Thrombus

Image by Andre E.X. Brown

Scientists say they have created drug-loaded nanocapsules that can target and destroy blood clots by exploiting the intrinsic properties of thrombosis.

These polymer capsules are “inherently responsive” to thrombus microenvironments.

They home to activated platelets, where exposure to thrombin prompts the capsules to degrade and release a thrombolytic drug—urokinase plasminogen activator—at the site of thrombosis.

Christoph Hagemeyer, PhD, of Baker IDI Heart and Diabetes Institute in Melbourne, Victoria, Australia, and his colleagues described the creation and testing of these capsules in Advanced Materials.

“We’ve created a nanocapsule that contains a clot-busting drug,” Dr Hagemeyer explained. “The drug-loaded nanocapsule is coated with an antibody that specifically targets activated platelets . . . .”

“Once located at the site of the blood clot, thrombin (a molecule at the center of the clotting process) breaks open the outer layer of the nanocapsule, releasing the clot-busting drug. We are effectively hijacking the blood-clotting system to initiate the removal of the blockage in the blood vessel.”

Specifically, Dr Hagemeyer and his colleagues created the capsules via layer-by-layer assembly of brushlike poly(2-ethyl-2-oxazoline) with alkyne functional groups on mesoporous silica particle templates.

The team loaded the capsules with the thrombolytic agent urokinase plasminogen activator and incorporated a thrombin-sensitive cross-linker to activate capsule degradation and drug release at the site of thrombosis.

So the capsules would target activated platelets, the researchers attached an antibody to the capsules’ surface. The team used a phage-display-derived single-chain antibody that is specific for the fibrinogen receptor GPIIb/IIIa in its activated form.

Flow chamber experiments showed that the capsules do target surface-bound GPIIb/IIIa receptors expressed on activated platelets.

And exposing the capsules to thrombin revealed concentration-dependent degradation and drug release. The researchers exposed loaded capsules to simulated thrombotic conditions with a range of thrombin concentrations.

In the presence of 1 unit mL⁻¹, capsules degraded/released their cargo after 4 hours. With higher thrombin concentrations—5 or 10 units mL⁻¹—capsules released their cargo within 15 minutes.

Thrombus

Image by Andre E.X. Brown

Scientists say they have created drug-loaded nanocapsules that can target and destroy blood clots by exploiting the intrinsic properties of thrombosis.

These polymer capsules are “inherently responsive” to thrombus microenvironments.

They home to activated platelets, where exposure to thrombin prompts the capsules to degrade and release a thrombolytic drug—urokinase plasminogen activator—at the site of thrombosis.

Christoph Hagemeyer, PhD, of Baker IDI Heart and Diabetes Institute in Melbourne, Victoria, Australia, and his colleagues described the creation and testing of these capsules in Advanced Materials.

“We’ve created a nanocapsule that contains a clot-busting drug,” Dr Hagemeyer explained. “The drug-loaded nanocapsule is coated with an antibody that specifically targets activated platelets . . . .”

“Once located at the site of the blood clot, thrombin (a molecule at the center of the clotting process) breaks open the outer layer of the nanocapsule, releasing the clot-busting drug. We are effectively hijacking the blood-clotting system to initiate the removal of the blockage in the blood vessel.”

Specifically, Dr Hagemeyer and his colleagues created the capsules via layer-by-layer assembly of brushlike poly(2-ethyl-2-oxazoline) with alkyne functional groups on mesoporous silica particle templates.

The team loaded the capsules with the thrombolytic agent urokinase plasminogen activator and incorporated a thrombin-sensitive cross-linker to activate capsule degradation and drug release at the site of thrombosis.

So the capsules would target activated platelets, the researchers attached an antibody to the capsules’ surface. The team used a phage-display-derived single-chain antibody that is specific for the fibrinogen receptor GPIIb/IIIa in its activated form.

Flow chamber experiments showed that the capsules do target surface-bound GPIIb/IIIa receptors expressed on activated platelets.

And exposing the capsules to thrombin revealed concentration-dependent degradation and drug release. The researchers exposed loaded capsules to simulated thrombotic conditions with a range of thrombin concentrations.

In the presence of 1 unit mL⁻¹, capsules degraded/released their cargo after 4 hours. With higher thrombin concentrations—5 or 10 units mL⁻¹—capsules released their cargo within 15 minutes.

Thrombus

Image by Andre E.X. Brown

Scientists say they have created drug-loaded nanocapsules that can target and destroy blood clots by exploiting the intrinsic properties of thrombosis.

These polymer capsules are “inherently responsive” to thrombus microenvironments.

They home to activated platelets, where exposure to thrombin prompts the capsules to degrade and release a thrombolytic drug—urokinase plasminogen activator—at the site of thrombosis.

Christoph Hagemeyer, PhD, of Baker IDI Heart and Diabetes Institute in Melbourne, Victoria, Australia, and his colleagues described the creation and testing of these capsules in Advanced Materials.

“We’ve created a nanocapsule that contains a clot-busting drug,” Dr Hagemeyer explained. “The drug-loaded nanocapsule is coated with an antibody that specifically targets activated platelets . . . .”

“Once located at the site of the blood clot, thrombin (a molecule at the center of the clotting process) breaks open the outer layer of the nanocapsule, releasing the clot-busting drug. We are effectively hijacking the blood-clotting system to initiate the removal of the blockage in the blood vessel.”

Specifically, Dr Hagemeyer and his colleagues created the capsules via layer-by-layer assembly of brushlike poly(2-ethyl-2-oxazoline) with alkyne functional groups on mesoporous silica particle templates.

The team loaded the capsules with the thrombolytic agent urokinase plasminogen activator and incorporated a thrombin-sensitive cross-linker to activate capsule degradation and drug release at the site of thrombosis.

So the capsules would target activated platelets, the researchers attached an antibody to the capsules’ surface. The team used a phage-display-derived single-chain antibody that is specific for the fibrinogen receptor GPIIb/IIIa in its activated form.

Flow chamber experiments showed that the capsules do target surface-bound GPIIb/IIIa receptors expressed on activated platelets.

And exposing the capsules to thrombin revealed concentration-dependent degradation and drug release. The researchers exposed loaded capsules to simulated thrombotic conditions with a range of thrombin concentrations.

In the presence of 1 unit mL⁻¹, capsules degraded/released their cargo after 4 hours. With higher thrombin concentrations—5 or 10 units mL⁻¹—capsules released their cargo within 15 minutes.

Micrograph showing CTCL

The European Commission has granted orphan drug designation to synthetic hypericin, the active pharmaceutical ingredient in SGX301, for the treatment of cutaneous T-cell lymphoma (CTCL).

SGX301 is a first-in-class, photodynamic therapy utilizing safe, visible light for activation. Synthetic hypericin is a potent photosensitizer that is topically applied to skin lesions and activated by visible fluorescent light 16 to 24 hours later.

This treatment approach is intended to prevent the secondary malignancies that may occur following chemotherapy or photodynamic therapies that are dependent on ultraviolet exposure.

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients.

Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

Soligenix, Inc., the company developing SGX301, is currently working with CTCL centers, the National Organization for Rare Disorders, and the Cutaneous Lymphoma Foundation to begin a 120-subject phase 3 trial of SGX301.

About orphan designation

The European Commission grants orphan designation to medicines designed to treat a life-threatening or chronically debilitating condition that affects no more than 5 in 10,000 persons in the European Union and has no satisfactory treatment available.

In addition to a 10-year period of marketing exclusivity after product approval, orphan drug designation provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase, as well as direct access to the centralized authorization procedure.

SGX301 has both orphan designation and fast track designation from the US Food and Drug Administration for the first-line treatment of CTCL.

Micrograph showing CTCL

The European Commission has granted orphan drug designation to synthetic hypericin, the active pharmaceutical ingredient in SGX301, for the treatment of cutaneous T-cell lymphoma (CTCL).

SGX301 is a first-in-class, photodynamic therapy utilizing safe, visible light for activation. Synthetic hypericin is a potent photosensitizer that is topically applied to skin lesions and activated by visible fluorescent light 16 to 24 hours later.

This treatment approach is intended to prevent the secondary malignancies that may occur following chemotherapy or photodynamic therapies that are dependent on ultraviolet exposure.

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients.

Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

Soligenix, Inc., the company developing SGX301, is currently working with CTCL centers, the National Organization for Rare Disorders, and the Cutaneous Lymphoma Foundation to begin a 120-subject phase 3 trial of SGX301.

About orphan designation

The European Commission grants orphan designation to medicines designed to treat a life-threatening or chronically debilitating condition that affects no more than 5 in 10,000 persons in the European Union and has no satisfactory treatment available.

In addition to a 10-year period of marketing exclusivity after product approval, orphan drug designation provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase, as well as direct access to the centralized authorization procedure.

SGX301 has both orphan designation and fast track designation from the US Food and Drug Administration for the first-line treatment of CTCL.

Micrograph showing CTCL

The European Commission has granted orphan drug designation to synthetic hypericin, the active pharmaceutical ingredient in SGX301, for the treatment of cutaneous T-cell lymphoma (CTCL).

SGX301 is a first-in-class, photodynamic therapy utilizing safe, visible light for activation. Synthetic hypericin is a potent photosensitizer that is topically applied to skin lesions and activated by visible fluorescent light 16 to 24 hours later.

This treatment approach is intended to prevent the secondary malignancies that may occur following chemotherapy or photodynamic therapies that are dependent on ultraviolet exposure.

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients.

Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

Soligenix, Inc., the company developing SGX301, is currently working with CTCL centers, the National Organization for Rare Disorders, and the Cutaneous Lymphoma Foundation to begin a 120-subject phase 3 trial of SGX301.

About orphan designation

The European Commission grants orphan designation to medicines designed to treat a life-threatening or chronically debilitating condition that affects no more than 5 in 10,000 persons in the European Union and has no satisfactory treatment available.

In addition to a 10-year period of marketing exclusivity after product approval, orphan drug designation provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase, as well as direct access to the centralized authorization procedure.

SGX301 has both orphan designation and fast track designation from the US Food and Drug Administration for the first-line treatment of CTCL.

Prescription medications

Photo courtesy of the CDC

A new study suggests less is more when it comes to antithrombotic therapy for higher-risk older patients with atrial fibrillation who have a heart attack and undergo percutaneous coronary intervention (PCI).

At 2 years of follow-up, patients who had received triple therapy—warfarin, aspirin, and P2Y₁₂ inhibitor—after PCI had similar rates of major adverse cardiac events (MACE) as patients who received dual antiplatelet therapy (DAPT)—aspirin and P2Y₁₂ inhibitor.

But patients on triple therapy had a higher incidence of intracranial hemorrhage and bleeding that required hospitalization.

These results appear in the Journal of the American College of Cardiology alongside a related editorial.

Researchers examined data from the National Cardiovascular Data Registry ACTION Registry-GWTG linked with Centers for Medicare and Medicaid Services data, looking at records from January 2007 through December 2010.

They identified 4959 patients aged 65 and older with a history of atrial fibrillation who presented with acute myocardial infarction (MI) and underwent PCI. Most patients (72.4%, n=3589) were discharged on DAPT, but 27.6% (n=1370) were discharged on triple therapy.

In the DAPT arm, 97.2% of patients (n=3490) received clopidogrel, 2.5% (n=89) received prasugrel, and 0.3% (n=10) received ticlopidine. In the triple therapy arm, 98.2% of patients (n=1346) received clopidogrel, 1.4% (n=19) received prasugrel, and 0.4% (n=5) received ticlopidine.

Patients receiving triple therapy were more likely to be male, have a history of either angioplasty or coronary artery bypass surgery, and have a history of stroke. These patients were frequently already on warfarin before they were admitted to the hospital.

Patients who were released on DAPT were more likely to have had an in-hospital major bleeding event.

Incidence of MACE

Two years after discharge, the risk of MACE—death, hospital readmission for MI, or stroke readmission—was similar between the DAPT and triple therapy arms. The unadjusted cumulative incidence rate of MACE was 32.6% in the triple therapy arm and 32.7% in the DAPT arm (P=0.99).

The unadjusted cumulative incidence rates of the individual MACE components were also similar between the triple therapy and DAPT arms. All-cause mortality occurred in 23.8% and 24.8%, respectively (P=0.70), MI readmission occurred in 8.5% and 8.1%, respectively (P=0.54), and stroke readmission occurred in 4.7% and 5.3%, respectively (P=0.23).

After the researchers adjusted for patient, treatment, and hospital characteristics, there was still no significant difference between the arms with regard to the incidence of MACE or MACE components.

The adjusted hazard ratio (HR) was 0.99 for MACE (P=0.94), 0.98 for all-cause mortality (P=0.82), 1.03 for MI readmission (P=0.83), and 0.85 for stroke readmission (P=0.38).

Bleeding incidence

The cumulative incidence of bleeding requiring hospitalization within 2 years of discharge after PCI was significantly higher for the triple therapy arm than the DAPT arm—17.6% and 11.0%, respectively (P<0.0001).

The difference remained significant after the researchers adjusted for patient, treatment, and hospital characteristics. The adjusted HR was 1.61 (P<0.0001).

Similarly, the unadjusted cumulative incidence of intracranial hemorrhage was significantly higher for the triple therapy arm than the DAPT arm—3.4% and 1.5%, respectively (P<0.001).

This difference remained significant after adjustment. The adjusted HR was 2.04 (P<0.01).

“The increased risk of bleeding without apparent benefit of triple therapy observed in this study suggests that clinicians should carefully consider the risk-to-benefit ratio of triple therapy use in older atrial fibrillation patients who have had a heart attack treated with angioplasty,” said Connie N. Hess, MD, of the Duke University School of Medicine in Durham, North Carolina.

“Further prospective studies of different combinations of anticlotting agents are needed to define the optimal treatment regimen for this population.”

Prescription medications

Photo courtesy of the CDC

A new study suggests less is more when it comes to antithrombotic therapy for higher-risk older patients with atrial fibrillation who have a heart attack and undergo percutaneous coronary intervention (PCI).

At 2 years of follow-up, patients who had received triple therapy—warfarin, aspirin, and P2Y₁₂ inhibitor—after PCI had similar rates of major adverse cardiac events (MACE) as patients who received dual antiplatelet therapy (DAPT)—aspirin and P2Y₁₂ inhibitor.

But patients on triple therapy had a higher incidence of intracranial hemorrhage and bleeding that required hospitalization.

These results appear in the Journal of the American College of Cardiology alongside a related editorial.

Researchers examined data from the National Cardiovascular Data Registry ACTION Registry-GWTG linked with Centers for Medicare and Medicaid Services data, looking at records from January 2007 through December 2010.

They identified 4959 patients aged 65 and older with a history of atrial fibrillation who presented with acute myocardial infarction (MI) and underwent PCI. Most patients (72.4%, n=3589) were discharged on DAPT, but 27.6% (n=1370) were discharged on triple therapy.

In the DAPT arm, 97.2% of patients (n=3490) received clopidogrel, 2.5% (n=89) received prasugrel, and 0.3% (n=10) received ticlopidine. In the triple therapy arm, 98.2% of patients (n=1346) received clopidogrel, 1.4% (n=19) received prasugrel, and 0.4% (n=5) received ticlopidine.

Patients receiving triple therapy were more likely to be male, have a history of either angioplasty or coronary artery bypass surgery, and have a history of stroke. These patients were frequently already on warfarin before they were admitted to the hospital.

Patients who were released on DAPT were more likely to have had an in-hospital major bleeding event.

Incidence of MACE

Two years after discharge, the risk of MACE—death, hospital readmission for MI, or stroke readmission—was similar between the DAPT and triple therapy arms. The unadjusted cumulative incidence rate of MACE was 32.6% in the triple therapy arm and 32.7% in the DAPT arm (P=0.99).

The unadjusted cumulative incidence rates of the individual MACE components were also similar between the triple therapy and DAPT arms. All-cause mortality occurred in 23.8% and 24.8%, respectively (P=0.70), MI readmission occurred in 8.5% and 8.1%, respectively (P=0.54), and stroke readmission occurred in 4.7% and 5.3%, respectively (P=0.23).

After the researchers adjusted for patient, treatment, and hospital characteristics, there was still no significant difference between the arms with regard to the incidence of MACE or MACE components.

The adjusted hazard ratio (HR) was 0.99 for MACE (P=0.94), 0.98 for all-cause mortality (P=0.82), 1.03 for MI readmission (P=0.83), and 0.85 for stroke readmission (P=0.38).

Bleeding incidence

The cumulative incidence of bleeding requiring hospitalization within 2 years of discharge after PCI was significantly higher for the triple therapy arm than the DAPT arm—17.6% and 11.0%, respectively (P<0.0001).

The difference remained significant after the researchers adjusted for patient, treatment, and hospital characteristics. The adjusted HR was 1.61 (P<0.0001).

Similarly, the unadjusted cumulative incidence of intracranial hemorrhage was significantly higher for the triple therapy arm than the DAPT arm—3.4% and 1.5%, respectively (P<0.001).

This difference remained significant after adjustment. The adjusted HR was 2.04 (P<0.01).

“The increased risk of bleeding without apparent benefit of triple therapy observed in this study suggests that clinicians should carefully consider the risk-to-benefit ratio of triple therapy use in older atrial fibrillation patients who have had a heart attack treated with angioplasty,” said Connie N. Hess, MD, of the Duke University School of Medicine in Durham, North Carolina.

“Further prospective studies of different combinations of anticlotting agents are needed to define the optimal treatment regimen for this population.”

