SAN DIEGO – Anti-CD19 chimeric antigen receptor (CAR) T cells engineered with a “safety switch” yielded high rates of complete response and an acceptable toxicity profile in chemotherapy-resistant B cell acute lymphoblastic leukemia, according to a multicenter phase I/II trial.

Importantly, high tumor burden did not increase the risk of cytokine release syndrome, said Lung-Ji Chang, PhD, of Shenzhen (China) Genoimmune Medical Institute and the University of Florida in Gainesville. “This reliable, standardized CAR T-cell preparation protocol has now served more than 30 major medical centers in China,” he said at the annual meeting of the American Society of Hematology.

Anti-CD19 CAR T cells have shown dramatic potential for treating B-cell malignancies, but toxicities have been a concern. One potentially serious adverse reaction is cytokine release syndrome, in which patients develop marked rises in blood levels of several types of cytokines. Another problem is that anti-CD19 CAR T cells can trigger loss of CD19 B cells, ultimately leading to humoral deficiencies, Dr. Chang noted. Consequently, researchers have searched for ways to continue controlling the activity of CAR T cells even after infusing them into patients.

As part of that effort, Dr. Chang and his associates developed a standardized protocol for engineering next-generation anti-CD19 CAR T cells based on the established concept of a “safety switch.” After collecting T cells from patients with chemotherapy-resistant ALL, they used a lentiviral vector to transform them into CAR T cells with fusion proteins consisting of a proapoptotic molecule called caspase-9 that is linked to modified human FK506-binding proteins, or FKBP. The addition of iCaspase9-FKBP enables clinicians to induce CAR T cell apoptosis by treating patients with a synthetic dimerizer called AP1903.

Apoptosis occurs about 45 minutes after this drug is given, according to Dr. Chang. This “safety switch” also enables clinicians to eliminate anti-CD19 CAR T cells after tumor cells are eradicated so that patients can recover their humoral immunity. He and his associates further modified these anti-CD19 CAR T cells by introducing four intracellular signaling domains that are associated with T-cell activation, survival, and longevity, he said.

A total of 22 treatment centers helped test this approach in a phase I/II trial of 110 leukemia patients, about half of whom were children with a median age of 9 years. The median age of adults was 37 years, and the oldest patient was 70. Cancer types included Philadelphia chromosome–positive ALL, Philadelphia chromosome–negative ALL, and chronic myeloid leukemia with blast crisis. About a third of patients had bone marrow samples with at least 50% blasts, and a similar proportion had already undergone hematopoietic stem cell transplantation.

Cytokine release syndrome affected 86% of patients with low or no tumor burden, but only 53% of patients with bone marrow blasts exceeding 5%, Dr. Chang reported. He emphasized that patients with high tumor burden were no more likely to develop moderate or severe cytokine release syndrome than were patients with little or no tumor burden (P = .3). Furthermore, among 17 patients with more than 80% bone marrow involvement, only three developed grade 3-4 cytokine release syndrome, while eight developed grade 1 cytokine release syndrome.

A total of 96 patients (87%) had a complete response to this CAR T cell regimen, including 51 children and 45 adults, Dr. Chang reported. Median overall survival was 222 days (range, 23-1,041 days), and 60% of patients lived at least 400 days after treatment. Patients survived a median of 115 days without relapsing (range, 0-455 days), and 55% ultimately relapsed. Age did not appear to predict relapse, he noted.

Kaplan-Meier curves revealed no major differences in rates of overall survival (OS) between adults and children at 400-day data cutoff, Dr. Chang said. However, patients with more than 50% blast cells in their bone marrow had significantly lower rates of survival (P = .02) than did patients with less advanced ALL. A lower T-cell dose predicted lower survival in children (P = .04), but not in adults. Dr. Chang and his colleagues now dose patients of all ages with 106 cells per kilogram, he said.

Survival was significantly more likely when CAR T cell recipients went on to allogeneic hematopoietic stem cell transplantation (P = .0002) than otherwise. Based on the findings, Dr. Chang particularly recommends this approach for highly chemotherapy-resistant disease with a high tumor burden. Among patients who relapsed, repeating CAR T cell therapy led to better survival than administering combination chemotherapy-tyrosine kinase inhibitor therapy (P = .01).

These safety and efficacy results suggest that CAR T cell immunotherapy can benefit patients if they have very high-burden leukemia, Dr. Chang concluded. Patients outcomes remained consistent across centers due to a “highly standardized CAR T cell preparation profile,” he said.

Dr. Chang did not report funding sources. He reported having no relevant conflicts of interest.

SAN DIEGO – Anti-CD19 chimeric antigen receptor (CAR) T cells engineered with a “safety switch” yielded high rates of complete response and an acceptable toxicity profile in chemotherapy-resistant B cell acute lymphoblastic leukemia, according to a multicenter phase I/II trial.

Importantly, high tumor burden did not increase the risk of cytokine release syndrome, said Lung-Ji Chang, PhD, of Shenzhen (China) Genoimmune Medical Institute and the University of Florida in Gainesville. “This reliable, standardized CAR T-cell preparation protocol has now served more than 30 major medical centers in China,” he said at the annual meeting of the American Society of Hematology.

Anti-CD19 CAR T cells have shown dramatic potential for treating B-cell malignancies, but toxicities have been a concern. One potentially serious adverse reaction is cytokine release syndrome, in which patients develop marked rises in blood levels of several types of cytokines. Another problem is that anti-CD19 CAR T cells can trigger loss of CD19 B cells, ultimately leading to humoral deficiencies, Dr. Chang noted. Consequently, researchers have searched for ways to continue controlling the activity of CAR T cells even after infusing them into patients.

As part of that effort, Dr. Chang and his associates developed a standardized protocol for engineering next-generation anti-CD19 CAR T cells based on the established concept of a “safety switch.” After collecting T cells from patients with chemotherapy-resistant ALL, they used a lentiviral vector to transform them into CAR T cells with fusion proteins consisting of a proapoptotic molecule called caspase-9 that is linked to modified human FK506-binding proteins, or FKBP. The addition of iCaspase9-FKBP enables clinicians to induce CAR T cell apoptosis by treating patients with a synthetic dimerizer called AP1903.

Apoptosis occurs about 45 minutes after this drug is given, according to Dr. Chang. This “safety switch” also enables clinicians to eliminate anti-CD19 CAR T cells after tumor cells are eradicated so that patients can recover their humoral immunity. He and his associates further modified these anti-CD19 CAR T cells by introducing four intracellular signaling domains that are associated with T-cell activation, survival, and longevity, he said.

A total of 22 treatment centers helped test this approach in a phase I/II trial of 110 leukemia patients, about half of whom were children with a median age of 9 years. The median age of adults was 37 years, and the oldest patient was 70. Cancer types included Philadelphia chromosome–positive ALL, Philadelphia chromosome–negative ALL, and chronic myeloid leukemia with blast crisis. About a third of patients had bone marrow samples with at least 50% blasts, and a similar proportion had already undergone hematopoietic stem cell transplantation.

Cytokine release syndrome affected 86% of patients with low or no tumor burden, but only 53% of patients with bone marrow blasts exceeding 5%, Dr. Chang reported. He emphasized that patients with high tumor burden were no more likely to develop moderate or severe cytokine release syndrome than were patients with little or no tumor burden (P = .3). Furthermore, among 17 patients with more than 80% bone marrow involvement, only three developed grade 3-4 cytokine release syndrome, while eight developed grade 1 cytokine release syndrome.

A total of 96 patients (87%) had a complete response to this CAR T cell regimen, including 51 children and 45 adults, Dr. Chang reported. Median overall survival was 222 days (range, 23-1,041 days), and 60% of patients lived at least 400 days after treatment. Patients survived a median of 115 days without relapsing (range, 0-455 days), and 55% ultimately relapsed. Age did not appear to predict relapse, he noted.

Kaplan-Meier curves revealed no major differences in rates of overall survival (OS) between adults and children at 400-day data cutoff, Dr. Chang said. However, patients with more than 50% blast cells in their bone marrow had significantly lower rates of survival (P = .02) than did patients with less advanced ALL. A lower T-cell dose predicted lower survival in children (P = .04), but not in adults. Dr. Chang and his colleagues now dose patients of all ages with 106 cells per kilogram, he said.

Survival was significantly more likely when CAR T cell recipients went on to allogeneic hematopoietic stem cell transplantation (P = .0002) than otherwise. Based on the findings, Dr. Chang particularly recommends this approach for highly chemotherapy-resistant disease with a high tumor burden. Among patients who relapsed, repeating CAR T cell therapy led to better survival than administering combination chemotherapy-tyrosine kinase inhibitor therapy (P = .01).

These safety and efficacy results suggest that CAR T cell immunotherapy can benefit patients if they have very high-burden leukemia, Dr. Chang concluded. Patients outcomes remained consistent across centers due to a “highly standardized CAR T cell preparation profile,” he said.

Dr. Chang did not report funding sources. He reported having no relevant conflicts of interest.

SAN DIEGO – Anti-CD19 chimeric antigen receptor (CAR) T cells engineered with a “safety switch” yielded high rates of complete response and an acceptable toxicity profile in chemotherapy-resistant B cell acute lymphoblastic leukemia, according to a multicenter phase I/II trial.

Importantly, high tumor burden did not increase the risk of cytokine release syndrome, said Lung-Ji Chang, PhD, of Shenzhen (China) Genoimmune Medical Institute and the University of Florida in Gainesville. “This reliable, standardized CAR T-cell preparation protocol has now served more than 30 major medical centers in China,” he said at the annual meeting of the American Society of Hematology.

Anti-CD19 CAR T cells have shown dramatic potential for treating B-cell malignancies, but toxicities have been a concern. One potentially serious adverse reaction is cytokine release syndrome, in which patients develop marked rises in blood levels of several types of cytokines. Another problem is that anti-CD19 CAR T cells can trigger loss of CD19 B cells, ultimately leading to humoral deficiencies, Dr. Chang noted. Consequently, researchers have searched for ways to continue controlling the activity of CAR T cells even after infusing them into patients.

As part of that effort, Dr. Chang and his associates developed a standardized protocol for engineering next-generation anti-CD19 CAR T cells based on the established concept of a “safety switch.” After collecting T cells from patients with chemotherapy-resistant ALL, they used a lentiviral vector to transform them into CAR T cells with fusion proteins consisting of a proapoptotic molecule called caspase-9 that is linked to modified human FK506-binding proteins, or FKBP. The addition of iCaspase9-FKBP enables clinicians to induce CAR T cell apoptosis by treating patients with a synthetic dimerizer called AP1903.

Apoptosis occurs about 45 minutes after this drug is given, according to Dr. Chang. This “safety switch” also enables clinicians to eliminate anti-CD19 CAR T cells after tumor cells are eradicated so that patients can recover their humoral immunity. He and his associates further modified these anti-CD19 CAR T cells by introducing four intracellular signaling domains that are associated with T-cell activation, survival, and longevity, he said.

A total of 22 treatment centers helped test this approach in a phase I/II trial of 110 leukemia patients, about half of whom were children with a median age of 9 years. The median age of adults was 37 years, and the oldest patient was 70. Cancer types included Philadelphia chromosome–positive ALL, Philadelphia chromosome–negative ALL, and chronic myeloid leukemia with blast crisis. About a third of patients had bone marrow samples with at least 50% blasts, and a similar proportion had already undergone hematopoietic stem cell transplantation.

Cytokine release syndrome affected 86% of patients with low or no tumor burden, but only 53% of patients with bone marrow blasts exceeding 5%, Dr. Chang reported. He emphasized that patients with high tumor burden were no more likely to develop moderate or severe cytokine release syndrome than were patients with little or no tumor burden (P = .3). Furthermore, among 17 patients with more than 80% bone marrow involvement, only three developed grade 3-4 cytokine release syndrome, while eight developed grade 1 cytokine release syndrome.

A total of 96 patients (87%) had a complete response to this CAR T cell regimen, including 51 children and 45 adults, Dr. Chang reported. Median overall survival was 222 days (range, 23-1,041 days), and 60% of patients lived at least 400 days after treatment. Patients survived a median of 115 days without relapsing (range, 0-455 days), and 55% ultimately relapsed. Age did not appear to predict relapse, he noted.

Kaplan-Meier curves revealed no major differences in rates of overall survival (OS) between adults and children at 400-day data cutoff, Dr. Chang said. However, patients with more than 50% blast cells in their bone marrow had significantly lower rates of survival (P = .02) than did patients with less advanced ALL. A lower T-cell dose predicted lower survival in children (P = .04), but not in adults. Dr. Chang and his colleagues now dose patients of all ages with 106 cells per kilogram, he said.

