Betsy Bates

VANCOUVER, B.C. — Nearly a third of primary care patients met criteria for metabolic syndrome, yet just 1% had the powerful risk indicator noted in their charts, according to a cross-sectional audit of records from 30 primary care practices in Rhode Island.

“Metabolic syndrome is highly prevalent but seldom diagnosed,” concluded the authors of a poster presented at the annual meeting of the North American Primary Care Research Group.

The investigators found the cluster of factors defining metabolic syndrome in the charts of 32% (1,348) of 4,240 patients aged 20–80 years, but only 50 patients' charts reflected that diagnosis.

Subclinical metabolic syndrome—the term used to designate patients who lack diagnosed hypertension, diabetes, or hyperlipidemia, but who otherwise met criteria for the syndrome—was found in 113 patient charts (3%), reported Dr. David Anthony and his associates from the department of family medicine at Brown University, Providence, R.I., and the Brown University Center for Primary Care and Prevention.

Failure to recognize metabolic syndrome in the chart may have serious consequences, because it is intended to alert physicians to patients who may be at high risk of diabetes and cardiovascular disease based on a “perfect storm” of risk factors.

However, Dr. Anthony said in an interview that the low rate of metabolic syndrome diagnosis in charts may reflect the fact that the concept is “confusing and ultimately not helpful to primary care docs in communicating with their patients.”

“Primary care physicians have effective means of communicating cardiovascular risk using the Framingham risk score, but lack the same for diabetes risk,” he said.

“Metabolic syndrome attempts to combine the two in a way that is confusing to patients and doctors alike. What primary care docs really need is an effective and accurate predictor of a patient's risk of developing diabetes, along with useful tools for communicating that risk to their patients, so they can make good decisions about their health behaviors such as diet and exercise.”

Dr. Anthony and his associates used data from the Cholesterol Education and Research Trial to examine findings in patients' charts that would merit a diagnosis of metabolic syndrome according to the National Cholesterol Education Program, including three of the following five factors:

▸ Systolic blood pressure of less than 130 mm Hg, or diagnosed hypertension in the chart.

▸ Serum triglyceride level of 150 mg/dL or higher, adjusted for lipid medications in the study.

▸ HDL cholesterol level less than 40 mg/dL in men or less than 50 mg/dL in women, adjusted for lipid medications in the study.

▸ Fasting glucose of 110 mg/dL or higher, or diagnosed diabetes in the chart.

▸ Waist circumference greater than 102 cm in men or 88 cm in women, approximated from the body mass index for study purposes, according to the third National Health and Nutrition Examination Survey (NHANES III) adjustments.

Analysis showed that patients with metabolic syndrome in the study were older than those without the diagnosis (mean age 57 vs. 51 years); had a higher BMI (33 vs. 26 kg/m

Among patients with metabolic syndrome, 80% had hyperlipidemia, 73% had hypertension, and 26% had diabetes—rates significantly higher than those in the nonmetabolic syndrome population (P less than .001).

Their lipids were worse than those of nonmetabolic syndrome patients by every measure. They also were more likely to have gastroesophageal reflux disease and depression, and were significantly less likely to be physically active. In addition, they were slightly more likely to be smokers than were the nonmetabolic syndrome patients (15% vs. 12%), although this difference was not significant.

They were more likely to have received a referral to a nutritionist, been advised to increase their physical activity, and been counseled about smoking cessation, yet they were less likely to be at cholesterol or blood pressure goals than were patients without metabolic syndrome.

There was a stepwise increase by age in the percentage of patients who met criteria for metabolic syndrome: 19% of patients aged 40–49 years, 34% of those aged 50–59 years, 41% of those aged 60–69 years, and 48% of patients aged 70 years or older.

It is noteworthy that the metabolic syndrome patients were no more likely than were other patients to have a family history of early coronary artery disease.

The authors noted that most patients with metabolic syndrome had other major cardiovascular risk factors, which may have served to alert their physicians to their overall cardiometabolic risk, even when the metabolic syndrome diagnosis was missed.

Patients with subclinical metabolic syndrome may be less well recognized as being at elevated risk of diabetes and cardiovascular disease, because they may lack the telltale diagnoses of hypertension, diabetes, and hyperlipidemia, although they have other important risk factors.

VANCOUVER, B.C. — Nearly a third of primary care patients met criteria for metabolic syndrome, yet just 1% had the powerful risk indicator noted in their charts, according to a cross-sectional audit of records from 30 primary care practices in Rhode Island.

“Metabolic syndrome is highly prevalent but seldom diagnosed,” concluded the authors of a poster presented at the annual meeting of the North American Primary Care Research Group.

The investigators found the cluster of factors defining metabolic syndrome in the charts of 32% (1,348) of 4,240 patients aged 20–80 years, but only 50 patients' charts reflected that diagnosis.

Subclinical metabolic syndrome—the term used to designate patients who lack diagnosed hypertension, diabetes, or hyperlipidemia, but who otherwise met criteria for the syndrome—was found in 113 patient charts (3%), reported Dr. David Anthony and his associates from the department of family medicine at Brown University, Providence, R.I., and the Brown University Center for Primary Care and Prevention.

Failure to recognize metabolic syndrome in the chart may have serious consequences, because it is intended to alert physicians to patients who may be at high risk of diabetes and cardiovascular disease based on a “perfect storm” of risk factors.

However, Dr. Anthony said in an interview that the low rate of metabolic syndrome diagnosis in charts may reflect the fact that the concept is “confusing and ultimately not helpful to primary care docs in communicating with their patients.”

“Primary care physicians have effective means of communicating cardiovascular risk using the Framingham risk score, but lack the same for diabetes risk,” he said.

“Metabolic syndrome attempts to combine the two in a way that is confusing to patients and doctors alike. What primary care docs really need is an effective and accurate predictor of a patient's risk of developing diabetes, along with useful tools for communicating that risk to their patients, so they can make good decisions about their health behaviors such as diet and exercise.”

Dr. Anthony and his associates used data from the Cholesterol Education and Research Trial to examine findings in patients' charts that would merit a diagnosis of metabolic syndrome according to the National Cholesterol Education Program, including three of the following five factors:

▸ Systolic blood pressure of less than 130 mm Hg, or diagnosed hypertension in the chart.

▸ Serum triglyceride level of 150 mg/dL or higher, adjusted for lipid medications in the study.

▸ HDL cholesterol level less than 40 mg/dL in men or less than 50 mg/dL in women, adjusted for lipid medications in the study.

▸ Fasting glucose of 110 mg/dL or higher, or diagnosed diabetes in the chart.

▸ Waist circumference greater than 102 cm in men or 88 cm in women, approximated from the body mass index for study purposes, according to the third National Health and Nutrition Examination Survey (NHANES III) adjustments.

Analysis showed that patients with metabolic syndrome in the study were older than those without the diagnosis (mean age 57 vs. 51 years); had a higher BMI (33 vs. 26 kg/m

Among patients with metabolic syndrome, 80% had hyperlipidemia, 73% had hypertension, and 26% had diabetes—rates significantly higher than those in the nonmetabolic syndrome population (P less than .001).

Their lipids were worse than those of nonmetabolic syndrome patients by every measure. They also were more likely to have gastroesophageal reflux disease and depression, and were significantly less likely to be physically active. In addition, they were slightly more likely to be smokers than were the nonmetabolic syndrome patients (15% vs. 12%), although this difference was not significant.

They were more likely to have received a referral to a nutritionist, been advised to increase their physical activity, and been counseled about smoking cessation, yet they were less likely to be at cholesterol or blood pressure goals than were patients without metabolic syndrome.

There was a stepwise increase by age in the percentage of patients who met criteria for metabolic syndrome: 19% of patients aged 40–49 years, 34% of those aged 50–59 years, 41% of those aged 60–69 years, and 48% of patients aged 70 years or older.

It is noteworthy that the metabolic syndrome patients were no more likely than were other patients to have a family history of early coronary artery disease.

The authors noted that most patients with metabolic syndrome had other major cardiovascular risk factors, which may have served to alert their physicians to their overall cardiometabolic risk, even when the metabolic syndrome diagnosis was missed.

Patients with subclinical metabolic syndrome may be less well recognized as being at elevated risk of diabetes and cardiovascular disease, because they may lack the telltale diagnoses of hypertension, diabetes, and hyperlipidemia, although they have other important risk factors.

VANCOUVER, B.C. — Nearly a third of primary care patients met criteria for metabolic syndrome, yet just 1% had the powerful risk indicator noted in their charts, according to a cross-sectional audit of records from 30 primary care practices in Rhode Island.

“Metabolic syndrome is highly prevalent but seldom diagnosed,” concluded the authors of a poster presented at the annual meeting of the North American Primary Care Research Group.

The investigators found the cluster of factors defining metabolic syndrome in the charts of 32% (1,348) of 4,240 patients aged 20–80 years, but only 50 patients' charts reflected that diagnosis.

Subclinical metabolic syndrome—the term used to designate patients who lack diagnosed hypertension, diabetes, or hyperlipidemia, but who otherwise met criteria for the syndrome—was found in 113 patient charts (3%), reported Dr. David Anthony and his associates from the department of family medicine at Brown University, Providence, R.I., and the Brown University Center for Primary Care and Prevention.

Failure to recognize metabolic syndrome in the chart may have serious consequences, because it is intended to alert physicians to patients who may be at high risk of diabetes and cardiovascular disease based on a “perfect storm” of risk factors.

However, Dr. Anthony said in an interview that the low rate of metabolic syndrome diagnosis in charts may reflect the fact that the concept is “confusing and ultimately not helpful to primary care docs in communicating with their patients.”

“Primary care physicians have effective means of communicating cardiovascular risk using the Framingham risk score, but lack the same for diabetes risk,” he said.

“Metabolic syndrome attempts to combine the two in a way that is confusing to patients and doctors alike. What primary care docs really need is an effective and accurate predictor of a patient's risk of developing diabetes, along with useful tools for communicating that risk to their patients, so they can make good decisions about their health behaviors such as diet and exercise.”

Dr. Anthony and his associates used data from the Cholesterol Education and Research Trial to examine findings in patients' charts that would merit a diagnosis of metabolic syndrome according to the National Cholesterol Education Program, including three of the following five factors:

▸ Systolic blood pressure of less than 130 mm Hg, or diagnosed hypertension in the chart.

▸ Serum triglyceride level of 150 mg/dL or higher, adjusted for lipid medications in the study.

▸ HDL cholesterol level less than 40 mg/dL in men or less than 50 mg/dL in women, adjusted for lipid medications in the study.

▸ Fasting glucose of 110 mg/dL or higher, or diagnosed diabetes in the chart.

▸ Waist circumference greater than 102 cm in men or 88 cm in women, approximated from the body mass index for study purposes, according to the third National Health and Nutrition Examination Survey (NHANES III) adjustments.

Analysis showed that patients with metabolic syndrome in the study were older than those without the diagnosis (mean age 57 vs. 51 years); had a higher BMI (33 vs. 26 kg/m

Among patients with metabolic syndrome, 80% had hyperlipidemia, 73% had hypertension, and 26% had diabetes—rates significantly higher than those in the nonmetabolic syndrome population (P less than .001).

Their lipids were worse than those of nonmetabolic syndrome patients by every measure. They also were more likely to have gastroesophageal reflux disease and depression, and were significantly less likely to be physically active. In addition, they were slightly more likely to be smokers than were the nonmetabolic syndrome patients (15% vs. 12%), although this difference was not significant.

