corticosteroids for giant cell arteritis.^11,12

There has been no evidence of efficacy for the new TNF antagonists in either a small study on Sjögren’s syndrome (n=14)¹³ or a larger study on Wegener’s granulomatosis (n=180).¹⁴

The studies for use of DMARDs in lupus or scleroderma are of limited quality.

Recommendations from others

The Italian Society for Rheumatology consensus guidelines recommends TNF antagonists be considered in active psoriatic arthritis resistant to (a) NSAIDs, (b) at least 2 local steroid injections, and (c) at least 2 conventional DMARDs for patients with peripheral arthritis or enthesitis. They also recommend TNF antagonists be considered for psoriatic spondylitis resistant to NSAIDs.¹⁵

The Assessment in Ankylosing Spondylitis (ASAS) International Working Group and the European League Against Rheumatism (EULAR) recommendations for the treatment of ankylosing spondylitis, based on a systematic review of the literature and expert opinion, indicate that:

• There is good evidence for using NSAIDs and COX-2 inhibitors for symptomatic treatment.
• Conventional DMARDs are not well supported.
• TNF antagonists show a large benefit in both pain and function.

The ASAS/EULAR recommendation indicate that there is no evidence that any of these treatments actually modify the disease progression.¹⁶

Acknowledgments

The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the US Air Force medical service or the US Air Force at large.

Evidence summary

The use of DMARDs has become standard of care for rheumatoid arthritis, for both therapy and prevention of progression of this debilitating disease. However, the use of DMARDs in nonrheumatoid rheumatologic disease is still under investigation, and at this point, the use of DMARDs as first-line therapy is not recommended; however, second-line therapy with DMARDs is common.

For psoriatic arthritis, DMARDs are beneficial as a second-line therapy

A Cochrane systematic review identified 13 randomized controlled trials enrolling a combined 1022 patients with psoriatic arthritis randomly assigned to receive a DMARD—methotrexate, sulfasalazine (Azulfidine), azathioprine (Imuran/ Azasan), or etretinate (Tegison; no longer available in the US)—compared with placebo.² All agents were better than placebo; however, only 2 agents (parenteral high-dose methotrexate and sulfasalazine) had clinically important benefits for more than half the patients. The studies were too small to establish toxicity or to evaluate the other agents.

NSAIDs are still the preferred first-line therapy, concluded a recent publication on the treatment of psoriatic arthritis, which looked at 54 different studies; however, second-line therapy could include methotrexate, sulfasalazine, etanercept (Enbrel), infliximab (Remicade), cyclosporine, or combination therapy.³ Sulfasalazine appeared to be clinically beneficial for peripheral psoriatic arthritis.

Etanercept vs placebo. An initial study (60 patients) of etanercept vs placebo among patients who were permitted to stay on methotrexate or prednisone showed a response rate of 87% vs 23% (P<.0001; number needed to treat [NNT]=1.56).⁴

Infliximab vs placebo. A study of infliximab vs placebo involving 104 patients had similar results, with good response in 65% vs 10% (NNT=1.81) at 16 weeks; infliximab also inhibited radiographic progression by 22%.⁵

Cyclosporine. Although it is effective, reserve cyclosporine for patients who do not improve on other regimens, because of its nephrotoxicity.³

DMARDs show some benefit in treating ankylosing spondylitis

Two recent Cochrane systematic reviews on ankylosing spondylitis examined the use of sulfasalazine and methotrexate as second-line agents.^6,7 Eleven trials were included in the sulfasalazine analysis, with a total of 895 patients. Sulfasalazine demonstrated some benefit in reducing erythrocyte sedimentation rates (ESRs) and morning stiffness, but there was no evidence that the drug reduced pain or improved physical function, spinal mobility, or rate of enthesitis. Sulfasalazine was well tolerated and may be useful in early mild disease for patients with peripheral arthritis and high ESRs. On the other hand, evidence was insufficient to determine whether methotrexate benefited patients with ankylosing spondylitis.

In other trials, infliximab and etanercept showed good potential for benefit in treating ankylosing spondylitis.

One study of infliximab vs placebo showed 61.2% vs 19.2% patients with good clinical benefit at 24 weeks and only mild or moderate adverse events (P<.001; NNT=2.38).⁸

Similarly, a smaller study (84 patients) showed that 60% of patients on etanercept vs 20% on placebo had good clinical benefit at only 12 weeks (P<.001, NNT=2.5).⁹

For other rheumatic diseases, studies are mixed

Due to cyclosporine’s toxicity, less toxic DMARDs are being evaluated to replace it for treatment of other rheumatic diseases. A recent randomized controlled trial of 100 patients with antineutrophil cytoplasmic antibody–associated systemic vasculitis showed methotrexate may be able to replace cyclosporine for both induction of remission (methotrexate=89.8% vs cyclosporine=93.5%; P=.041) and maintenance of remission (69.5% vs 46.5% at 18 months; P=.023).¹⁰

Initial trials on other rheumatic diseases have been small and have had varied results. There are mixed studies on the effectiveness of adding methotrexate to corticosteroids for giant cell arteritis.^11,12

There has been no evidence of efficacy for the new TNF antagonists in either a small study on Sjögren’s syndrome (n=14)¹³ or a larger study on Wegener’s granulomatosis (n=180).¹⁴

The studies for use of DMARDs in lupus or scleroderma are of limited quality.