Survival was significantly more likely when CAR T cell recipients went on to allogeneic hematopoietic stem cell transplantation (P = .0002) than otherwise. Based on the findings, Dr. Chang particularly recommends this approach for highly chemotherapy-resistant disease with a high tumor burden. Among patients who relapsed, repeating CAR T cell therapy led to better survival than administering combination chemotherapy-tyrosine kinase inhibitor therapy (P = .01).

These safety and efficacy results suggest that CAR T cell immunotherapy can benefit patients if they have very high-burden leukemia, Dr. Chang concluded. Patients outcomes remained consistent across centers due to a “highly standardized CAR T cell preparation profile,” he said.

Dr. Chang did not report funding sources. He reported having no relevant conflicts of interest.

VIENNA – Stereotactic body radiotherapy (SBRT) proved too toxic for many of patients recruited into a multinational phase II trial with centrally-located lung tumors.

The majority of patients experienced some type of adverse effect, with 28% experiencing serious (grade 3-5) adverse effects.

“Our major concern now is that we had six cases of grade 5 bleedings,” Karen Lindberg, MD, said at the World Conference on Lung Cancer. “Tumor location seems to be a risk factor for bleeding,” she added, with five of the six cases seen in patients who had tumors close to a main bronchus (group A). The other case was in patient who had tumors close to a lobular bronchus (group B).

“The classical definition of a centrally-located lung tumor is a tumor residing within or touching an imaginary zone 2 cm around the proximal bronchial tree,” explained Dr. Lindberg of Karolinska University Hospital and the Karolinska Institutet in Stockholm, who presented the first results of the Nordic HILUS Trial.

“When we designed this study we wanted to look at very centrally located tumors, so we tightened up this definition to look at tumors that occurred within 1 cm around the proximal bronchial tree,” she said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

During the trial, SBRT was to be delivered at a dose of 7 Gray (Gy) in 8 fractions at 65%-75% isodose lines to ultra-centrally-located tumors. Dose constraints were stipulated for tumors situated very close to the spinal cord, contralateral main bronchus, and trachea, with some dosing recommendations on reducing the dose delivered to tumors that were ipsilateral to the main bronchus, or very close to the esophagus or heart.

A total of 74 patients with centrally-located, locally progressive tumors, which were less than 5 cm in size and due to non–small-cell lung cancer (NSCLC) or metastatic lung disease from another solid tumor, were recruited. Patients had to have a good performance status and life expectancy of 3 months.

Patients with brain metastases or tumors that reached through the wall of a main bronchus were excluded as were those who were taking any concomitant systemic therapy.

The mean age of the recruited patients was 71 years; 58 (78%) had NSCLC, of which 20 (27%) had adenomas and 19 (26%) had squamous cell cancers. Of those with secondary lung tumors, eight (11%), had primary renal cell carcinoma and four (5%) had colorectal cancer.

After a follow-up of 18.6 months, 31 (42%) patients had died.

The most common adverse events reported were grade 1-2 dyspnea, cough, and fatigue. However, there was a high rate of grade 3 (dyspnea, fatigue, pain, pneumonitis, and heart rhythm disturbance), 4 (pain, lung infection, fever, heart rhythm disturbance, fistula, and pneumothorax) and 5 toxicities (pneumonitis and bleeding).

Bleeding often occurred without warning and had an acute onset and toll.

Seven patients (six in group A and one in group B) may have suffered grade 5 side effects; six patients experienced lethal hemoptysis after a median of 15.5 months (2.5-21 months) and one patient suffered from a lethal pneumonitis 5 months post study treatment. The reintroduction of TKIs may also have played a role, Dr. Lindberg suggested.

SBRT for early stage NSCLC is very effective and “generates outstanding tumor control”, said Feng-Ming Kong, MD, of Indiana University, Indianapolis, who was invited to comment on the findings.

Most studies of SBRT have looked at peripherally-located tumors, however, so the study by the NORDIC Study Group provides valuable information on a more centrally-located approach. The big question of course is what caused the bleeding.

“What percentage of TKI patients had bleeding and how many of them had a TKI without bleeding?” Dr. Kong asked. Other questions around dosing remain: How much radiation was delivered to the great vessels such as the pulmonary artery, and how much of the dose hit critical structures? And, were tumors invading the pulmonary artery?

“SBRT may be applied for centrally-located tumors safely with other prescription regimens, she suggested, such as 10-11 Gy given in 5 fractions. That is assuming that “the dose limits of normal tissues are strictly controlled and the patients are carefully selected to exclude T4 diseases for adjacent organ invasion.”

The NORDIC SBRT Study Group conducted the study. Dr. Lindberg had no conflicts of interest to disclose. Dr. Kong has received research grants from the National Cancer Institute (part of the National Institutes of Health) and speakers honorarium and travel support from Varian Medical.

VIENNA – Stereotactic body radiotherapy (SBRT) proved too toxic for many of patients recruited into a multinational phase II trial with centrally-located lung tumors.

The majority of patients experienced some type of adverse effect, with 28% experiencing serious (grade 3-5) adverse effects.

“Our major concern now is that we had six cases of grade 5 bleedings,” Karen Lindberg, MD, said at the World Conference on Lung Cancer. “Tumor location seems to be a risk factor for bleeding,” she added, with five of the six cases seen in patients who had tumors close to a main bronchus (group A). The other case was in patient who had tumors close to a lobular bronchus (group B).

“The classical definition of a centrally-located lung tumor is a tumor residing within or touching an imaginary zone 2 cm around the proximal bronchial tree,” explained Dr. Lindberg of Karolinska University Hospital and the Karolinska Institutet in Stockholm, who presented the first results of the Nordic HILUS Trial.

“When we designed this study we wanted to look at very centrally located tumors, so we tightened up this definition to look at tumors that occurred within 1 cm around the proximal bronchial tree,” she said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

During the trial, SBRT was to be delivered at a dose of 7 Gray (Gy) in 8 fractions at 65%-75% isodose lines to ultra-centrally-located tumors. Dose constraints were stipulated for tumors situated very close to the spinal cord, contralateral main bronchus, and trachea, with some dosing recommendations on reducing the dose delivered to tumors that were ipsilateral to the main bronchus, or very close to the esophagus or heart.

A total of 74 patients with centrally-located, locally progressive tumors, which were less than 5 cm in size and due to non–small-cell lung cancer (NSCLC) or metastatic lung disease from another solid tumor, were recruited. Patients had to have a good performance status and life expectancy of 3 months.

Patients with brain metastases or tumors that reached through the wall of a main bronchus were excluded as were those who were taking any concomitant systemic therapy.

The mean age of the recruited patients was 71 years; 58 (78%) had NSCLC, of which 20 (27%) had adenomas and 19 (26%) had squamous cell cancers. Of those with secondary lung tumors, eight (11%), had primary renal cell carcinoma and four (5%) had colorectal cancer.

After a follow-up of 18.6 months, 31 (42%) patients had died.

The most common adverse events reported were grade 1-2 dyspnea, cough, and fatigue. However, there was a high rate of grade 3 (dyspnea, fatigue, pain, pneumonitis, and heart rhythm disturbance), 4 (pain, lung infection, fever, heart rhythm disturbance, fistula, and pneumothorax) and 5 toxicities (pneumonitis and bleeding).

Bleeding often occurred without warning and had an acute onset and toll.

Seven patients (six in group A and one in group B) may have suffered grade 5 side effects; six patients experienced lethal hemoptysis after a median of 15.5 months (2.5-21 months) and one patient suffered from a lethal pneumonitis 5 months post study treatment. The reintroduction of TKIs may also have played a role, Dr. Lindberg suggested.

SBRT for early stage NSCLC is very effective and “generates outstanding tumor control”, said Feng-Ming Kong, MD, of Indiana University, Indianapolis, who was invited to comment on the findings.

Most studies of SBRT have looked at peripherally-located tumors, however, so the study by the NORDIC Study Group provides valuable information on a more centrally-located approach. The big question of course is what caused the bleeding.

“What percentage of TKI patients had bleeding and how many of them had a TKI without bleeding?” Dr. Kong asked. Other questions around dosing remain: How much radiation was delivered to the great vessels such as the pulmonary artery, and how much of the dose hit critical structures? And, were tumors invading the pulmonary artery?

“SBRT may be applied for centrally-located tumors safely with other prescription regimens, she suggested, such as 10-11 Gy given in 5 fractions. That is assuming that “the dose limits of normal tissues are strictly controlled and the patients are carefully selected to exclude T4 diseases for adjacent organ invasion.”

The NORDIC SBRT Study Group conducted the study. Dr. Lindberg had no conflicts of interest to disclose. Dr. Kong has received research grants from the National Cancer Institute (part of the National Institutes of Health) and speakers honorarium and travel support from Varian Medical.

VIENNA – Stereotactic body radiotherapy (SBRT) proved too toxic for many of patients recruited into a multinational phase II trial with centrally-located lung tumors.

The majority of patients experienced some type of adverse effect, with 28% experiencing serious (grade 3-5) adverse effects.

“Our major concern now is that we had six cases of grade 5 bleedings,” Karen Lindberg, MD, said at the World Conference on Lung Cancer. “Tumor location seems to be a risk factor for bleeding,” she added, with five of the six cases seen in patients who had tumors close to a main bronchus (group A). The other case was in patient who had tumors close to a lobular bronchus (group B).

“The classical definition of a centrally-located lung tumor is a tumor residing within or touching an imaginary zone 2 cm around the proximal bronchial tree,” explained Dr. Lindberg of Karolinska University Hospital and the Karolinska Institutet in Stockholm, who presented the first results of the Nordic HILUS Trial.

“When we designed this study we wanted to look at very centrally located tumors, so we tightened up this definition to look at tumors that occurred within 1 cm around the proximal bronchial tree,” she said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

During the trial, SBRT was to be delivered at a dose of 7 Gray (Gy) in 8 fractions at 65%-75% isodose lines to ultra-centrally-located tumors. Dose constraints were stipulated for tumors situated very close to the spinal cord, contralateral main bronchus, and trachea, with some dosing recommendations on reducing the dose delivered to tumors that were ipsilateral to the main bronchus, or very close to the esophagus or heart.

A total of 74 patients with centrally-located, locally progressive tumors, which were less than 5 cm in size and due to non–small-cell lung cancer (NSCLC) or metastatic lung disease from another solid tumor, were recruited. Patients had to have a good performance status and life expectancy of 3 months.

Patients with brain metastases or tumors that reached through the wall of a main bronchus were excluded as were those who were taking any concomitant systemic therapy.

The mean age of the recruited patients was 71 years; 58 (78%) had NSCLC, of which 20 (27%) had adenomas and 19 (26%) had squamous cell cancers. Of those with secondary lung tumors, eight (11%), had primary renal cell carcinoma and four (5%) had colorectal cancer.

After a follow-up of 18.6 months, 31 (42%) patients had died.

The most common adverse events reported were grade 1-2 dyspnea, cough, and fatigue. However, there was a high rate of grade 3 (dyspnea, fatigue, pain, pneumonitis, and heart rhythm disturbance), 4 (pain, lung infection, fever, heart rhythm disturbance, fistula, and pneumothorax) and 5 toxicities (pneumonitis and bleeding).

Bleeding often occurred without warning and had an acute onset and toll.

Seven patients (six in group A and one in group B) may have suffered grade 5 side effects; six patients experienced lethal hemoptysis after a median of 15.5 months (2.5-21 months) and one patient suffered from a lethal pneumonitis 5 months post study treatment. The reintroduction of TKIs may also have played a role, Dr. Lindberg suggested.

SBRT for early stage NSCLC is very effective and “generates outstanding tumor control”, said Feng-Ming Kong, MD, of Indiana University, Indianapolis, who was invited to comment on the findings.

Most studies of SBRT have looked at peripherally-located tumors, however, so the study by the NORDIC Study Group provides valuable information on a more centrally-located approach. The big question of course is what caused the bleeding.

“What percentage of TKI patients had bleeding and how many of them had a TKI without bleeding?” Dr. Kong asked. Other questions around dosing remain: How much radiation was delivered to the great vessels such as the pulmonary artery, and how much of the dose hit critical structures? And, were tumors invading the pulmonary artery?

“SBRT may be applied for centrally-located tumors safely with other prescription regimens, she suggested, such as 10-11 Gy given in 5 fractions. That is assuming that “the dose limits of normal tissues are strictly controlled and the patients are carefully selected to exclude T4 diseases for adjacent organ invasion.”

The NORDIC SBRT Study Group conducted the study. Dr. Lindberg had no conflicts of interest to disclose. Dr. Kong has received research grants from the National Cancer Institute (part of the National Institutes of Health) and speakers honorarium and travel support from Varian Medical.