They were more likely to have received a referral to a nutritionist, been advised to increase their physical activity, and been counseled about smoking cessation, yet they were less likely to be at cholesterol or blood pressure goals than were patients without metabolic syndrome.

There was a stepwise increase by age in the percentage of patients who met criteria for metabolic syndrome: 19% of patients aged 40–49 years, 34% of those aged 50–59 years, 41% of those aged 60–69 years, and 48% of patients aged 70 years or older.

It is noteworthy that the metabolic syndrome patients were no more likely than were other patients to have a family history of early coronary artery disease.

The authors noted that most patients with metabolic syndrome had other major cardiovascular risk factors, which may have served to alert their physicians to their overall cardiometabolic risk, even when the metabolic syndrome diagnosis was missed.

Patients with subclinical metabolic syndrome may be less well recognized as being at elevated risk of diabetes and cardiovascular disease, because they may lack the telltale diagnoses of hypertension, diabetes, and hyperlipidemia, although they have other important risk factors.

MONTEREY, CALIF. — Although most physicians are familiar with the basic facts concerning the newly introduced Gardasil and Zostavax vaccines, questions still surround their use.

Zostavax, a 14-fold concentrated version of Varivax, the varicella zoster vaccine to prevent chicken pox in children, was approved by the Food and Drug Administration in May 2006 for adults aged 60 years and older.

A month later, approval was issued for Gardasil in girls and young women across the age range of 9 to 26 years to prevent cervical cancer, precancerous genital lesions, and genital warts caused by HPV types 6, 11, 16, and 18.

Dr. Stephen K. Tyring, professor of dermatology at the University of Texas Health Sciences Center in Houston, discussed commonly asked patient questions about the vaccines at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Gardasil

▸ “I'm 30, and I'm in the dating scene. Should I get the Gardasil vaccine even though it's only approved for ages 9–26?”

The vaccine was studied in younger women, but “there's no reason in the world in terms of safety and efficacy” that older women who are sexually active shouldn't receive the vaccine, said Dr. Tyring. However, most insurance companies probably will not cover the cost of the vaccine in children or young women outside of the FDA-specified age groups.

▸ “Shouldn't we be vaccinating boys and young men too?”

Men obviously play an important role in the cycle of spread of oncogenic papilloma viruses, but women suffered more anogenital malignancies in the countries in which the vaccine was studied, so they were included in the trials, he explained. Ongoing studies will establish “at least the safety if not the efficacy” of the vaccine in males.

▸ “Why isn't Gardasil being used to treat cervical cancer?”

The few published studies assessing Gardasil's efficacy in treating cervical cancer have had unimpressive results; therefore, its role remains preventive.

▸ “How long will the viral protection last?”

“We don't know,” said Dr. Tyring. The duration of protection was at least 5 years in trial participants. “We hope it's a lifetime.”

▸ “I've already had genital warts. What would be the point of my getting the vaccine now?”

If a patient's gynecologist has demonstrated that a patient has been exposed only to HPV types 6 and 11, studies have proved she could still receive protection against HPV types 16 and 18, which cause cervical cancer. The American Cancer Society predicts more than 11,000 women will be diagnosed with cervical cancer in the United States this year, and nearly 3,700 will die of the disease.

Zostavax

▸ “I've heard the Zostavax vaccine isn't very effective. Why should I get it?”

In a pivotal trial, the Zostavax vaccine prevented herpes zoster in 51% of adults aged 60 and older, a fairly impressive result considering it was being used to do something quite extraordinary: prevent reemergence of a virus that had been lying dormant in the dorsal root ganglia for decades, said Dr. Tyring. And even among those who did get shingles after receiving the vaccine, the rate of postherpetic neuralgia was reduced by two-thirds.

▸ “I'm 55, but I've seen what shingles was like in my dad, and I don't want to get it. Should I get the vaccine?”

Dr. Tyring and associates have given the vaccine to people in their 50s and found that their immunogenicity is superior to that of older adults. Fortunately, trials will be underway very soon that may lead to approval in younger adults, but until that time, there may be no reimbursement for what appears to be a safe and effective vaccine.

▸ “I have had shingles, and I never want to go through it again. Will the disease prevent recurrence?”

Even without the vaccine, an immunocompetent person has only a 5% chance of getting shingles a second time. So while there is likely no harm in giving the vaccine to someone who has had the disease, it would cost approximately $250 (again, unlikely to be reimbursed) to reduce the risk from 5% to 4%. The vaccine is contraindicated in immunocompromised patients, since it is a live attenuated vaccine.

▸ “I don't think I even had chickenpox as a child, so would the vaccine be unnecessary?”

Fully 99% of people over age 60 are seropositive, whether or not they recall staying home from school with scratchy bumps. Dr. Tyring said all people over 60 can be presumed to be at risk for shingles and therefore could potentially benefit from the vaccine. Dr. Tyring receives research support and has served on the speaker's bureau and as a consultant to Merck, maker of both vaccines.

MONTEREY, CALIF. — Although most physicians are familiar with the basic facts concerning the newly introduced Gardasil and Zostavax vaccines, questions still surround their use.

Zostavax, a 14-fold concentrated version of Varivax, the varicella zoster vaccine to prevent chicken pox in children, was approved by the Food and Drug Administration in May 2006 for adults aged 60 years and older.

A month later, approval was issued for Gardasil in girls and young women across the age range of 9 to 26 years to prevent cervical cancer, precancerous genital lesions, and genital warts caused by HPV types 6, 11, 16, and 18.

Dr. Stephen K. Tyring, professor of dermatology at the University of Texas Health Sciences Center in Houston, discussed commonly asked patient questions about the vaccines at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Gardasil

▸ “I'm 30, and I'm in the dating scene. Should I get the Gardasil vaccine even though it's only approved for ages 9–26?”

The vaccine was studied in younger women, but “there's no reason in the world in terms of safety and efficacy” that older women who are sexually active shouldn't receive the vaccine, said Dr. Tyring. However, most insurance companies probably will not cover the cost of the vaccine in children or young women outside of the FDA-specified age groups.

▸ “Shouldn't we be vaccinating boys and young men too?”

Men obviously play an important role in the cycle of spread of oncogenic papilloma viruses, but women suffered more anogenital malignancies in the countries in which the vaccine was studied, so they were included in the trials, he explained. Ongoing studies will establish “at least the safety if not the efficacy” of the vaccine in males.

▸ “Why isn't Gardasil being used to treat cervical cancer?”

The few published studies assessing Gardasil's efficacy in treating cervical cancer have had unimpressive results; therefore, its role remains preventive.

▸ “How long will the viral protection last?”

“We don't know,” said Dr. Tyring. The duration of protection was at least 5 years in trial participants. “We hope it's a lifetime.”

▸ “I've already had genital warts. What would be the point of my getting the vaccine now?”

If a patient's gynecologist has demonstrated that a patient has been exposed only to HPV types 6 and 11, studies have proved she could still receive protection against HPV types 16 and 18, which cause cervical cancer. The American Cancer Society predicts more than 11,000 women will be diagnosed with cervical cancer in the United States this year, and nearly 3,700 will die of the disease.

Zostavax

▸ “I've heard the Zostavax vaccine isn't very effective. Why should I get it?”

In a pivotal trial, the Zostavax vaccine prevented herpes zoster in 51% of adults aged 60 and older, a fairly impressive result considering it was being used to do something quite extraordinary: prevent reemergence of a virus that had been lying dormant in the dorsal root ganglia for decades, said Dr. Tyring. And even among those who did get shingles after receiving the vaccine, the rate of postherpetic neuralgia was reduced by two-thirds.

▸ “I'm 55, but I've seen what shingles was like in my dad, and I don't want to get it. Should I get the vaccine?”

Dr. Tyring and associates have given the vaccine to people in their 50s and found that their immunogenicity is superior to that of older adults. Fortunately, trials will be underway very soon that may lead to approval in younger adults, but until that time, there may be no reimbursement for what appears to be a safe and effective vaccine.

▸ “I have had shingles, and I never want to go through it again. Will the disease prevent recurrence?”

Even without the vaccine, an immunocompetent person has only a 5% chance of getting shingles a second time. So while there is likely no harm in giving the vaccine to someone who has had the disease, it would cost approximately $250 (again, unlikely to be reimbursed) to reduce the risk from 5% to 4%. The vaccine is contraindicated in immunocompromised patients, since it is a live attenuated vaccine.

▸ “I don't think I even had chickenpox as a child, so would the vaccine be unnecessary?”

Fully 99% of people over age 60 are seropositive, whether or not they recall staying home from school with scratchy bumps. Dr. Tyring said all people over 60 can be presumed to be at risk for shingles and therefore could potentially benefit from the vaccine. Dr. Tyring receives research support and has served on the speaker's bureau and as a consultant to Merck, maker of both vaccines.

MONTEREY, CALIF. — Although most physicians are familiar with the basic facts concerning the newly introduced Gardasil and Zostavax vaccines, questions still surround their use.

Zostavax, a 14-fold concentrated version of Varivax, the varicella zoster vaccine to prevent chicken pox in children, was approved by the Food and Drug Administration in May 2006 for adults aged 60 years and older.

A month later, approval was issued for Gardasil in girls and young women across the age range of 9 to 26 years to prevent cervical cancer, precancerous genital lesions, and genital warts caused by HPV types 6, 11, 16, and 18.

Dr. Stephen K. Tyring, professor of dermatology at the University of Texas Health Sciences Center in Houston, discussed commonly asked patient questions about the vaccines at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Gardasil

▸ “I'm 30, and I'm in the dating scene. Should I get the Gardasil vaccine even though it's only approved for ages 9–26?”

The vaccine was studied in younger women, but “there's no reason in the world in terms of safety and efficacy” that older women who are sexually active shouldn't receive the vaccine, said Dr. Tyring. However, most insurance companies probably will not cover the cost of the vaccine in children or young women outside of the FDA-specified age groups.

▸ “Shouldn't we be vaccinating boys and young men too?”

Men obviously play an important role in the cycle of spread of oncogenic papilloma viruses, but women suffered more anogenital malignancies in the countries in which the vaccine was studied, so they were included in the trials, he explained. Ongoing studies will establish “at least the safety if not the efficacy” of the vaccine in males.

▸ “Why isn't Gardasil being used to treat cervical cancer?”

The few published studies assessing Gardasil's efficacy in treating cervical cancer have had unimpressive results; therefore, its role remains preventive.

▸ “How long will the viral protection last?”

“We don't know,” said Dr. Tyring. The duration of protection was at least 5 years in trial participants. “We hope it's a lifetime.”

▸ “I've already had genital warts. What would be the point of my getting the vaccine now?”

If a patient's gynecologist has demonstrated that a patient has been exposed only to HPV types 6 and 11, studies have proved she could still receive protection against HPV types 16 and 18, which cause cervical cancer. The American Cancer Society predicts more than 11,000 women will be diagnosed with cervical cancer in the United States this year, and nearly 3,700 will die of the disease.

Zostavax

▸ “I've heard the Zostavax vaccine isn't very effective. Why should I get it?”

In a pivotal trial, the Zostavax vaccine prevented herpes zoster in 51% of adults aged 60 and older, a fairly impressive result considering it was being used to do something quite extraordinary: prevent reemergence of a virus that had been lying dormant in the dorsal root ganglia for decades, said Dr. Tyring. And even among those who did get shingles after receiving the vaccine, the rate of postherpetic neuralgia was reduced by two-thirds.

▸ “I'm 55, but I've seen what shingles was like in my dad, and I don't want to get it. Should I get the vaccine?”