Prescription medications

Photo courtesy of the CDC

A new study suggests less is more when it comes to antithrombotic therapy for higher-risk older patients with atrial fibrillation who have a heart attack and undergo percutaneous coronary intervention (PCI).

At 2 years of follow-up, patients who had received triple therapy—warfarin, aspirin, and P2Y₁₂ inhibitor—after PCI had similar rates of major adverse cardiac events (MACE) as patients who received dual antiplatelet therapy (DAPT)—aspirin and P2Y₁₂ inhibitor.

But patients on triple therapy had a higher incidence of intracranial hemorrhage and bleeding that required hospitalization.

These results appear in the Journal of the American College of Cardiology alongside a related editorial.

Researchers examined data from the National Cardiovascular Data Registry ACTION Registry-GWTG linked with Centers for Medicare and Medicaid Services data, looking at records from January 2007 through December 2010.

They identified 4959 patients aged 65 and older with a history of atrial fibrillation who presented with acute myocardial infarction (MI) and underwent PCI. Most patients (72.4%, n=3589) were discharged on DAPT, but 27.6% (n=1370) were discharged on triple therapy.

In the DAPT arm, 97.2% of patients (n=3490) received clopidogrel, 2.5% (n=89) received prasugrel, and 0.3% (n=10) received ticlopidine. In the triple therapy arm, 98.2% of patients (n=1346) received clopidogrel, 1.4% (n=19) received prasugrel, and 0.4% (n=5) received ticlopidine.

Patients receiving triple therapy were more likely to be male, have a history of either angioplasty or coronary artery bypass surgery, and have a history of stroke. These patients were frequently already on warfarin before they were admitted to the hospital.

Patients who were released on DAPT were more likely to have had an in-hospital major bleeding event.

Incidence of MACE

Two years after discharge, the risk of MACE—death, hospital readmission for MI, or stroke readmission—was similar between the DAPT and triple therapy arms. The unadjusted cumulative incidence rate of MACE was 32.6% in the triple therapy arm and 32.7% in the DAPT arm (P=0.99).

The unadjusted cumulative incidence rates of the individual MACE components were also similar between the triple therapy and DAPT arms. All-cause mortality occurred in 23.8% and 24.8%, respectively (P=0.70), MI readmission occurred in 8.5% and 8.1%, respectively (P=0.54), and stroke readmission occurred in 4.7% and 5.3%, respectively (P=0.23).

After the researchers adjusted for patient, treatment, and hospital characteristics, there was still no significant difference between the arms with regard to the incidence of MACE or MACE components.

The adjusted hazard ratio (HR) was 0.99 for MACE (P=0.94), 0.98 for all-cause mortality (P=0.82), 1.03 for MI readmission (P=0.83), and 0.85 for stroke readmission (P=0.38).

Bleeding incidence

The cumulative incidence of bleeding requiring hospitalization within 2 years of discharge after PCI was significantly higher for the triple therapy arm than the DAPT arm—17.6% and 11.0%, respectively (P<0.0001).

The difference remained significant after the researchers adjusted for patient, treatment, and hospital characteristics. The adjusted HR was 1.61 (P<0.0001).

Similarly, the unadjusted cumulative incidence of intracranial hemorrhage was significantly higher for the triple therapy arm than the DAPT arm—3.4% and 1.5%, respectively (P<0.001).

This difference remained significant after adjustment. The adjusted HR was 2.04 (P<0.01).

“The increased risk of bleeding without apparent benefit of triple therapy observed in this study suggests that clinicians should carefully consider the risk-to-benefit ratio of triple therapy use in older atrial fibrillation patients who have had a heart attack treated with angioplasty,” said Connie N. Hess, MD, of the Duke University School of Medicine in Durham, North Carolina.

“Further prospective studies of different combinations of anticlotting agents are needed to define the optimal treatment regimen for this population.”

Pediatric cancer patient

Photo by Bill Branson

Children with cancer can benefit from “adapted” physical activities, according to a pilot study published in ecancermedicalscience.

Investigators followed 11 cancer patients, ages 10 to 18, on a dog sledding expedition, which involved adapted training activities.

All of the patients completed the training and the expedition, and they exhibited significant improvements in physical and psychological health after completing the program.

“What I learned from this study is that we doctors have the false belief that kids with cancer cannot practice sport because they are too tired or weak from their treatments,” said study author Nicolas André, MD, PhD, of Hôpital d'Enfants de la Timone in Marseille, France.

“These perceptions are at least partly wrong. Adapted physical activities can be performed by most children with cancer, even during their treatment, and can bring a lot to children.”

To arrive at these conclusions, Dr André and his colleagues measured the effects of a 6-week long adapted physical activity program on children and adolescents with cancer.

The study included 11 patients—4 girls and 7 boys—with a mean age of 14.3 ± 2.9 years. Seven of the patients were still receiving treatment.

About the program

The patients first completed a physical preparation program consisting of general conditioning to improve their strength, speed, endurance, flexibility, skill, and ability to handle greater workloads.

Typically, these activities lasted from 60 to 120 minutes and took place 1 to 5 times a week. The intensity of physical activity was adjusted to each subject.

After completing the preparation, the patients began a 5-day long expedition in Quebec, Canada. They completed a session of physical training in the snow and had their first contact with the pack of dogs and the sleds the day before departure.

Overall, the subjects engaged in physical activity 4 to 5 hours per day during the expedition.

Results

The patients performed a series of physical tests and completed psychological questionnaires before and after the program. The results showed improvements in all physical and psychological parameters.

After completing the program, the subjects reported significant improvements in global self-esteem (P=0.02), perceived sport competence (P=0.02), and perceived physical strength (P=0.001).

They also demonstrated significant improvements in their ability to do sit-ups (P=0.01), their muscle tone (P=0.01), and their resting heart rate (P=0.03).

“Based on our work over the last 8 years, we all are convinced that practicing adapted physical activity is very positive for children with cancer,” said study author Laurent Grélot, PhD, of Aix Marseille University in France.

“It avoids cardiovascular and muscular deconditioning, can decrease treatment-induced fatigue, and can help maintaining social integration.”

Based on the success of this pilot study, the investigators are conducting a randomized trial to evaluate the benefits of adapted physical activities for children with cancer.

Pediatric cancer patient

Photo by Bill Branson

Children with cancer can benefit from “adapted” physical activities, according to a pilot study published in ecancermedicalscience.

Investigators followed 11 cancer patients, ages 10 to 18, on a dog sledding expedition, which involved adapted training activities.

All of the patients completed the training and the expedition, and they exhibited significant improvements in physical and psychological health after completing the program.

“What I learned from this study is that we doctors have the false belief that kids with cancer cannot practice sport because they are too tired or weak from their treatments,” said study author Nicolas André, MD, PhD, of Hôpital d'Enfants de la Timone in Marseille, France.

“These perceptions are at least partly wrong. Adapted physical activities can be performed by most children with cancer, even during their treatment, and can bring a lot to children.”

To arrive at these conclusions, Dr André and his colleagues measured the effects of a 6-week long adapted physical activity program on children and adolescents with cancer.

The study included 11 patients—4 girls and 7 boys—with a mean age of 14.3 ± 2.9 years. Seven of the patients were still receiving treatment.

About the program

The patients first completed a physical preparation program consisting of general conditioning to improve their strength, speed, endurance, flexibility, skill, and ability to handle greater workloads.

Typically, these activities lasted from 60 to 120 minutes and took place 1 to 5 times a week. The intensity of physical activity was adjusted to each subject.

After completing the preparation, the patients began a 5-day long expedition in Quebec, Canada. They completed a session of physical training in the snow and had their first contact with the pack of dogs and the sleds the day before departure.

Overall, the subjects engaged in physical activity 4 to 5 hours per day during the expedition.

Results

The patients performed a series of physical tests and completed psychological questionnaires before and after the program. The results showed improvements in all physical and psychological parameters.

After completing the program, the subjects reported significant improvements in global self-esteem (P=0.02), perceived sport competence (P=0.02), and perceived physical strength (P=0.001).

They also demonstrated significant improvements in their ability to do sit-ups (P=0.01), their muscle tone (P=0.01), and their resting heart rate (P=0.03).

“Based on our work over the last 8 years, we all are convinced that practicing adapted physical activity is very positive for children with cancer,” said study author Laurent Grélot, PhD, of Aix Marseille University in France.

“It avoids cardiovascular and muscular deconditioning, can decrease treatment-induced fatigue, and can help maintaining social integration.”

Based on the success of this pilot study, the investigators are conducting a randomized trial to evaluate the benefits of adapted physical activities for children with cancer.

Pediatric cancer patient

Photo by Bill Branson

Children with cancer can benefit from “adapted” physical activities, according to a pilot study published in ecancermedicalscience.

Investigators followed 11 cancer patients, ages 10 to 18, on a dog sledding expedition, which involved adapted training activities.

All of the patients completed the training and the expedition, and they exhibited significant improvements in physical and psychological health after completing the program.

“What I learned from this study is that we doctors have the false belief that kids with cancer cannot practice sport because they are too tired or weak from their treatments,” said study author Nicolas André, MD, PhD, of Hôpital d'Enfants de la Timone in Marseille, France.

“These perceptions are at least partly wrong. Adapted physical activities can be performed by most children with cancer, even during their treatment, and can bring a lot to children.”

To arrive at these conclusions, Dr André and his colleagues measured the effects of a 6-week long adapted physical activity program on children and adolescents with cancer.

The study included 11 patients—4 girls and 7 boys—with a mean age of 14.3 ± 2.9 years. Seven of the patients were still receiving treatment.

About the program

The patients first completed a physical preparation program consisting of general conditioning to improve their strength, speed, endurance, flexibility, skill, and ability to handle greater workloads.

Typically, these activities lasted from 60 to 120 minutes and took place 1 to 5 times a week. The intensity of physical activity was adjusted to each subject.

After completing the preparation, the patients began a 5-day long expedition in Quebec, Canada. They completed a session of physical training in the snow and had their first contact with the pack of dogs and the sleds the day before departure.

Overall, the subjects engaged in physical activity 4 to 5 hours per day during the expedition.

Results

The patients performed a series of physical tests and completed psychological questionnaires before and after the program. The results showed improvements in all physical and psychological parameters.

After completing the program, the subjects reported significant improvements in global self-esteem (P=0.02), perceived sport competence (P=0.02), and perceived physical strength (P=0.001).

They also demonstrated significant improvements in their ability to do sit-ups (P=0.01), their muscle tone (P=0.01), and their resting heart rate (P=0.03).

“Based on our work over the last 8 years, we all are convinced that practicing adapted physical activity is very positive for children with cancer,” said study author Laurent Grélot, PhD, of Aix Marseille University in France.

“It avoids cardiovascular and muscular deconditioning, can decrease treatment-induced fatigue, and can help maintaining social integration.”

Based on the success of this pilot study, the investigators are conducting a randomized trial to evaluate the benefits of adapted physical activities for children with cancer.

SUPPLEMENTS FOR EXPECTANT/NEW MOMS
Premama^®, a line of natural powdered drink mixes formulated to support the nutritional needs of expectant and new mothers, has introduced 2 products for preconception and postpartum health.

Fertility delivers a supplement formulation that includes myo-Inositol, which is clinically shown to help improve ovulatory function and healthy egg production, and folic acid to support prenatal health, according to Premama. Fertility is an unflavored drink mix that comes in packets of 2.2 g to be mixed with at least 12 oz of water or other noncarbonated flavored liquids such as juices or smoothies and taken daily.

Lactation is a berry-flavored drink mix daily supplement that is formulated with fenugreek, fennel seed, and blessed thistle to help support healthy milk production, according to Premama. Also included in Lactation are folic acid, Vitamin D3, calcium, and other essential nutrients for both mother and baby. A Lactation 2.5-mg packet mixes with at least 12 oz of water until blended well, or with noncarbonated, flavored liquids such as juices or smoothies.

All Premama products are physician approved, vegetarian, gluten free, and made in the United States. Premama products are available at retailers nationwide or online.

FOR MORE INFORMATION, VISIT www.drinkpremama.com

FREE EKG TRAINING APP FROM SYNDAVER
SynDaver™ Labs has released a free medical training electrocardiogram (EKG)simulator app for android devices on Google Play. The SynDaver EKG Simulator is a digital platform that can function with any medical training manikin, according to SynDaver. Currently available variables include heartbeats per minute, systolic pressure, diastolic pressure, respiration rate, SpO₂, and temperature. Values are displayed both numerically and by color coordinated dynamic waveform with mutable audio indicators for heart rate.

The EKG Simulator app allows for 2 android devices to be paired using Bluetooth, which, says the manufacturer, is ideal for a classroom setting because it allows the instructor to update the display remotely to modify the training scenario. Download the free EKG Simulator at http://syndaver.com/shop/new/ekg-simulator/.

FOR MORE INFORMATION, VISIT www.syndaver.com

MEDICAL SCRIBES AND CODING TOOLS
ScribeAmerica was established in 2004 as a clinical documentation solution for providers transitioning to electronic health records (EHRs). ScribeAmerica says its focus on improving the accuracy and quality of patient documentation has resulted in higher patient satisfaction scores, improved revenue cycle, and better continuity of care. 

ScribeAmerica recruits, trains, and manages over 7,300 scribes in nearly 900 locations nationwide. Certified Medical Scribes, current with all American College of Medical Scribe Specialists guidelines and testing, specialize in collecting medical data and entering it into a clinician’s EHR, resulting in improved operational workflow, claims ScribeAmerica. ScribeAmerica’s medical scribe programs are found in rural and urban hospitals, teaching facilities, private practices, and political organizations.

LiveCode Point of Service Coding is a real-time coding solution that reduces the latency in feedback and improves overall efficacy of the revenue cycle.

The Individualized Clinical Documentation Advisor (ICD-Advisor) provides custom reports tailored to the codes used most often in a specific practice. ScribeAmerica says its ICD-Advisor is fast, individualized to a practice’s needs, and affordable.

FOR MORE INFORMATION, VISIT www.scribeamerica.com

XOFT CERVICAL APPLICATOR FOR EBX
iCAD, Inc. has added a cervical applicator to the Xoft^® Axxent^® Electronic Brachytherapy (eBX) System^® for intracavitary treatment of multiple gynecologic cancers in a minimally shielded setting. The cervical applicator is used to deliver a precise dose of radiation to larger target areas of the cervix while minimizing exposure to healthy tissue, according to iCAD. 

Using proprietary miniaturized x-ray as the radiation source, the Xoft eBX System delivers isotope-free radiation treatment in a targeted prescribed dose directly to the site where cancer recurrence is most likely, designed to minimize exposure to healthy tissue such as the bladder and rectum. The system requires minimal shielding and therefore does not require room redesign or construction investment and also allows medical personnel to remain in the room with the patient during treatment, says iCAD.

FOR MORE INFORMATION, VISIT www.xoftinc.com

SUPPLEMENTS FOR EXPECTANT/NEW MOMS
Premama^®, a line of natural powdered drink mixes formulated to support the nutritional needs of expectant and new mothers, has introduced 2 products for preconception and postpartum health.

Fertility delivers a supplement formulation that includes myo-Inositol, which is clinically shown to help improve ovulatory function and healthy egg production, and folic acid to support prenatal health, according to Premama. Fertility is an unflavored drink mix that comes in packets of 2.2 g to be mixed with at least 12 oz of water or other noncarbonated flavored liquids such as juices or smoothies and taken daily.

Lactation is a berry-flavored drink mix daily supplement that is formulated with fenugreek, fennel seed, and blessed thistle to help support healthy milk production, according to Premama. Also included in Lactation are folic acid, Vitamin D3, calcium, and other essential nutrients for both mother and baby. A Lactation 2.5-mg packet mixes with at least 12 oz of water until blended well, or with noncarbonated, flavored liquids such as juices or smoothies.

All Premama products are physician approved, vegetarian, gluten free, and made in the United States. Premama products are available at retailers nationwide or online.

FOR MORE INFORMATION, VISIT www.drinkpremama.com

FREE EKG TRAINING APP FROM SYNDAVER
SynDaver™ Labs has released a free medical training electrocardiogram (EKG)simulator app for android devices on Google Play. The SynDaver EKG Simulator is a digital platform that can function with any medical training manikin, according to SynDaver. Currently available variables include heartbeats per minute, systolic pressure, diastolic pressure, respiration rate, SpO₂, and temperature. Values are displayed both numerically and by color coordinated dynamic waveform with mutable audio indicators for heart rate.

The EKG Simulator app allows for 2 android devices to be paired using Bluetooth, which, says the manufacturer, is ideal for a classroom setting because it allows the instructor to update the display remotely to modify the training scenario. Download the free EKG Simulator at http://syndaver.com/shop/new/ekg-simulator/.

FOR MORE INFORMATION, VISIT www.syndaver.com

MEDICAL SCRIBES AND CODING TOOLS
ScribeAmerica was established in 2004 as a clinical documentation solution for providers transitioning to electronic health records (EHRs). ScribeAmerica says its focus on improving the accuracy and quality of patient documentation has resulted in higher patient satisfaction scores, improved revenue cycle, and better continuity of care. 

ScribeAmerica recruits, trains, and manages over 7,300 scribes in nearly 900 locations nationwide. Certified Medical Scribes, current with all American College of Medical Scribe Specialists guidelines and testing, specialize in collecting medical data and entering it into a clinician’s EHR, resulting in improved operational workflow, claims ScribeAmerica. ScribeAmerica’s medical scribe programs are found in rural and urban hospitals, teaching facilities, private practices, and political organizations.

LiveCode Point of Service Coding is a real-time coding solution that reduces the latency in feedback and improves overall efficacy of the revenue cycle.