Recommendations from others

The Italian Society for Rheumatology consensus guidelines recommends TNF antagonists be considered in active psoriatic arthritis resistant to (a) NSAIDs, (b) at least 2 local steroid injections, and (c) at least 2 conventional DMARDs for patients with peripheral arthritis or enthesitis. They also recommend TNF antagonists be considered for psoriatic spondylitis resistant to NSAIDs.¹⁵

The Assessment in Ankylosing Spondylitis (ASAS) International Working Group and the European League Against Rheumatism (EULAR) recommendations for the treatment of ankylosing spondylitis, based on a systematic review of the literature and expert opinion, indicate that:

• There is good evidence for using NSAIDs and COX-2 inhibitors for symptomatic treatment.
• Conventional DMARDs are not well supported.
• TNF antagonists show a large benefit in both pain and function.

The ASAS/EULAR recommendation indicate that there is no evidence that any of these treatments actually modify the disease progression.¹⁶

Acknowledgments

The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the US Air Force medical service or the US Air Force at large.

Evidence summary

The use of DMARDs has become standard of care for rheumatoid arthritis, for both therapy and prevention of progression of this debilitating disease. However, the use of DMARDs in nonrheumatoid rheumatologic disease is still under investigation, and at this point, the use of DMARDs as first-line therapy is not recommended; however, second-line therapy with DMARDs is common.

For psoriatic arthritis, DMARDs are beneficial as a second-line therapy

A Cochrane systematic review identified 13 randomized controlled trials enrolling a combined 1022 patients with psoriatic arthritis randomly assigned to receive a DMARD—methotrexate, sulfasalazine (Azulfidine), azathioprine (Imuran/ Azasan), or etretinate (Tegison; no longer available in the US)—compared with placebo.² All agents were better than placebo; however, only 2 agents (parenteral high-dose methotrexate and sulfasalazine) had clinically important benefits for more than half the patients. The studies were too small to establish toxicity or to evaluate the other agents.

NSAIDs are still the preferred first-line therapy, concluded a recent publication on the treatment of psoriatic arthritis, which looked at 54 different studies; however, second-line therapy could include methotrexate, sulfasalazine, etanercept (Enbrel), infliximab (Remicade), cyclosporine, or combination therapy.³ Sulfasalazine appeared to be clinically beneficial for peripheral psoriatic arthritis.

Etanercept vs placebo. An initial study (60 patients) of etanercept vs placebo among patients who were permitted to stay on methotrexate or prednisone showed a response rate of 87% vs 23% (P<.0001; number needed to treat [NNT]=1.56).⁴

Infliximab vs placebo. A study of infliximab vs placebo involving 104 patients had similar results, with good response in 65% vs 10% (NNT=1.81) at 16 weeks; infliximab also inhibited radiographic progression by 22%.⁵

Cyclosporine. Although it is effective, reserve cyclosporine for patients who do not improve on other regimens, because of its nephrotoxicity.³

DMARDs show some benefit in treating ankylosing spondylitis

Two recent Cochrane systematic reviews on ankylosing spondylitis examined the use of sulfasalazine and methotrexate as second-line agents.^6,7 Eleven trials were included in the sulfasalazine analysis, with a total of 895 patients. Sulfasalazine demonstrated some benefit in reducing erythrocyte sedimentation rates (ESRs) and morning stiffness, but there was no evidence that the drug reduced pain or improved physical function, spinal mobility, or rate of enthesitis. Sulfasalazine was well tolerated and may be useful in early mild disease for patients with peripheral arthritis and high ESRs. On the other hand, evidence was insufficient to determine whether methotrexate benefited patients with ankylosing spondylitis.

In other trials, infliximab and etanercept showed good potential for benefit in treating ankylosing spondylitis.

One study of infliximab vs placebo showed 61.2% vs 19.2% patients with good clinical benefit at 24 weeks and only mild or moderate adverse events (P<.001; NNT=2.38).⁸

Similarly, a smaller study (84 patients) showed that 60% of patients on etanercept vs 20% on placebo had good clinical benefit at only 12 weeks (P<.001, NNT=2.5).⁹

For other rheumatic diseases, studies are mixed

Due to cyclosporine’s toxicity, less toxic DMARDs are being evaluated to replace it for treatment of other rheumatic diseases. A recent randomized controlled trial of 100 patients with antineutrophil cytoplasmic antibody–associated systemic vasculitis showed methotrexate may be able to replace cyclosporine for both induction of remission (methotrexate=89.8% vs cyclosporine=93.5%; P=.041) and maintenance of remission (69.5% vs 46.5% at 18 months; P=.023).¹⁰

Initial trials on other rheumatic diseases have been small and have had varied results. There are mixed studies on the effectiveness of adding methotrexate to corticosteroids for giant cell arteritis.^11,12

There has been no evidence of efficacy for the new TNF antagonists in either a small study on Sjögren’s syndrome (n=14)¹³ or a larger study on Wegener’s granulomatosis (n=180).¹⁴

The studies for use of DMARDs in lupus or scleroderma are of limited quality.

Recommendations from others

The Italian Society for Rheumatology consensus guidelines recommends TNF antagonists be considered in active psoriatic arthritis resistant to (a) NSAIDs, (b) at least 2 local steroid injections, and (c) at least 2 conventional DMARDs for patients with peripheral arthritis or enthesitis. They also recommend TNF antagonists be considered for psoriatic spondylitis resistant to NSAIDs.¹⁵

The Assessment in Ankylosing Spondylitis (ASAS) International Working Group and the European League Against Rheumatism (EULAR) recommendations for the treatment of ankylosing spondylitis, based on a systematic review of the literature and expert opinion, indicate that:

• There is good evidence for using NSAIDs and COX-2 inhibitors for symptomatic treatment.
• Conventional DMARDs are not well supported.
• TNF antagonists show a large benefit in both pain and function.

The ASAS/EULAR recommendation indicate that there is no evidence that any of these treatments actually modify the disease progression.¹⁶

Acknowledgments

The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the US Air Force medical service or the US Air Force at large.