Dr. Tyring and associates have given the vaccine to people in their 50s and found that their immunogenicity is superior to that of older adults. Fortunately, trials will be underway very soon that may lead to approval in younger adults, but until that time, there may be no reimbursement for what appears to be a safe and effective vaccine.

▸ “I have had shingles, and I never want to go through it again. Will the disease prevent recurrence?”

Even without the vaccine, an immunocompetent person has only a 5% chance of getting shingles a second time. So while there is likely no harm in giving the vaccine to someone who has had the disease, it would cost approximately $250 (again, unlikely to be reimbursed) to reduce the risk from 5% to 4%. The vaccine is contraindicated in immunocompromised patients, since it is a live attenuated vaccine.

▸ “I don't think I even had chickenpox as a child, so would the vaccine be unnecessary?”

Fully 99% of people over age 60 are seropositive, whether or not they recall staying home from school with scratchy bumps. Dr. Tyring said all people over 60 can be presumed to be at risk for shingles and therefore could potentially benefit from the vaccine. Dr. Tyring receives research support and has served on the speaker's bureau and as a consultant to Merck, maker of both vaccines.

Arthritis creates work limitations for about a third of working-age adults with the disease, impacting nearly 7% of the total U.S. workforce, according to a state-by-state study by the Centers for Disease Control.

The first-of-its-kind survey, drawing on data from the Behavioral Risk Factor Surveillance System, may foreshadow a profound challenge to the economy as the population ages. Arthritis today affects 46 million Americans, with an estimated economic toll of $128 billion a year, according to the Arthritis Foundation.

The random digit-dialed telephone survey of more than 200,000 households queried working-age adults in every state, Washington, Guam, Puerto Rico, and the U.S. Virgin Islands about whether they had been diagnosed with arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia. Respondents with arthritis were asked whether arthritis or joint symptoms affected whether they were employed and the type and amount of work they could do.

The responses are weighted to represent the adult population in each state.

A high degree of variability was found in the state-specific prevalence of arthritis-related work limitations among all adults 18–64 years of age, from 3.4% of adults in Hawaii to 15% in Kentucky, reported Kristina A. Theis and associates at the National Center for Chronic Disease Prevention and the National Center on Birth Defects and Developmental Disability at the CDC (MMWR 2007;56:1045–9).

Among adults with diagnosed arthritis and related conditions, work limitations were reported by a median 33%, from 25.1% in Nevada to 51.3% in Kentucky.

“That's huge,” said Ms. Theis in a telephone interview. “In Kentucky, that represents every other person with arthritis a doctor might be seeing.”

Preventing or minimizing work-related limitations through timely therapy, rehabilitation, and workplace accommodation impacts not only the economy as a whole, but the patients' independence, self-esteem, and financial well-being, she stressed.

“It is not always on the physicians' radar screen to inquire, 'How's your function? How's your pain? And by the way, how is that function and pain impacting you at work?'” said Ms. Theis.

Rheumatologists in the states bookending the new statistics said patient characteristics and availability of services may play into differences seen across states.

In Elizabethtown, Ken., rheumatologist Dr. Daksha Mehta said that some patients travel more than 100 miles to see her. And although there is a nationwide shortage of board-certified rheumatologists, “I'm sure it's worse in Kentucky,” she said.

Access to medical specialists, as well as experts in occupational therapy and workplace ergonomics, may be limited in small, isolated rural communities. Additionally, many patients still do not recognize the need for early diagnosis and treatment.

“I have patients with arthritis who are still working at their factory jobs, still farming, but that's with appropriate therapy … optimizing medications, having physical and occupational therapy, doing home strengthening exercises,” said Dr. Mehta of the Center for Arthritis and Osteoporosis.

Rheumatologist Rex Adams of Arthritis Associates of Nevada in Reno said he doubted the types of jobs performed in his state differ much from those practiced in Kentucky, which has doubled the prevalence of work-related limitations reported by working-aged adults with arthritis.

“Mining is big in Nevada, and there are a lot of service industry workers here,” he said. “Maybe it's because we're just good rheumatologists who keep everyone working!” he joked.

Dr. Adams speculated the variation might be explained by systemic factors, like differences in state disability programs, or perhaps populations. Nevada has a “pretty young, healthy population” with a large percentage of workers who recently moved from other locations. Kentucky's population may be older and more stationary.

In both states, rheumatologists said they advocate a team approach to arthritis management, with an emphasis on therapy and lifestyle modifications as well as medication. Occupational and physical therapy are offered on-site in a growing number of group rheumatology practices.

Such trends could make a difference in patients' ability to perform their jobs, said Ms. Theis from the CDC's Division of Adult and Community Health.

Preliminary findings from a separate CDC study build on a growing body of published research suggesting that physician recommendations concerning arthritis management are highly influential in terms of patient behavior, she explained.

When a physician recommends weight loss, an arthritis-focused exercise program, or workplace accommodations in conjunction with the Americans with Disabilities Act, for example, patients are much more likely to attempt to follow that advice.

“We're hoping physicians will say, 'I have a really important voice that carries a lot of weight on a lot of levels,'” said Ms. Theis. “We see them as one of our most important audiences.”

Sometimes, the physician's role on minimizing work limitations is direct, perhaps by prescribing traditional therapy regimens and even biologic therapy.

Other times, a physician may refer a patient to physical or occupational therapy, or to a hand surgeon for a customized thumb or wrist splint that permits normal workplace activities, said Diana Baldwin, an occupational therapist at the Missouri Arthritis Rehabilitation and Training Center.

“We've found that it isn't enough to tell people, 'Cut back on your hours,' or 'Be more flexible,' or 'Don't do things that hurt,'” she said. “For the average working person with arthritis, that is not useful.”

What is useful is when physicians explain to patients that their joints are vulnerable, and provide a rationale to implement protective strategies, she said.

The Missouri Training Center in Columbia is currently completing a federally funded study that has randomized 84 adults with arthritis to receive either written materials about arthritis in the workplace or interventions conducted by Ms. Baldwin in the work setting, be it a manufacturing workshop, business office, or classroom. She has spent 1.5–2 hours interviewing these workers with arthritis and then has studied them as they work, taking pictures that she will later diagram to show movements that stress the joints including twisting, grabbing, reaching, and bending.

She has investigated ergonomic surgical tools to aid an anesthesiologist, adapted the car of a traveling salesman, and added a step stool to ease a manufacturing specialist's reach to a drill press.

Making such changes early on appears to keep people working longer, more effectively, and with less pain, she said.

But economic realities have proved to be a barrier to early workplace interventions. No janitors have agreed to allow Ms. Baldwin to come to their workplaces to identify practices that might be exacerbating their arthritis, for example. “They're not going to expose the fact that they have arthritis on the job,” she said.

Before modification, the low cart height required the worker to bend forward.

The modification of a raised handle decreased painful bending posture.

Unmodified task required static overreaching and bending of the trunk.

Before modification, leaning forward created greater tension on back muscles. PHOTOS COURTESY DIANA BALDWIN

Arthritis creates work limitations for about a third of working-age adults with the disease, impacting nearly 7% of the total U.S. workforce, according to a state-by-state study by the Centers for Disease Control.

The first-of-its-kind survey, drawing on data from the Behavioral Risk Factor Surveillance System, may foreshadow a profound challenge to the economy as the population ages. Arthritis today affects 46 million Americans, with an estimated economic toll of $128 billion a year, according to the Arthritis Foundation.

The random digit-dialed telephone survey of more than 200,000 households queried working-age adults in every state, Washington, Guam, Puerto Rico, and the U.S. Virgin Islands about whether they had been diagnosed with arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia. Respondents with arthritis were asked whether arthritis or joint symptoms affected whether they were employed and the type and amount of work they could do.

The responses are weighted to represent the adult population in each state.

A high degree of variability was found in the state-specific prevalence of arthritis-related work limitations among all adults 18–64 years of age, from 3.4% of adults in Hawaii to 15% in Kentucky, reported Kristina A. Theis and associates at the National Center for Chronic Disease Prevention and the National Center on Birth Defects and Developmental Disability at the CDC (MMWR 2007;56:1045–9).

Among adults with diagnosed arthritis and related conditions, work limitations were reported by a median 33%, from 25.1% in Nevada to 51.3% in Kentucky.

“That's huge,” said Ms. Theis in a telephone interview. “In Kentucky, that represents every other person with arthritis a doctor might be seeing.”

Preventing or minimizing work-related limitations through timely therapy, rehabilitation, and workplace accommodation impacts not only the economy as a whole, but the patients' independence, self-esteem, and financial well-being, she stressed.

“It is not always on the physicians' radar screen to inquire, 'How's your function? How's your pain? And by the way, how is that function and pain impacting you at work?'” said Ms. Theis.

Rheumatologists in the states bookending the new statistics said patient characteristics and availability of services may play into differences seen across states.

In Elizabethtown, Ken., rheumatologist Dr. Daksha Mehta said that some patients travel more than 100 miles to see her. And although there is a nationwide shortage of board-certified rheumatologists, “I'm sure it's worse in Kentucky,” she said.

Access to medical specialists, as well as experts in occupational therapy and workplace ergonomics, may be limited in small, isolated rural communities. Additionally, many patients still do not recognize the need for early diagnosis and treatment.

“I have patients with arthritis who are still working at their factory jobs, still farming, but that's with appropriate therapy … optimizing medications, having physical and occupational therapy, doing home strengthening exercises,” said Dr. Mehta of the Center for Arthritis and Osteoporosis.

Rheumatologist Rex Adams of Arthritis Associates of Nevada in Reno said he doubted the types of jobs performed in his state differ much from those practiced in Kentucky, which has doubled the prevalence of work-related limitations reported by working-aged adults with arthritis.

“Mining is big in Nevada, and there are a lot of service industry workers here,” he said. “Maybe it's because we're just good rheumatologists who keep everyone working!” he joked.

Dr. Adams speculated the variation might be explained by systemic factors, like differences in state disability programs, or perhaps populations. Nevada has a “pretty young, healthy population” with a large percentage of workers who recently moved from other locations. Kentucky's population may be older and more stationary.

In both states, rheumatologists said they advocate a team approach to arthritis management, with an emphasis on therapy and lifestyle modifications as well as medication. Occupational and physical therapy are offered on-site in a growing number of group rheumatology practices.

Such trends could make a difference in patients' ability to perform their jobs, said Ms. Theis from the CDC's Division of Adult and Community Health.

Preliminary findings from a separate CDC study build on a growing body of published research suggesting that physician recommendations concerning arthritis management are highly influential in terms of patient behavior, she explained.

When a physician recommends weight loss, an arthritis-focused exercise program, or workplace accommodations in conjunction with the Americans with Disabilities Act, for example, patients are much more likely to attempt to follow that advice.

“We're hoping physicians will say, 'I have a really important voice that carries a lot of weight on a lot of levels,'” said Ms. Theis. “We see them as one of our most important audiences.”

Sometimes, the physician's role on minimizing work limitations is direct, perhaps by prescribing traditional therapy regimens and even biologic therapy.

Other times, a physician may refer a patient to physical or occupational therapy, or to a hand surgeon for a customized thumb or wrist splint that permits normal workplace activities, said Diana Baldwin, an occupational therapist at the Missouri Arthritis Rehabilitation and Training Center.

“We've found that it isn't enough to tell people, 'Cut back on your hours,' or 'Be more flexible,' or 'Don't do things that hurt,'” she said. “For the average working person with arthritis, that is not useful.”