The Individualized Clinical Documentation Advisor (ICD-Advisor) provides custom reports tailored to the codes used most often in a specific practice. ScribeAmerica says its ICD-Advisor is fast, individualized to a practice’s needs, and affordable.

FOR MORE INFORMATION, VISIT www.scribeamerica.com

XOFT CERVICAL APPLICATOR FOR EBX
iCAD, Inc. has added a cervical applicator to the Xoft^® Axxent^® Electronic Brachytherapy (eBX) System^® for intracavitary treatment of multiple gynecologic cancers in a minimally shielded setting. The cervical applicator is used to deliver a precise dose of radiation to larger target areas of the cervix while minimizing exposure to healthy tissue, according to iCAD. 

Using proprietary miniaturized x-ray as the radiation source, the Xoft eBX System delivers isotope-free radiation treatment in a targeted prescribed dose directly to the site where cancer recurrence is most likely, designed to minimize exposure to healthy tissue such as the bladder and rectum. The system requires minimal shielding and therefore does not require room redesign or construction investment and also allows medical personnel to remain in the room with the patient during treatment, says iCAD.

FOR MORE INFORMATION, VISIT www.xoftinc.com

SUPPLEMENTS FOR EXPECTANT/NEW MOMS
Premama^®, a line of natural powdered drink mixes formulated to support the nutritional needs of expectant and new mothers, has introduced 2 products for preconception and postpartum health.

Fertility delivers a supplement formulation that includes myo-Inositol, which is clinically shown to help improve ovulatory function and healthy egg production, and folic acid to support prenatal health, according to Premama. Fertility is an unflavored drink mix that comes in packets of 2.2 g to be mixed with at least 12 oz of water or other noncarbonated flavored liquids such as juices or smoothies and taken daily.

Lactation is a berry-flavored drink mix daily supplement that is formulated with fenugreek, fennel seed, and blessed thistle to help support healthy milk production, according to Premama. Also included in Lactation are folic acid, Vitamin D3, calcium, and other essential nutrients for both mother and baby. A Lactation 2.5-mg packet mixes with at least 12 oz of water until blended well, or with noncarbonated, flavored liquids such as juices or smoothies.

All Premama products are physician approved, vegetarian, gluten free, and made in the United States. Premama products are available at retailers nationwide or online.

FOR MORE INFORMATION, VISIT www.drinkpremama.com

FREE EKG TRAINING APP FROM SYNDAVER
SynDaver™ Labs has released a free medical training electrocardiogram (EKG)simulator app for android devices on Google Play. The SynDaver EKG Simulator is a digital platform that can function with any medical training manikin, according to SynDaver. Currently available variables include heartbeats per minute, systolic pressure, diastolic pressure, respiration rate, SpO₂, and temperature. Values are displayed both numerically and by color coordinated dynamic waveform with mutable audio indicators for heart rate.

The EKG Simulator app allows for 2 android devices to be paired using Bluetooth, which, says the manufacturer, is ideal for a classroom setting because it allows the instructor to update the display remotely to modify the training scenario. Download the free EKG Simulator at http://syndaver.com/shop/new/ekg-simulator/.

FOR MORE INFORMATION, VISIT www.syndaver.com

MEDICAL SCRIBES AND CODING TOOLS
ScribeAmerica was established in 2004 as a clinical documentation solution for providers transitioning to electronic health records (EHRs). ScribeAmerica says its focus on improving the accuracy and quality of patient documentation has resulted in higher patient satisfaction scores, improved revenue cycle, and better continuity of care. 

ScribeAmerica recruits, trains, and manages over 7,300 scribes in nearly 900 locations nationwide. Certified Medical Scribes, current with all American College of Medical Scribe Specialists guidelines and testing, specialize in collecting medical data and entering it into a clinician’s EHR, resulting in improved operational workflow, claims ScribeAmerica. ScribeAmerica’s medical scribe programs are found in rural and urban hospitals, teaching facilities, private practices, and political organizations.

LiveCode Point of Service Coding is a real-time coding solution that reduces the latency in feedback and improves overall efficacy of the revenue cycle.

The Individualized Clinical Documentation Advisor (ICD-Advisor) provides custom reports tailored to the codes used most often in a specific practice. ScribeAmerica says its ICD-Advisor is fast, individualized to a practice’s needs, and affordable.

FOR MORE INFORMATION, VISIT www.scribeamerica.com

XOFT CERVICAL APPLICATOR FOR EBX
iCAD, Inc. has added a cervical applicator to the Xoft^® Axxent^® Electronic Brachytherapy (eBX) System^® for intracavitary treatment of multiple gynecologic cancers in a minimally shielded setting. The cervical applicator is used to deliver a precise dose of radiation to larger target areas of the cervix while minimizing exposure to healthy tissue, according to iCAD. 

Using proprietary miniaturized x-ray as the radiation source, the Xoft eBX System delivers isotope-free radiation treatment in a targeted prescribed dose directly to the site where cancer recurrence is most likely, designed to minimize exposure to healthy tissue such as the bladder and rectum. The system requires minimal shielding and therefore does not require room redesign or construction investment and also allows medical personnel to remain in the room with the patient during treatment, says iCAD.

FOR MORE INFORMATION, VISIT www.xoftinc.com

“Dad, Jason said that you saw him in the office today.”

“Gee, Nick, it was very busy. I don’t remember anything about his visit.”

My response to my son was a lie, but I have always been willing to feign ignorance to protect my patients’ privacy. When our kids were home and within earshot I never mentioned that I had seen one of their friends or schoolmates in the office. In fact, I pretty much never talked about my professional life when they were around. They knew my work took a big chunk of my time and, in the remaining few hours, we had other things to talk about. Unfortunately, all three of my children may have mistaken my silence as an indicator that I didn’t like my job, which was far from the truth.

After hearing enough evasive answers, they realized that I had no intention of sharing anything about their peers’ medical history, regardless of how trivial the incident may have been. Even before HIPAA, I knew that my children shouldn’t be trusted to keep even the most innocent-sounding tidbit within the boundaries of our home. After all they were just children.

I suspect that most of you are equally cautious about sharing patient information with your children, even your adult children. But what about your spouse? Let’s be honest here: How HIPAA-compliant is your home? Does pillow talk sometimes drift over the line and compromise doctor-patient confidentiality? I suspect that we all share stories about interesting cases with our spouses hoping that we haven’t revealed enough information for them to figure out who were are talking about.

Of course, “interesting” is a relative term. If your spouse’s postgraduate degree is in computer science and not in medicine, he or she may not find your story about “the highest creatinine I have ever seen” very titillating. But, the story that begins, “You won’t believe what this mother was feeding her 6-month-old” might get his or her attention.

Although you may have known it wasn’t professional, I suspect that there may have been a few times when you have thrown caution to the wind and made no attempt to disguise the identity of the patient even though it was someone with whom your spouse was familiar. It may not have happened to you, but I can’t believe it never happens. Marriages are, or at least should be, very intimate and trusting relationships.

I think that many, maybe most, of the patients and parents in your practice assume that you have shared their stories with your spouse. My wife has often encountered a patient in the grocery store who launches into a story about their child’s illness and is surprised that Marilyn had no idea that the child had even been sick.

I also think that those people who believe the doctors share patient information with their spouses also believe that one of the marriage vows includes a clause in which spouses of physicians swear to keep those shared stories within the confines of the marriage.

Mind you, I’m not advocating that physicians should feel free to share any and all patient information with their spouses. In fact, I think as a rule, it shouldn’t happen, if for no other reason than it puts pressure on a spouse, who may fear that he or she might spread the tidbit inadvertently. But I think we have to be honest, human nature being what it is. Intramarital information sharing happens. Do you agree?

“Dad, Jason said that you saw him in the office today.”

“Gee, Nick, it was very busy. I don’t remember anything about his visit.”

My response to my son was a lie, but I have always been willing to feign ignorance to protect my patients’ privacy. When our kids were home and within earshot I never mentioned that I had seen one of their friends or schoolmates in the office. In fact, I pretty much never talked about my professional life when they were around. They knew my work took a big chunk of my time and, in the remaining few hours, we had other things to talk about. Unfortunately, all three of my children may have mistaken my silence as an indicator that I didn’t like my job, which was far from the truth.

After hearing enough evasive answers, they realized that I had no intention of sharing anything about their peers’ medical history, regardless of how trivial the incident may have been. Even before HIPAA, I knew that my children shouldn’t be trusted to keep even the most innocent-sounding tidbit within the boundaries of our home. After all they were just children.

I suspect that most of you are equally cautious about sharing patient information with your children, even your adult children. But what about your spouse? Let’s be honest here: How HIPAA-compliant is your home? Does pillow talk sometimes drift over the line and compromise doctor-patient confidentiality? I suspect that we all share stories about interesting cases with our spouses hoping that we haven’t revealed enough information for them to figure out who were are talking about.

Of course, “interesting” is a relative term. If your spouse’s postgraduate degree is in computer science and not in medicine, he or she may not find your story about “the highest creatinine I have ever seen” very titillating. But, the story that begins, “You won’t believe what this mother was feeding her 6-month-old” might get his or her attention.

Although you may have known it wasn’t professional, I suspect that there may have been a few times when you have thrown caution to the wind and made no attempt to disguise the identity of the patient even though it was someone with whom your spouse was familiar. It may not have happened to you, but I can’t believe it never happens. Marriages are, or at least should be, very intimate and trusting relationships.

I think that many, maybe most, of the patients and parents in your practice assume that you have shared their stories with your spouse. My wife has often encountered a patient in the grocery store who launches into a story about their child’s illness and is surprised that Marilyn had no idea that the child had even been sick.

I also think that those people who believe the doctors share patient information with their spouses also believe that one of the marriage vows includes a clause in which spouses of physicians swear to keep those shared stories within the confines of the marriage.

Mind you, I’m not advocating that physicians should feel free to share any and all patient information with their spouses. In fact, I think as a rule, it shouldn’t happen, if for no other reason than it puts pressure on a spouse, who may fear that he or she might spread the tidbit inadvertently. But I think we have to be honest, human nature being what it is. Intramarital information sharing happens. Do you agree?

“Dad, Jason said that you saw him in the office today.”

“Gee, Nick, it was very busy. I don’t remember anything about his visit.”

My response to my son was a lie, but I have always been willing to feign ignorance to protect my patients’ privacy. When our kids were home and within earshot I never mentioned that I had seen one of their friends or schoolmates in the office. In fact, I pretty much never talked about my professional life when they were around. They knew my work took a big chunk of my time and, in the remaining few hours, we had other things to talk about. Unfortunately, all three of my children may have mistaken my silence as an indicator that I didn’t like my job, which was far from the truth.

After hearing enough evasive answers, they realized that I had no intention of sharing anything about their peers’ medical history, regardless of how trivial the incident may have been. Even before HIPAA, I knew that my children shouldn’t be trusted to keep even the most innocent-sounding tidbit within the boundaries of our home. After all they were just children.

I suspect that most of you are equally cautious about sharing patient information with your children, even your adult children. But what about your spouse? Let’s be honest here: How HIPAA-compliant is your home? Does pillow talk sometimes drift over the line and compromise doctor-patient confidentiality? I suspect that we all share stories about interesting cases with our spouses hoping that we haven’t revealed enough information for them to figure out who were are talking about.

Of course, “interesting” is a relative term. If your spouse’s postgraduate degree is in computer science and not in medicine, he or she may not find your story about “the highest creatinine I have ever seen” very titillating. But, the story that begins, “You won’t believe what this mother was feeding her 6-month-old” might get his or her attention.

Although you may have known it wasn’t professional, I suspect that there may have been a few times when you have thrown caution to the wind and made no attempt to disguise the identity of the patient even though it was someone with whom your spouse was familiar. It may not have happened to you, but I can’t believe it never happens. Marriages are, or at least should be, very intimate and trusting relationships.

I think that many, maybe most, of the patients and parents in your practice assume that you have shared their stories with your spouse. My wife has often encountered a patient in the grocery store who launches into a story about their child’s illness and is surprised that Marilyn had no idea that the child had even been sick.

I also think that those people who believe the doctors share patient information with their spouses also believe that one of the marriage vows includes a clause in which spouses of physicians swear to keep those shared stories within the confines of the marriage.

Mind you, I’m not advocating that physicians should feel free to share any and all patient information with their spouses. In fact, I think as a rule, it shouldn’t happen, if for no other reason than it puts pressure on a spouse, who may fear that he or she might spread the tidbit inadvertently. But I think we have to be honest, human nature being what it is. Intramarital information sharing happens. Do you agree?

The anterior cruciate ligament (ACL) restrains anterior translation of the tibia on the femur and controls rotation of the knee. The natural primary healing potential of the ACL has been extremely poor in clinical and experimental studies, and primary suture repair has not provided stability to the joint in most patients.^1-8 This has led surgeons to reconstruct the ACL, rather than to attempt nonoperative treatment. Anterior cruciate ligament reconstruction is recommended to help patients maintain activities that place shear and torque forces on the knee or to ameliorate persistent pain due to instability.⁹ Reconstruction of the ACL in adults is one of the most common procedures performed by orthopedic surgeons. However, reconstruction in the ACL-deficient adolescent remains a controversial subject, with debates surrounding operative timing and surgical technique.

This case report presents a skeletally immature patient who suffered a complete traumatic rupture of his ACL, which intrinsically healed. The patient had a protracted treatment course, complicated by an open tibial fracture with delayed union. He responded to a progressive rehabilitation program and has made a good functional recovery. Review of the literature has demonstrated limited evidence of intrinsic ACL healing, none of which has been shown to occur in a skeletally immature patient. The patient’s mother provided written informed consent for print and electronic publication of this case report.

Case Report

A 12-year-old boy was brought to our level I trauma center by ambulance after being hit by a car while riding a motorized scooter. He presented with a grade IIIB open tibial fracture and a distal fibula fracture of his left lower extremity and was taken to the operating room that night for irrigation and débridement, percutaneous fixation of the fibula, and intramedullary flexible nail fixation of the tibia. On postoperative day 1, he had increasing pain and, once his splint was removed, his compartments were found to be very tense. He was taken emergently to the operating room for 4 compartment fasciotomies of the left lower extremity with wound vacuum-assisted closure (VAC) placement. This was changed on hospital day 4 and was removed with definitive closure on day 7. Examination under anesthesia prior to the final wound VAC change was performed given the patient’s complaints during physical therapy. This showed anterior and posterior ligamentous instability of the knee, and he was placed in a knee immobilizer. He was discharged on hospital day 11.

At 2-week follow-up, the patient was doing well, except that he was nonadherent with the knee immobilizer and unable to fully extend his left knee. On examination, a posterior drawer sign was noted; therefore, the patient was referred for magnetic resonance imaging (MRI) to evaluate his ligaments. His MRI, 9 weeks after injury, showed: (1) complete tears of both the anterior and posterior cruciate ligaments (PCLs) (Figures 1A, 1B); (2) medial meniscus and lateral meniscus tears; (3) 2.0-cm plate-like avulsion fracture of the posterolateral femoral metaphysis involving the insertion of the lateral head of the gastrocnemius muscle, fibular collateral ligament, and popliteus muscle (Figure 2); and (4) left posterior lateral tibial plateau contusion.

The patient was started on a 6-week course of physical therapy with active and active-assisted extension exercises. At follow-up approximately 3½ months after injury, he was found to have a 35º flexion contracture with pain at the end extension. Unfortunately, his tibial fracture showed minimal signs of healing, and the decision was made to delay surgical intervention on the knee until the tibial fracture had healed. He was given a knee orthotic to wear at night to help regain his knee extension.

Six months after injury, the patient underwent open removal of the avulsed bony fragment, posterior knee capsule release, and autograft of the delayed union tibial fracture. He was placed in a straight leg cast postoperatively and was discharged home on postoperative day 2. He transitioned to a knee immobilizer after 2 weeks. Six weeks after the last surgery, he had range of motion of 0º to 130º. Ligamentous examination at this time showed anterior and posterior drawer signs, positive Lachman test, and dial test with 90º of external rotation. He was placed in physical therapy for a total of 10 weeks to work on his quadriceps muscle strength and 15º extension lag.

On 13-month postinjury radiographs, the patient was noted to have adequate healing of his tibial fracture, and ligamentous reconstruction was discussed. At this time, the patient did not have any instability or pain in the knee. Examination demonstrated a very mild effusion of the left knee. Range of motion determined by goniometer was from -3º to 140º, and Lachman test was positive but with solid 2+ endpoint. He also had a positive posterior drawer sign with no endpoint, positive sag sign of his tibia, and positive active quadriceps test of the left leg. His dial test showed some increased external rotation at 90º but was equivocal at 30º when compared with the contralateral knee, demonstrating involvement of the posterolateral corner.

Sixteen months after injury, repeat MRI to further evaluate the posterolateral corner showed: (1) complete medial and lateral meniscal healing without evidence of residual or recurrent tear, and (2) interval healing of the remote ACL and PCL tears with intact insertions (Figures 3A, 3B). This scan showed an end-to-end continuous ACL with homogeneous signal and disappearance of the secondary signs. Physical examination at this time showed a very firm endpoint on Lachman test but some laxity with his posterior drawer. Given these findings, the patient was given a brace and continued in physical therapy to strengthen his quadriceps muscle. By 20 months after injury, he had returned to competitive hockey and had no complaints of pain or instability. His physical examination showed full range of motion in a ligamentously stable knee with firm endpoint. The patient’s condition was unchanged at 29-month follow-up.