Keratoacanthomas (KAs) are rapidly growing tumors most prominently found on sun-exposed areas of the skin. The normal progression of a KA is to show rapid growth followed by spontaneous resolution.¹ Most KAs are solitary; however, there are several variants of multiple KAs including the familial Ferguson-Smith type, Gryzbowski syndrome (generalized eruptive KAs), KA centrifugum marginatum, Muir-Torre syndrome, and xeroderma pigmentosum.^2-4 Keratoacanthomas also may develop in areas of trauma, including burns, laser treatment, radiation, and surgical margins from excisional biopsies or skin grafting.⁵ Treatment of multiple KAs can be difficult due to a potentially large field size and number of lesions.⁶ We present a case of multiple KAs developing both in the surgical margins and de novo that responded dramatically to treatment with intralesional methotrexate (MTX).

Case Report

A 55-year-old man with a history of a surgically treated squamous cell carcinoma (SCC) on the anterior aspect of the right leg developed multiple nodules involving the surgical scar. He previously underwent Mohs micrographic surgery (MMS); within a month after the second surgery the patient noticed increased pruritus along with scaly pink changes at the site of the surgical scar.

One month prior to presentation, biopsies from the anterior aspect of the right leg demonstrated well-differentiated SCC and he was subsequently treated with MMS; however, examination 1 month after MMS revealed an 11×7-cm indurated plaque with multiple nodules ranging from 1 to 2 cm near the periphery of the plaque with central atrophy and scarring, reminiscent of KA centrifugum marginatum (Figure, A). In a similar fashion, an 8×5-cm plaque composed of 7 nodular areas was noted on the posterior aspect of the right leg (Figure, B). The patient denied any history of trauma to this area. There was no palpable regional lymphadenopathy and the remainder of the skin examination was normal, except for signs of venous stasis in both legs.

Based on the location and morphology of the lesions, the clinical presentation was consistent with multiple KAs. Histologic examination from punch biopsies taken from the plaque's periphery demonstrated well-differentiated SCC (KA type), as well as a lichenoid inflammatory process, epidermal hyperplasia, and cystic and endophytic squamous proliferation suggestive of hypertrophic lichen planus (HLP).

In consideration of the size and number of the lesions as well as the prolonged wound healing with prior surgery, the patient consented to treatment with intralesional MTX (1 mL of 12.5 mg/mL every 2 weeks) rather than undergoing further surgery. The MTX injection was distributed between the lesions on the anterior and posterior aspects of the lower right leg. At each injection session, the size, thickness, and nodularity of the tumor decreased with markedly less pruritus and symptomatic relief was achieved. After 3 injection sessions, resulting in a total of 3 mL of 12.5 mg/mL of MTX, biopsies were taken from the residual atrophic scar on the anterior aspect of the right leg and the remaining 3 papules on the posterior aspect of the right leg to rule out HLP and invasive SCC. The pathology report commented on the presence of prurigo nodules without any evidence of SCC.

At 3-month follow-up, the patient demonstrated no new lesions or recurrence (Figure, C and D). The right leg continued to heal with scarring and postinflammatory pigmentary changes. The patient was monitored for recurrence and to determine the diagnosis of HLP.

Comment

We report the development of multiple KAs arising both from within surgical margins and de novo, and resolution with intralesional MTX. Keratoacanthomas, especially various KA types, have been observed to develop due to various types of trauma, including sites of surgical scars, lichen planus, tattoos, thermal burns, radiation, and discoid lupus erythematosus, and within skin grafts and donor sites.^5-19

Hypertrophic lichen planus is a chronic variant of lichen planus that often is found on the pretibial areas of the lower legs.¹³ Both SCC and reactive KAs have been observed to develop within lesions of HLP.¹⁴ Our pathologist commented on the presence of a lichenoid infiltrate with necrotic keratinocytes and epidermal hyperplasia suspicious for HLP, with a small focus of cystic and endophytic squamous proliferation. The latter lacked notable atypia or an invasive component and could represent an irritated infundibular cyst versus an early evolving KA.

The lichenoid inflammation is suspicious for HLP, which has been associated with eruptive KAs^13-16 and may have contributed to the development of persistent KAs in our patient, both in sites of surgical scars (the anterior aspect of the leg) and in uninvolved skin (the posterior aspect of the leg). Trauma from the prior surgery may have stimulated a local inflammatory response and, if coupled with a preexisting underlying chronic inflammatory condition such as HLP, may have triggered the development of new lesions on the posterior leg. Skin pathergy reactions also are caused by an upregulated inflammatory response, which is reduced with immunosuppressive agents such as MTX.¹²

In our patient, there was both an isotopic and isomorphic response. The term isotopic response refers to the occurrence of a new skin disorder at the site of another unrelated and already healed skin disease. It was first defined by Wolf and Wolf²⁰ in 1985 and hence is also known as Wolf isotopic response. The isotopic response in our patient occurred in the setting of lichen planus. The isomorphic response indicates the appearance of typical skin lesions of an existing dermatosis at sites of other skin injuries.

Initially, we thought the patient had recurrence of SCC, but with the rapid development of multiple lesions, the diagnosis of multiple KAs was more likely. Kimyai-Asadi et al⁸ demonstrated that surgical trauma can precede the development of KAs, as they reported a patient who developed a KA at an excision site. Tamir et al⁷ reported the simultaneous appearance of KAs in burn scars and skin graft donor sites 4 months after a 40% total body surface area burn. Hamilton et al¹¹ described surgical trauma from a split-skin graft donor site as a trigger for the onset of a KA.

Multiple treatment alternatives exist for KAs, with the standard of care for large or high-risk KAs being excisional surgery^21,22; however, other approaches may need to be considered in certain cases, such as with multiple KAs in which lesions may be large and extensive, thereby yielding poor cosmetic outcomes, or with increased surgical risk.²³ Furthermore, multiple KAs that develop in the setting of surgical scars require special consideration. Topical 5-fluorouracil, various systemic and intralesional agents (eg, retinoids, interferon, bleomycin, MTX), laser therapy, electrodesiccation and curettage, radiotherapy, and photodynamic therapy all have been reported as methods employed for the treatment of KA.^23-27 Goldberg et al⁵ reported cases of resolution of eruptive KAs arising in both surgical and nonsurgical sites with a combination of deep shave excision, MMS, curettage and desiccation, and oral isotretinoin.

For our patient, we opted for treatment with intralesional MTX, both due to its effectiveness for solitary KAs and reasonably decreased risk of morbidity compared to surgical excision of regions of the pretibial calves. Treatment with MTX would not have been attempted if there was any clinical doubt that the lesions were not the well-differentiated KA type. Also, we had a low threshold for discontinuing therapy and reverting to MMS treatment if any of the lesions displayed a paradoxical growth post-MTX treatment or failed to respond after 3 treatments. Intralesional MTX is less invasive, relatively inexpensive, and a treatment modality with decreased morbidity for KAs, especially for multiple KAs. It should be considered as a potential alternative to surgery in such cases.^23-27

Keratoacanthomas (KAs) are rapidly growing tumors most prominently found on sun-exposed areas of the skin. The normal progression of a KA is to show rapid growth followed by spontaneous resolution.¹ Most KAs are solitary; however, there are several variants of multiple KAs including the familial Ferguson-Smith type, Gryzbowski syndrome (generalized eruptive KAs), KA centrifugum marginatum, Muir-Torre syndrome, and xeroderma pigmentosum.^2-4 Keratoacanthomas also may develop in areas of trauma, including burns, laser treatment, radiation, and surgical margins from excisional biopsies or skin grafting.⁵ Treatment of multiple KAs can be difficult due to a potentially large field size and number of lesions.⁶ We present a case of multiple KAs developing both in the surgical margins and de novo that responded dramatically to treatment with intralesional methotrexate (MTX).

Case Report

A 55-year-old man with a history of a surgically treated squamous cell carcinoma (SCC) on the anterior aspect of the right leg developed multiple nodules involving the surgical scar. He previously underwent Mohs micrographic surgery (MMS); within a month after the second surgery the patient noticed increased pruritus along with scaly pink changes at the site of the surgical scar.

One month prior to presentation, biopsies from the anterior aspect of the right leg demonstrated well-differentiated SCC and he was subsequently treated with MMS; however, examination 1 month after MMS revealed an 11×7-cm indurated plaque with multiple nodules ranging from 1 to 2 cm near the periphery of the plaque with central atrophy and scarring, reminiscent of KA centrifugum marginatum (Figure, A). In a similar fashion, an 8×5-cm plaque composed of 7 nodular areas was noted on the posterior aspect of the right leg (Figure, B). The patient denied any history of trauma to this area. There was no palpable regional lymphadenopathy and the remainder of the skin examination was normal, except for signs of venous stasis in both legs.

Based on the location and morphology of the lesions, the clinical presentation was consistent with multiple KAs. Histologic examination from punch biopsies taken from the plaque's periphery demonstrated well-differentiated SCC (KA type), as well as a lichenoid inflammatory process, epidermal hyperplasia, and cystic and endophytic squamous proliferation suggestive of hypertrophic lichen planus (HLP).

In consideration of the size and number of the lesions as well as the prolonged wound healing with prior surgery, the patient consented to treatment with intralesional MTX (1 mL of 12.5 mg/mL every 2 weeks) rather than undergoing further surgery. The MTX injection was distributed between the lesions on the anterior and posterior aspects of the lower right leg. At each injection session, the size, thickness, and nodularity of the tumor decreased with markedly less pruritus and symptomatic relief was achieved. After 3 injection sessions, resulting in a total of 3 mL of 12.5 mg/mL of MTX, biopsies were taken from the residual atrophic scar on the anterior aspect of the right leg and the remaining 3 papules on the posterior aspect of the right leg to rule out HLP and invasive SCC. The pathology report commented on the presence of prurigo nodules without any evidence of SCC.

At 3-month follow-up, the patient demonstrated no new lesions or recurrence (Figure, C and D). The right leg continued to heal with scarring and postinflammatory pigmentary changes. The patient was monitored for recurrence and to determine the diagnosis of HLP.

Comment

We report the development of multiple KAs arising both from within surgical margins and de novo, and resolution with intralesional MTX. Keratoacanthomas, especially various KA types, have been observed to develop due to various types of trauma, including sites of surgical scars, lichen planus, tattoos, thermal burns, radiation, and discoid lupus erythematosus, and within skin grafts and donor sites.^5-19

Hypertrophic lichen planus is a chronic variant of lichen planus that often is found on the pretibial areas of the lower legs.¹³ Both SCC and reactive KAs have been observed to develop within lesions of HLP.¹⁴ Our pathologist commented on the presence of a lichenoid infiltrate with necrotic keratinocytes and epidermal hyperplasia suspicious for HLP, with a small focus of cystic and endophytic squamous proliferation. The latter lacked notable atypia or an invasive component and could represent an irritated infundibular cyst versus an early evolving KA.

The lichenoid inflammation is suspicious for HLP, which has been associated with eruptive KAs^13-16 and may have contributed to the development of persistent KAs in our patient, both in sites of surgical scars (the anterior aspect of the leg) and in uninvolved skin (the posterior aspect of the leg). Trauma from the prior surgery may have stimulated a local inflammatory response and, if coupled with a preexisting underlying chronic inflammatory condition such as HLP, may have triggered the development of new lesions on the posterior leg. Skin pathergy reactions also are caused by an upregulated inflammatory response, which is reduced with immunosuppressive agents such as MTX.¹²

In our patient, there was both an isotopic and isomorphic response. The term isotopic response refers to the occurrence of a new skin disorder at the site of another unrelated and already healed skin disease. It was first defined by Wolf and Wolf²⁰ in 1985 and hence is also known as Wolf isotopic response. The isotopic response in our patient occurred in the setting of lichen planus. The isomorphic response indicates the appearance of typical skin lesions of an existing dermatosis at sites of other skin injuries.

Initially, we thought the patient had recurrence of SCC, but with the rapid development of multiple lesions, the diagnosis of multiple KAs was more likely. Kimyai-Asadi et al⁸ demonstrated that surgical trauma can precede the development of KAs, as they reported a patient who developed a KA at an excision site. Tamir et al⁷ reported the simultaneous appearance of KAs in burn scars and skin graft donor sites 4 months after a 40% total body surface area burn. Hamilton et al¹¹ described surgical trauma from a split-skin graft donor site as a trigger for the onset of a KA.