What is useful is when physicians explain to patients that their joints are vulnerable, and provide a rationale to implement protective strategies, she said.

The Missouri Training Center in Columbia is currently completing a federally funded study that has randomized 84 adults with arthritis to receive either written materials about arthritis in the workplace or interventions conducted by Ms. Baldwin in the work setting, be it a manufacturing workshop, business office, or classroom. She has spent 1.5–2 hours interviewing these workers with arthritis and then has studied them as they work, taking pictures that she will later diagram to show movements that stress the joints including twisting, grabbing, reaching, and bending.

She has investigated ergonomic surgical tools to aid an anesthesiologist, adapted the car of a traveling salesman, and added a step stool to ease a manufacturing specialist's reach to a drill press.

Making such changes early on appears to keep people working longer, more effectively, and with less pain, she said.

But economic realities have proved to be a barrier to early workplace interventions. No janitors have agreed to allow Ms. Baldwin to come to their workplaces to identify practices that might be exacerbating their arthritis, for example. “They're not going to expose the fact that they have arthritis on the job,” she said.

Before modification, the low cart height required the worker to bend forward.

The modification of a raised handle decreased painful bending posture.

Unmodified task required static overreaching and bending of the trunk.

Before modification, leaning forward created greater tension on back muscles. PHOTOS COURTESY DIANA BALDWIN

Arthritis creates work limitations for about a third of working-age adults with the disease, impacting nearly 7% of the total U.S. workforce, according to a state-by-state study by the Centers for Disease Control.

The first-of-its-kind survey, drawing on data from the Behavioral Risk Factor Surveillance System, may foreshadow a profound challenge to the economy as the population ages. Arthritis today affects 46 million Americans, with an estimated economic toll of $128 billion a year, according to the Arthritis Foundation.

The random digit-dialed telephone survey of more than 200,000 households queried working-age adults in every state, Washington, Guam, Puerto Rico, and the U.S. Virgin Islands about whether they had been diagnosed with arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia. Respondents with arthritis were asked whether arthritis or joint symptoms affected whether they were employed and the type and amount of work they could do.

The responses are weighted to represent the adult population in each state.

A high degree of variability was found in the state-specific prevalence of arthritis-related work limitations among all adults 18–64 years of age, from 3.4% of adults in Hawaii to 15% in Kentucky, reported Kristina A. Theis and associates at the National Center for Chronic Disease Prevention and the National Center on Birth Defects and Developmental Disability at the CDC (MMWR 2007;56:1045–9).

Among adults with diagnosed arthritis and related conditions, work limitations were reported by a median 33%, from 25.1% in Nevada to 51.3% in Kentucky.

“That's huge,” said Ms. Theis in a telephone interview. “In Kentucky, that represents every other person with arthritis a doctor might be seeing.”

Preventing or minimizing work-related limitations through timely therapy, rehabilitation, and workplace accommodation impacts not only the economy as a whole, but the patients' independence, self-esteem, and financial well-being, she stressed.

“It is not always on the physicians' radar screen to inquire, 'How's your function? How's your pain? And by the way, how is that function and pain impacting you at work?'” said Ms. Theis.

Rheumatologists in the states bookending the new statistics said patient characteristics and availability of services may play into differences seen across states.

In Elizabethtown, Ken., rheumatologist Dr. Daksha Mehta said that some patients travel more than 100 miles to see her. And although there is a nationwide shortage of board-certified rheumatologists, “I'm sure it's worse in Kentucky,” she said.

Access to medical specialists, as well as experts in occupational therapy and workplace ergonomics, may be limited in small, isolated rural communities. Additionally, many patients still do not recognize the need for early diagnosis and treatment.

“I have patients with arthritis who are still working at their factory jobs, still farming, but that's with appropriate therapy … optimizing medications, having physical and occupational therapy, doing home strengthening exercises,” said Dr. Mehta of the Center for Arthritis and Osteoporosis.

Rheumatologist Rex Adams of Arthritis Associates of Nevada in Reno said he doubted the types of jobs performed in his state differ much from those practiced in Kentucky, which has doubled the prevalence of work-related limitations reported by working-aged adults with arthritis.

“Mining is big in Nevada, and there are a lot of service industry workers here,” he said. “Maybe it's because we're just good rheumatologists who keep everyone working!” he joked.

Dr. Adams speculated the variation might be explained by systemic factors, like differences in state disability programs, or perhaps populations. Nevada has a “pretty young, healthy population” with a large percentage of workers who recently moved from other locations. Kentucky's population may be older and more stationary.

In both states, rheumatologists said they advocate a team approach to arthritis management, with an emphasis on therapy and lifestyle modifications as well as medication. Occupational and physical therapy are offered on-site in a growing number of group rheumatology practices.

Such trends could make a difference in patients' ability to perform their jobs, said Ms. Theis from the CDC's Division of Adult and Community Health.

Preliminary findings from a separate CDC study build on a growing body of published research suggesting that physician recommendations concerning arthritis management are highly influential in terms of patient behavior, she explained.

When a physician recommends weight loss, an arthritis-focused exercise program, or workplace accommodations in conjunction with the Americans with Disabilities Act, for example, patients are much more likely to attempt to follow that advice.

“We're hoping physicians will say, 'I have a really important voice that carries a lot of weight on a lot of levels,'” said Ms. Theis. “We see them as one of our most important audiences.”

Sometimes, the physician's role on minimizing work limitations is direct, perhaps by prescribing traditional therapy regimens and even biologic therapy.

Other times, a physician may refer a patient to physical or occupational therapy, or to a hand surgeon for a customized thumb or wrist splint that permits normal workplace activities, said Diana Baldwin, an occupational therapist at the Missouri Arthritis Rehabilitation and Training Center.

“We've found that it isn't enough to tell people, 'Cut back on your hours,' or 'Be more flexible,' or 'Don't do things that hurt,'” she said. “For the average working person with arthritis, that is not useful.”

What is useful is when physicians explain to patients that their joints are vulnerable, and provide a rationale to implement protective strategies, she said.

The Missouri Training Center in Columbia is currently completing a federally funded study that has randomized 84 adults with arthritis to receive either written materials about arthritis in the workplace or interventions conducted by Ms. Baldwin in the work setting, be it a manufacturing workshop, business office, or classroom. She has spent 1.5–2 hours interviewing these workers with arthritis and then has studied them as they work, taking pictures that she will later diagram to show movements that stress the joints including twisting, grabbing, reaching, and bending.

She has investigated ergonomic surgical tools to aid an anesthesiologist, adapted the car of a traveling salesman, and added a step stool to ease a manufacturing specialist's reach to a drill press.

Making such changes early on appears to keep people working longer, more effectively, and with less pain, she said.

But economic realities have proved to be a barrier to early workplace interventions. No janitors have agreed to allow Ms. Baldwin to come to their workplaces to identify practices that might be exacerbating their arthritis, for example. “They're not going to expose the fact that they have arthritis on the job,” she said.

Before modification, the low cart height required the worker to bend forward.

The modification of a raised handle decreased painful bending posture.

Unmodified task required static overreaching and bending of the trunk.

Before modification, leaning forward created greater tension on back muscles. PHOTOS COURTESY DIANA BALDWIN

STANFORD, CALIF. — The Ottawa Ankle Rules for children and adolescents can take some of the guesswork out of evaluating ankle injuries and cut down on the number of needless x-rays of sprains.

“Is it broken? Is it not broken? In the emergency department, it's the bane of our existence,” said Dr. Bernard W. Dannenberg, director of pediatric emergency medicine at the Stanford (Calif.) University Medical Center.

Simplicity is key to the rules, first developed for adults and later validated for children at the University of Ottawa and the University of Manitoba in Winnipeg (Acad. Emer. Med. 1999;6:1005–9).

The rules follow several criteria, simply stated:

▸ Has the child been able to walk four steps or more on the injured ankle, either at the time of the injury or any time since?

▸ Is there an absence of significant pain when the physician presses with a thumb on the posterior edge or tip of the lateral or medial malleolar zones?

▸ Is there an absence of significant tenderness at the base of the fifth metatarsal or navicular bone (in the case of suspicion of a fracture in the mid-foot)?

If the answers to these questions are affirmative, the injury can safely be bandaged with an Ace wrap for comfort and the patient instructed to use crutches without obtaining an x-ray, Dr. Dannenberg said at a pediatric update sponsored by Stanford University.

The rules have been found to be 100% sensitive for a fracture of the ankle or mid-foot in children aged 2–16 years, and 24% and 36% specific for fractures of the ankle and mid-foot, respectively. Following the rules has the potential of reducing the number of ankle and mid-foot x-ray series by 16%–29%, according to the authors of the pediatric validation study.

STANFORD, CALIF. — The Ottawa Ankle Rules for children and adolescents can take some of the guesswork out of evaluating ankle injuries and cut down on the number of needless x-rays of sprains.

“Is it broken? Is it not broken? In the emergency department, it's the bane of our existence,” said Dr. Bernard W. Dannenberg, director of pediatric emergency medicine at the Stanford (Calif.) University Medical Center.

Simplicity is key to the rules, first developed for adults and later validated for children at the University of Ottawa and the University of Manitoba in Winnipeg (Acad. Emer. Med. 1999;6:1005–9).

The rules follow several criteria, simply stated:

▸ Has the child been able to walk four steps or more on the injured ankle, either at the time of the injury or any time since?

▸ Is there an absence of significant pain when the physician presses with a thumb on the posterior edge or tip of the lateral or medial malleolar zones?

▸ Is there an absence of significant tenderness at the base of the fifth metatarsal or navicular bone (in the case of suspicion of a fracture in the mid-foot)?

If the answers to these questions are affirmative, the injury can safely be bandaged with an Ace wrap for comfort and the patient instructed to use crutches without obtaining an x-ray, Dr. Dannenberg said at a pediatric update sponsored by Stanford University.

The rules have been found to be 100% sensitive for a fracture of the ankle or mid-foot in children aged 2–16 years, and 24% and 36% specific for fractures of the ankle and mid-foot, respectively. Following the rules has the potential of reducing the number of ankle and mid-foot x-ray series by 16%–29%, according to the authors of the pediatric validation study.

STANFORD, CALIF. — The Ottawa Ankle Rules for children and adolescents can take some of the guesswork out of evaluating ankle injuries and cut down on the number of needless x-rays of sprains.

“Is it broken? Is it not broken? In the emergency department, it's the bane of our existence,” said Dr. Bernard W. Dannenberg, director of pediatric emergency medicine at the Stanford (Calif.) University Medical Center.

Simplicity is key to the rules, first developed for adults and later validated for children at the University of Ottawa and the University of Manitoba in Winnipeg (Acad. Emer. Med. 1999;6:1005–9).

The rules follow several criteria, simply stated:

▸ Has the child been able to walk four steps or more on the injured ankle, either at the time of the injury or any time since?

▸ Is there an absence of significant pain when the physician presses with a thumb on the posterior edge or tip of the lateral or medial malleolar zones?

▸ Is there an absence of significant tenderness at the base of the fifth metatarsal or navicular bone (in the case of suspicion of a fracture in the mid-foot)?

If the answers to these questions are affirmative, the injury can safely be bandaged with an Ace wrap for comfort and the patient instructed to use crutches without obtaining an x-ray, Dr. Dannenberg said at a pediatric update sponsored by Stanford University.

The rules have been found to be 100% sensitive for a fracture of the ankle or mid-foot in children aged 2–16 years, and 24% and 36% specific for fractures of the ankle and mid-foot, respectively. Following the rules has the potential of reducing the number of ankle and mid-foot x-ray series by 16%–29%, according to the authors of the pediatric validation study.