Discussion

There is a body of evidence that states a completely ruptured ACL does not heal.^3,6,10 In animal models, the ACL has been shown to have poor healing potential.^3,11 Some studies have suggested this is secondary to poor blood supply. Blood supply to the ACL is derived from a periligamentous, then endoligamentous, arterial network with a less vascularized area in the middle third of the ACL. Additionally, there is no blood supply from the tibia or femur, meaning the areas of attachment of the ligament are poorly vascularized.¹² With a minimal blood supply to the ACL, the supply of undifferentiated mesenchymal cells from the surrounding tissue during the initial healing process is limited. In vitro cell cultures of these cells have showed a reduced potential for proliferation and migration.⁹ Cells of the ACL have a lower response to growth factors than human medial collateral ligament cells, further suggesting a decreased reparative capacity.⁷ Joint fluid has been shown to inhibit the proliferation of these cells, further reducing their regenerative potential.¹³ Additionally, biomechanical factors that alter signaling pathways, sites of ligament reattachment, and injury to proprioceptive structures have been shown to negatively influence the healing response.^14-18

Review of the literature on healing of ACLs includes 2 case reports, totaling 3 patients, and 3 level IV therapeutic studies involving 74 patients total.^10,19-22 In most cases, the authors of these studies have indicated a nonoperative treatment protocol with bracing and a specific rehabilitation program. Malanga and colleagues¹⁰ demonstrated that an ACL torn from its attachment on the femur, with the majority of the ligament in good condition and no compromise in the length, healed back onto the femur. Kurosaka and coauthors²⁰ described case reports of isolated distal or proximal midsubstance tears that have healed spontaneously. However, none of the patients described in the literature were under the age of 20 years.

Treatment for pediatric patients with open physes causes some debate. Nonoperative management of ACL deficiency in adolescents is generally not recommended because the continued instability of the joint leads to intra-articular injury, functional impairment, and joint degeneration.^23-25 A recent systematic review found only 1 study that showed no increase in secondary intra-articular injury when surgery was delayed until skeletal maturity.²⁶ 

Our patient was a 12-year-old boy whose traumatic knee injury with multiple ruptured ligaments healed over the course of 20 months. It is likely that bracing associated with the patient’s second surgery and delayed union of his tibial fracture allowed healing tissue to be protected from excessive stress until it remodeled with sufficient strength. Most would assume that healing would occur early, during the first 6 to 9 months; however, our patient regained his stability between 8 and 13 months. It is possible that the hostile healing environment of the ACL, including the low blood supply, poor response to growth factors, and biomechanical environment, as described previously, played a factor in this delay.^7,9,12,13

It is important to recognize that our patient tore his ACL during a traumatic motorized scooter rollover collision, not the more common noncontact twisting injury. Additionally, given the patient’s knee surgery that was performed 6 months after the initial injury, it is possible that intra-articular scar formation contributed to his healing capacity. While this patient did not undergo arthroscopy to visualize the tear in the ACL, or its reconstitution, recent evidence suggests that the accuracy of MRI in diagnosing pediatric ACL injuries is excellent.^27,28 The diagnostic accuracy with new MRI machines has sensitivity and specificity approaching 100%.²⁹ Additionally, the patient’s subjective and objective improvements argue for a change in anatomy over a change in the quality of his examination.

Conclusion

The goal of ACL reconstruction in adolescents is to provide long-term stability to the knee while minimizing the risk of growth disturbance. This goal was achieved in our patient through the in situ healing of his ACL. Intrinsic reconstitution of a torn ACL is rare, and it is difficult to speculate which patients may have some healing potential. While this patient was an extreme example, his case demonstrated that protection of the knee from undue stress could favorably alter the environment of the knee to allow for healing of ACL tears. Such information could be valuable in managing select pediatric patients with open physes and ACL injuries nonoperatively, sparing them from the risks associated with surgical treatment. While we do not recommend nonoperative treatment for patients with acute tears of the ACL, we believe more investigation into the healing potential of the ACL, and potential pathways to augment this, is warranted.

The anterior cruciate ligament (ACL) restrains anterior translation of the tibia on the femur and controls rotation of the knee. The natural primary healing potential of the ACL has been extremely poor in clinical and experimental studies, and primary suture repair has not provided stability to the joint in most patients.^1-8 This has led surgeons to reconstruct the ACL, rather than to attempt nonoperative treatment. Anterior cruciate ligament reconstruction is recommended to help patients maintain activities that place shear and torque forces on the knee or to ameliorate persistent pain due to instability.⁹ Reconstruction of the ACL in adults is one of the most common procedures performed by orthopedic surgeons. However, reconstruction in the ACL-deficient adolescent remains a controversial subject, with debates surrounding operative timing and surgical technique.

This case report presents a skeletally immature patient who suffered a complete traumatic rupture of his ACL, which intrinsically healed. The patient had a protracted treatment course, complicated by an open tibial fracture with delayed union. He responded to a progressive rehabilitation program and has made a good functional recovery. Review of the literature has demonstrated limited evidence of intrinsic ACL healing, none of which has been shown to occur in a skeletally immature patient. The patient’s mother provided written informed consent for print and electronic publication of this case report.

Case Report

A 12-year-old boy was brought to our level I trauma center by ambulance after being hit by a car while riding a motorized scooter. He presented with a grade IIIB open tibial fracture and a distal fibula fracture of his left lower extremity and was taken to the operating room that night for irrigation and débridement, percutaneous fixation of the fibula, and intramedullary flexible nail fixation of the tibia. On postoperative day 1, he had increasing pain and, once his splint was removed, his compartments were found to be very tense. He was taken emergently to the operating room for 4 compartment fasciotomies of the left lower extremity with wound vacuum-assisted closure (VAC) placement. This was changed on hospital day 4 and was removed with definitive closure on day 7. Examination under anesthesia prior to the final wound VAC change was performed given the patient’s complaints during physical therapy. This showed anterior and posterior ligamentous instability of the knee, and he was placed in a knee immobilizer. He was discharged on hospital day 11.

At 2-week follow-up, the patient was doing well, except that he was nonadherent with the knee immobilizer and unable to fully extend his left knee. On examination, a posterior drawer sign was noted; therefore, the patient was referred for magnetic resonance imaging (MRI) to evaluate his ligaments. His MRI, 9 weeks after injury, showed: (1) complete tears of both the anterior and posterior cruciate ligaments (PCLs) (Figures 1A, 1B); (2) medial meniscus and lateral meniscus tears; (3) 2.0-cm plate-like avulsion fracture of the posterolateral femoral metaphysis involving the insertion of the lateral head of the gastrocnemius muscle, fibular collateral ligament, and popliteus muscle (Figure 2); and (4) left posterior lateral tibial plateau contusion.

The patient was started on a 6-week course of physical therapy with active and active-assisted extension exercises. At follow-up approximately 3½ months after injury, he was found to have a 35º flexion contracture with pain at the end extension. Unfortunately, his tibial fracture showed minimal signs of healing, and the decision was made to delay surgical intervention on the knee until the tibial fracture had healed. He was given a knee orthotic to wear at night to help regain his knee extension.

Six months after injury, the patient underwent open removal of the avulsed bony fragment, posterior knee capsule release, and autograft of the delayed union tibial fracture. He was placed in a straight leg cast postoperatively and was discharged home on postoperative day 2. He transitioned to a knee immobilizer after 2 weeks. Six weeks after the last surgery, he had range of motion of 0º to 130º. Ligamentous examination at this time showed anterior and posterior drawer signs, positive Lachman test, and dial test with 90º of external rotation. He was placed in physical therapy for a total of 10 weeks to work on his quadriceps muscle strength and 15º extension lag.

On 13-month postinjury radiographs, the patient was noted to have adequate healing of his tibial fracture, and ligamentous reconstruction was discussed. At this time, the patient did not have any instability or pain in the knee. Examination demonstrated a very mild effusion of the left knee. Range of motion determined by goniometer was from -3º to 140º, and Lachman test was positive but with solid 2+ endpoint. He also had a positive posterior drawer sign with no endpoint, positive sag sign of his tibia, and positive active quadriceps test of the left leg. His dial test showed some increased external rotation at 90º but was equivocal at 30º when compared with the contralateral knee, demonstrating involvement of the posterolateral corner.

Sixteen months after injury, repeat MRI to further evaluate the posterolateral corner showed: (1) complete medial and lateral meniscal healing without evidence of residual or recurrent tear, and (2) interval healing of the remote ACL and PCL tears with intact insertions (Figures 3A, 3B). This scan showed an end-to-end continuous ACL with homogeneous signal and disappearance of the secondary signs. Physical examination at this time showed a very firm endpoint on Lachman test but some laxity with his posterior drawer. Given these findings, the patient was given a brace and continued in physical therapy to strengthen his quadriceps muscle. By 20 months after injury, he had returned to competitive hockey and had no complaints of pain or instability. His physical examination showed full range of motion in a ligamentously stable knee with firm endpoint. The patient’s condition was unchanged at 29-month follow-up.

Discussion

There is a body of evidence that states a completely ruptured ACL does not heal.^3,6,10 In animal models, the ACL has been shown to have poor healing potential.^3,11 Some studies have suggested this is secondary to poor blood supply. Blood supply to the ACL is derived from a periligamentous, then endoligamentous, arterial network with a less vascularized area in the middle third of the ACL. Additionally, there is no blood supply from the tibia or femur, meaning the areas of attachment of the ligament are poorly vascularized.¹² With a minimal blood supply to the ACL, the supply of undifferentiated mesenchymal cells from the surrounding tissue during the initial healing process is limited. In vitro cell cultures of these cells have showed a reduced potential for proliferation and migration.⁹ Cells of the ACL have a lower response to growth factors than human medial collateral ligament cells, further suggesting a decreased reparative capacity.⁷ Joint fluid has been shown to inhibit the proliferation of these cells, further reducing their regenerative potential.¹³ Additionally, biomechanical factors that alter signaling pathways, sites of ligament reattachment, and injury to proprioceptive structures have been shown to negatively influence the healing response.^14-18

Review of the literature on healing of ACLs includes 2 case reports, totaling 3 patients, and 3 level IV therapeutic studies involving 74 patients total.^10,19-22 In most cases, the authors of these studies have indicated a nonoperative treatment protocol with bracing and a specific rehabilitation program. Malanga and colleagues¹⁰ demonstrated that an ACL torn from its attachment on the femur, with the majority of the ligament in good condition and no compromise in the length, healed back onto the femur. Kurosaka and coauthors²⁰ described case reports of isolated distal or proximal midsubstance tears that have healed spontaneously. However, none of the patients described in the literature were under the age of 20 years.

Treatment for pediatric patients with open physes causes some debate. Nonoperative management of ACL deficiency in adolescents is generally not recommended because the continued instability of the joint leads to intra-articular injury, functional impairment, and joint degeneration.^23-25 A recent systematic review found only 1 study that showed no increase in secondary intra-articular injury when surgery was delayed until skeletal maturity.²⁶ 

Our patient was a 12-year-old boy whose traumatic knee injury with multiple ruptured ligaments healed over the course of 20 months. It is likely that bracing associated with the patient’s second surgery and delayed union of his tibial fracture allowed healing tissue to be protected from excessive stress until it remodeled with sufficient strength. Most would assume that healing would occur early, during the first 6 to 9 months; however, our patient regained his stability between 8 and 13 months. It is possible that the hostile healing environment of the ACL, including the low blood supply, poor response to growth factors, and biomechanical environment, as described previously, played a factor in this delay.^7,9,12,13

It is important to recognize that our patient tore his ACL during a traumatic motorized scooter rollover collision, not the more common noncontact twisting injury. Additionally, given the patient’s knee surgery that was performed 6 months after the initial injury, it is possible that intra-articular scar formation contributed to his healing capacity. While this patient did not undergo arthroscopy to visualize the tear in the ACL, or its reconstitution, recent evidence suggests that the accuracy of MRI in diagnosing pediatric ACL injuries is excellent.^27,28 The diagnostic accuracy with new MRI machines has sensitivity and specificity approaching 100%.²⁹ Additionally, the patient’s subjective and objective improvements argue for a change in anatomy over a change in the quality of his examination.

Conclusion

The goal of ACL reconstruction in adolescents is to provide long-term stability to the knee while minimizing the risk of growth disturbance. This goal was achieved in our patient through the in situ healing of his ACL. Intrinsic reconstitution of a torn ACL is rare, and it is difficult to speculate which patients may have some healing potential. While this patient was an extreme example, his case demonstrated that protection of the knee from undue stress could favorably alter the environment of the knee to allow for healing of ACL tears. Such information could be valuable in managing select pediatric patients with open physes and ACL injuries nonoperatively, sparing them from the risks associated with surgical treatment. While we do not recommend nonoperative treatment for patients with acute tears of the ACL, we believe more investigation into the healing potential of the ACL, and potential pathways to augment this, is warranted.

The anterior cruciate ligament (ACL) restrains anterior translation of the tibia on the femur and controls rotation of the knee. The natural primary healing potential of the ACL has been extremely poor in clinical and experimental studies, and primary suture repair has not provided stability to the joint in most patients.^1-8 This has led surgeons to reconstruct the ACL, rather than to attempt nonoperative treatment. Anterior cruciate ligament reconstruction is recommended to help patients maintain activities that place shear and torque forces on the knee or to ameliorate persistent pain due to instability.⁹ Reconstruction of the ACL in adults is one of the most common procedures performed by orthopedic surgeons. However, reconstruction in the ACL-deficient adolescent remains a controversial subject, with debates surrounding operative timing and surgical technique.

This case report presents a skeletally immature patient who suffered a complete traumatic rupture of his ACL, which intrinsically healed. The patient had a protracted treatment course, complicated by an open tibial fracture with delayed union. He responded to a progressive rehabilitation program and has made a good functional recovery. Review of the literature has demonstrated limited evidence of intrinsic ACL healing, none of which has been shown to occur in a skeletally immature patient. The patient’s mother provided written informed consent for print and electronic publication of this case report.

Case Report

A 12-year-old boy was brought to our level I trauma center by ambulance after being hit by a car while riding a motorized scooter. He presented with a grade IIIB open tibial fracture and a distal fibula fracture of his left lower extremity and was taken to the operating room that night for irrigation and débridement, percutaneous fixation of the fibula, and intramedullary flexible nail fixation of the tibia. On postoperative day 1, he had increasing pain and, once his splint was removed, his compartments were found to be very tense. He was taken emergently to the operating room for 4 compartment fasciotomies of the left lower extremity with wound vacuum-assisted closure (VAC) placement. This was changed on hospital day 4 and was removed with definitive closure on day 7. Examination under anesthesia prior to the final wound VAC change was performed given the patient’s complaints during physical therapy. This showed anterior and posterior ligamentous instability of the knee, and he was placed in a knee immobilizer. He was discharged on hospital day 11.

At 2-week follow-up, the patient was doing well, except that he was nonadherent with the knee immobilizer and unable to fully extend his left knee. On examination, a posterior drawer sign was noted; therefore, the patient was referred for magnetic resonance imaging (MRI) to evaluate his ligaments. His MRI, 9 weeks after injury, showed: (1) complete tears of both the anterior and posterior cruciate ligaments (PCLs) (Figures 1A, 1B); (2) medial meniscus and lateral meniscus tears; (3) 2.0-cm plate-like avulsion fracture of the posterolateral femoral metaphysis involving the insertion of the lateral head of the gastrocnemius muscle, fibular collateral ligament, and popliteus muscle (Figure 2); and (4) left posterior lateral tibial plateau contusion.

The patient was started on a 6-week course of physical therapy with active and active-assisted extension exercises. At follow-up approximately 3½ months after injury, he was found to have a 35º flexion contracture with pain at the end extension. Unfortunately, his tibial fracture showed minimal signs of healing, and the decision was made to delay surgical intervention on the knee until the tibial fracture had healed. He was given a knee orthotic to wear at night to help regain his knee extension.

Six months after injury, the patient underwent open removal of the avulsed bony fragment, posterior knee capsule release, and autograft of the delayed union tibial fracture. He was placed in a straight leg cast postoperatively and was discharged home on postoperative day 2. He transitioned to a knee immobilizer after 2 weeks. Six weeks after the last surgery, he had range of motion of 0º to 130º. Ligamentous examination at this time showed anterior and posterior drawer signs, positive Lachman test, and dial test with 90º of external rotation. He was placed in physical therapy for a total of 10 weeks to work on his quadriceps muscle strength and 15º extension lag.

On 13-month postinjury radiographs, the patient was noted to have adequate healing of his tibial fracture, and ligamentous reconstruction was discussed. At this time, the patient did not have any instability or pain in the knee. Examination demonstrated a very mild effusion of the left knee. Range of motion determined by goniometer was from -3º to 140º, and Lachman test was positive but with solid 2+ endpoint. He also had a positive posterior drawer sign with no endpoint, positive sag sign of his tibia, and positive active quadriceps test of the left leg. His dial test showed some increased external rotation at 90º but was equivocal at 30º when compared with the contralateral knee, demonstrating involvement of the posterolateral corner.

Sixteen months after injury, repeat MRI to further evaluate the posterolateral corner showed: (1) complete medial and lateral meniscal healing without evidence of residual or recurrent tear, and (2) interval healing of the remote ACL and PCL tears with intact insertions (Figures 3A, 3B). This scan showed an end-to-end continuous ACL with homogeneous signal and disappearance of the secondary signs. Physical examination at this time showed a very firm endpoint on Lachman test but some laxity with his posterior drawer. Given these findings, the patient was given a brace and continued in physical therapy to strengthen his quadriceps muscle. By 20 months after injury, he had returned to competitive hockey and had no complaints of pain or instability. His physical examination showed full range of motion in a ligamentously stable knee with firm endpoint. The patient’s condition was unchanged at 29-month follow-up.