Multiple treatment alternatives exist for KAs, with the standard of care for large or high-risk KAs being excisional surgery^21,22; however, other approaches may need to be considered in certain cases, such as with multiple KAs in which lesions may be large and extensive, thereby yielding poor cosmetic outcomes, or with increased surgical risk.²³ Furthermore, multiple KAs that develop in the setting of surgical scars require special consideration. Topical 5-fluorouracil, various systemic and intralesional agents (eg, retinoids, interferon, bleomycin, MTX), laser therapy, electrodesiccation and curettage, radiotherapy, and photodynamic therapy all have been reported as methods employed for the treatment of KA.^23-27 Goldberg et al⁵ reported cases of resolution of eruptive KAs arising in both surgical and nonsurgical sites with a combination of deep shave excision, MMS, curettage and desiccation, and oral isotretinoin.

For our patient, we opted for treatment with intralesional MTX, both due to its effectiveness for solitary KAs and reasonably decreased risk of morbidity compared to surgical excision of regions of the pretibial calves. Treatment with MTX would not have been attempted if there was any clinical doubt that the lesions were not the well-differentiated KA type. Also, we had a low threshold for discontinuing therapy and reverting to MMS treatment if any of the lesions displayed a paradoxical growth post-MTX treatment or failed to respond after 3 treatments. Intralesional MTX is less invasive, relatively inexpensive, and a treatment modality with decreased morbidity for KAs, especially for multiple KAs. It should be considered as a potential alternative to surgery in such cases.^23-27

Keratoacanthomas (KAs) are rapidly growing tumors most prominently found on sun-exposed areas of the skin. The normal progression of a KA is to show rapid growth followed by spontaneous resolution.¹ Most KAs are solitary; however, there are several variants of multiple KAs including the familial Ferguson-Smith type, Gryzbowski syndrome (generalized eruptive KAs), KA centrifugum marginatum, Muir-Torre syndrome, and xeroderma pigmentosum.^2-4 Keratoacanthomas also may develop in areas of trauma, including burns, laser treatment, radiation, and surgical margins from excisional biopsies or skin grafting.⁵ Treatment of multiple KAs can be difficult due to a potentially large field size and number of lesions.⁶ We present a case of multiple KAs developing both in the surgical margins and de novo that responded dramatically to treatment with intralesional methotrexate (MTX).

Case Report

A 55-year-old man with a history of a surgically treated squamous cell carcinoma (SCC) on the anterior aspect of the right leg developed multiple nodules involving the surgical scar. He previously underwent Mohs micrographic surgery (MMS); within a month after the second surgery the patient noticed increased pruritus along with scaly pink changes at the site of the surgical scar.

One month prior to presentation, biopsies from the anterior aspect of the right leg demonstrated well-differentiated SCC and he was subsequently treated with MMS; however, examination 1 month after MMS revealed an 11×7-cm indurated plaque with multiple nodules ranging from 1 to 2 cm near the periphery of the plaque with central atrophy and scarring, reminiscent of KA centrifugum marginatum (Figure, A). In a similar fashion, an 8×5-cm plaque composed of 7 nodular areas was noted on the posterior aspect of the right leg (Figure, B). The patient denied any history of trauma to this area. There was no palpable regional lymphadenopathy and the remainder of the skin examination was normal, except for signs of venous stasis in both legs.

Based on the location and morphology of the lesions, the clinical presentation was consistent with multiple KAs. Histologic examination from punch biopsies taken from the plaque's periphery demonstrated well-differentiated SCC (KA type), as well as a lichenoid inflammatory process, epidermal hyperplasia, and cystic and endophytic squamous proliferation suggestive of hypertrophic lichen planus (HLP).

In consideration of the size and number of the lesions as well as the prolonged wound healing with prior surgery, the patient consented to treatment with intralesional MTX (1 mL of 12.5 mg/mL every 2 weeks) rather than undergoing further surgery. The MTX injection was distributed between the lesions on the anterior and posterior aspects of the lower right leg. At each injection session, the size, thickness, and nodularity of the tumor decreased with markedly less pruritus and symptomatic relief was achieved. After 3 injection sessions, resulting in a total of 3 mL of 12.5 mg/mL of MTX, biopsies were taken from the residual atrophic scar on the anterior aspect of the right leg and the remaining 3 papules on the posterior aspect of the right leg to rule out HLP and invasive SCC. The pathology report commented on the presence of prurigo nodules without any evidence of SCC.

At 3-month follow-up, the patient demonstrated no new lesions or recurrence (Figure, C and D). The right leg continued to heal with scarring and postinflammatory pigmentary changes. The patient was monitored for recurrence and to determine the diagnosis of HLP.

Comment

We report the development of multiple KAs arising both from within surgical margins and de novo, and resolution with intralesional MTX. Keratoacanthomas, especially various KA types, have been observed to develop due to various types of trauma, including sites of surgical scars, lichen planus, tattoos, thermal burns, radiation, and discoid lupus erythematosus, and within skin grafts and donor sites.^5-19

Hypertrophic lichen planus is a chronic variant of lichen planus that often is found on the pretibial areas of the lower legs.¹³ Both SCC and reactive KAs have been observed to develop within lesions of HLP.¹⁴ Our pathologist commented on the presence of a lichenoid infiltrate with necrotic keratinocytes and epidermal hyperplasia suspicious for HLP, with a small focus of cystic and endophytic squamous proliferation. The latter lacked notable atypia or an invasive component and could represent an irritated infundibular cyst versus an early evolving KA.

The lichenoid inflammation is suspicious for HLP, which has been associated with eruptive KAs^13-16 and may have contributed to the development of persistent KAs in our patient, both in sites of surgical scars (the anterior aspect of the leg) and in uninvolved skin (the posterior aspect of the leg). Trauma from the prior surgery may have stimulated a local inflammatory response and, if coupled with a preexisting underlying chronic inflammatory condition such as HLP, may have triggered the development of new lesions on the posterior leg. Skin pathergy reactions also are caused by an upregulated inflammatory response, which is reduced with immunosuppressive agents such as MTX.¹²

In our patient, there was both an isotopic and isomorphic response. The term isotopic response refers to the occurrence of a new skin disorder at the site of another unrelated and already healed skin disease. It was first defined by Wolf and Wolf²⁰ in 1985 and hence is also known as Wolf isotopic response. The isotopic response in our patient occurred in the setting of lichen planus. The isomorphic response indicates the appearance of typical skin lesions of an existing dermatosis at sites of other skin injuries.

Initially, we thought the patient had recurrence of SCC, but with the rapid development of multiple lesions, the diagnosis of multiple KAs was more likely. Kimyai-Asadi et al⁸ demonstrated that surgical trauma can precede the development of KAs, as they reported a patient who developed a KA at an excision site. Tamir et al⁷ reported the simultaneous appearance of KAs in burn scars and skin graft donor sites 4 months after a 40% total body surface area burn. Hamilton et al¹¹ described surgical trauma from a split-skin graft donor site as a trigger for the onset of a KA.

Multiple treatment alternatives exist for KAs, with the standard of care for large or high-risk KAs being excisional surgery^21,22; however, other approaches may need to be considered in certain cases, such as with multiple KAs in which lesions may be large and extensive, thereby yielding poor cosmetic outcomes, or with increased surgical risk.²³ Furthermore, multiple KAs that develop in the setting of surgical scars require special consideration. Topical 5-fluorouracil, various systemic and intralesional agents (eg, retinoids, interferon, bleomycin, MTX), laser therapy, electrodesiccation and curettage, radiotherapy, and photodynamic therapy all have been reported as methods employed for the treatment of KA.^23-27 Goldberg et al⁵ reported cases of resolution of eruptive KAs arising in both surgical and nonsurgical sites with a combination of deep shave excision, MMS, curettage and desiccation, and oral isotretinoin.

For our patient, we opted for treatment with intralesional MTX, both due to its effectiveness for solitary KAs and reasonably decreased risk of morbidity compared to surgical excision of regions of the pretibial calves. Treatment with MTX would not have been attempted if there was any clinical doubt that the lesions were not the well-differentiated KA type. Also, we had a low threshold for discontinuing therapy and reverting to MMS treatment if any of the lesions displayed a paradoxical growth post-MTX treatment or failed to respond after 3 treatments. Intralesional MTX is less invasive, relatively inexpensive, and a treatment modality with decreased morbidity for KAs, especially for multiple KAs. It should be considered as a potential alternative to surgery in such cases.^23-27

To improve patient care and outcomes, leading dermatologists offered their recommendations on self-tanners. Consideration must be given to:

• Anthelios 50 Mineral Tinted
  La Roche-Posay Laboratoire Dermatologique
  Recommended by Gary Goldenberg, MD, New York, New York

• St. Tropez Self Tan products
  PZ Cussons Beauty LLP
  “It helps to produce an even and natural-looking skin tone.”—Anthony M. Rossi, MD, New York, New York

• Sun-Free Self-Tanning Formula
  Kiehl’s
  Recommended by Gary Goldenberg, MD, New York, New York

• Sunless Tanning Towelette
  Sun Bum
  “This product is easy to use. Make sure to use it in conjunction with a broad-spectrum sunscreen.”—Shari Lipner, MD, PhD, New York, New York

Cutis invites readers to send us their recommendations. Cleansing devices, skin-lightening products, and athlete’s foot treatments will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on self-tanners. Consideration must be given to:

• Anthelios 50 Mineral Tinted
  La Roche-Posay Laboratoire Dermatologique
  Recommended by Gary Goldenberg, MD, New York, New York

• St. Tropez Self Tan products
  PZ Cussons Beauty LLP
  “It helps to produce an even and natural-looking skin tone.”—Anthony M. Rossi, MD, New York, New York

• Sun-Free Self-Tanning Formula
  Kiehl’s
  Recommended by Gary Goldenberg, MD, New York, New York

• Sunless Tanning Towelette
  Sun Bum
  “This product is easy to use. Make sure to use it in conjunction with a broad-spectrum sunscreen.”—Shari Lipner, MD, PhD, New York, New York

Cutis invites readers to send us their recommendations. Cleansing devices, skin-lightening products, and athlete’s foot treatments will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on self-tanners. Consideration must be given to:

• Anthelios 50 Mineral Tinted
  La Roche-Posay Laboratoire Dermatologique
  Recommended by Gary Goldenberg, MD, New York, New York

• St. Tropez Self Tan products
  PZ Cussons Beauty LLP
  “It helps to produce an even and natural-looking skin tone.”—Anthony M. Rossi, MD, New York, New York

• Sun-Free Self-Tanning Formula
  Kiehl’s
  Recommended by Gary Goldenberg, MD, New York, New York

• Sunless Tanning Towelette
  Sun Bum
  “This product is easy to use. Make sure to use it in conjunction with a broad-spectrum sunscreen.”—Shari Lipner, MD, PhD, New York, New York

Cutis invites readers to send us their recommendations. Cleansing devices, skin-lightening products, and athlete’s foot treatments will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

ORLANDO – Direct visualization with sonovaginography had greater success in predicting rectal/rectosigmoid deep infiltrating endometriosis than did negative transvaginal ultrasound uterine “sliding sign,” according to the findings of a prospective study of 189 women.

“Both performed quite well,” but sonovaginography was superior for predicting rectal deep infiltrating endometriosis on all measures, including accuracy – 92% vs. 88%, said Bassem Gerges, MBBS, an ob.gyn. at the University of Sydney, Kingswood.

Dr. Gerges and his colleagues evaluated 189 women of reproductive age who were scheduled for operative laparoscopy at a tertiary referral center for women. The patients had a history of chronic pelvic pain and/or endometriosis and presented between 2009 and 2013.

The women first had transvaginal ultrasound to determine if their uterine sliding sign was positive or negative, followed by sonovaginography to assess the posterior pelvic compartment for rectal or rectosigmoid deep infiltrating endometriosis. All patients then underwent laparoscopic surgery for endometriosis.

Laparoscopy revealed pouch of Douglas obliteration in 47 of the 189 women and rectal and/or rectosigmoid deep infiltrating endometriosis in 43 women.

The sensitivity of sonovaginography to predict deep infiltrating endometriosis was 88%, compared with 74% for the sliding-sign approach. Specificity was the same with the two methods at 93%. The positive predictive value was 79% vs. 74%, respectively, and the negative predictive value was 97% vs. 93%.

“These findings can help clinicians with preoperative planning,” Dr. Gerges said at the meeting, which was sponsored by AAGL.

Dr. Gerges and his colleagues also identified 11 false-negative cases in which the sliding sign was positive but laparoscopy confirmed rectal deep infiltrating endometriosis.