MONTEREY, CALIF. — Melanocytic tumors of unknown malignant potential represent some of the most difficult cases in pediatric dermatology, since little agreement exists about their diagnostic criteria, management, or outcome.

“They cause everyone, including pathologists, referring dermatologists, and surgeons, to lose sleep,” said Dr. Susan Swetter, director of Stanford (Calif.) University's pigmented lesion and cutaneous melanoma clinic, at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Dr. Swetter described the management of an 8-mm raised, blue-black nodule that appeared behind the right ear of an 11-year-old girl. Satellite blue-black macules appeared on the periphery of the lesion.

A partial 5-mm punch biopsy was reviewed by pathologists at Stanford; the University of California, San Francisco; and Massachusetts General Hospital, Boston. The conclusion was that the lesion was a melanocytic tumor of unknown malignant potential (MELTUMP) with decidedly mixed signals: no ulceration but a relatively high mitotic rate (4/mm

Differential diagnoses included a pigmented epithelioid melanocytoma, an agminated Spitz nevus, or a “low-grade” melanoma (Clark's level III, Breslow thickness 3.7 mm).

The patient underwent a “fairly intuitive” comprehensive work-up, including a thorough personal and family history, a review of the timing and speed of growth of the lesion, and a total body skin examination and physical examination, including palpation of regional lymph node basins to assess for metastasis.

Melanoma experts agree that MELTUMP lesions should be completely excised, but the specifics about recommended margins remain hazy, Dr. Swetter explained. Some experts would decide to perform a wide excision in such a case, perhaps including sentinel lymph node biopsy, as if they were treating a melanoma.

At Stanford, where the patient was seen, the decision was made to take a 1-cm margin, narrower than the 2-cm margin that would be appropriate for a 3.7-mm melanoma, and to await the pathology results before deciding whether to perform a sentinel lymph node biopsy or lymph node dissection.

The histology on the wide excision specimen showed that the lesion was symmetrical and well circumscribed with a polypoid proliferation of darkly pigmented melanocytes and a mitotic rate “well below 1/mm

Dr. Swetter described the applicable histology images as revealing “deeply pigmented epithelial spindle cells and unmistakable angiolymphatic invasion.” “Our pathologists thought this was most consistent with a melanocytoma diagnosis,” and noted its rarity as well as its “uncertain biological behavior,” said Dr. Swetter.

A comparative genomic hybridization study was ordered from the UCSF laboratory, but results were estimated to take 6–8 weeks, a period of time that could compromise afferent lymphatic drainage from a scalp lesion and reduce the accuracy of the sentinel node biopsy.

After extensive discussions with the child's parents, the Stanford team elected to perform a sentinel lymph node biopsy but to await the outcome of the comparative genomic hybridization studies prior to performing complete lymph node dissection in the event that the sentinel node specimen was positive. A metastatic work-up with PET/CT scanning was performed “in part … to allay some of the parental concern about metastatic disease.” Parenthetically, Dr. Swetter noted that such a scan would not generally be indicated in an asymptomatic patient with no signs of metastatic disease and would not preclude the possibility of a positive sentinel node biopsy. The scans were negative.

Two sentinel lymph nodes were identified and removed in the right cervical neck. One was positive for subcapsular and parenchymal metastatic foci of pigmented epithelioid melanocytoma and stained strongly positive for S100, MelanA, and HMB45. MELTUMP lesions have been associated with a very high rate of sentinel lymph node positivity in the two largest retrospective studies to date (44%–50%, compared with about 20% for typical melanomas with Breslow thickness greater than 1 mm.)

However, the picture is confusing, because studies also associate atypical Spitz tumors with a very high survival rate despite apparent micrometastases.

“The question is, What is the clinical significance [of the high rate of positive sentinel lymph nodes in these tumors]? Does it imply a fatal outcome?” she asked.

In the case of Dr. Swetter's patient, a comparative genomic hybridization offered what appeared to be optimistic information, since the lesion contained aberrations on chromosome 11, a finding that has been exclusively associated with Spitz nevi in comparative studies with other benign nevi and melanomas. The patient has been followed clinically for more than a year without evidence of recurrent disease.

Much uncertainty exists around the management of MELTUMPs; which are characterized by a lack of agreement among pathologists, even those specializing in melanoma pathology.

The lesions should be completely excised, and treated similarly to melanomas when they are characterized by frank atypia or uncertain biologic behavior.

Until more data can be gathered from the national pediatric melanoma and melanocytic neoplasms, Dr. Swetter urged frank discussions among medical professionals and families about the diagnostic uncertainty regarding these lesions.

The melanocytic tumor of unknown malignant potential on the 11-year-old girl is shown here. Stanford University Departments of Dermatology and Pathology and the Melanoma Care Coalition, Pharmadura, LLC

MONTEREY, CALIF. — Melanocytic tumors of unknown malignant potential represent some of the most difficult cases in pediatric dermatology, since little agreement exists about their diagnostic criteria, management, or outcome.

“They cause everyone, including pathologists, referring dermatologists, and surgeons, to lose sleep,” said Dr. Susan Swetter, director of Stanford (Calif.) University's pigmented lesion and cutaneous melanoma clinic, at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Dr. Swetter described the management of an 8-mm raised, blue-black nodule that appeared behind the right ear of an 11-year-old girl. Satellite blue-black macules appeared on the periphery of the lesion.

A partial 5-mm punch biopsy was reviewed by pathologists at Stanford; the University of California, San Francisco; and Massachusetts General Hospital, Boston. The conclusion was that the lesion was a melanocytic tumor of unknown malignant potential (MELTUMP) with decidedly mixed signals: no ulceration but a relatively high mitotic rate (4/mm

Differential diagnoses included a pigmented epithelioid melanocytoma, an agminated Spitz nevus, or a “low-grade” melanoma (Clark's level III, Breslow thickness 3.7 mm).

The patient underwent a “fairly intuitive” comprehensive work-up, including a thorough personal and family history, a review of the timing and speed of growth of the lesion, and a total body skin examination and physical examination, including palpation of regional lymph node basins to assess for metastasis.

Melanoma experts agree that MELTUMP lesions should be completely excised, but the specifics about recommended margins remain hazy, Dr. Swetter explained. Some experts would decide to perform a wide excision in such a case, perhaps including sentinel lymph node biopsy, as if they were treating a melanoma.

At Stanford, where the patient was seen, the decision was made to take a 1-cm margin, narrower than the 2-cm margin that would be appropriate for a 3.7-mm melanoma, and to await the pathology results before deciding whether to perform a sentinel lymph node biopsy or lymph node dissection.

The histology on the wide excision specimen showed that the lesion was symmetrical and well circumscribed with a polypoid proliferation of darkly pigmented melanocytes and a mitotic rate “well below 1/mm

Dr. Swetter described the applicable histology images as revealing “deeply pigmented epithelial spindle cells and unmistakable angiolymphatic invasion.” “Our pathologists thought this was most consistent with a melanocytoma diagnosis,” and noted its rarity as well as its “uncertain biological behavior,” said Dr. Swetter.

A comparative genomic hybridization study was ordered from the UCSF laboratory, but results were estimated to take 6–8 weeks, a period of time that could compromise afferent lymphatic drainage from a scalp lesion and reduce the accuracy of the sentinel node biopsy.

After extensive discussions with the child's parents, the Stanford team elected to perform a sentinel lymph node biopsy but to await the outcome of the comparative genomic hybridization studies prior to performing complete lymph node dissection in the event that the sentinel node specimen was positive. A metastatic work-up with PET/CT scanning was performed “in part … to allay some of the parental concern about metastatic disease.” Parenthetically, Dr. Swetter noted that such a scan would not generally be indicated in an asymptomatic patient with no signs of metastatic disease and would not preclude the possibility of a positive sentinel node biopsy. The scans were negative.

Two sentinel lymph nodes were identified and removed in the right cervical neck. One was positive for subcapsular and parenchymal metastatic foci of pigmented epithelioid melanocytoma and stained strongly positive for S100, MelanA, and HMB45. MELTUMP lesions have been associated with a very high rate of sentinel lymph node positivity in the two largest retrospective studies to date (44%–50%, compared with about 20% for typical melanomas with Breslow thickness greater than 1 mm.)

However, the picture is confusing, because studies also associate atypical Spitz tumors with a very high survival rate despite apparent micrometastases.

“The question is, What is the clinical significance [of the high rate of positive sentinel lymph nodes in these tumors]? Does it imply a fatal outcome?” she asked.

In the case of Dr. Swetter's patient, a comparative genomic hybridization offered what appeared to be optimistic information, since the lesion contained aberrations on chromosome 11, a finding that has been exclusively associated with Spitz nevi in comparative studies with other benign nevi and melanomas. The patient has been followed clinically for more than a year without evidence of recurrent disease.

Much uncertainty exists around the management of MELTUMPs; which are characterized by a lack of agreement among pathologists, even those specializing in melanoma pathology.

The lesions should be completely excised, and treated similarly to melanomas when they are characterized by frank atypia or uncertain biologic behavior.

Until more data can be gathered from the national pediatric melanoma and melanocytic neoplasms, Dr. Swetter urged frank discussions among medical professionals and families about the diagnostic uncertainty regarding these lesions.

The melanocytic tumor of unknown malignant potential on the 11-year-old girl is shown here. Stanford University Departments of Dermatology and Pathology and the Melanoma Care Coalition, Pharmadura, LLC

MONTEREY, CALIF. — Melanocytic tumors of unknown malignant potential represent some of the most difficult cases in pediatric dermatology, since little agreement exists about their diagnostic criteria, management, or outcome.

“They cause everyone, including pathologists, referring dermatologists, and surgeons, to lose sleep,” said Dr. Susan Swetter, director of Stanford (Calif.) University's pigmented lesion and cutaneous melanoma clinic, at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Dr. Swetter described the management of an 8-mm raised, blue-black nodule that appeared behind the right ear of an 11-year-old girl. Satellite blue-black macules appeared on the periphery of the lesion.

A partial 5-mm punch biopsy was reviewed by pathologists at Stanford; the University of California, San Francisco; and Massachusetts General Hospital, Boston. The conclusion was that the lesion was a melanocytic tumor of unknown malignant potential (MELTUMP) with decidedly mixed signals: no ulceration but a relatively high mitotic rate (4/mm

Differential diagnoses included a pigmented epithelioid melanocytoma, an agminated Spitz nevus, or a “low-grade” melanoma (Clark's level III, Breslow thickness 3.7 mm).

The patient underwent a “fairly intuitive” comprehensive work-up, including a thorough personal and family history, a review of the timing and speed of growth of the lesion, and a total body skin examination and physical examination, including palpation of regional lymph node basins to assess for metastasis.

Melanoma experts agree that MELTUMP lesions should be completely excised, but the specifics about recommended margins remain hazy, Dr. Swetter explained. Some experts would decide to perform a wide excision in such a case, perhaps including sentinel lymph node biopsy, as if they were treating a melanoma.

At Stanford, where the patient was seen, the decision was made to take a 1-cm margin, narrower than the 2-cm margin that would be appropriate for a 3.7-mm melanoma, and to await the pathology results before deciding whether to perform a sentinel lymph node biopsy or lymph node dissection.