Discussion

There is a body of evidence that states a completely ruptured ACL does not heal.^3,6,10 In animal models, the ACL has been shown to have poor healing potential.^3,11 Some studies have suggested this is secondary to poor blood supply. Blood supply to the ACL is derived from a periligamentous, then endoligamentous, arterial network with a less vascularized area in the middle third of the ACL. Additionally, there is no blood supply from the tibia or femur, meaning the areas of attachment of the ligament are poorly vascularized.¹² With a minimal blood supply to the ACL, the supply of undifferentiated mesenchymal cells from the surrounding tissue during the initial healing process is limited. In vitro cell cultures of these cells have showed a reduced potential for proliferation and migration.⁹ Cells of the ACL have a lower response to growth factors than human medial collateral ligament cells, further suggesting a decreased reparative capacity.⁷ Joint fluid has been shown to inhibit the proliferation of these cells, further reducing their regenerative potential.¹³ Additionally, biomechanical factors that alter signaling pathways, sites of ligament reattachment, and injury to proprioceptive structures have been shown to negatively influence the healing response.^14-18

Review of the literature on healing of ACLs includes 2 case reports, totaling 3 patients, and 3 level IV therapeutic studies involving 74 patients total.^10,19-22 In most cases, the authors of these studies have indicated a nonoperative treatment protocol with bracing and a specific rehabilitation program. Malanga and colleagues¹⁰ demonstrated that an ACL torn from its attachment on the femur, with the majority of the ligament in good condition and no compromise in the length, healed back onto the femur. Kurosaka and coauthors²⁰ described case reports of isolated distal or proximal midsubstance tears that have healed spontaneously. However, none of the patients described in the literature were under the age of 20 years.

Treatment for pediatric patients with open physes causes some debate. Nonoperative management of ACL deficiency in adolescents is generally not recommended because the continued instability of the joint leads to intra-articular injury, functional impairment, and joint degeneration.^23-25 A recent systematic review found only 1 study that showed no increase in secondary intra-articular injury when surgery was delayed until skeletal maturity.²⁶ 

Our patient was a 12-year-old boy whose traumatic knee injury with multiple ruptured ligaments healed over the course of 20 months. It is likely that bracing associated with the patient’s second surgery and delayed union of his tibial fracture allowed healing tissue to be protected from excessive stress until it remodeled with sufficient strength. Most would assume that healing would occur early, during the first 6 to 9 months; however, our patient regained his stability between 8 and 13 months. It is possible that the hostile healing environment of the ACL, including the low blood supply, poor response to growth factors, and biomechanical environment, as described previously, played a factor in this delay.^7,9,12,13

It is important to recognize that our patient tore his ACL during a traumatic motorized scooter rollover collision, not the more common noncontact twisting injury. Additionally, given the patient’s knee surgery that was performed 6 months after the initial injury, it is possible that intra-articular scar formation contributed to his healing capacity. While this patient did not undergo arthroscopy to visualize the tear in the ACL, or its reconstitution, recent evidence suggests that the accuracy of MRI in diagnosing pediatric ACL injuries is excellent.^27,28 The diagnostic accuracy with new MRI machines has sensitivity and specificity approaching 100%.²⁹ Additionally, the patient’s subjective and objective improvements argue for a change in anatomy over a change in the quality of his examination.

Conclusion

The goal of ACL reconstruction in adolescents is to provide long-term stability to the knee while minimizing the risk of growth disturbance. This goal was achieved in our patient through the in situ healing of his ACL. Intrinsic reconstitution of a torn ACL is rare, and it is difficult to speculate which patients may have some healing potential. While this patient was an extreme example, his case demonstrated that protection of the knee from undue stress could favorably alter the environment of the knee to allow for healing of ACL tears. Such information could be valuable in managing select pediatric patients with open physes and ACL injuries nonoperatively, sparing them from the risks associated with surgical treatment. While we do not recommend nonoperative treatment for patients with acute tears of the ACL, we believe more investigation into the healing potential of the ACL, and potential pathways to augment this, is warranted.

Fracture blisters are a relatively uncommon complication of high-energy fractures, with an incidence of 2.9%.¹ In the lower extremity, fracture blisters almost always occur distal to the knee.¹ Histologically, the blisters represent an injury to the dermoepidermal junction.² On physical examination, there are tense blood- and/or clear fluid–filled bullae overlying markedly swollen and edematous soft tissue,¹ resembling a second-degree burn.³ Infection may develop after fracture blisters,¹ and this is perhaps the most dreaded complication of total knee arthroplasty (TKA). The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 71-year-old man with end-stage osteoarthritis of the right knee underwent an elective TKA with cemented components (Legion PS; Smith & Nephew). His medical history included venous insufficiency, type 2 diabetes mellitus, chronic obstructive sleep apnea, hypertension, morbid obesity (body mass index, 50), and a previous uneventful left TKA. Tourniquet time was 78 minutes and estimated blood loss was 100 mL. An intra-articular drain was used and was removed on the first postoperative day. After wound closure, a soft splint bandage consisting of 2 to 3 layers of cotton and bias wrap was applied. Deep vein thrombosis (DVT) prophylaxis with enoxaparin 40 mg once daily was started on the first postoperative day.

Upon removal of the surgical dressings on the second postoperative day, the anterior leg was found to have a combination of tense clear fluid– and blood-filled blisters on markedly swollen and erythematous skin. The incision was minimally involved (Figure A). There was diffuse 2+ pitting edema with hyperesthesia in the affected skin distal to the knee. Prior to these findings, the patient had complained of increasing pain in his operative leg, but there was no escalation in analgesic requirements. There was no evidence of compartment syndrome on serial examinations. An ultrasound of the lower extremity was negative for DVT. Plain films did not show iatrogenic fractures. There was no intraoperative vascular injury, and the foot pulses remained unchanged between the time the patient was in the preoperative holding unit, the postanesthesia care unit, and the orthopedic ward. The operative leg was treated with elevation and loosely applied Kerlix roll gauze (Kendall, Covidien), but active blister formation continued for another 2 days. A 10-day prophylactic course of trimethoprim/sulfamethoxazole was initiated on the third postoperative day after the blisters started to rupture. The patient was allowed to bear weight as tolerated, but his physical therapy (PT) course was limited by pain and fear “of losing his leg.” He declined several PT sessions and was hesitant to use continuous passive motion. The patient was discharged to a short-term rehabilitation facility with weekly outpatient follow-up. On the second postoperative week, his fluid-filled blisters completely reepithelialized, but the blood-filled blisters required an additional week for reepithelialization (Figure B). While the patient’s knee was stiff because of limited PT participation, it was not until the second postoperative week when most of the fracture blisters had healed that he was able to resume an intensive knee exercise program, avoiding the need for manipulation under anesthesia.

Discussion

Giordano and colleagues² identified 2 types of fracture blisters: clear fluid– and blood-filled. While both types involved disruption of the dermoepidermal junction, greater disruption and complete absence of dermal epithelial cells was observed in the hemorrhagic type. Clinical follow-up of the patients in the study by Giordano and colleagues² showed that the mean time for reepithelialization was 12 days for fluid-filled blisters and 16 days for blood-filled blisters. These findings are similar to what we observed in our case report. In particular, the fluid-filled blisters healed in 2 weeks, whereas the blood-filled blisters required 3 weeks to heal.

The etiology of the fracture blisters in this patient is likely multifactorial and related to age, obesity, venous insufficiency, and diabetes mellitus. Farage and colleagues⁴ described a series of progressive degenerative changes in the aging skin, including vascular atrophy and degradation of dermal connective tissue, leading to compromised skin competence. The integrity of the dermis can be further reduced in patients with diabetes through glycosylation of collagen fibrils.⁵ Compared with age-matched normal controls, patients with insulin-dependent diabetes have a reduced threshold to suction-induced blister formation.⁶ Obesity is another potential contributing factor, with multiple studies showing significantly impaired venous flow in obese patients.^7,8 Taken together, soft-tissue swelling after surgery in the setting of chronic venous insufficiency and compromised skin due to advanced age and diabetes may lead to markedly elevated interstitial pressure. One mechanism to relieve such abnormally high pressure is the formation of fracture blisters.¹

Surgical risk factors that could have contributed to the complication in this case include the surgical skin preparation solution (ChloraPrep; CareFusion), use of adhesive antimicrobial drape (Ioban, 3M), tourniquet time, dressing choice, and DVT prophylaxis regimen. While the skin preparation solution is an unlikely culprit since the presentation is not consistent with contact dermatitis, inappropriate strapping or removal of the adhesive drape could result in stretch injury of the skin, shearing the dermoepidermal junction and causing tension blisters.⁹ There were no intraoperative complications and the tourniquet time was appropriate (78 minutes). Postoperatively, no compressive or adhesive dressings were used. With regards to DVT prophylaxis, the patient received a single dose of enoxaparin on the first postoperative day. While heparin-induced hemorrhagic blisters have been reported,¹⁰ I do not feel that the use of enoxaparin was a contributing factor. Heparin-induced blisters have been described as systemic blisters,¹⁰ whereas the blisters in this case were confined to the operative extremity. The patient was not taking any nutritional supplements (eg, fish oil, vitamin E) that could have increased his risk of bleeding. Throughout his hospital stay, he was hemodynamically stable and did not require blood transfusion.

Management of fracture blisters is controversial, and there is no consensus on appropriate soft-tissue handling. In this patient, the blisters were left intact. Blister fluid has been shown to be sterile, containing growth factors, opsonins, and activated neutrophils that aid in healing and infection prevention.¹ Giordano and Koval¹¹ found no difference in the outcome of 3 soft-tissue treatment techniques: (1) aspiration of the blister, (2) deroofing of the blister followed by application of a topical antibiotic cream or coverage with nonadherent dressing, or (3) keeping the blister intact and covered with loose dressing or exposed to air. In contrast, Strauss and colleagues¹² found that deroofing the fracture blister to healthy tissue followed by twice-daily application of silver sulfadiazine antibiotic cream promoted reepithelialization and resulted in better cosmetic appearance and higher patient satisfaction. 

The optimal dressing for fracture blisters remains elusive. Madden and colleagues¹³ showed that the use of occlusive nonadherent dressing was associated with significantly faster healing and less pain compared with semiocclusive, antibiotic-impregnated dressings. In another study, Varela and colleagues¹ found no differences in blister healing between patients treated with either (1) dry dressing and casting, (2) Silvadene dressing (King Pharmaceuticals), or (3) whirlpool débridement and Silvadene dressing.

Infection is perhaps the most dreaded complication of fracture blisters after TKA. Varela and colleagues¹ showed that, while the fluid in intact blisters was a sterile transudate, polymicrobial colonization with skin flora often occurred soon after blister rupture and persisted until reepithelialization. Our patient received a 10-day course of prophylactic antibiotics and no superficial or deep infection developed; however, the real contribution of antibiotic prophylaxis to the absence of infection cannot be established based solely on 1 case.

Pain is another concern associated with fracture blisters. Our patient had significant pain that limited his ability to participate in PT, resulting in limited knee range of motion and eventual discharge to a short-term rehabilitation facility. Fortunately, after resolution of the fracture blisters, he was able to participate in an aggressive rehabilitation program. By 6 weeks after surgery, he had significant improvement in his knee motion, avoiding the need for manipulation under anesthesia.

Conclusion

This case represents the first reported fracture blisters after primary TKA. The risk of deep surgical site infection, a devastating complication after TKA, is perhaps the most frightening concern of this rare complication. While the etiology and the management are controversial, there is evidence to recommend prophylactic antibiotics after blister rupture and skin desquamation. The decision to withhold DVT prophylaxis should be based on individual patient risk factors and blister type (blood-filled vs clear fluid–filled). Patients should be encouraged to continue knee exercises during reepithelialization to avoid stiffness.

Fracture blisters are a relatively uncommon complication of high-energy fractures, with an incidence of 2.9%.¹ In the lower extremity, fracture blisters almost always occur distal to the knee.¹ Histologically, the blisters represent an injury to the dermoepidermal junction.² On physical examination, there are tense blood- and/or clear fluid–filled bullae overlying markedly swollen and edematous soft tissue,¹ resembling a second-degree burn.³ Infection may develop after fracture blisters,¹ and this is perhaps the most dreaded complication of total knee arthroplasty (TKA). The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 71-year-old man with end-stage osteoarthritis of the right knee underwent an elective TKA with cemented components (Legion PS; Smith & Nephew). His medical history included venous insufficiency, type 2 diabetes mellitus, chronic obstructive sleep apnea, hypertension, morbid obesity (body mass index, 50), and a previous uneventful left TKA. Tourniquet time was 78 minutes and estimated blood loss was 100 mL. An intra-articular drain was used and was removed on the first postoperative day. After wound closure, a soft splint bandage consisting of 2 to 3 layers of cotton and bias wrap was applied. Deep vein thrombosis (DVT) prophylaxis with enoxaparin 40 mg once daily was started on the first postoperative day.

Upon removal of the surgical dressings on the second postoperative day, the anterior leg was found to have a combination of tense clear fluid– and blood-filled blisters on markedly swollen and erythematous skin. The incision was minimally involved (Figure A). There was diffuse 2+ pitting edema with hyperesthesia in the affected skin distal to the knee. Prior to these findings, the patient had complained of increasing pain in his operative leg, but there was no escalation in analgesic requirements. There was no evidence of compartment syndrome on serial examinations. An ultrasound of the lower extremity was negative for DVT. Plain films did not show iatrogenic fractures. There was no intraoperative vascular injury, and the foot pulses remained unchanged between the time the patient was in the preoperative holding unit, the postanesthesia care unit, and the orthopedic ward. The operative leg was treated with elevation and loosely applied Kerlix roll gauze (Kendall, Covidien), but active blister formation continued for another 2 days. A 10-day prophylactic course of trimethoprim/sulfamethoxazole was initiated on the third postoperative day after the blisters started to rupture. The patient was allowed to bear weight as tolerated, but his physical therapy (PT) course was limited by pain and fear “of losing his leg.” He declined several PT sessions and was hesitant to use continuous passive motion. The patient was discharged to a short-term rehabilitation facility with weekly outpatient follow-up. On the second postoperative week, his fluid-filled blisters completely reepithelialized, but the blood-filled blisters required an additional week for reepithelialization (Figure B). While the patient’s knee was stiff because of limited PT participation, it was not until the second postoperative week when most of the fracture blisters had healed that he was able to resume an intensive knee exercise program, avoiding the need for manipulation under anesthesia.

Discussion

Giordano and colleagues² identified 2 types of fracture blisters: clear fluid– and blood-filled. While both types involved disruption of the dermoepidermal junction, greater disruption and complete absence of dermal epithelial cells was observed in the hemorrhagic type. Clinical follow-up of the patients in the study by Giordano and colleagues² showed that the mean time for reepithelialization was 12 days for fluid-filled blisters and 16 days for blood-filled blisters. These findings are similar to what we observed in our case report. In particular, the fluid-filled blisters healed in 2 weeks, whereas the blood-filled blisters required 3 weeks to heal.

The etiology of the fracture blisters in this patient is likely multifactorial and related to age, obesity, venous insufficiency, and diabetes mellitus. Farage and colleagues⁴ described a series of progressive degenerative changes in the aging skin, including vascular atrophy and degradation of dermal connective tissue, leading to compromised skin competence. The integrity of the dermis can be further reduced in patients with diabetes through glycosylation of collagen fibrils.⁵ Compared with age-matched normal controls, patients with insulin-dependent diabetes have a reduced threshold to suction-induced blister formation.⁶ Obesity is another potential contributing factor, with multiple studies showing significantly impaired venous flow in obese patients.^7,8 Taken together, soft-tissue swelling after surgery in the setting of chronic venous insufficiency and compromised skin due to advanced age and diabetes may lead to markedly elevated interstitial pressure. One mechanism to relieve such abnormally high pressure is the formation of fracture blisters.¹

Surgical risk factors that could have contributed to the complication in this case include the surgical skin preparation solution (ChloraPrep; CareFusion), use of adhesive antimicrobial drape (Ioban, 3M), tourniquet time, dressing choice, and DVT prophylaxis regimen. While the skin preparation solution is an unlikely culprit since the presentation is not consistent with contact dermatitis, inappropriate strapping or removal of the adhesive drape could result in stretch injury of the skin, shearing the dermoepidermal junction and causing tension blisters.⁹ There were no intraoperative complications and the tourniquet time was appropriate (78 minutes). Postoperatively, no compressive or adhesive dressings were used. With regards to DVT prophylaxis, the patient received a single dose of enoxaparin on the first postoperative day. While heparin-induced hemorrhagic blisters have been reported,¹⁰ I do not feel that the use of enoxaparin was a contributing factor. Heparin-induced blisters have been described as systemic blisters,¹⁰ whereas the blisters in this case were confined to the operative extremity. The patient was not taking any nutritional supplements (eg, fish oil, vitamin E) that could have increased his risk of bleeding. Throughout his hospital stay, he was hemodynamically stable and did not require blood transfusion.

Management of fracture blisters is controversial, and there is no consensus on appropriate soft-tissue handling. In this patient, the blisters were left intact. Blister fluid has been shown to be sterile, containing growth factors, opsonins, and activated neutrophils that aid in healing and infection prevention.¹ Giordano and Koval¹¹ found no difference in the outcome of 3 soft-tissue treatment techniques: (1) aspiration of the blister, (2) deroofing of the blister followed by application of a topical antibiotic cream or coverage with nonadherent dressing, or (3) keeping the blister intact and covered with loose dressing or exposed to air. In contrast, Strauss and colleagues¹² found that deroofing the fracture blister to healthy tissue followed by twice-daily application of silver sulfadiazine antibiotic cream promoted reepithelialization and resulted in better cosmetic appearance and higher patient satisfaction. 