Previous research suggests that, in women with suspected endometriosis, a negative transvaginal ultrasound uterine sliding sign can predict rectal or rectosigmoid deep infiltrating endometriosis (Ultrasound Obstet Gynecol. 2013;41[6]:692-5, J Ultrasound Med. 2014;33:315-21). A negative sliding sign indicates the presence of uterorectal adhesions and whether the pouch of Douglas might be obliterated. The current study, however, suggested that sonovaginography might be the better method.

Dr. Gerges reported having no relevant financial disclosures.

ORLANDO – Direct visualization with sonovaginography had greater success in predicting rectal/rectosigmoid deep infiltrating endometriosis than did negative transvaginal ultrasound uterine “sliding sign,” according to the findings of a prospective study of 189 women.

“Both performed quite well,” but sonovaginography was superior for predicting rectal deep infiltrating endometriosis on all measures, including accuracy – 92% vs. 88%, said Bassem Gerges, MBBS, an ob.gyn. at the University of Sydney, Kingswood.

Dr. Gerges and his colleagues evaluated 189 women of reproductive age who were scheduled for operative laparoscopy at a tertiary referral center for women. The patients had a history of chronic pelvic pain and/or endometriosis and presented between 2009 and 2013.

The women first had transvaginal ultrasound to determine if their uterine sliding sign was positive or negative, followed by sonovaginography to assess the posterior pelvic compartment for rectal or rectosigmoid deep infiltrating endometriosis. All patients then underwent laparoscopic surgery for endometriosis.

Laparoscopy revealed pouch of Douglas obliteration in 47 of the 189 women and rectal and/or rectosigmoid deep infiltrating endometriosis in 43 women.

The sensitivity of sonovaginography to predict deep infiltrating endometriosis was 88%, compared with 74% for the sliding-sign approach. Specificity was the same with the two methods at 93%. The positive predictive value was 79% vs. 74%, respectively, and the negative predictive value was 97% vs. 93%.

“These findings can help clinicians with preoperative planning,” Dr. Gerges said at the meeting, which was sponsored by AAGL.

Dr. Gerges and his colleagues also identified 11 false-negative cases in which the sliding sign was positive but laparoscopy confirmed rectal deep infiltrating endometriosis.

Previous research suggests that, in women with suspected endometriosis, a negative transvaginal ultrasound uterine sliding sign can predict rectal or rectosigmoid deep infiltrating endometriosis (Ultrasound Obstet Gynecol. 2013;41[6]:692-5, J Ultrasound Med. 2014;33:315-21). A negative sliding sign indicates the presence of uterorectal adhesions and whether the pouch of Douglas might be obliterated. The current study, however, suggested that sonovaginography might be the better method.

Dr. Gerges reported having no relevant financial disclosures.

ORLANDO – Direct visualization with sonovaginography had greater success in predicting rectal/rectosigmoid deep infiltrating endometriosis than did negative transvaginal ultrasound uterine “sliding sign,” according to the findings of a prospective study of 189 women.

“Both performed quite well,” but sonovaginography was superior for predicting rectal deep infiltrating endometriosis on all measures, including accuracy – 92% vs. 88%, said Bassem Gerges, MBBS, an ob.gyn. at the University of Sydney, Kingswood.

Dr. Gerges and his colleagues evaluated 189 women of reproductive age who were scheduled for operative laparoscopy at a tertiary referral center for women. The patients had a history of chronic pelvic pain and/or endometriosis and presented between 2009 and 2013.

The women first had transvaginal ultrasound to determine if their uterine sliding sign was positive or negative, followed by sonovaginography to assess the posterior pelvic compartment for rectal or rectosigmoid deep infiltrating endometriosis. All patients then underwent laparoscopic surgery for endometriosis.

Laparoscopy revealed pouch of Douglas obliteration in 47 of the 189 women and rectal and/or rectosigmoid deep infiltrating endometriosis in 43 women.

The sensitivity of sonovaginography to predict deep infiltrating endometriosis was 88%, compared with 74% for the sliding-sign approach. Specificity was the same with the two methods at 93%. The positive predictive value was 79% vs. 74%, respectively, and the negative predictive value was 97% vs. 93%.

“These findings can help clinicians with preoperative planning,” Dr. Gerges said at the meeting, which was sponsored by AAGL.

Dr. Gerges and his colleagues also identified 11 false-negative cases in which the sliding sign was positive but laparoscopy confirmed rectal deep infiltrating endometriosis.

Previous research suggests that, in women with suspected endometriosis, a negative transvaginal ultrasound uterine sliding sign can predict rectal or rectosigmoid deep infiltrating endometriosis (Ultrasound Obstet Gynecol. 2013;41[6]:692-5, J Ultrasound Med. 2014;33:315-21). A negative sliding sign indicates the presence of uterorectal adhesions and whether the pouch of Douglas might be obliterated. The current study, however, suggested that sonovaginography might be the better method.

Dr. Gerges reported having no relevant financial disclosures.

ORLANDO – The first study to directly compare plasma energy treatment of ovarian endometriomas to cystectomy demonstrates similar postintervention pregnancy rates, suggesting that plasma energy ablation may be a comparable treatment option.

Researchers evaluated 104 women seeking pregnancy after 1 year or more of infertility. Women presented with unilateral or bilateral ovarian endometriomas larger than 3 cm between January 2009 and June 2014. Clinicians treated 64 patients with plasma energy ablation and another 40 with cystectomy and followed them to compare pregnancy rates.

After at least 1 year of follow-up, pregnancy rates were 68% following plasma energy ablation, compared with 80% after cystectomy. Of the 76 pregnancies, 24 were due to spontaneous conception, including 40% of pregnancies in the plasma energy group and 18% in the cystectomy group. Even after adjustment for multiple factors, the type of intervention had no statistically significant impact on achieving a subsequent pregnancy.

“Ablation using plasma energy may be considered a valuable tool that allows a high pregnancy rate,” Basma Darwish, MD, an ob.gyn. at Rouen (France) University Hospital, said at the meeting, which was sponsored by AAGL.

These similar outcomes were observed despite a higher prevalence of risk predictors for infertility in the plasma energy group at baseline. For instance, women in this cohort were significantly older and had significantly higher revised American Fertility Society (rAFS) classification scores, as well as higher rates of pouch of Douglas obliteration, deep endometriosis, and colorectal localizations.

“Endometrial ablation using plasma energy allows good postoperative [pregnancy] rates, that is well known,” Dr. Darwish said, but the technique has not been directly compared with cystectomy outcomes.

Pregnancy rates remained similar in both groups at 24 and 36 months. The probability of pregnancy was 61% in the plasma energy group versus 69% in the cystectomy group at 24 months. At 36 months, these rates changed to 84% and 78%, respectively.

A unique property of plasma energy ablation is “very limited thermal spread, both in depth and laterally,” Dr. Darwish said.

A lack of randomization is a potential limitation of the study. “Each surgeon chose the technique he or she was best at, which may have explained our good outcomes.” Dr. Darwish said. Strengths of the study include a prospective design and follow-up to 5 years. In addition, the six centers involved in the study included both private and public hospitals, “so it’s a good reflection of what happens in real life.”

The investigators plan to conduct a randomized controlled trial to confirm these findings.

ORLANDO – The first study to directly compare plasma energy treatment of ovarian endometriomas to cystectomy demonstrates similar postintervention pregnancy rates, suggesting that plasma energy ablation may be a comparable treatment option.

Researchers evaluated 104 women seeking pregnancy after 1 year or more of infertility. Women presented with unilateral or bilateral ovarian endometriomas larger than 3 cm between January 2009 and June 2014. Clinicians treated 64 patients with plasma energy ablation and another 40 with cystectomy and followed them to compare pregnancy rates.

After at least 1 year of follow-up, pregnancy rates were 68% following plasma energy ablation, compared with 80% after cystectomy. Of the 76 pregnancies, 24 were due to spontaneous conception, including 40% of pregnancies in the plasma energy group and 18% in the cystectomy group. Even after adjustment for multiple factors, the type of intervention had no statistically significant impact on achieving a subsequent pregnancy.

“Ablation using plasma energy may be considered a valuable tool that allows a high pregnancy rate,” Basma Darwish, MD, an ob.gyn. at Rouen (France) University Hospital, said at the meeting, which was sponsored by AAGL.

These similar outcomes were observed despite a higher prevalence of risk predictors for infertility in the plasma energy group at baseline. For instance, women in this cohort were significantly older and had significantly higher revised American Fertility Society (rAFS) classification scores, as well as higher rates of pouch of Douglas obliteration, deep endometriosis, and colorectal localizations.

“Endometrial ablation using plasma energy allows good postoperative [pregnancy] rates, that is well known,” Dr. Darwish said, but the technique has not been directly compared with cystectomy outcomes.

Pregnancy rates remained similar in both groups at 24 and 36 months. The probability of pregnancy was 61% in the plasma energy group versus 69% in the cystectomy group at 24 months. At 36 months, these rates changed to 84% and 78%, respectively.

A unique property of plasma energy ablation is “very limited thermal spread, both in depth and laterally,” Dr. Darwish said.

A lack of randomization is a potential limitation of the study. “Each surgeon chose the technique he or she was best at, which may have explained our good outcomes.” Dr. Darwish said. Strengths of the study include a prospective design and follow-up to 5 years. In addition, the six centers involved in the study included both private and public hospitals, “so it’s a good reflection of what happens in real life.”

The investigators plan to conduct a randomized controlled trial to confirm these findings.

ORLANDO – The first study to directly compare plasma energy treatment of ovarian endometriomas to cystectomy demonstrates similar postintervention pregnancy rates, suggesting that plasma energy ablation may be a comparable treatment option.

Researchers evaluated 104 women seeking pregnancy after 1 year or more of infertility. Women presented with unilateral or bilateral ovarian endometriomas larger than 3 cm between January 2009 and June 2014. Clinicians treated 64 patients with plasma energy ablation and another 40 with cystectomy and followed them to compare pregnancy rates.

After at least 1 year of follow-up, pregnancy rates were 68% following plasma energy ablation, compared with 80% after cystectomy. Of the 76 pregnancies, 24 were due to spontaneous conception, including 40% of pregnancies in the plasma energy group and 18% in the cystectomy group. Even after adjustment for multiple factors, the type of intervention had no statistically significant impact on achieving a subsequent pregnancy.

“Ablation using plasma energy may be considered a valuable tool that allows a high pregnancy rate,” Basma Darwish, MD, an ob.gyn. at Rouen (France) University Hospital, said at the meeting, which was sponsored by AAGL.

These similar outcomes were observed despite a higher prevalence of risk predictors for infertility in the plasma energy group at baseline. For instance, women in this cohort were significantly older and had significantly higher revised American Fertility Society (rAFS) classification scores, as well as higher rates of pouch of Douglas obliteration, deep endometriosis, and colorectal localizations.

“Endometrial ablation using plasma energy allows good postoperative [pregnancy] rates, that is well known,” Dr. Darwish said, but the technique has not been directly compared with cystectomy outcomes.

Pregnancy rates remained similar in both groups at 24 and 36 months. The probability of pregnancy was 61% in the plasma energy group versus 69% in the cystectomy group at 24 months. At 36 months, these rates changed to 84% and 78%, respectively.

A unique property of plasma energy ablation is “very limited thermal spread, both in depth and laterally,” Dr. Darwish said.

A lack of randomization is a potential limitation of the study. “Each surgeon chose the technique he or she was best at, which may have explained our good outcomes.” Dr. Darwish said. Strengths of the study include a prospective design and follow-up to 5 years. In addition, the six centers involved in the study included both private and public hospitals, “so it’s a good reflection of what happens in real life.”

The investigators plan to conduct a randomized controlled trial to confirm these findings.

Acute ankle injuries are common problems treated by orthopedic surgeons. In the United States, nearly 2 million ankle sprains occur each year,¹ and ankle fractures account for 9% to 18% of all fractures treated in emergency departments.^2,3 Ankle injuries that involve the syndesmotic ligaments may result in instability and require specific treatment beyond fixation of the malleolar fractures.

The usual mechanism of syndesmotic injury is external rotation of the ankle with hyperdorsiflexion of a pronated or supinated foot.^4,5 Syndesmotic injuries are estimated to occur in up to 10% of ankle sprains⁶ and up to 23% of all ankle fractures.⁷ Overall US incidence of syndesmotic injury is estimated at 6445 injuries per year.⁸ Syndesmotic injury occurs in 39% to 45% of supination-external rotation IV ankle fractures.^9,10 Pronation-external rotation ankle fractures have the highest rate of syndesmotic injury. Syndesmotic injury may be less common in other types of malleolar fracture, but the exact incidence has not been reliably reported.