The histology on the wide excision specimen showed that the lesion was symmetrical and well circumscribed with a polypoid proliferation of darkly pigmented melanocytes and a mitotic rate “well below 1/mm

Dr. Swetter described the applicable histology images as revealing “deeply pigmented epithelial spindle cells and unmistakable angiolymphatic invasion.” “Our pathologists thought this was most consistent with a melanocytoma diagnosis,” and noted its rarity as well as its “uncertain biological behavior,” said Dr. Swetter.

A comparative genomic hybridization study was ordered from the UCSF laboratory, but results were estimated to take 6–8 weeks, a period of time that could compromise afferent lymphatic drainage from a scalp lesion and reduce the accuracy of the sentinel node biopsy.

After extensive discussions with the child's parents, the Stanford team elected to perform a sentinel lymph node biopsy but to await the outcome of the comparative genomic hybridization studies prior to performing complete lymph node dissection in the event that the sentinel node specimen was positive. A metastatic work-up with PET/CT scanning was performed “in part … to allay some of the parental concern about metastatic disease.” Parenthetically, Dr. Swetter noted that such a scan would not generally be indicated in an asymptomatic patient with no signs of metastatic disease and would not preclude the possibility of a positive sentinel node biopsy. The scans were negative.

Two sentinel lymph nodes were identified and removed in the right cervical neck. One was positive for subcapsular and parenchymal metastatic foci of pigmented epithelioid melanocytoma and stained strongly positive for S100, MelanA, and HMB45. MELTUMP lesions have been associated with a very high rate of sentinel lymph node positivity in the two largest retrospective studies to date (44%–50%, compared with about 20% for typical melanomas with Breslow thickness greater than 1 mm.)

However, the picture is confusing, because studies also associate atypical Spitz tumors with a very high survival rate despite apparent micrometastases.

“The question is, What is the clinical significance [of the high rate of positive sentinel lymph nodes in these tumors]? Does it imply a fatal outcome?” she asked.

In the case of Dr. Swetter's patient, a comparative genomic hybridization offered what appeared to be optimistic information, since the lesion contained aberrations on chromosome 11, a finding that has been exclusively associated with Spitz nevi in comparative studies with other benign nevi and melanomas. The patient has been followed clinically for more than a year without evidence of recurrent disease.

Much uncertainty exists around the management of MELTUMPs; which are characterized by a lack of agreement among pathologists, even those specializing in melanoma pathology.

The lesions should be completely excised, and treated similarly to melanomas when they are characterized by frank atypia or uncertain biologic behavior.

Until more data can be gathered from the national pediatric melanoma and melanocytic neoplasms, Dr. Swetter urged frank discussions among medical professionals and families about the diagnostic uncertainty regarding these lesions.

The melanocytic tumor of unknown malignant potential on the 11-year-old girl is shown here. Stanford University Departments of Dermatology and Pathology and the Melanoma Care Coalition, Pharmadura, LLC

MONTEREY, CALIF. — Although most physicians are familiar with the basic facts concerning the newly introduced Gardasil and Zostavax vaccines, patients still have many questions about their use.

Zostavax, a 14-fold concentrated version of Varivax, the varicella zoster vaccine to prevent chicken pox in children, was approved by the Food and Drug Administration in May 2006 for adults aged 60 years and older.

A month later, Gardasil was approved for girls and young women aged 9–26 years to prevent cervical cancer, precancerous genital lesions, and genital warts caused by HPV types 6, 11, 16, and 18.

Dr. Stephen K. Tyring provided some answers that patients often ask about the vaccines at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Gardasil

▸ “I'm 30, and I'm in the dating scene. Should I get the Gardasil vaccine even though it's only approved for ages 9–26?”

The vaccine was studied in younger women, but “there's no reason in the world in terms of safety and efficacy” that older women who are sexually active shouldn't receive the vaccine, said Dr. Tyring, professor of dermatology at the University of Texas Health Sciences Center in Houston. However, most insurance companies probably will not cover the cost of the vaccine in children or young women outside of the FDA-specified age groups.

▸ “What about vaccinating boys and young men?”

Men obviously play an important role in the cycle of spread of oncogenic papilloma viruses, but women suffered more anogenital malignancies in the countries where the vaccine was studied, so they were included in the trials, he said. Ongoing studies will establish “at least the safety if not the efficacy” of the vaccine in males.

▸ “Why isn't Gardasil being used to treat cervical cancer?”

Studies assessing its efficacy in treating cervical cancer have had unimpressive results; therefore its role remains preventive.

▸ “How long will the viral protection last?”

“We don't know,” said Dr. Tyring. Protection lasted at least 5 years in trial participants. “We hope it's a lifetime.”

▸ “I've had genital warts. What would be the point of my getting the vaccine now?”

If a patient's gynecologist has demonstrated a patient has been exposed only to HPV types 6 and 11, studies have proven she could still receive protection against HPV types 16 and 18, which cause cervical cancer.

Zostavax

▸ “I've heard the Zostavax vaccine isn't very effective. Why should I get it?”

In a pivotal trial, the Zostavax vaccine prevented herpes zoster in 51% of adults aged 60 and older, a fairly impressive result considering it was being used to do something quite extraordinary: prevent reemergence of a virus that had been lying dormant in the dorsal root ganglia for decades, said Dr. Tyring. And even among those who did get shingles after receiving the vaccine, the rate of postherpetic neuralgia was reduced by two-thirds.

▸ “I'm 55, but I've seen what shingles was like in my dad, and I don't want to get it. Should I get the vaccine?”

Dr. Tyring and associates have given the vaccine to people in their 50s and found that their immunogenicity is superior to that of older adults. Trials will soon be underway that may lead to approval in younger adults, but until that time, there may be no reimbursement for what appears to be a safe and effective vaccine.

▸ “I've had shingles and never want it again. Will the disease prevent recurrence?”

Even without the vaccine, an immunocompetent person has only a 5% chance of getting shingles a second time. Although there is likely no harm in giving the vaccine to someone who has had the disease, it would cost about $250 (again, unlikely to be reimbursed) to reduce the risk from 5% to 4%. The vaccine is contraindicated in immunocompromised patients, since it is a live attenuated vaccine.

▸ “I don't think I had chicken pox as a child. Would the vaccine be unnecessary?”

Of people over age 60, nearly 99% are seropositive, whether or not they've had chicken pox. Everyone over 60 can be presumed to be at risk for shingles and could benefit from the vaccine, said Dr. Tyring, who is a consultant for and receives funding from Merck, maker of both vaccines, and has served on its speaker's bureau.

MONTEREY, CALIF. — Although most physicians are familiar with the basic facts concerning the newly introduced Gardasil and Zostavax vaccines, patients still have many questions about their use.

Zostavax, a 14-fold concentrated version of Varivax, the varicella zoster vaccine to prevent chicken pox in children, was approved by the Food and Drug Administration in May 2006 for adults aged 60 years and older.

A month later, Gardasil was approved for girls and young women aged 9–26 years to prevent cervical cancer, precancerous genital lesions, and genital warts caused by HPV types 6, 11, 16, and 18.

Dr. Stephen K. Tyring provided some answers that patients often ask about the vaccines at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Gardasil

▸ “I'm 30, and I'm in the dating scene. Should I get the Gardasil vaccine even though it's only approved for ages 9–26?”

The vaccine was studied in younger women, but “there's no reason in the world in terms of safety and efficacy” that older women who are sexually active shouldn't receive the vaccine, said Dr. Tyring, professor of dermatology at the University of Texas Health Sciences Center in Houston. However, most insurance companies probably will not cover the cost of the vaccine in children or young women outside of the FDA-specified age groups.

▸ “What about vaccinating boys and young men?”

Men obviously play an important role in the cycle of spread of oncogenic papilloma viruses, but women suffered more anogenital malignancies in the countries where the vaccine was studied, so they were included in the trials, he said. Ongoing studies will establish “at least the safety if not the efficacy” of the vaccine in males.

▸ “Why isn't Gardasil being used to treat cervical cancer?”

Studies assessing its efficacy in treating cervical cancer have had unimpressive results; therefore its role remains preventive.

▸ “How long will the viral protection last?”

“We don't know,” said Dr. Tyring. Protection lasted at least 5 years in trial participants. “We hope it's a lifetime.”

▸ “I've had genital warts. What would be the point of my getting the vaccine now?”

If a patient's gynecologist has demonstrated a patient has been exposed only to HPV types 6 and 11, studies have proven she could still receive protection against HPV types 16 and 18, which cause cervical cancer.

Zostavax

▸ “I've heard the Zostavax vaccine isn't very effective. Why should I get it?”

In a pivotal trial, the Zostavax vaccine prevented herpes zoster in 51% of adults aged 60 and older, a fairly impressive result considering it was being used to do something quite extraordinary: prevent reemergence of a virus that had been lying dormant in the dorsal root ganglia for decades, said Dr. Tyring. And even among those who did get shingles after receiving the vaccine, the rate of postherpetic neuralgia was reduced by two-thirds.

▸ “I'm 55, but I've seen what shingles was like in my dad, and I don't want to get it. Should I get the vaccine?”

Dr. Tyring and associates have given the vaccine to people in their 50s and found that their immunogenicity is superior to that of older adults. Trials will soon be underway that may lead to approval in younger adults, but until that time, there may be no reimbursement for what appears to be a safe and effective vaccine.

▸ “I've had shingles and never want it again. Will the disease prevent recurrence?”

Even without the vaccine, an immunocompetent person has only a 5% chance of getting shingles a second time. Although there is likely no harm in giving the vaccine to someone who has had the disease, it would cost about $250 (again, unlikely to be reimbursed) to reduce the risk from 5% to 4%. The vaccine is contraindicated in immunocompromised patients, since it is a live attenuated vaccine.

▸ “I don't think I had chicken pox as a child. Would the vaccine be unnecessary?”

Of people over age 60, nearly 99% are seropositive, whether or not they've had chicken pox. Everyone over 60 can be presumed to be at risk for shingles and could benefit from the vaccine, said Dr. Tyring, who is a consultant for and receives funding from Merck, maker of both vaccines, and has served on its speaker's bureau.

MONTEREY, CALIF. — Although most physicians are familiar with the basic facts concerning the newly introduced Gardasil and Zostavax vaccines, patients still have many questions about their use.

Zostavax, a 14-fold concentrated version of Varivax, the varicella zoster vaccine to prevent chicken pox in children, was approved by the Food and Drug Administration in May 2006 for adults aged 60 years and older.

A month later, Gardasil was approved for girls and young women aged 9–26 years to prevent cervical cancer, precancerous genital lesions, and genital warts caused by HPV types 6, 11, 16, and 18.

Dr. Stephen K. Tyring provided some answers that patients often ask about the vaccines at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Gardasil

▸ “I'm 30, and I'm in the dating scene. Should I get the Gardasil vaccine even though it's only approved for ages 9–26?”

The vaccine was studied in younger women, but “there's no reason in the world in terms of safety and efficacy” that older women who are sexually active shouldn't receive the vaccine, said Dr. Tyring, professor of dermatology at the University of Texas Health Sciences Center in Houston. However, most insurance companies probably will not cover the cost of the vaccine in children or young women outside of the FDA-specified age groups.

▸ “What about vaccinating boys and young men?”

Men obviously play an important role in the cycle of spread of oncogenic papilloma viruses, but women suffered more anogenital malignancies in the countries where the vaccine was studied, so they were included in the trials, he said. Ongoing studies will establish “at least the safety if not the efficacy” of the vaccine in males.

▸ “Why isn't Gardasil being used to treat cervical cancer?”

Studies assessing its efficacy in treating cervical cancer have had unimpressive results; therefore its role remains preventive.

▸ “How long will the viral protection last?”