The optimal dressing for fracture blisters remains elusive. Madden and colleagues¹³ showed that the use of occlusive nonadherent dressing was associated with significantly faster healing and less pain compared with semiocclusive, antibiotic-impregnated dressings. In another study, Varela and colleagues¹ found no differences in blister healing between patients treated with either (1) dry dressing and casting, (2) Silvadene dressing (King Pharmaceuticals), or (3) whirlpool débridement and Silvadene dressing.

Infection is perhaps the most dreaded complication of fracture blisters after TKA. Varela and colleagues¹ showed that, while the fluid in intact blisters was a sterile transudate, polymicrobial colonization with skin flora often occurred soon after blister rupture and persisted until reepithelialization. Our patient received a 10-day course of prophylactic antibiotics and no superficial or deep infection developed; however, the real contribution of antibiotic prophylaxis to the absence of infection cannot be established based solely on 1 case.

Pain is another concern associated with fracture blisters. Our patient had significant pain that limited his ability to participate in PT, resulting in limited knee range of motion and eventual discharge to a short-term rehabilitation facility. Fortunately, after resolution of the fracture blisters, he was able to participate in an aggressive rehabilitation program. By 6 weeks after surgery, he had significant improvement in his knee motion, avoiding the need for manipulation under anesthesia.

Conclusion

This case represents the first reported fracture blisters after primary TKA. The risk of deep surgical site infection, a devastating complication after TKA, is perhaps the most frightening concern of this rare complication. While the etiology and the management are controversial, there is evidence to recommend prophylactic antibiotics after blister rupture and skin desquamation. The decision to withhold DVT prophylaxis should be based on individual patient risk factors and blister type (blood-filled vs clear fluid–filled). Patients should be encouraged to continue knee exercises during reepithelialization to avoid stiffness.

Fracture blisters are a relatively uncommon complication of high-energy fractures, with an incidence of 2.9%.¹ In the lower extremity, fracture blisters almost always occur distal to the knee.¹ Histologically, the blisters represent an injury to the dermoepidermal junction.² On physical examination, there are tense blood- and/or clear fluid–filled bullae overlying markedly swollen and edematous soft tissue,¹ resembling a second-degree burn.³ Infection may develop after fracture blisters,¹ and this is perhaps the most dreaded complication of total knee arthroplasty (TKA). The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 71-year-old man with end-stage osteoarthritis of the right knee underwent an elective TKA with cemented components (Legion PS; Smith & Nephew). His medical history included venous insufficiency, type 2 diabetes mellitus, chronic obstructive sleep apnea, hypertension, morbid obesity (body mass index, 50), and a previous uneventful left TKA. Tourniquet time was 78 minutes and estimated blood loss was 100 mL. An intra-articular drain was used and was removed on the first postoperative day. After wound closure, a soft splint bandage consisting of 2 to 3 layers of cotton and bias wrap was applied. Deep vein thrombosis (DVT) prophylaxis with enoxaparin 40 mg once daily was started on the first postoperative day.

Upon removal of the surgical dressings on the second postoperative day, the anterior leg was found to have a combination of tense clear fluid– and blood-filled blisters on markedly swollen and erythematous skin. The incision was minimally involved (Figure A). There was diffuse 2+ pitting edema with hyperesthesia in the affected skin distal to the knee. Prior to these findings, the patient had complained of increasing pain in his operative leg, but there was no escalation in analgesic requirements. There was no evidence of compartment syndrome on serial examinations. An ultrasound of the lower extremity was negative for DVT. Plain films did not show iatrogenic fractures. There was no intraoperative vascular injury, and the foot pulses remained unchanged between the time the patient was in the preoperative holding unit, the postanesthesia care unit, and the orthopedic ward. The operative leg was treated with elevation and loosely applied Kerlix roll gauze (Kendall, Covidien), but active blister formation continued for another 2 days. A 10-day prophylactic course of trimethoprim/sulfamethoxazole was initiated on the third postoperative day after the blisters started to rupture. The patient was allowed to bear weight as tolerated, but his physical therapy (PT) course was limited by pain and fear “of losing his leg.” He declined several PT sessions and was hesitant to use continuous passive motion. The patient was discharged to a short-term rehabilitation facility with weekly outpatient follow-up. On the second postoperative week, his fluid-filled blisters completely reepithelialized, but the blood-filled blisters required an additional week for reepithelialization (Figure B). While the patient’s knee was stiff because of limited PT participation, it was not until the second postoperative week when most of the fracture blisters had healed that he was able to resume an intensive knee exercise program, avoiding the need for manipulation under anesthesia.

Discussion

Giordano and colleagues² identified 2 types of fracture blisters: clear fluid– and blood-filled. While both types involved disruption of the dermoepidermal junction, greater disruption and complete absence of dermal epithelial cells was observed in the hemorrhagic type. Clinical follow-up of the patients in the study by Giordano and colleagues² showed that the mean time for reepithelialization was 12 days for fluid-filled blisters and 16 days for blood-filled blisters. These findings are similar to what we observed in our case report. In particular, the fluid-filled blisters healed in 2 weeks, whereas the blood-filled blisters required 3 weeks to heal.

The etiology of the fracture blisters in this patient is likely multifactorial and related to age, obesity, venous insufficiency, and diabetes mellitus. Farage and colleagues⁴ described a series of progressive degenerative changes in the aging skin, including vascular atrophy and degradation of dermal connective tissue, leading to compromised skin competence. The integrity of the dermis can be further reduced in patients with diabetes through glycosylation of collagen fibrils.⁵ Compared with age-matched normal controls, patients with insulin-dependent diabetes have a reduced threshold to suction-induced blister formation.⁶ Obesity is another potential contributing factor, with multiple studies showing significantly impaired venous flow in obese patients.^7,8 Taken together, soft-tissue swelling after surgery in the setting of chronic venous insufficiency and compromised skin due to advanced age and diabetes may lead to markedly elevated interstitial pressure. One mechanism to relieve such abnormally high pressure is the formation of fracture blisters.¹

Surgical risk factors that could have contributed to the complication in this case include the surgical skin preparation solution (ChloraPrep; CareFusion), use of adhesive antimicrobial drape (Ioban, 3M), tourniquet time, dressing choice, and DVT prophylaxis regimen. While the skin preparation solution is an unlikely culprit since the presentation is not consistent with contact dermatitis, inappropriate strapping or removal of the adhesive drape could result in stretch injury of the skin, shearing the dermoepidermal junction and causing tension blisters.⁹ There were no intraoperative complications and the tourniquet time was appropriate (78 minutes). Postoperatively, no compressive or adhesive dressings were used. With regards to DVT prophylaxis, the patient received a single dose of enoxaparin on the first postoperative day. While heparin-induced hemorrhagic blisters have been reported,¹⁰ I do not feel that the use of enoxaparin was a contributing factor. Heparin-induced blisters have been described as systemic blisters,¹⁰ whereas the blisters in this case were confined to the operative extremity. The patient was not taking any nutritional supplements (eg, fish oil, vitamin E) that could have increased his risk of bleeding. Throughout his hospital stay, he was hemodynamically stable and did not require blood transfusion.

Management of fracture blisters is controversial, and there is no consensus on appropriate soft-tissue handling. In this patient, the blisters were left intact. Blister fluid has been shown to be sterile, containing growth factors, opsonins, and activated neutrophils that aid in healing and infection prevention.¹ Giordano and Koval¹¹ found no difference in the outcome of 3 soft-tissue treatment techniques: (1) aspiration of the blister, (2) deroofing of the blister followed by application of a topical antibiotic cream or coverage with nonadherent dressing, or (3) keeping the blister intact and covered with loose dressing or exposed to air. In contrast, Strauss and colleagues¹² found that deroofing the fracture blister to healthy tissue followed by twice-daily application of silver sulfadiazine antibiotic cream promoted reepithelialization and resulted in better cosmetic appearance and higher patient satisfaction. 

The optimal dressing for fracture blisters remains elusive. Madden and colleagues¹³ showed that the use of occlusive nonadherent dressing was associated with significantly faster healing and less pain compared with semiocclusive, antibiotic-impregnated dressings. In another study, Varela and colleagues¹ found no differences in blister healing between patients treated with either (1) dry dressing and casting, (2) Silvadene dressing (King Pharmaceuticals), or (3) whirlpool débridement and Silvadene dressing.

Infection is perhaps the most dreaded complication of fracture blisters after TKA. Varela and colleagues¹ showed that, while the fluid in intact blisters was a sterile transudate, polymicrobial colonization with skin flora often occurred soon after blister rupture and persisted until reepithelialization. Our patient received a 10-day course of prophylactic antibiotics and no superficial or deep infection developed; however, the real contribution of antibiotic prophylaxis to the absence of infection cannot be established based solely on 1 case.

Pain is another concern associated with fracture blisters. Our patient had significant pain that limited his ability to participate in PT, resulting in limited knee range of motion and eventual discharge to a short-term rehabilitation facility. Fortunately, after resolution of the fracture blisters, he was able to participate in an aggressive rehabilitation program. By 6 weeks after surgery, he had significant improvement in his knee motion, avoiding the need for manipulation under anesthesia.

Conclusion

This case represents the first reported fracture blisters after primary TKA. The risk of deep surgical site infection, a devastating complication after TKA, is perhaps the most frightening concern of this rare complication. While the etiology and the management are controversial, there is evidence to recommend prophylactic antibiotics after blister rupture and skin desquamation. The decision to withhold DVT prophylaxis should be based on individual patient risk factors and blister type (blood-filled vs clear fluid–filled). Patients should be encouraged to continue knee exercises during reepithelialization to avoid stiffness.

Synovial chondromatosis (SCM) is a relatively rare benign lesion of the synovium.¹ Its pathogenesis has been thought to be a chondral metaplasia of the subintimal layer of the intra- or extra-articular synovium.² However, evidence supporting a neoplastic cause of the disease is emerging.³ When intra-articular, any joint can be affected, though large joints are more prone to the disease; the knee, hip, and elbow are the most common locations.⁴ The synovial layer of tendons or bursae can be the origin of extra-articular SCM.⁵

Synovial chondrosarcoma (SCS), an even rarer pathology, can be caused by malignant transformation of SCM or can appear de novo on a synovial background.⁶ Histologic differentiation from SCM might be difficult because of the high incidence of hypercellularity, cellular atypia, and binucleated cells.⁶ Some features, such as presence of a very large mass or erosion of the surrounding bones, have been indicated as possible signs of malignancy.³ An unusual presentation of SCM, giant solitary synovial chondromatosis (GSSCM), can be hard to distinguish from SCS because of the large volume and possible aggressive radiologic findings.⁷ Some histologic features, such as presence of necrosis and mitotic cells, have been suggested as distinctive criteria for malignancy.⁸

In this article, we present a case of benign GSSCM with a histologic feature that has not been considered typical for benign SCM. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

An 18-year-old woman presented with a large mass over the right hip. The mass had been growing slowly for 2 years. One year before presentation, a radiograph showed a large hip mass with fluffy calcification (Figure 1), and magnetic resonance imaging (MRI) showed a large nonhomogeneous mass anterior to the hip capsule and extending into the hip joint back to the posterior part of the joint (Figures 2A, 2B). Open incisional biopsy was performed in a local hospital at the time, and the histologic analysis revealed presence of atypical binucleated cells and pleomorphism, in addition to some mitotic activity (0 to 1 per high-power field) (Figure 3). These findings suggested malignancy. The patient declined surgery up until the time she presented to our hospital, 1 year later.

Clinical examination findings on admission to our hospital were striking. The patient had a large mass in the groin region. It was fairly tender and firm to palpation, immobile, and close to the skin. Hip motion was mildly painful but obviously restricted.

The mass was restaged. New radiographs and MRI did not show any significant changes since the previous year, computed tomography (CT) did not show any bone erosion (Figure 4), and chest radiograph, CT, and whole-body bone scan did not demonstrate any signs of metastasis.

Given the clinical presentation and previous histopathologic findings, a diagnosis of GSSCM with possible malignant transformation was made. The patient was scheduled for surgery. During surgery, the tumor was exposed through the Smith-Petersen approach. The mass was extruding under the fascia between the femoral neurovascular bundle medially and iliopsoas muscle laterally. There was no adhesion of the surrounding structures, including the femoral neurovascular bundle, to the mass. The muscle was sitting on the anterolateral surface of the mass, which was considered located in the iliopsoas bursa but extending to the joint. In the vertical plane, the mass extended down to the subtrochanteric area. The entire solid extra-articular mass was excised en bloc, and hip capsulotomy was performed inferior to the area of emergence of the mass. The joint was occupied by a single solid cartilaginous mass molding around the femoral neck, filling the piriformis fossa and propagating to the posterior joint space. Obtaining enough exposure to the back of the joint required surgical hip dislocation. The visualized acetabular fossa revealed chondral fragments, which were excised. Bone erosion or significant osteoarthritis was not detected in any part of the joint. A nearly total synovectomy was performed, leaving the ascending retinacular vessels intact. Meticulous technique was used to avoid contaminating the extra-articular tissues. The wound was closed in the routine way after hip relocation.

The 16×9.5×9-cm mass (Figure 5A) had a conglomerated internal structure (Figure 5B). Multiple specimens from the intra- and extra-articular portions of the mass were sent for histopathologic analysis, which revealed clusters of mature chondrocytes arranged in a lobular pattern and separated by thin fibrous bands. Areas of calcification and ossification were appreciated as well (Figures 6A-6C). No necrosis, mitosis, or bone permeation was detected. These findings were compatible with typical SCM. Given these pathologic findings and the lack of clinical deterioration over the previous year, a diagnosis of GSSCM with extension along the iliopsoas and obturator externus bursae was made. The already-performed marginal excision was deemed sufficient treatment. At most recent follow-up, 38 months after surgery, the patient was pain-free and had good hip range of motion and no indication of recurrence.

Discussion

SCM is a benign disorder emerging from the synovium as a result of proliferative changes in the synovial membrane of the joints, tendon sheaths, or bursae, leading to the formation of numerous cartilaginous nodules, usually a few millimeters in diameter.⁸ In a rare presentation of the disease, the nodules may coalesce to form a large mass, or a single cartilaginous nodule may enlarge to form a mass. Edeiken and colleagues⁷ named this previously unrecognized SCM feature as GSSCM when there was a major single mass larger than 1 cm in diameter. There have been other SCM cases with multiple giant masses.^9,10 In the English-language literature, we found 15 GSSCM cases, which include the first reported, by Edeiken and colleagues⁷ (Table). However, earlier SCM cases would be reclassified GSSCM according to their definition.¹¹

The present case brings the total to 16. Nine of the 16 patients were male. Mean age at presentation was 41 years (range, 10-80 years). The knee was the most common GSSCM site (6 cases), followed by the temporomandibular and hip joints (3 each). Regarding gross pathology, 10 lesions were solid, and 6 (including the present one) were formed by conglomeration of the chondromatosis nodules. Lesions varied in size (16-200 mm), and 2 were primarily extra-articular (foot). One common issue with most of the cases was the initial diagnosis of chondrosarcoma. The exact surgical technique used was described for 6 cases (cases 11-16); the technique was marginal excision. In no case was recurrence 14 to 60 months after surgery reported.

This chondroproliferative process is potentially a diagnostic challenge, as distinguishing it from a chondrosarcoma, a more common lesion, could be difficult based on clinical and imaging findings, and, as is true for other chondral lesions, even histologic differentiation of the conditions might not be conclusive.^12,13 Confusion in diagnosis was almost universal in this series of patients.

One important differentiating feature of benign and malignant skeletal lesions is the time course of the disease. Malignant tumors are expected to demonstrate rapid enlargement and local or systemic spread. Unfortunately, often SCS cannot be distinguished by this characteristic, as grade I or II chondrosarcoma is usually a slow-growing tumor and does not metastasize early.¹⁴ Although lack of recurrence is assuring, recurrence is not necessarily a sign of malignancy, as a considerable percentage of benign chondromatosis lesions recur.⁸

Radiologic differentiation between SCM and SCS is another challenge. Although bone erosion caused by a lesion not originating from bone is usually considered a sign of malignancy, GSSCM was reported as causing bone erosion in 5 of the 16 cases in our literature review.^7,15 Our patient did not experience any bone erosion. However, lack of bone erosion is not a reliable criterion for excluding SCS, and bone erosion was noted in only 3 of the 9 SCS cases in the series reported by Bertoni and colleagues.⁶ Moreover, tumor size and propagation of tumor to surrounding tissue could be surprising in GSSCM. Large size (up to 20 cm) and extra-articular spread of a lesion originating in a joint are common findings.^6,16 Our case was an obvious extension of a hip GSSCM to the iliopsoas and obturator externus bursa, which is the most common pattern of extracapsular spread of hip SCM.¹⁷ An interesting feature of the present case, however, was the relatively superficial location of the mass immediately under the fascia.

Calcified matrix is key in diagnosing a chondral lesion on imaging studies, but, in some cases, SCM does not demonstrate any radiographically detectable calcification at time of diagnosis.¹⁸ However, all the GSSCM cases reported to date had obvious calcified matrix.