Traditionally, isolated nondisplaced syndesmotic injuries are treated nonoperatively, and syndesmotic injuries with concomitant malleolar fractures are treated surgically. Various options are available for syndesmotic fixation. The gold standard is syndesmotic screw placement from the lateral aspect of the fibula through the tibia. Fixation may be achieved with screws in a variety of configurations and formats. However, fixation with two 4.5-mm screws is stronger.^11,12 Functional outcomes are similar, regardless of screw material,^13-16 number of cortices,¹⁷ or number of screws.¹⁸ Disadvantages specific to screw fixation include altered ankle biomechanics,^19,20 potential for screw breakage,²¹ and need for implant removal.³Alternatively, suture button fixation is said to be equally as effective as screw fixation in achieving syndesmotic reduction, and their functional outcomes are similar.^22,23 The initial cost of suture button fixation is higher than that of screw fixation, but the difference may be offset by potential elimination of a second surgery for syndesmotic screw removal.²⁴ Soft-tissue irritation caused by the suture material and local osteolysis are reported complications of suture button fixation.^25-27

Regardless of fixation method used, achieving anatomical reduction of the syndesmosis is considered the most important factor in optimizing functional outcomes.^28-31 However, achieving and verifying anatomical reduction of the syndesmosis during surgery can be quite challenging.^30,32-34 Various methods of lowering the malreduction risk, including direct visualization of the tibiofibular joint during reduction^30,35 and intraoperative 3-dimensional imaging,^33,36 have been proposed.

In the study reported here, we used a US insurance database to determine the incidence and rate of syndesmotic stabilization within various ankle injuries and fracture patterns.

Materials and Methods

All data for this study were obtained from a publicly available for-fee healthcare database, the PearlDiver Patient Records Database, which includes procedural volumes and demographic information for patients with International Classification of Diseases, Ninth Revision (ICD-9) diagnoses and procedures or Current Procedural Terminology (CPT) codes. Data for the study were derived from 2 databases within PearlDiver: a private-payer database, which has its largest contribution (>30 million individual patient records for 2007-2011) from United HealthCare, and a Medicare database (>50 million patient records for 2007-2011). Access to the database was granted by PearlDiver Technologies for the purpose of academic research. The database was stored on a password-protected server maintained by PearlDiver.

We searched the database for cases of ankle fracture fixation, including fixation of isolated lateral malleolus (CPT 27792), bimalleolar (CPT 27814), and trimalleolar (CPTs 27822 and 27823) fractures. CPT 27829 was used to search for syndesmotic fixation, and CPT 20680 for implant removal. These codes were used individually and in combination.

Overall procedural volume data are reported as number of patients with the given CPT(s) in the database output and as incidence, calculated as number of patients with the CPT of interest normalized to total number of patients in the database for that particular subgroup. Results of age group and sex analyses are reported as number of patients reported in the database output and as percentage of patients who had the CPT procedure of interest that year. As United HealthCare is the largest contributor to the private-payer portion of the database and is represented most prominently in the southern region, data for the regional analysis are presented only as incidence. This incidence was calculated as number of patients in a particular region and year normalized to total number of patients in the database for that region or year. The regions were Midwest (IA, IL, IN, KS, MI, MN, MO, ND, NE, OH, SD, WI), Northeast (CT, MA, ME, NH, NJ, NY, PA, RI, VT), South (AL, AR, DC, DE, FL, GA, KY, LA, MD, MI, NC, OK, SC, TN, TX, VA, WV), and West (AK, AZ, CA, CO, HI, ID, MT, NM, NV, OR, UT, WA, WY).

Chi-square linear-by-linear association analysis was used to determine the statistical significance of time trends in procedural volume, sex, age group, and region. For all statistical comparisons, P < .05 was considered significant.

Results

Number of open reduction and internal fixation (ORIF) procedures increased for all ankle fracture types over the period 2007 to 2011 (Table 1).

ORIF was performed for an ankle injury in 54,767 patients during the period 2007 to 2011, resulting in a cumulative incidence of 64.2 per 1000 patients (Table 2).

Discussion

The present study found no significant change in number of lateral malleolus, bimalleolar, and trimalleolar ankle fracture ORIF procedures performed over the period 2007 to 2011. However, over the same period, incidence of syndesmosis fixation increased significantly in patients with isolated syndesmotic injuries and in patients with concomitant ankle fracture and syndesmotic injury. The largest percentage change was found in the bimalleolar ORIF group, which showed nearly a doubling of syndesmotic fixation over the 4-year study period, followed by a 38.1% increase in syndesmotic fixation in the trimalleolar ORIF group. Both groups had a syndesmotic fixation percentage change about twice that seen in the isolated lateral malleolus group.

There are several explanations for these trends. First, bimalleolar and trimalleolar fractures are more severe ankle fractures that tend to result from a more forceful mechanism, allowing for a higher rate of syndesmotic injury. Second, these trends likely do not reflect a true increase in the rate of syndesmosis injury but, rather, increased recognition of syndesmotic injury. Third, the data likely reflect a well-established approach to ankle fracture fixation and an increase in thinking that syndesmotic injuries should be stabilized in the setting of ankle fixation.

Incidence of syndesmotic injury as indicated by stabilization procedures can be compared with the data of Vosseller and colleagues,⁸ who reported an incidence of 6445 syndesmotic injuries per year in the United States. Our data showed fewer syndesmotic injuries, which may be related to use of CPT codes rather than ICD-9 codes for database searches, such that only operative syndesmotic injuries are represented in our data. Population differences between the 2 studies could also account for some of the differences in syndesmotic injury incidence.

We also found a significant change in the rate of hardware removal after syndesmosis ORIF. Across all treatment groups, incidence of screw removal decreased—a trend likely reflecting a change in attitude about the need for routine screw removal. Studies have shown that patients have favorable outcomes in the setting of syndesmotic screw loosening and screw breakage.³⁷ Some authors have suggested that screw breakage or removal could be advantageous, as it allows the syndesmosis to settle into a more anatomical position after imperfect reduction.³⁸ In addition, the trend of decreased syndesmotic screw removal could also have resulted from increased suture button fixation, which may less frequently require implant removal. Regardless, the overall trend is that routine syndesmotic implant removal has become less common.

This study had several limitations. First are the many limitations inherent to all studies that use large administrative databases, such as PearlDiver. The power of analysis depends on data quality; potential sources of error include accuracy of billing codes and physicians’ miscoding or noncoding. Although we tried to accurately represent a large population of interest through use of this database, we cannot be sure that the database represents a true cross-section of the United States. In addition, as we could not determine the method of syndesmotic fixation—the same CPT code is used for both suture button fixation and screw fixation—we could not establish trends for the rate of each method. More research is needed to establish these trends, and this research likely will require analysis of data from a large trauma center or from multiple centers.

Potential regional differences are another limitation. In the PearlDiver database, the South and Midwest are highly represented, the Northeast and West much less so. The South, Midwest, and West (but not the Northeast) had similar overall incidence and subgroup incidence of ankle ORIF. However, any regional differences in the rate of syndesmotic fixation could have skewed our data.

Ankle fractures and associated syndesmotic injuries remain a common problem. Although the prevalence of ankle fracture fixation has been relatively constant, the rate of syndesmosis stabilization has increased significantly. Young adults have the highest incidence of ankle fracture and associated syndesmotic fixation, but more ankle fractures occur in the large and growing elderly population. Increased awareness of syndesmotic injury likely has contributed to the recent rise in syndesmosis fixation seen in the present study. Given this trend, we recommend further analysis of outcome data and to establish treatment guidelines.

Am J Orthop. 2016;45(7):E472-E477. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Acute ankle injuries are common problems treated by orthopedic surgeons. In the United States, nearly 2 million ankle sprains occur each year,¹ and ankle fractures account for 9% to 18% of all fractures treated in emergency departments.^2,3 Ankle injuries that involve the syndesmotic ligaments may result in instability and require specific treatment beyond fixation of the malleolar fractures.

The usual mechanism of syndesmotic injury is external rotation of the ankle with hyperdorsiflexion of a pronated or supinated foot.^4,5 Syndesmotic injuries are estimated to occur in up to 10% of ankle sprains⁶ and up to 23% of all ankle fractures.⁷ Overall US incidence of syndesmotic injury is estimated at 6445 injuries per year.⁸ Syndesmotic injury occurs in 39% to 45% of supination-external rotation IV ankle fractures.^9,10 Pronation-external rotation ankle fractures have the highest rate of syndesmotic injury. Syndesmotic injury may be less common in other types of malleolar fracture, but the exact incidence has not been reliably reported.

Traditionally, isolated nondisplaced syndesmotic injuries are treated nonoperatively, and syndesmotic injuries with concomitant malleolar fractures are treated surgically. Various options are available for syndesmotic fixation. The gold standard is syndesmotic screw placement from the lateral aspect of the fibula through the tibia. Fixation may be achieved with screws in a variety of configurations and formats. However, fixation with two 4.5-mm screws is stronger.^11,12 Functional outcomes are similar, regardless of screw material,^13-16 number of cortices,¹⁷ or number of screws.¹⁸ Disadvantages specific to screw fixation include altered ankle biomechanics,^19,20 potential for screw breakage,²¹ and need for implant removal.³Alternatively, suture button fixation is said to be equally as effective as screw fixation in achieving syndesmotic reduction, and their functional outcomes are similar.^22,23 The initial cost of suture button fixation is higher than that of screw fixation, but the difference may be offset by potential elimination of a second surgery for syndesmotic screw removal.²⁴ Soft-tissue irritation caused by the suture material and local osteolysis are reported complications of suture button fixation.^25-27

Regardless of fixation method used, achieving anatomical reduction of the syndesmosis is considered the most important factor in optimizing functional outcomes.^28-31 However, achieving and verifying anatomical reduction of the syndesmosis during surgery can be quite challenging.^30,32-34 Various methods of lowering the malreduction risk, including direct visualization of the tibiofibular joint during reduction^30,35 and intraoperative 3-dimensional imaging,^33,36 have been proposed.

In the study reported here, we used a US insurance database to determine the incidence and rate of syndesmotic stabilization within various ankle injuries and fracture patterns.

Materials and Methods

All data for this study were obtained from a publicly available for-fee healthcare database, the PearlDiver Patient Records Database, which includes procedural volumes and demographic information for patients with International Classification of Diseases, Ninth Revision (ICD-9) diagnoses and procedures or Current Procedural Terminology (CPT) codes. Data for the study were derived from 2 databases within PearlDiver: a private-payer database, which has its largest contribution (>30 million individual patient records for 2007-2011) from United HealthCare, and a Medicare database (>50 million patient records for 2007-2011). Access to the database was granted by PearlDiver Technologies for the purpose of academic research. The database was stored on a password-protected server maintained by PearlDiver.

We searched the database for cases of ankle fracture fixation, including fixation of isolated lateral malleolus (CPT 27792), bimalleolar (CPT 27814), and trimalleolar (CPTs 27822 and 27823) fractures. CPT 27829 was used to search for syndesmotic fixation, and CPT 20680 for implant removal. These codes were used individually and in combination.

Overall procedural volume data are reported as number of patients with the given CPT(s) in the database output and as incidence, calculated as number of patients with the CPT of interest normalized to total number of patients in the database for that particular subgroup. Results of age group and sex analyses are reported as number of patients reported in the database output and as percentage of patients who had the CPT procedure of interest that year. As United HealthCare is the largest contributor to the private-payer portion of the database and is represented most prominently in the southern region, data for the regional analysis are presented only as incidence. This incidence was calculated as number of patients in a particular region and year normalized to total number of patients in the database for that region or year. The regions were Midwest (IA, IL, IN, KS, MI, MN, MO, ND, NE, OH, SD, WI), Northeast (CT, MA, ME, NH, NJ, NY, PA, RI, VT), South (AL, AR, DC, DE, FL, GA, KY, LA, MD, MI, NC, OK, SC, TN, TX, VA, WV), and West (AK, AZ, CA, CO, HI, ID, MT, NM, NV, OR, UT, WA, WY).

Chi-square linear-by-linear association analysis was used to determine the statistical significance of time trends in procedural volume, sex, age group, and region. For all statistical comparisons, P < .05 was considered significant.

Results

Number of open reduction and internal fixation (ORIF) procedures increased for all ankle fracture types over the period 2007 to 2011 (Table 1).

ORIF was performed for an ankle injury in 54,767 patients during the period 2007 to 2011, resulting in a cumulative incidence of 64.2 per 1000 patients (Table 2).