“We don't know,” said Dr. Tyring. Protection lasted at least 5 years in trial participants. “We hope it's a lifetime.”

▸ “I've had genital warts. What would be the point of my getting the vaccine now?”

If a patient's gynecologist has demonstrated a patient has been exposed only to HPV types 6 and 11, studies have proven she could still receive protection against HPV types 16 and 18, which cause cervical cancer.

Zostavax

▸ “I've heard the Zostavax vaccine isn't very effective. Why should I get it?”

In a pivotal trial, the Zostavax vaccine prevented herpes zoster in 51% of adults aged 60 and older, a fairly impressive result considering it was being used to do something quite extraordinary: prevent reemergence of a virus that had been lying dormant in the dorsal root ganglia for decades, said Dr. Tyring. And even among those who did get shingles after receiving the vaccine, the rate of postherpetic neuralgia was reduced by two-thirds.

▸ “I'm 55, but I've seen what shingles was like in my dad, and I don't want to get it. Should I get the vaccine?”

Dr. Tyring and associates have given the vaccine to people in their 50s and found that their immunogenicity is superior to that of older adults. Trials will soon be underway that may lead to approval in younger adults, but until that time, there may be no reimbursement for what appears to be a safe and effective vaccine.

▸ “I've had shingles and never want it again. Will the disease prevent recurrence?”

Even without the vaccine, an immunocompetent person has only a 5% chance of getting shingles a second time. Although there is likely no harm in giving the vaccine to someone who has had the disease, it would cost about $250 (again, unlikely to be reimbursed) to reduce the risk from 5% to 4%. The vaccine is contraindicated in immunocompromised patients, since it is a live attenuated vaccine.

▸ “I don't think I had chicken pox as a child. Would the vaccine be unnecessary?”

Of people over age 60, nearly 99% are seropositive, whether or not they've had chicken pox. Everyone over 60 can be presumed to be at risk for shingles and could benefit from the vaccine, said Dr. Tyring, who is a consultant for and receives funding from Merck, maker of both vaccines, and has served on its speaker's bureau.

LAS VEGAS — Not long ago, Dr. C. Daniel Smith showed a slide at an American College of Surgeons meeting that proclaimed endoluminal approaches to gastroesophageal reflux disease were “here to stay.”

A mere 2 years later, he's not so sure. “We're already reading obits for several of these procedures,” said Dr. Smith, chairman of surgery at the Mayo Clinic in Jacksonville, Fla., at the spring meeting of the ACS.

The curtain closed rapidly on several of the new stars in endoluminal GERD technology, sharply reducing the number of devices and procedures available for use in the United States.

Back in 2005, four devices had been approved and were being marketed for U.S. use and one—the Gatekeeper—appeared to be nearing Food and Drug Administration approval.

But in the interim between then and now, there have been several new developments:

▸ Medtronic Inc. withdrew its application for the Gatekeeper device because of concerns over efficacy.

▸ Boston Scientific Inc. voluntarily recalled the Enteryx liquid chemical polymer augmentation system in response to reports of serious adverse events, including deaths.

▸ Curon Medical Inc., maker of the Stretta device, declared bankruptcy, ending sales of that radiofrequency system, at least for now.

The endoluminal GERD device market now includes only the EndoCinch suturing system and the Plicator device, which uses jaws to create a “pleat” of tissue at the gastroesophageal junction.

For reasons that are both economic and practical, it would make sense to have a safe, predictable, and efficacious minimally invasive procedure for GERD, said Dr. Smith. Each year, 700,000 GERD-related endoscopies are performed and 200,000 patients are evaluated for possible antireflux surgery (although only about 70,000 patients undergo such a procedure).

But any endoluminal approach involves challenges, including the question of whether it would be reimbursed as an endoscopic procedure or as a more lucrative surgical procedure, which specialists would perform it, and whether it would prove truly efficacious in the long term.

The current state-of-the-art surgical alternative, laparoscopic Nissen fundoplication, “is a pretty good operation,” Dr. Smith said. “The gold standard … is going to have to be unseated before any of the endoluminal therapies gain acceptance.”

The EndoCinch suturing system by Bard Medical Inc., which cinches the lower esophageal sphincter, is not highly efficacious, according to Dr. Smith. Results of using the EndoCinch system at the Mayo Clinic parallel those of published studies, revealing that just 25%–38% of GERD patients are able to discontinue proton pump inhibitor (PPI) medications following the procedure.

The Plicator device from NDO Surgical Inc. has had better outcomes, with studies showing that more than half of patients can stop taking PPIs and experience significant improvements in their health-related quality of life after they have been treated with the jawlike device.

Results of Stretta trials were promising; although results were not seen after 6 months, outcomes were better at 12-month follow-up evaluations. This may be because, following the radiofrequency ablation to the deep submucosal space at the lower esophageal sphincter, collagen deposition needed time to mature.

Dr. Smith disclosed that he is on the scientific advisory committee for Endogastric Solutions Inc., manufacturer of the EsophyX device, currently available only in Europe. This device allows the operator to isolate the distal esophagus with suction.

The EsophyX then is advanced into the stomach, where it partially retroflexes to allow placement of fasteners around the circumference of the esophagus.

In one study of 84 patients treated using the EsophyX, 77 were no longer taking PPI medications 3 months after the procedure, he said.

LAS VEGAS — Not long ago, Dr. C. Daniel Smith showed a slide at an American College of Surgeons meeting that proclaimed endoluminal approaches to gastroesophageal reflux disease were “here to stay.”

A mere 2 years later, he's not so sure. “We're already reading obits for several of these procedures,” said Dr. Smith, chairman of surgery at the Mayo Clinic in Jacksonville, Fla., at the spring meeting of the ACS.

The curtain closed rapidly on several of the new stars in endoluminal GERD technology, sharply reducing the number of devices and procedures available for use in the United States.

Back in 2005, four devices had been approved and were being marketed for U.S. use and one—the Gatekeeper—appeared to be nearing Food and Drug Administration approval.

But in the interim between then and now, there have been several new developments:

▸ Medtronic Inc. withdrew its application for the Gatekeeper device because of concerns over efficacy.

▸ Boston Scientific Inc. voluntarily recalled the Enteryx liquid chemical polymer augmentation system in response to reports of serious adverse events, including deaths.

▸ Curon Medical Inc., maker of the Stretta device, declared bankruptcy, ending sales of that radiofrequency system, at least for now.

The endoluminal GERD device market now includes only the EndoCinch suturing system and the Plicator device, which uses jaws to create a “pleat” of tissue at the gastroesophageal junction.

For reasons that are both economic and practical, it would make sense to have a safe, predictable, and efficacious minimally invasive procedure for GERD, said Dr. Smith. Each year, 700,000 GERD-related endoscopies are performed and 200,000 patients are evaluated for possible antireflux surgery (although only about 70,000 patients undergo such a procedure).

But any endoluminal approach involves challenges, including the question of whether it would be reimbursed as an endoscopic procedure or as a more lucrative surgical procedure, which specialists would perform it, and whether it would prove truly efficacious in the long term.

The current state-of-the-art surgical alternative, laparoscopic Nissen fundoplication, “is a pretty good operation,” Dr. Smith said. “The gold standard … is going to have to be unseated before any of the endoluminal therapies gain acceptance.”

The EndoCinch suturing system by Bard Medical Inc., which cinches the lower esophageal sphincter, is not highly efficacious, according to Dr. Smith. Results of using the EndoCinch system at the Mayo Clinic parallel those of published studies, revealing that just 25%–38% of GERD patients are able to discontinue proton pump inhibitor (PPI) medications following the procedure.

The Plicator device from NDO Surgical Inc. has had better outcomes, with studies showing that more than half of patients can stop taking PPIs and experience significant improvements in their health-related quality of life after they have been treated with the jawlike device.

Results of Stretta trials were promising; although results were not seen after 6 months, outcomes were better at 12-month follow-up evaluations. This may be because, following the radiofrequency ablation to the deep submucosal space at the lower esophageal sphincter, collagen deposition needed time to mature.

Dr. Smith disclosed that he is on the scientific advisory committee for Endogastric Solutions Inc., manufacturer of the EsophyX device, currently available only in Europe. This device allows the operator to isolate the distal esophagus with suction.

The EsophyX then is advanced into the stomach, where it partially retroflexes to allow placement of fasteners around the circumference of the esophagus.

In one study of 84 patients treated using the EsophyX, 77 were no longer taking PPI medications 3 months after the procedure, he said.

LAS VEGAS — Not long ago, Dr. C. Daniel Smith showed a slide at an American College of Surgeons meeting that proclaimed endoluminal approaches to gastroesophageal reflux disease were “here to stay.”

A mere 2 years later, he's not so sure. “We're already reading obits for several of these procedures,” said Dr. Smith, chairman of surgery at the Mayo Clinic in Jacksonville, Fla., at the spring meeting of the ACS.

The curtain closed rapidly on several of the new stars in endoluminal GERD technology, sharply reducing the number of devices and procedures available for use in the United States.

Back in 2005, four devices had been approved and were being marketed for U.S. use and one—the Gatekeeper—appeared to be nearing Food and Drug Administration approval.

But in the interim between then and now, there have been several new developments:

▸ Medtronic Inc. withdrew its application for the Gatekeeper device because of concerns over efficacy.

▸ Boston Scientific Inc. voluntarily recalled the Enteryx liquid chemical polymer augmentation system in response to reports of serious adverse events, including deaths.

▸ Curon Medical Inc., maker of the Stretta device, declared bankruptcy, ending sales of that radiofrequency system, at least for now.

The endoluminal GERD device market now includes only the EndoCinch suturing system and the Plicator device, which uses jaws to create a “pleat” of tissue at the gastroesophageal junction.

For reasons that are both economic and practical, it would make sense to have a safe, predictable, and efficacious minimally invasive procedure for GERD, said Dr. Smith. Each year, 700,000 GERD-related endoscopies are performed and 200,000 patients are evaluated for possible antireflux surgery (although only about 70,000 patients undergo such a procedure).

But any endoluminal approach involves challenges, including the question of whether it would be reimbursed as an endoscopic procedure or as a more lucrative surgical procedure, which specialists would perform it, and whether it would prove truly efficacious in the long term.

The current state-of-the-art surgical alternative, laparoscopic Nissen fundoplication, “is a pretty good operation,” Dr. Smith said. “The gold standard … is going to have to be unseated before any of the endoluminal therapies gain acceptance.”

The EndoCinch suturing system by Bard Medical Inc., which cinches the lower esophageal sphincter, is not highly efficacious, according to Dr. Smith. Results of using the EndoCinch system at the Mayo Clinic parallel those of published studies, revealing that just 25%–38% of GERD patients are able to discontinue proton pump inhibitor (PPI) medications following the procedure.

The Plicator device from NDO Surgical Inc. has had better outcomes, with studies showing that more than half of patients can stop taking PPIs and experience significant improvements in their health-related quality of life after they have been treated with the jawlike device.

Results of Stretta trials were promising; although results were not seen after 6 months, outcomes were better at 12-month follow-up evaluations. This may be because, following the radiofrequency ablation to the deep submucosal space at the lower esophageal sphincter, collagen deposition needed time to mature.

Dr. Smith disclosed that he is on the scientific advisory committee for Endogastric Solutions Inc., manufacturer of the EsophyX device, currently available only in Europe. This device allows the operator to isolate the distal esophagus with suction.

The EsophyX then is advanced into the stomach, where it partially retroflexes to allow placement of fasteners around the circumference of the esophagus.