The hypercellularity, cellular atypia, binucleated cells, and pleomorphism in the histologic examination of the present case are not features of malignancy in SCM.⁸ On the contrary, several other characteristics, including qualitative differences in the arrangement of chondrocytes (sheets rather than clusters), myxoid matrix, hypercellularity with crowding and spindling of the nuclei at the periphery, necrosis, and, most important, permeation of the trabecular bone with the filling up of marrow spaces, have been assumed to be indicative of malignancy.⁸ Furthermore, Davis and colleagues⁸ found no mitotic activity in the histopathologic investigation of 53 SCM cases. Even in 3 cases that developed malignant transformation to SCS, mitosis was not found in the initial biopsy specimens before transformation. This was compatible with the common opinion that SCM is not a neoplastic, but a metaplastic, process. Histopathologic data were available for only 8 of the previous 15 GSSCM cases. There were no reports of mitosis, and necrosis was found in only 1 case.¹⁶ In our patient’s case, however, the first biopsy did show remarkable mitotic activity. This was not the case for the second biopsy, when mature chondrocytes associated with marked calcification and ossification were prominent features (Figures 6A, 6B). We presume that, within a limited period during earlier stages of tissue maturation in SCM, mitotic activity might be a possible finding. Of note, none of the other aforementioned histologic criteria for malignancy was seen in the first or second biopsy in the present case (Figures 3, 6C).

The original idea that SCM originates from a metaplasia in the subintimal layer of the synovium, where the synovium is in direct contact with the articular cartilage, has been challenged. The high incidence of hypercellularity, binucleated cells, and cellular atypia was always an argument against a metaplastic origin for the disease. Evidence of clonal chromosomal changes, like translocation of chromosome 1218 and chromosome 5 and 6 abnormalities,^19,20 in addition to other alterations,^19,21 provide some evidence supporting a neoplastic rather than a metaplastic origin for SCM. Given the presence of mitosis in the present case, the lack of mitotic activity in SCM, as stated by other authors,²² is not a universal feature and cannot be used as an argument against a neoplastic origin for SCM.

Although mitotic activity is uncommon in SCM, the present case illustrates the possible presence of mitotic activity in GSSCM. The simple presence of mitotic activity, a common finding in some other chondral tumors,23,24 does not preclude the diagnosis of benign SCM, as suggested before,8 and correlation of the clinical and radiologic manifestations with histopathologic findings is crucial for a correct diagnosis.

Synovial chondromatosis (SCM) is a relatively rare benign lesion of the synovium.¹ Its pathogenesis has been thought to be a chondral metaplasia of the subintimal layer of the intra- or extra-articular synovium.² However, evidence supporting a neoplastic cause of the disease is emerging.³ When intra-articular, any joint can be affected, though large joints are more prone to the disease; the knee, hip, and elbow are the most common locations.⁴ The synovial layer of tendons or bursae can be the origin of extra-articular SCM.⁵

Synovial chondrosarcoma (SCS), an even rarer pathology, can be caused by malignant transformation of SCM or can appear de novo on a synovial background.⁶ Histologic differentiation from SCM might be difficult because of the high incidence of hypercellularity, cellular atypia, and binucleated cells.⁶ Some features, such as presence of a very large mass or erosion of the surrounding bones, have been indicated as possible signs of malignancy.³ An unusual presentation of SCM, giant solitary synovial chondromatosis (GSSCM), can be hard to distinguish from SCS because of the large volume and possible aggressive radiologic findings.⁷ Some histologic features, such as presence of necrosis and mitotic cells, have been suggested as distinctive criteria for malignancy.⁸

In this article, we present a case of benign GSSCM with a histologic feature that has not been considered typical for benign SCM. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

An 18-year-old woman presented with a large mass over the right hip. The mass had been growing slowly for 2 years. One year before presentation, a radiograph showed a large hip mass with fluffy calcification (Figure 1), and magnetic resonance imaging (MRI) showed a large nonhomogeneous mass anterior to the hip capsule and extending into the hip joint back to the posterior part of the joint (Figures 2A, 2B). Open incisional biopsy was performed in a local hospital at the time, and the histologic analysis revealed presence of atypical binucleated cells and pleomorphism, in addition to some mitotic activity (0 to 1 per high-power field) (Figure 3). These findings suggested malignancy. The patient declined surgery up until the time she presented to our hospital, 1 year later.

Clinical examination findings on admission to our hospital were striking. The patient had a large mass in the groin region. It was fairly tender and firm to palpation, immobile, and close to the skin. Hip motion was mildly painful but obviously restricted.

The mass was restaged. New radiographs and MRI did not show any significant changes since the previous year, computed tomography (CT) did not show any bone erosion (Figure 4), and chest radiograph, CT, and whole-body bone scan did not demonstrate any signs of metastasis.

Given the clinical presentation and previous histopathologic findings, a diagnosis of GSSCM with possible malignant transformation was made. The patient was scheduled for surgery. During surgery, the tumor was exposed through the Smith-Petersen approach. The mass was extruding under the fascia between the femoral neurovascular bundle medially and iliopsoas muscle laterally. There was no adhesion of the surrounding structures, including the femoral neurovascular bundle, to the mass. The muscle was sitting on the anterolateral surface of the mass, which was considered located in the iliopsoas bursa but extending to the joint. In the vertical plane, the mass extended down to the subtrochanteric area. The entire solid extra-articular mass was excised en bloc, and hip capsulotomy was performed inferior to the area of emergence of the mass. The joint was occupied by a single solid cartilaginous mass molding around the femoral neck, filling the piriformis fossa and propagating to the posterior joint space. Obtaining enough exposure to the back of the joint required surgical hip dislocation. The visualized acetabular fossa revealed chondral fragments, which were excised. Bone erosion or significant osteoarthritis was not detected in any part of the joint. A nearly total synovectomy was performed, leaving the ascending retinacular vessels intact. Meticulous technique was used to avoid contaminating the extra-articular tissues. The wound was closed in the routine way after hip relocation.

The 16×9.5×9-cm mass (Figure 5A) had a conglomerated internal structure (Figure 5B). Multiple specimens from the intra- and extra-articular portions of the mass were sent for histopathologic analysis, which revealed clusters of mature chondrocytes arranged in a lobular pattern and separated by thin fibrous bands. Areas of calcification and ossification were appreciated as well (Figures 6A-6C). No necrosis, mitosis, or bone permeation was detected. These findings were compatible with typical SCM. Given these pathologic findings and the lack of clinical deterioration over the previous year, a diagnosis of GSSCM with extension along the iliopsoas and obturator externus bursae was made. The already-performed marginal excision was deemed sufficient treatment. At most recent follow-up, 38 months after surgery, the patient was pain-free and had good hip range of motion and no indication of recurrence.

Discussion

SCM is a benign disorder emerging from the synovium as a result of proliferative changes in the synovial membrane of the joints, tendon sheaths, or bursae, leading to the formation of numerous cartilaginous nodules, usually a few millimeters in diameter.⁸ In a rare presentation of the disease, the nodules may coalesce to form a large mass, or a single cartilaginous nodule may enlarge to form a mass. Edeiken and colleagues⁷ named this previously unrecognized SCM feature as GSSCM when there was a major single mass larger than 1 cm in diameter. There have been other SCM cases with multiple giant masses.^9,10 In the English-language literature, we found 15 GSSCM cases, which include the first reported, by Edeiken and colleagues⁷ (Table). However, earlier SCM cases would be reclassified GSSCM according to their definition.¹¹

The present case brings the total to 16. Nine of the 16 patients were male. Mean age at presentation was 41 years (range, 10-80 years). The knee was the most common GSSCM site (6 cases), followed by the temporomandibular and hip joints (3 each). Regarding gross pathology, 10 lesions were solid, and 6 (including the present one) were formed by conglomeration of the chondromatosis nodules. Lesions varied in size (16-200 mm), and 2 were primarily extra-articular (foot). One common issue with most of the cases was the initial diagnosis of chondrosarcoma. The exact surgical technique used was described for 6 cases (cases 11-16); the technique was marginal excision. In no case was recurrence 14 to 60 months after surgery reported.

This chondroproliferative process is potentially a diagnostic challenge, as distinguishing it from a chondrosarcoma, a more common lesion, could be difficult based on clinical and imaging findings, and, as is true for other chondral lesions, even histologic differentiation of the conditions might not be conclusive.^12,13 Confusion in diagnosis was almost universal in this series of patients.

One important differentiating feature of benign and malignant skeletal lesions is the time course of the disease. Malignant tumors are expected to demonstrate rapid enlargement and local or systemic spread. Unfortunately, often SCS cannot be distinguished by this characteristic, as grade I or II chondrosarcoma is usually a slow-growing tumor and does not metastasize early.¹⁴ Although lack of recurrence is assuring, recurrence is not necessarily a sign of malignancy, as a considerable percentage of benign chondromatosis lesions recur.⁸

Radiologic differentiation between SCM and SCS is another challenge. Although bone erosion caused by a lesion not originating from bone is usually considered a sign of malignancy, GSSCM was reported as causing bone erosion in 5 of the 16 cases in our literature review.^7,15 Our patient did not experience any bone erosion. However, lack of bone erosion is not a reliable criterion for excluding SCS, and bone erosion was noted in only 3 of the 9 SCS cases in the series reported by Bertoni and colleagues.⁶ Moreover, tumor size and propagation of tumor to surrounding tissue could be surprising in GSSCM. Large size (up to 20 cm) and extra-articular spread of a lesion originating in a joint are common findings.^6,16 Our case was an obvious extension of a hip GSSCM to the iliopsoas and obturator externus bursa, which is the most common pattern of extracapsular spread of hip SCM.¹⁷ An interesting feature of the present case, however, was the relatively superficial location of the mass immediately under the fascia.

Calcified matrix is key in diagnosing a chondral lesion on imaging studies, but, in some cases, SCM does not demonstrate any radiographically detectable calcification at time of diagnosis.¹⁸ However, all the GSSCM cases reported to date had obvious calcified matrix.

The hypercellularity, cellular atypia, binucleated cells, and pleomorphism in the histologic examination of the present case are not features of malignancy in SCM.⁸ On the contrary, several other characteristics, including qualitative differences in the arrangement of chondrocytes (sheets rather than clusters), myxoid matrix, hypercellularity with crowding and spindling of the nuclei at the periphery, necrosis, and, most important, permeation of the trabecular bone with the filling up of marrow spaces, have been assumed to be indicative of malignancy.⁸ Furthermore, Davis and colleagues⁸ found no mitotic activity in the histopathologic investigation of 53 SCM cases. Even in 3 cases that developed malignant transformation to SCS, mitosis was not found in the initial biopsy specimens before transformation. This was compatible with the common opinion that SCM is not a neoplastic, but a metaplastic, process. Histopathologic data were available for only 8 of the previous 15 GSSCM cases. There were no reports of mitosis, and necrosis was found in only 1 case.¹⁶ In our patient’s case, however, the first biopsy did show remarkable mitotic activity. This was not the case for the second biopsy, when mature chondrocytes associated with marked calcification and ossification were prominent features (Figures 6A, 6B). We presume that, within a limited period during earlier stages of tissue maturation in SCM, mitotic activity might be a possible finding. Of note, none of the other aforementioned histologic criteria for malignancy was seen in the first or second biopsy in the present case (Figures 3, 6C).

The original idea that SCM originates from a metaplasia in the subintimal layer of the synovium, where the synovium is in direct contact with the articular cartilage, has been challenged. The high incidence of hypercellularity, binucleated cells, and cellular atypia was always an argument against a metaplastic origin for the disease. Evidence of clonal chromosomal changes, like translocation of chromosome 1218 and chromosome 5 and 6 abnormalities,^19,20 in addition to other alterations,^19,21 provide some evidence supporting a neoplastic rather than a metaplastic origin for SCM. Given the presence of mitosis in the present case, the lack of mitotic activity in SCM, as stated by other authors,²² is not a universal feature and cannot be used as an argument against a neoplastic origin for SCM.

Although mitotic activity is uncommon in SCM, the present case illustrates the possible presence of mitotic activity in GSSCM. The simple presence of mitotic activity, a common finding in some other chondral tumors,23,24 does not preclude the diagnosis of benign SCM, as suggested before,8 and correlation of the clinical and radiologic manifestations with histopathologic findings is crucial for a correct diagnosis.

Synovial chondromatosis (SCM) is a relatively rare benign lesion of the synovium.¹ Its pathogenesis has been thought to be a chondral metaplasia of the subintimal layer of the intra- or extra-articular synovium.² However, evidence supporting a neoplastic cause of the disease is emerging.³ When intra-articular, any joint can be affected, though large joints are more prone to the disease; the knee, hip, and elbow are the most common locations.⁴ The synovial layer of tendons or bursae can be the origin of extra-articular SCM.⁵

Synovial chondrosarcoma (SCS), an even rarer pathology, can be caused by malignant transformation of SCM or can appear de novo on a synovial background.⁶ Histologic differentiation from SCM might be difficult because of the high incidence of hypercellularity, cellular atypia, and binucleated cells.⁶ Some features, such as presence of a very large mass or erosion of the surrounding bones, have been indicated as possible signs of malignancy.³ An unusual presentation of SCM, giant solitary synovial chondromatosis (GSSCM), can be hard to distinguish from SCS because of the large volume and possible aggressive radiologic findings.⁷ Some histologic features, such as presence of necrosis and mitotic cells, have been suggested as distinctive criteria for malignancy.⁸

In this article, we present a case of benign GSSCM with a histologic feature that has not been considered typical for benign SCM. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

An 18-year-old woman presented with a large mass over the right hip. The mass had been growing slowly for 2 years. One year before presentation, a radiograph showed a large hip mass with fluffy calcification (Figure 1), and magnetic resonance imaging (MRI) showed a large nonhomogeneous mass anterior to the hip capsule and extending into the hip joint back to the posterior part of the joint (Figures 2A, 2B). Open incisional biopsy was performed in a local hospital at the time, and the histologic analysis revealed presence of atypical binucleated cells and pleomorphism, in addition to some mitotic activity (0 to 1 per high-power field) (Figure 3). These findings suggested malignancy. The patient declined surgery up until the time she presented to our hospital, 1 year later.

Clinical examination findings on admission to our hospital were striking. The patient had a large mass in the groin region. It was fairly tender and firm to palpation, immobile, and close to the skin. Hip motion was mildly painful but obviously restricted.

The mass was restaged. New radiographs and MRI did not show any significant changes since the previous year, computed tomography (CT) did not show any bone erosion (Figure 4), and chest radiograph, CT, and whole-body bone scan did not demonstrate any signs of metastasis.

Given the clinical presentation and previous histopathologic findings, a diagnosis of GSSCM with possible malignant transformation was made. The patient was scheduled for surgery. During surgery, the tumor was exposed through the Smith-Petersen approach. The mass was extruding under the fascia between the femoral neurovascular bundle medially and iliopsoas muscle laterally. There was no adhesion of the surrounding structures, including the femoral neurovascular bundle, to the mass. The muscle was sitting on the anterolateral surface of the mass, which was considered located in the iliopsoas bursa but extending to the joint. In the vertical plane, the mass extended down to the subtrochanteric area. The entire solid extra-articular mass was excised en bloc, and hip capsulotomy was performed inferior to the area of emergence of the mass. The joint was occupied by a single solid cartilaginous mass molding around the femoral neck, filling the piriformis fossa and propagating to the posterior joint space. Obtaining enough exposure to the back of the joint required surgical hip dislocation. The visualized acetabular fossa revealed chondral fragments, which were excised. Bone erosion or significant osteoarthritis was not detected in any part of the joint. A nearly total synovectomy was performed, leaving the ascending retinacular vessels intact. Meticulous technique was used to avoid contaminating the extra-articular tissues. The wound was closed in the routine way after hip relocation.

The 16×9.5×9-cm mass (Figure 5A) had a conglomerated internal structure (Figure 5B). Multiple specimens from the intra- and extra-articular portions of the mass were sent for histopathologic analysis, which revealed clusters of mature chondrocytes arranged in a lobular pattern and separated by thin fibrous bands. Areas of calcification and ossification were appreciated as well (Figures 6A-6C). No necrosis, mitosis, or bone permeation was detected. These findings were compatible with typical SCM. Given these pathologic findings and the lack of clinical deterioration over the previous year, a diagnosis of GSSCM with extension along the iliopsoas and obturator externus bursae was made. The already-performed marginal excision was deemed sufficient treatment. At most recent follow-up, 38 months after surgery, the patient was pain-free and had good hip range of motion and no indication of recurrence.

Discussion

SCM is a benign disorder emerging from the synovium as a result of proliferative changes in the synovial membrane of the joints, tendon sheaths, or bursae, leading to the formation of numerous cartilaginous nodules, usually a few millimeters in diameter.⁸ In a rare presentation of the disease, the nodules may coalesce to form a large mass, or a single cartilaginous nodule may enlarge to form a mass. Edeiken and colleagues⁷ named this previously unrecognized SCM feature as GSSCM when there was a major single mass larger than 1 cm in diameter. There have been other SCM cases with multiple giant masses.^9,10 In the English-language literature, we found 15 GSSCM cases, which include the first reported, by Edeiken and colleagues⁷ (Table). However, earlier SCM cases would be reclassified GSSCM according to their definition.¹¹

The present case brings the total to 16. Nine of the 16 patients were male. Mean age at presentation was 41 years (range, 10-80 years). The knee was the most common GSSCM site (6 cases), followed by the temporomandibular and hip joints (3 each). Regarding gross pathology, 10 lesions were solid, and 6 (including the present one) were formed by conglomeration of the chondromatosis nodules. Lesions varied in size (16-200 mm), and 2 were primarily extra-articular (foot). One common issue with most of the cases was the initial diagnosis of chondrosarcoma. The exact surgical technique used was described for 6 cases (cases 11-16); the technique was marginal excision. In no case was recurrence 14 to 60 months after surgery reported.