Discussion

The present study found no significant change in number of lateral malleolus, bimalleolar, and trimalleolar ankle fracture ORIF procedures performed over the period 2007 to 2011. However, over the same period, incidence of syndesmosis fixation increased significantly in patients with isolated syndesmotic injuries and in patients with concomitant ankle fracture and syndesmotic injury. The largest percentage change was found in the bimalleolar ORIF group, which showed nearly a doubling of syndesmotic fixation over the 4-year study period, followed by a 38.1% increase in syndesmotic fixation in the trimalleolar ORIF group. Both groups had a syndesmotic fixation percentage change about twice that seen in the isolated lateral malleolus group.

There are several explanations for these trends. First, bimalleolar and trimalleolar fractures are more severe ankle fractures that tend to result from a more forceful mechanism, allowing for a higher rate of syndesmotic injury. Second, these trends likely do not reflect a true increase in the rate of syndesmosis injury but, rather, increased recognition of syndesmotic injury. Third, the data likely reflect a well-established approach to ankle fracture fixation and an increase in thinking that syndesmotic injuries should be stabilized in the setting of ankle fixation.

Incidence of syndesmotic injury as indicated by stabilization procedures can be compared with the data of Vosseller and colleagues,⁸ who reported an incidence of 6445 syndesmotic injuries per year in the United States. Our data showed fewer syndesmotic injuries, which may be related to use of CPT codes rather than ICD-9 codes for database searches, such that only operative syndesmotic injuries are represented in our data. Population differences between the 2 studies could also account for some of the differences in syndesmotic injury incidence.

We also found a significant change in the rate of hardware removal after syndesmosis ORIF. Across all treatment groups, incidence of screw removal decreased—a trend likely reflecting a change in attitude about the need for routine screw removal. Studies have shown that patients have favorable outcomes in the setting of syndesmotic screw loosening and screw breakage.³⁷ Some authors have suggested that screw breakage or removal could be advantageous, as it allows the syndesmosis to settle into a more anatomical position after imperfect reduction.³⁸ In addition, the trend of decreased syndesmotic screw removal could also have resulted from increased suture button fixation, which may less frequently require implant removal. Regardless, the overall trend is that routine syndesmotic implant removal has become less common.

This study had several limitations. First are the many limitations inherent to all studies that use large administrative databases, such as PearlDiver. The power of analysis depends on data quality; potential sources of error include accuracy of billing codes and physicians’ miscoding or noncoding. Although we tried to accurately represent a large population of interest through use of this database, we cannot be sure that the database represents a true cross-section of the United States. In addition, as we could not determine the method of syndesmotic fixation—the same CPT code is used for both suture button fixation and screw fixation—we could not establish trends for the rate of each method. More research is needed to establish these trends, and this research likely will require analysis of data from a large trauma center or from multiple centers.

Potential regional differences are another limitation. In the PearlDiver database, the South and Midwest are highly represented, the Northeast and West much less so. The South, Midwest, and West (but not the Northeast) had similar overall incidence and subgroup incidence of ankle ORIF. However, any regional differences in the rate of syndesmotic fixation could have skewed our data.

Ankle fractures and associated syndesmotic injuries remain a common problem. Although the prevalence of ankle fracture fixation has been relatively constant, the rate of syndesmosis stabilization has increased significantly. Young adults have the highest incidence of ankle fracture and associated syndesmotic fixation, but more ankle fractures occur in the large and growing elderly population. Increased awareness of syndesmotic injury likely has contributed to the recent rise in syndesmosis fixation seen in the present study. Given this trend, we recommend further analysis of outcome data and to establish treatment guidelines.

Am J Orthop. 2016;45(7):E472-E477. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Acute ankle injuries are common problems treated by orthopedic surgeons. In the United States, nearly 2 million ankle sprains occur each year,¹ and ankle fractures account for 9% to 18% of all fractures treated in emergency departments.^2,3 Ankle injuries that involve the syndesmotic ligaments may result in instability and require specific treatment beyond fixation of the malleolar fractures.

The usual mechanism of syndesmotic injury is external rotation of the ankle with hyperdorsiflexion of a pronated or supinated foot.^4,5 Syndesmotic injuries are estimated to occur in up to 10% of ankle sprains⁶ and up to 23% of all ankle fractures.⁷ Overall US incidence of syndesmotic injury is estimated at 6445 injuries per year.⁸ Syndesmotic injury occurs in 39% to 45% of supination-external rotation IV ankle fractures.^9,10 Pronation-external rotation ankle fractures have the highest rate of syndesmotic injury. Syndesmotic injury may be less common in other types of malleolar fracture, but the exact incidence has not been reliably reported.

Traditionally, isolated nondisplaced syndesmotic injuries are treated nonoperatively, and syndesmotic injuries with concomitant malleolar fractures are treated surgically. Various options are available for syndesmotic fixation. The gold standard is syndesmotic screw placement from the lateral aspect of the fibula through the tibia. Fixation may be achieved with screws in a variety of configurations and formats. However, fixation with two 4.5-mm screws is stronger.^11,12 Functional outcomes are similar, regardless of screw material,^13-16 number of cortices,¹⁷ or number of screws.¹⁸ Disadvantages specific to screw fixation include altered ankle biomechanics,^19,20 potential for screw breakage,²¹ and need for implant removal.³Alternatively, suture button fixation is said to be equally as effective as screw fixation in achieving syndesmotic reduction, and their functional outcomes are similar.^22,23 The initial cost of suture button fixation is higher than that of screw fixation, but the difference may be offset by potential elimination of a second surgery for syndesmotic screw removal.²⁴ Soft-tissue irritation caused by the suture material and local osteolysis are reported complications of suture button fixation.^25-27

Regardless of fixation method used, achieving anatomical reduction of the syndesmosis is considered the most important factor in optimizing functional outcomes.^28-31 However, achieving and verifying anatomical reduction of the syndesmosis during surgery can be quite challenging.^30,32-34 Various methods of lowering the malreduction risk, including direct visualization of the tibiofibular joint during reduction^30,35 and intraoperative 3-dimensional imaging,^33,36 have been proposed.

In the study reported here, we used a US insurance database to determine the incidence and rate of syndesmotic stabilization within various ankle injuries and fracture patterns.

Materials and Methods

All data for this study were obtained from a publicly available for-fee healthcare database, the PearlDiver Patient Records Database, which includes procedural volumes and demographic information for patients with International Classification of Diseases, Ninth Revision (ICD-9) diagnoses and procedures or Current Procedural Terminology (CPT) codes. Data for the study were derived from 2 databases within PearlDiver: a private-payer database, which has its largest contribution (>30 million individual patient records for 2007-2011) from United HealthCare, and a Medicare database (>50 million patient records for 2007-2011). Access to the database was granted by PearlDiver Technologies for the purpose of academic research. The database was stored on a password-protected server maintained by PearlDiver.

We searched the database for cases of ankle fracture fixation, including fixation of isolated lateral malleolus (CPT 27792), bimalleolar (CPT 27814), and trimalleolar (CPTs 27822 and 27823) fractures. CPT 27829 was used to search for syndesmotic fixation, and CPT 20680 for implant removal. These codes were used individually and in combination.

Overall procedural volume data are reported as number of patients with the given CPT(s) in the database output and as incidence, calculated as number of patients with the CPT of interest normalized to total number of patients in the database for that particular subgroup. Results of age group and sex analyses are reported as number of patients reported in the database output and as percentage of patients who had the CPT procedure of interest that year. As United HealthCare is the largest contributor to the private-payer portion of the database and is represented most prominently in the southern region, data for the regional analysis are presented only as incidence. This incidence was calculated as number of patients in a particular region and year normalized to total number of patients in the database for that region or year. The regions were Midwest (IA, IL, IN, KS, MI, MN, MO, ND, NE, OH, SD, WI), Northeast (CT, MA, ME, NH, NJ, NY, PA, RI, VT), South (AL, AR, DC, DE, FL, GA, KY, LA, MD, MI, NC, OK, SC, TN, TX, VA, WV), and West (AK, AZ, CA, CO, HI, ID, MT, NM, NV, OR, UT, WA, WY).

Chi-square linear-by-linear association analysis was used to determine the statistical significance of time trends in procedural volume, sex, age group, and region. For all statistical comparisons, P < .05 was considered significant.

Results

Number of open reduction and internal fixation (ORIF) procedures increased for all ankle fracture types over the period 2007 to 2011 (Table 1).

ORIF was performed for an ankle injury in 54,767 patients during the period 2007 to 2011, resulting in a cumulative incidence of 64.2 per 1000 patients (Table 2).

Discussion

The present study found no significant change in number of lateral malleolus, bimalleolar, and trimalleolar ankle fracture ORIF procedures performed over the period 2007 to 2011. However, over the same period, incidence of syndesmosis fixation increased significantly in patients with isolated syndesmotic injuries and in patients with concomitant ankle fracture and syndesmotic injury. The largest percentage change was found in the bimalleolar ORIF group, which showed nearly a doubling of syndesmotic fixation over the 4-year study period, followed by a 38.1% increase in syndesmotic fixation in the trimalleolar ORIF group. Both groups had a syndesmotic fixation percentage change about twice that seen in the isolated lateral malleolus group.

There are several explanations for these trends. First, bimalleolar and trimalleolar fractures are more severe ankle fractures that tend to result from a more forceful mechanism, allowing for a higher rate of syndesmotic injury. Second, these trends likely do not reflect a true increase in the rate of syndesmosis injury but, rather, increased recognition of syndesmotic injury. Third, the data likely reflect a well-established approach to ankle fracture fixation and an increase in thinking that syndesmotic injuries should be stabilized in the setting of ankle fixation.

Incidence of syndesmotic injury as indicated by stabilization procedures can be compared with the data of Vosseller and colleagues,⁸ who reported an incidence of 6445 syndesmotic injuries per year in the United States. Our data showed fewer syndesmotic injuries, which may be related to use of CPT codes rather than ICD-9 codes for database searches, such that only operative syndesmotic injuries are represented in our data. Population differences between the 2 studies could also account for some of the differences in syndesmotic injury incidence.

We also found a significant change in the rate of hardware removal after syndesmosis ORIF. Across all treatment groups, incidence of screw removal decreased—a trend likely reflecting a change in attitude about the need for routine screw removal. Studies have shown that patients have favorable outcomes in the setting of syndesmotic screw loosening and screw breakage.³⁷ Some authors have suggested that screw breakage or removal could be advantageous, as it allows the syndesmosis to settle into a more anatomical position after imperfect reduction.³⁸ In addition, the trend of decreased syndesmotic screw removal could also have resulted from increased suture button fixation, which may less frequently require implant removal. Regardless, the overall trend is that routine syndesmotic implant removal has become less common.

This study had several limitations. First are the many limitations inherent to all studies that use large administrative databases, such as PearlDiver. The power of analysis depends on data quality; potential sources of error include accuracy of billing codes and physicians’ miscoding or noncoding. Although we tried to accurately represent a large population of interest through use of this database, we cannot be sure that the database represents a true cross-section of the United States. In addition, as we could not determine the method of syndesmotic fixation—the same CPT code is used for both suture button fixation and screw fixation—we could not establish trends for the rate of each method. More research is needed to establish these trends, and this research likely will require analysis of data from a large trauma center or from multiple centers.

Potential regional differences are another limitation. In the PearlDiver database, the South and Midwest are highly represented, the Northeast and West much less so. The South, Midwest, and West (but not the Northeast) had similar overall incidence and subgroup incidence of ankle ORIF. However, any regional differences in the rate of syndesmotic fixation could have skewed our data.

Ankle fractures and associated syndesmotic injuries remain a common problem. Although the prevalence of ankle fracture fixation has been relatively constant, the rate of syndesmosis stabilization has increased significantly. Young adults have the highest incidence of ankle fracture and associated syndesmotic fixation, but more ankle fractures occur in the large and growing elderly population. Increased awareness of syndesmotic injury likely has contributed to the recent rise in syndesmosis fixation seen in the present study. Given this trend, we recommend further analysis of outcome data and to establish treatment guidelines.

Am J Orthop. 2016;45(7):E472-E477. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Malignant melanoma has continually shown a pattern of increased incidence and mortality over the last 50 years, especially in fair-skinned individuals. In fact, malignant melanoma has the highest mortality rate of all skin cancers in white individuals. Currently, wide local surgical excision is the mainstay of treatment of primary cutaneous melanomas.¹ The margins vary in size according to the Breslow thickness (or depth) of the involved tumor. As such, advancements in melanoma treatment continue to be studied. We present the case of a patient with invasive melanoma that was cleared with topical imiquimod.

Case Report

A 71-year-old man presented with biopsy-proven malignant melanoma on the right posterior scalp that was diagnosed a few weeks prior. The melanoma was invasive with a depth of 0.73 mm. The patient also had an approximately 8-cm, irregular, patchy area of hyperpigmentation involving almost the entire crown of the head (Figure 1A). The biopsy site used for melanoma diagnosis was on the right posterior aspect of the hyperpigmented area where a symptomatic pigmented papule was located. To determine if the rest of this macule represented an extension of the proven malignancy, surveillance biopsies were taken at the 12 o'clock (anterior aspect), 3 o'clock, 6 o'clock, and 9 o'clock positions on the head. All of the biopsies came back as lentigo simplex, which presented a clinical problem in that the boundaries of the invasive melanoma merged with the lentigo simplex and were not clinically apparent. Because an exact boundary could not be visualized, the entire area was treated with imiquimod cream 5% once nightly at bedtime for 4 weeks prior to excision of the original biopsy site. There was a notable decrease in hyperpigmentation in the treated area after 4 weeks of therapy (Figure 1B). The original biopsy site was then excised with a 0.6-cm margin and a complex linear repair was performed. Histologic examination of the excised specimen showed no residual melanoma.

Comment

Although surgical excision is the recommended treatment of cutaneous melanoma,¹ in some cases the defect following an excision can be quite large or even disfiguring. To minimize the size of the excision site, other treatment modalities should be studied. Imiquimod is an immunomodulating agent that exerts antitumor and antiviral effects. The US Food and Drug Administration has approved imiquimod for treatment of genital warts, actinic keratoses, and superficial basal cell carcinoma.² The most common side effects of topical imiquimod involve application-site reactions such as erythema, swelling, and crusting of the treated area. Ulceration of the skin also is possible. A small percentage of individuals have experienced systemic flulike symptoms after using topical imiquimod. Topical imiquimod has been used off label to treat noninvasive forms of melanoma. The topical therapy has been reported to clear melanoma in situ and lentigo maligna.^2,3 In addition, imiquimod has been used as a palliative therapy for cutaneous metastatic melanoma.^4,5 In another case of a primary melanoma that responded to topical imiquimod, clinical and histological clearance of a recurrent oral mucosa melanoma was obtained.⁶

Moon and Spencer⁷ reported a case of an invasive melanoma that was cleared with topical imiquimod. A 93-year-old woman presented with a central 2.75-mm thick invasive melanoma surrounded by a large area of melanoma in situ involving the left cheek and eyelid. The excised tissue was stained for CD31 and D2-40 to rule out intravascular and intralymphatic spread (Figure 2A). The standard-of-care treatment for this case would involve surgical excision with 2-cm margins and a sentinel lymph node biopsy, but given the morbidity involved with the surgery, an alternative treatment plan was made with the patient. The patient completed 5 weeks of topical imiquimod therapy and then underwent wide local excision with a 1-cm margin. Extensive histological examination of the excised specimen showed no residual melanoma; in fact, there was a near absence of junctional melanocytes that would normally have been seen. The specimen underwent immunoperoxidase staining for Melan-A (Figure 2B). The patient was followed for 14 months with no evidence of recurrence.⁷

Conclusion

We describe a patient who achieved complete histologic clearance of invasive melanoma following treatment with topical imiquimod. Four weeks of topical therapy completely cleared an invasive melanoma that was 0.73-mm thick. Follow-up was recommended for the patient because long-term outcomes of this therapy are unknown. More studies demonstrating reliability and reproducibility are needed to evaluate the role of topical imiquimod in melanoma treatment; however, our case shows the potential of this topical modality.

Malignant melanoma has continually shown a pattern of increased incidence and mortality over the last 50 years, especially in fair-skinned individuals. In fact, malignant melanoma has the highest mortality rate of all skin cancers in white individuals. Currently, wide local surgical excision is the mainstay of treatment of primary cutaneous melanomas.¹ The margins vary in size according to the Breslow thickness (or depth) of the involved tumor. As such, advancements in melanoma treatment continue to be studied. We present the case of a patient with invasive melanoma that was cleared with topical imiquimod.

Case Report

A 71-year-old man presented with biopsy-proven malignant melanoma on the right posterior scalp that was diagnosed a few weeks prior. The melanoma was invasive with a depth of 0.73 mm. The patient also had an approximately 8-cm, irregular, patchy area of hyperpigmentation involving almost the entire crown of the head (Figure 1A). The biopsy site used for melanoma diagnosis was on the right posterior aspect of the hyperpigmented area where a symptomatic pigmented papule was located. To determine if the rest of this macule represented an extension of the proven malignancy, surveillance biopsies were taken at the 12 o'clock (anterior aspect), 3 o'clock, 6 o'clock, and 9 o'clock positions on the head. All of the biopsies came back as lentigo simplex, which presented a clinical problem in that the boundaries of the invasive melanoma merged with the lentigo simplex and were not clinically apparent. Because an exact boundary could not be visualized, the entire area was treated with imiquimod cream 5% once nightly at bedtime for 4 weeks prior to excision of the original biopsy site. There was a notable decrease in hyperpigmentation in the treated area after 4 weeks of therapy (Figure 1B). The original biopsy site was then excised with a 0.6-cm margin and a complex linear repair was performed. Histologic examination of the excised specimen showed no residual melanoma.

Comment

Although surgical excision is the recommended treatment of cutaneous melanoma,¹ in some cases the defect following an excision can be quite large or even disfiguring. To minimize the size of the excision site, other treatment modalities should be studied. Imiquimod is an immunomodulating agent that exerts antitumor and antiviral effects. The US Food and Drug Administration has approved imiquimod for treatment of genital warts, actinic keratoses, and superficial basal cell carcinoma.² The most common side effects of topical imiquimod involve application-site reactions such as erythema, swelling, and crusting of the treated area. Ulceration of the skin also is possible. A small percentage of individuals have experienced systemic flulike symptoms after using topical imiquimod. Topical imiquimod has been used off label to treat noninvasive forms of melanoma. The topical therapy has been reported to clear melanoma in situ and lentigo maligna.^2,3 In addition, imiquimod has been used as a palliative therapy for cutaneous metastatic melanoma.^4,5 In another case of a primary melanoma that responded to topical imiquimod, clinical and histological clearance of a recurrent oral mucosa melanoma was obtained.⁶

Moon and Spencer⁷ reported a case of an invasive melanoma that was cleared with topical imiquimod. A 93-year-old woman presented with a central 2.75-mm thick invasive melanoma surrounded by a large area of melanoma in situ involving the left cheek and eyelid. The excised tissue was stained for CD31 and D2-40 to rule out intravascular and intralymphatic spread (Figure 2A). The standard-of-care treatment for this case would involve surgical excision with 2-cm margins and a sentinel lymph node biopsy, but given the morbidity involved with the surgery, an alternative treatment plan was made with the patient. The patient completed 5 weeks of topical imiquimod therapy and then underwent wide local excision with a 1-cm margin. Extensive histological examination of the excised specimen showed no residual melanoma; in fact, there was a near absence of junctional melanocytes that would normally have been seen. The specimen underwent immunoperoxidase staining for Melan-A (Figure 2B). The patient was followed for 14 months with no evidence of recurrence.⁷

Conclusion

We describe a patient who achieved complete histologic clearance of invasive melanoma following treatment with topical imiquimod. Four weeks of topical therapy completely cleared an invasive melanoma that was 0.73-mm thick. Follow-up was recommended for the patient because long-term outcomes of this therapy are unknown. More studies demonstrating reliability and reproducibility are needed to evaluate the role of topical imiquimod in melanoma treatment; however, our case shows the potential of this topical modality.

Malignant melanoma has continually shown a pattern of increased incidence and mortality over the last 50 years, especially in fair-skinned individuals. In fact, malignant melanoma has the highest mortality rate of all skin cancers in white individuals. Currently, wide local surgical excision is the mainstay of treatment of primary cutaneous melanomas.¹ The margins vary in size according to the Breslow thickness (or depth) of the involved tumor. As such, advancements in melanoma treatment continue to be studied. We present the case of a patient with invasive melanoma that was cleared with topical imiquimod.

Case Report

A 71-year-old man presented with biopsy-proven malignant melanoma on the right posterior scalp that was diagnosed a few weeks prior. The melanoma was invasive with a depth of 0.73 mm. The patient also had an approximately 8-cm, irregular, patchy area of hyperpigmentation involving almost the entire crown of the head (Figure 1A). The biopsy site used for melanoma diagnosis was on the right posterior aspect of the hyperpigmented area where a symptomatic pigmented papule was located. To determine if the rest of this macule represented an extension of the proven malignancy, surveillance biopsies were taken at the 12 o'clock (anterior aspect), 3 o'clock, 6 o'clock, and 9 o'clock positions on the head. All of the biopsies came back as lentigo simplex, which presented a clinical problem in that the boundaries of the invasive melanoma merged with the lentigo simplex and were not clinically apparent. Because an exact boundary could not be visualized, the entire area was treated with imiquimod cream 5% once nightly at bedtime for 4 weeks prior to excision of the original biopsy site. There was a notable decrease in hyperpigmentation in the treated area after 4 weeks of therapy (Figure 1B). The original biopsy site was then excised with a 0.6-cm margin and a complex linear repair was performed. Histologic examination of the excised specimen showed no residual melanoma.

Comment

Although surgical excision is the recommended treatment of cutaneous melanoma,¹ in some cases the defect following an excision can be quite large or even disfiguring. To minimize the size of the excision site, other treatment modalities should be studied. Imiquimod is an immunomodulating agent that exerts antitumor and antiviral effects. The US Food and Drug Administration has approved imiquimod for treatment of genital warts, actinic keratoses, and superficial basal cell carcinoma.² The most common side effects of topical imiquimod involve application-site reactions such as erythema, swelling, and crusting of the treated area. Ulceration of the skin also is possible. A small percentage of individuals have experienced systemic flulike symptoms after using topical imiquimod. Topical imiquimod has been used off label to treat noninvasive forms of melanoma. The topical therapy has been reported to clear melanoma in situ and lentigo maligna.^2,3 In addition, imiquimod has been used as a palliative therapy for cutaneous metastatic melanoma.^4,5 In another case of a primary melanoma that responded to topical imiquimod, clinical and histological clearance of a recurrent oral mucosa melanoma was obtained.⁶

Moon and Spencer⁷ reported a case of an invasive melanoma that was cleared with topical imiquimod. A 93-year-old woman presented with a central 2.75-mm thick invasive melanoma surrounded by a large area of melanoma in situ involving the left cheek and eyelid. The excised tissue was stained for CD31 and D2-40 to rule out intravascular and intralymphatic spread (Figure 2A). The standard-of-care treatment for this case would involve surgical excision with 2-cm margins and a sentinel lymph node biopsy, but given the morbidity involved with the surgery, an alternative treatment plan was made with the patient. The patient completed 5 weeks of topical imiquimod therapy and then underwent wide local excision with a 1-cm margin. Extensive histological examination of the excised specimen showed no residual melanoma; in fact, there was a near absence of junctional melanocytes that would normally have been seen. The specimen underwent immunoperoxidase staining for Melan-A (Figure 2B). The patient was followed for 14 months with no evidence of recurrence.⁷

Conclusion

We describe a patient who achieved complete histologic clearance of invasive melanoma following treatment with topical imiquimod. Four weeks of topical therapy completely cleared an invasive melanoma that was 0.73-mm thick. Follow-up was recommended for the patient because long-term outcomes of this therapy are unknown. More studies demonstrating reliability and reproducibility are needed to evaluate the role of topical imiquimod in melanoma treatment; however, our case shows the potential of this topical modality.

WASHINGTON – MRI can help to differentiate between neurosarcoidosis and primary angiitis of the central nervous system, according to a single-center study comparing the two conditions.

Patients with neurosarcoidosis were significantly more likely to display spinal cord, basal meningeal, and cranial nerve involvements than were patients with primary angiitis of the central nervous system (PACNS), making MRI an efficient tool in distinguishing between the two.

Deepak Chitnis/Frontline Medical News

[email protected]

WASHINGTON – MRI can help to differentiate between neurosarcoidosis and primary angiitis of the central nervous system, according to a single-center study comparing the two conditions.

Patients with neurosarcoidosis were significantly more likely to display spinal cord, basal meningeal, and cranial nerve involvements than were patients with primary angiitis of the central nervous system (PACNS), making MRI an efficient tool in distinguishing between the two.

Deepak Chitnis/Frontline Medical News

[email protected]

WASHINGTON – MRI can help to differentiate between neurosarcoidosis and primary angiitis of the central nervous system, according to a single-center study comparing the two conditions.

Patients with neurosarcoidosis were significantly more likely to display spinal cord, basal meningeal, and cranial nerve involvements than were patients with primary angiitis of the central nervous system (PACNS), making MRI an efficient tool in distinguishing between the two.

Deepak Chitnis/Frontline Medical News

[email protected]