This chondroproliferative process is potentially a diagnostic challenge, as distinguishing it from a chondrosarcoma, a more common lesion, could be difficult based on clinical and imaging findings, and, as is true for other chondral lesions, even histologic differentiation of the conditions might not be conclusive.^12,13 Confusion in diagnosis was almost universal in this series of patients.

One important differentiating feature of benign and malignant skeletal lesions is the time course of the disease. Malignant tumors are expected to demonstrate rapid enlargement and local or systemic spread. Unfortunately, often SCS cannot be distinguished by this characteristic, as grade I or II chondrosarcoma is usually a slow-growing tumor and does not metastasize early.¹⁴ Although lack of recurrence is assuring, recurrence is not necessarily a sign of malignancy, as a considerable percentage of benign chondromatosis lesions recur.⁸

Radiologic differentiation between SCM and SCS is another challenge. Although bone erosion caused by a lesion not originating from bone is usually considered a sign of malignancy, GSSCM was reported as causing bone erosion in 5 of the 16 cases in our literature review.^7,15 Our patient did not experience any bone erosion. However, lack of bone erosion is not a reliable criterion for excluding SCS, and bone erosion was noted in only 3 of the 9 SCS cases in the series reported by Bertoni and colleagues.⁶ Moreover, tumor size and propagation of tumor to surrounding tissue could be surprising in GSSCM. Large size (up to 20 cm) and extra-articular spread of a lesion originating in a joint are common findings.^6,16 Our case was an obvious extension of a hip GSSCM to the iliopsoas and obturator externus bursa, which is the most common pattern of extracapsular spread of hip SCM.¹⁷ An interesting feature of the present case, however, was the relatively superficial location of the mass immediately under the fascia.

Calcified matrix is key in diagnosing a chondral lesion on imaging studies, but, in some cases, SCM does not demonstrate any radiographically detectable calcification at time of diagnosis.¹⁸ However, all the GSSCM cases reported to date had obvious calcified matrix.

The hypercellularity, cellular atypia, binucleated cells, and pleomorphism in the histologic examination of the present case are not features of malignancy in SCM.⁸ On the contrary, several other characteristics, including qualitative differences in the arrangement of chondrocytes (sheets rather than clusters), myxoid matrix, hypercellularity with crowding and spindling of the nuclei at the periphery, necrosis, and, most important, permeation of the trabecular bone with the filling up of marrow spaces, have been assumed to be indicative of malignancy.⁸ Furthermore, Davis and colleagues⁸ found no mitotic activity in the histopathologic investigation of 53 SCM cases. Even in 3 cases that developed malignant transformation to SCS, mitosis was not found in the initial biopsy specimens before transformation. This was compatible with the common opinion that SCM is not a neoplastic, but a metaplastic, process. Histopathologic data were available for only 8 of the previous 15 GSSCM cases. There were no reports of mitosis, and necrosis was found in only 1 case.¹⁶ In our patient’s case, however, the first biopsy did show remarkable mitotic activity. This was not the case for the second biopsy, when mature chondrocytes associated with marked calcification and ossification were prominent features (Figures 6A, 6B). We presume that, within a limited period during earlier stages of tissue maturation in SCM, mitotic activity might be a possible finding. Of note, none of the other aforementioned histologic criteria for malignancy was seen in the first or second biopsy in the present case (Figures 3, 6C).

The original idea that SCM originates from a metaplasia in the subintimal layer of the synovium, where the synovium is in direct contact with the articular cartilage, has been challenged. The high incidence of hypercellularity, binucleated cells, and cellular atypia was always an argument against a metaplastic origin for the disease. Evidence of clonal chromosomal changes, like translocation of chromosome 1218 and chromosome 5 and 6 abnormalities,^19,20 in addition to other alterations,^19,21 provide some evidence supporting a neoplastic rather than a metaplastic origin for SCM. Given the presence of mitosis in the present case, the lack of mitotic activity in SCM, as stated by other authors,²² is not a universal feature and cannot be used as an argument against a neoplastic origin for SCM.

Although mitotic activity is uncommon in SCM, the present case illustrates the possible presence of mitotic activity in GSSCM. The simple presence of mitotic activity, a common finding in some other chondral tumors,23,24 does not preclude the diagnosis of benign SCM, as suggested before,8 and correlation of the clinical and radiologic manifestations with histopathologic findings is crucial for a correct diagnosis.

Congenital absence of the anterior cruciate ligament (ACL) is a rare occurrence and has been seen most often in conjunction with conditions such as knee dislocation, knee dysplasia, proximal focal femoral deficiency, and fibular hemimelia.

We report on the incidental finding of ACL aplasia in a patient with a medial meniscal tear and history of leg-length discrepancy. Similar to earlier cases, this patient had hypertrophy of the meniscofemoral ligament of Humphrey, which likely provided stability. This case report emphasizes the importance of distinguishing between a stable and an unstable knee in congenital absence of the ACL. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 20-year-old woman presented for orthopedic evaluation with worsening medial left knee pain. Her pain was intermittent in nature, occurring about every 1 to 2 months and of 1 to 2 days’ duration. Onset was while using the elliptical machine, walking on uneven ground, or navigating stairs. She denied any buckling, catching, locking, instability, or swelling.

Her history was significant for a breech delivery and leg anisomelia, for which she had a contralateral distal femoral and proximal tibial percutaneous epiphysiodesis performed at age 10 years. Family history was negative for limb deformities.

Physical examination was notable for absence of global ligamentous laxity, overall valgus alignment of the left lower extremity, minimally decreased motion, trace effusion, positive medial joint line tenderness, positive McMurray test, and 1+ Lachman test with guarding on pivot shift testing.

Plain films showed valgus alignment with narrowing of the lateral compartment, narrow intercondylar notch, and hypoplasia of the tibial eminences and lateral femoral condyle (Figure 1). Magnetic resonance imaging showed a large tear in the posterior horn of the medial meniscus, hypertrophy of the meniscofemoral ligament of Humphrey (Figure 2A), and nonvisualization of the ACL with a small remnant (Figure 2B).

Arthroscopy showed complete absence of fibers of the ACL, hypertrophy of the meniscofemoral ligament of Humphrey, and a large posterior horn medial meniscal tear. A partial medial meniscectomy was performed. More than 2 years after surgery, the patient was doing very well without pain or instability, and was exercising regularly without difficulty.

Discussion

Our patient had left-sided congenital absence of the ACL with associated limb-length discrepancy of more than 2.5 cm. Isolated absence of the ACL has been described in a few case reports in the literature. Congenital ACL absence has most often been found in association with conditions such as knee dislocation (occurring with a frequency of .017/1000 births),¹ knee dysplasia,^2,3 fibular hemimelia,⁴ and proximal focal femoral deficiency.⁵ Johansson and Aparisi^5,6 linked the finding of ACL absence with instability in those patients with known limb-length discrepancy and symptomatic instability. This report presents a patient who has congenital absence of the ACL in a foreshortened limb and torn medial meniscus. The classification of the patient’s cruciate dysplasia would be type I, as described by Manner and colleagues.⁷ The incidence of meniscal tears in association with congenital ACL absence is unknown. There have been reports of absence of the ACL associated with a ring meniscus,⁸ absence of both cruciate ligaments and menisci,⁹ and a bucket-handle tear of the medial meniscus.¹⁰

Gabos and colleagues⁴ recommend reconstructive surgery for patients with congenital absence of the ACL and symptomatic knee instability. Limb lengthening/shortening and realignment procedures have allowed patients such as ours to have functionally anatomic limbs and high activity levels. Surgical treatment is pursued to restore mechanical alignment and stability. Our patient had no symptoms of instability.

Similar to 3 of the 4 patients presented by Gabos and colleagues,⁴ our patient had marked hypertrophy of the meniscofemoral ligament of Humphrey. The report by Gabos and colleagues⁴ of this finding was the first in the literature. The hypertrophy of this ligament suggests it has a role in stabilizing the knee with a congenitally absent ACL. Our patient had no instability in her left knee but presented because of episodes of pain.

Of significant concern is the long-term outcome of patients with congenital ACL aplasia. Crawford and colleagues¹¹ reported 11 patients with ACL deficiency and fibular hemimelia at a mean age of 37 years, showing similar functional outcomes  to age-matched controls. However, there was no radiographic follow-up reported in regard to the development of osteoarthritis. To our knowledge, there have been no series published comparing surgical and nonsurgical treatment of congenital absence of the ACL. In the study by Gabos and colleagues,⁴ all patients were treated with reconstruction because these patients had symptomatic instability.

Conclusion

This report presents a patient whose symptoms improved after resection of her medial meniscal tear. This patient will be followed long-term to delineate her clinical course and to monitor for instability and/or development of osteoarthritis. Future studies should compare the treatment of congenital absence of the ACL with reconstruction and with conservative management.

Congenital absence of the anterior cruciate ligament (ACL) is a rare occurrence and has been seen most often in conjunction with conditions such as knee dislocation, knee dysplasia, proximal focal femoral deficiency, and fibular hemimelia.

We report on the incidental finding of ACL aplasia in a patient with a medial meniscal tear and history of leg-length discrepancy. Similar to earlier cases, this patient had hypertrophy of the meniscofemoral ligament of Humphrey, which likely provided stability. This case report emphasizes the importance of distinguishing between a stable and an unstable knee in congenital absence of the ACL. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 20-year-old woman presented for orthopedic evaluation with worsening medial left knee pain. Her pain was intermittent in nature, occurring about every 1 to 2 months and of 1 to 2 days’ duration. Onset was while using the elliptical machine, walking on uneven ground, or navigating stairs. She denied any buckling, catching, locking, instability, or swelling.

Her history was significant for a breech delivery and leg anisomelia, for which she had a contralateral distal femoral and proximal tibial percutaneous epiphysiodesis performed at age 10 years. Family history was negative for limb deformities.

Physical examination was notable for absence of global ligamentous laxity, overall valgus alignment of the left lower extremity, minimally decreased motion, trace effusion, positive medial joint line tenderness, positive McMurray test, and 1+ Lachman test with guarding on pivot shift testing.

Plain films showed valgus alignment with narrowing of the lateral compartment, narrow intercondylar notch, and hypoplasia of the tibial eminences and lateral femoral condyle (Figure 1). Magnetic resonance imaging showed a large tear in the posterior horn of the medial meniscus, hypertrophy of the meniscofemoral ligament of Humphrey (Figure 2A), and nonvisualization of the ACL with a small remnant (Figure 2B).

Arthroscopy showed complete absence of fibers of the ACL, hypertrophy of the meniscofemoral ligament of Humphrey, and a large posterior horn medial meniscal tear. A partial medial meniscectomy was performed. More than 2 years after surgery, the patient was doing very well without pain or instability, and was exercising regularly without difficulty.

Discussion

Our patient had left-sided congenital absence of the ACL with associated limb-length discrepancy of more than 2.5 cm. Isolated absence of the ACL has been described in a few case reports in the literature. Congenital ACL absence has most often been found in association with conditions such as knee dislocation (occurring with a frequency of .017/1000 births),¹ knee dysplasia,^2,3 fibular hemimelia,⁴ and proximal focal femoral deficiency.⁵ Johansson and Aparisi^5,6 linked the finding of ACL absence with instability in those patients with known limb-length discrepancy and symptomatic instability. This report presents a patient who has congenital absence of the ACL in a foreshortened limb and torn medial meniscus. The classification of the patient’s cruciate dysplasia would be type I, as described by Manner and colleagues.⁷ The incidence of meniscal tears in association with congenital ACL absence is unknown. There have been reports of absence of the ACL associated with a ring meniscus,⁸ absence of both cruciate ligaments and menisci,⁹ and a bucket-handle tear of the medial meniscus.¹⁰

Gabos and colleagues⁴ recommend reconstructive surgery for patients with congenital absence of the ACL and symptomatic knee instability. Limb lengthening/shortening and realignment procedures have allowed patients such as ours to have functionally anatomic limbs and high activity levels. Surgical treatment is pursued to restore mechanical alignment and stability. Our patient had no symptoms of instability.

Similar to 3 of the 4 patients presented by Gabos and colleagues,⁴ our patient had marked hypertrophy of the meniscofemoral ligament of Humphrey. The report by Gabos and colleagues⁴ of this finding was the first in the literature. The hypertrophy of this ligament suggests it has a role in stabilizing the knee with a congenitally absent ACL. Our patient had no instability in her left knee but presented because of episodes of pain.

Of significant concern is the long-term outcome of patients with congenital ACL aplasia. Crawford and colleagues¹¹ reported 11 patients with ACL deficiency and fibular hemimelia at a mean age of 37 years, showing similar functional outcomes  to age-matched controls. However, there was no radiographic follow-up reported in regard to the development of osteoarthritis. To our knowledge, there have been no series published comparing surgical and nonsurgical treatment of congenital absence of the ACL. In the study by Gabos and colleagues,⁴ all patients were treated with reconstruction because these patients had symptomatic instability.

Conclusion

This report presents a patient whose symptoms improved after resection of her medial meniscal tear. This patient will be followed long-term to delineate her clinical course and to monitor for instability and/or development of osteoarthritis. Future studies should compare the treatment of congenital absence of the ACL with reconstruction and with conservative management.

Congenital absence of the anterior cruciate ligament (ACL) is a rare occurrence and has been seen most often in conjunction with conditions such as knee dislocation, knee dysplasia, proximal focal femoral deficiency, and fibular hemimelia.

We report on the incidental finding of ACL aplasia in a patient with a medial meniscal tear and history of leg-length discrepancy. Similar to earlier cases, this patient had hypertrophy of the meniscofemoral ligament of Humphrey, which likely provided stability. This case report emphasizes the importance of distinguishing between a stable and an unstable knee in congenital absence of the ACL. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 20-year-old woman presented for orthopedic evaluation with worsening medial left knee pain. Her pain was intermittent in nature, occurring about every 1 to 2 months and of 1 to 2 days’ duration. Onset was while using the elliptical machine, walking on uneven ground, or navigating stairs. She denied any buckling, catching, locking, instability, or swelling.

Her history was significant for a breech delivery and leg anisomelia, for which she had a contralateral distal femoral and proximal tibial percutaneous epiphysiodesis performed at age 10 years. Family history was negative for limb deformities.

Physical examination was notable for absence of global ligamentous laxity, overall valgus alignment of the left lower extremity, minimally decreased motion, trace effusion, positive medial joint line tenderness, positive McMurray test, and 1+ Lachman test with guarding on pivot shift testing.

Plain films showed valgus alignment with narrowing of the lateral compartment, narrow intercondylar notch, and hypoplasia of the tibial eminences and lateral femoral condyle (Figure 1). Magnetic resonance imaging showed a large tear in the posterior horn of the medial meniscus, hypertrophy of the meniscofemoral ligament of Humphrey (Figure 2A), and nonvisualization of the ACL with a small remnant (Figure 2B).

Arthroscopy showed complete absence of fibers of the ACL, hypertrophy of the meniscofemoral ligament of Humphrey, and a large posterior horn medial meniscal tear. A partial medial meniscectomy was performed. More than 2 years after surgery, the patient was doing very well without pain or instability, and was exercising regularly without difficulty.

Discussion

Our patient had left-sided congenital absence of the ACL with associated limb-length discrepancy of more than 2.5 cm. Isolated absence of the ACL has been described in a few case reports in the literature. Congenital ACL absence has most often been found in association with conditions such as knee dislocation (occurring with a frequency of .017/1000 births),¹ knee dysplasia,^2,3 fibular hemimelia,⁴ and proximal focal femoral deficiency.⁵ Johansson and Aparisi^5,6 linked the finding of ACL absence with instability in those patients with known limb-length discrepancy and symptomatic instability. This report presents a patient who has congenital absence of the ACL in a foreshortened limb and torn medial meniscus. The classification of the patient’s cruciate dysplasia would be type I, as described by Manner and colleagues.⁷ The incidence of meniscal tears in association with congenital ACL absence is unknown. There have been reports of absence of the ACL associated with a ring meniscus,⁸ absence of both cruciate ligaments and menisci,⁹ and a bucket-handle tear of the medial meniscus.¹⁰

Gabos and colleagues⁴ recommend reconstructive surgery for patients with congenital absence of the ACL and symptomatic knee instability. Limb lengthening/shortening and realignment procedures have allowed patients such as ours to have functionally anatomic limbs and high activity levels. Surgical treatment is pursued to restore mechanical alignment and stability. Our patient had no symptoms of instability.

Similar to 3 of the 4 patients presented by Gabos and colleagues,⁴ our patient had marked hypertrophy of the meniscofemoral ligament of Humphrey. The report by Gabos and colleagues⁴ of this finding was the first in the literature. The hypertrophy of this ligament suggests it has a role in stabilizing the knee with a congenitally absent ACL. Our patient had no instability in her left knee but presented because of episodes of pain.

Of significant concern is the long-term outcome of patients with congenital ACL aplasia. Crawford and colleagues¹¹ reported 11 patients with ACL deficiency and fibular hemimelia at a mean age of 37 years, showing similar functional outcomes  to age-matched controls. However, there was no radiographic follow-up reported in regard to the development of osteoarthritis. To our knowledge, there have been no series published comparing surgical and nonsurgical treatment of congenital absence of the ACL. In the study by Gabos and colleagues,⁴ all patients were treated with reconstruction because these patients had symptomatic instability.

Conclusion

This report presents a patient whose symptoms improved after resection of her medial meniscal tear. This patient will be followed long-term to delineate her clinical course and to monitor for instability and/or development of osteoarthritis. Future studies should compare the treatment of congenital absence of the ACL with reconstruction and with conservative management.