In one study of 84 patients treated using the EsophyX, 77 were no longer taking PPI medications 3 months after the procedure, he said.

MONTEREY, CALIF. — Although most physicians are familiar with the basic facts concerning the newly introduced Gardasil and Zostavax vaccines, questions still surround their use.

Zostavax, a 14-fold concentrated version of Varivax, the varicella zoster vaccine to prevent chicken pox in children, was approved by the Food and Drug Administration in May 2006 for adults aged 60 years and older.

A month later, approval was issued for Gardasil in girls and young women aged 9- to 26-years-old to prevent cervical cancer, precancerous genital lesions, and genital warts caused by HPV types 6, 11, 16, and 18.

Dr. Stephen K. Tyring, professor of dermatology at the University of Texas Health Sciences Center in Houston, discussed commonly asked patient questions about the vaccines at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Gardasil

PI"I'm 30, and I'm in the dating scene. Should I get the Gardasil vaccine even though it's only approved for ages 9–26?"

The vaccine was studied in younger women, but "there's no reason in the world in terms of safety and efficacy" that older women who are sexually active shouldn't receive the vaccine, said Dr. Tyring. However, most insurance companies probably will not cover the cost of the vaccine in children or young women outside of the FDA-specified age groups.

PI"Shouldn't we be vaccinating boys and young men too?"

Men obviously play an important role in the cycle of spread of oncogenic papillomaviruses, but women suffered more anogenital malignancies in the countries in which the vaccine was studied, so they were included in the trials, he explained. Ongoing studies will establish "at least the safety if not the efficacy" of the vaccine in males.

PI"Why isn't Gardasil being used to treat cervical cancer?"

The few published studies assessing Gardasil's efficacy in treating cervical cancer have had unimpressive results; therefore, its role remains preventive.

PI"How long will the viral protection last?"

"We don't know," said Dr. Tyring. The duration of protection was at least 5 years in trial participants. "We hope it's a lifetime."

PI"I've already had genital warts. What would be the point of my getting the vaccine now?"

If a patient's gynecologist has demonstrated a patient has been exposed only to HPV types 6 and 11, studies have proven she could still receive protection against HPV types 16 and 18, which cause cervical cancer.

The American Cancer Society predicts more than 11,000 women will be diagnosed with cervical cancer in the United States this year, and nearly 3,700 will die of the disease.

Zostavax

PI"I've heard the Zostavax vaccine isn't very effective. Why should I get it?"

In a pivotal trial, the Zostavax vaccine prevented herpes zoster in 51% of adults aged 60 years and older, a fairly impressive result considering it was being used to do something quite extraordinary: prevent reemergence of a virus that had been lying dormant in the dorsal root ganglia for decades, said Dr. Tyring. And even among those who did get shingles after receiving the vaccine, the rate of postherpetic neuralgia was reduced by two-thirds.

PI"I'm 55, but I've seen what shingles was like in my dad, and I don't want to get it. Should I get the vaccine?"

Dr. Tyring and his associates have given the vaccine to people in their 50s and found that their immunogenicity is superior to that of older adults. Fortunately, trials will be underway very soon that may lead to approval in younger adults, but until that time, there may be no reimbursement for what appears to be a safe and effective vaccine.

PI"I have had shingles, and I never want to go through it again. Will the disease prevent recurrence?"

Even without the vaccine, an immunocompetent person has only a 5% chance of getting shingles a second time. So while there is probably no harm in giving the vaccine to someone who has had the disease, it would cost approximately %250 (again, unlikely to be reimbursed) to reduce the risk from 5% to 4%. Vaccine administration is contraindicated in immunocompromised patients, since it is a live attenuated vaccine.

PI"I don't think I even had chicken pox as a child, so would the vaccine be unnecessary?"

Fully 99% of people over age 60 are seropositive, whether or not they recall staying home from school with scratchy bumps. Dr. Tyring said all people over 60 can be presumed to be at risk for shingles and therefore could potentially benefit from the vaccine.

Dr. Tyring receives research support and has served on the speakers' bureau and as a consultant to Merck, maker of both vaccines.

All people over 60 can be presumed to be at risk for shingles and therefore may benefit from Zostavax. DR. TYRING

MONTEREY, CALIF. — Although most physicians are familiar with the basic facts concerning the newly introduced Gardasil and Zostavax vaccines, questions still surround their use.

Zostavax, a 14-fold concentrated version of Varivax, the varicella zoster vaccine to prevent chicken pox in children, was approved by the Food and Drug Administration in May 2006 for adults aged 60 years and older.

A month later, approval was issued for Gardasil in girls and young women aged 9- to 26-years-old to prevent cervical cancer, precancerous genital lesions, and genital warts caused by HPV types 6, 11, 16, and 18.

Dr. Stephen K. Tyring, professor of dermatology at the University of Texas Health Sciences Center in Houston, discussed commonly asked patient questions about the vaccines at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Gardasil

PI"I'm 30, and I'm in the dating scene. Should I get the Gardasil vaccine even though it's only approved for ages 9–26?"

The vaccine was studied in younger women, but "there's no reason in the world in terms of safety and efficacy" that older women who are sexually active shouldn't receive the vaccine, said Dr. Tyring. However, most insurance companies probably will not cover the cost of the vaccine in children or young women outside of the FDA-specified age groups.

PI"Shouldn't we be vaccinating boys and young men too?"

Men obviously play an important role in the cycle of spread of oncogenic papillomaviruses, but women suffered more anogenital malignancies in the countries in which the vaccine was studied, so they were included in the trials, he explained. Ongoing studies will establish "at least the safety if not the efficacy" of the vaccine in males.

PI"Why isn't Gardasil being used to treat cervical cancer?"

The few published studies assessing Gardasil's efficacy in treating cervical cancer have had unimpressive results; therefore, its role remains preventive.

PI"How long will the viral protection last?"

"We don't know," said Dr. Tyring. The duration of protection was at least 5 years in trial participants. "We hope it's a lifetime."

PI"I've already had genital warts. What would be the point of my getting the vaccine now?"

If a patient's gynecologist has demonstrated a patient has been exposed only to HPV types 6 and 11, studies have proven she could still receive protection against HPV types 16 and 18, which cause cervical cancer.

The American Cancer Society predicts more than 11,000 women will be diagnosed with cervical cancer in the United States this year, and nearly 3,700 will die of the disease.

Zostavax

PI"I've heard the Zostavax vaccine isn't very effective. Why should I get it?"

In a pivotal trial, the Zostavax vaccine prevented herpes zoster in 51% of adults aged 60 years and older, a fairly impressive result considering it was being used to do something quite extraordinary: prevent reemergence of a virus that had been lying dormant in the dorsal root ganglia for decades, said Dr. Tyring. And even among those who did get shingles after receiving the vaccine, the rate of postherpetic neuralgia was reduced by two-thirds.

PI"I'm 55, but I've seen what shingles was like in my dad, and I don't want to get it. Should I get the vaccine?"

Dr. Tyring and his associates have given the vaccine to people in their 50s and found that their immunogenicity is superior to that of older adults. Fortunately, trials will be underway very soon that may lead to approval in younger adults, but until that time, there may be no reimbursement for what appears to be a safe and effective vaccine.

PI"I have had shingles, and I never want to go through it again. Will the disease prevent recurrence?"

Even without the vaccine, an immunocompetent person has only a 5% chance of getting shingles a second time. So while there is probably no harm in giving the vaccine to someone who has had the disease, it would cost approximately %250 (again, unlikely to be reimbursed) to reduce the risk from 5% to 4%. Vaccine administration is contraindicated in immunocompromised patients, since it is a live attenuated vaccine.

PI"I don't think I even had chicken pox as a child, so would the vaccine be unnecessary?"

Fully 99% of people over age 60 are seropositive, whether or not they recall staying home from school with scratchy bumps. Dr. Tyring said all people over 60 can be presumed to be at risk for shingles and therefore could potentially benefit from the vaccine.

Dr. Tyring receives research support and has served on the speakers' bureau and as a consultant to Merck, maker of both vaccines.

All people over 60 can be presumed to be at risk for shingles and therefore may benefit from Zostavax. DR. TYRING

MONTEREY, CALIF. — Although most physicians are familiar with the basic facts concerning the newly introduced Gardasil and Zostavax vaccines, questions still surround their use.

Zostavax, a 14-fold concentrated version of Varivax, the varicella zoster vaccine to prevent chicken pox in children, was approved by the Food and Drug Administration in May 2006 for adults aged 60 years and older.

A month later, approval was issued for Gardasil in girls and young women aged 9- to 26-years-old to prevent cervical cancer, precancerous genital lesions, and genital warts caused by HPV types 6, 11, 16, and 18.

Dr. Stephen K. Tyring, professor of dermatology at the University of Texas Health Sciences Center in Houston, discussed commonly asked patient questions about the vaccines at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Gardasil

PI"I'm 30, and I'm in the dating scene. Should I get the Gardasil vaccine even though it's only approved for ages 9–26?"

The vaccine was studied in younger women, but "there's no reason in the world in terms of safety and efficacy" that older women who are sexually active shouldn't receive the vaccine, said Dr. Tyring. However, most insurance companies probably will not cover the cost of the vaccine in children or young women outside of the FDA-specified age groups.

PI"Shouldn't we be vaccinating boys and young men too?"

Men obviously play an important role in the cycle of spread of oncogenic papillomaviruses, but women suffered more anogenital malignancies in the countries in which the vaccine was studied, so they were included in the trials, he explained. Ongoing studies will establish "at least the safety if not the efficacy" of the vaccine in males.

PI"Why isn't Gardasil being used to treat cervical cancer?"

The few published studies assessing Gardasil's efficacy in treating cervical cancer have had unimpressive results; therefore, its role remains preventive.

PI"How long will the viral protection last?"

"We don't know," said Dr. Tyring. The duration of protection was at least 5 years in trial participants. "We hope it's a lifetime."

PI"I've already had genital warts. What would be the point of my getting the vaccine now?"

If a patient's gynecologist has demonstrated a patient has been exposed only to HPV types 6 and 11, studies have proven she could still receive protection against HPV types 16 and 18, which cause cervical cancer.

The American Cancer Society predicts more than 11,000 women will be diagnosed with cervical cancer in the United States this year, and nearly 3,700 will die of the disease.

Zostavax

PI"I've heard the Zostavax vaccine isn't very effective. Why should I get it?"

In a pivotal trial, the Zostavax vaccine prevented herpes zoster in 51% of adults aged 60 years and older, a fairly impressive result considering it was being used to do something quite extraordinary: prevent reemergence of a virus that had been lying dormant in the dorsal root ganglia for decades, said Dr. Tyring. And even among those who did get shingles after receiving the vaccine, the rate of postherpetic neuralgia was reduced by two-thirds.

PI"I'm 55, but I've seen what shingles was like in my dad, and I don't want to get it. Should I get the vaccine?"

Dr. Tyring and his associates have given the vaccine to people in their 50s and found that their immunogenicity is superior to that of older adults. Fortunately, trials will be underway very soon that may lead to approval in younger adults, but until that time, there may be no reimbursement for what appears to be a safe and effective vaccine.

PI"I have had shingles, and I never want to go through it again. Will the disease prevent recurrence?"

Even without the vaccine, an immunocompetent person has only a 5% chance of getting shingles a second time. So while there is probably no harm in giving the vaccine to someone who has had the disease, it would cost approximately %250 (again, unlikely to be reimbursed) to reduce the risk from 5% to 4%. Vaccine administration is contraindicated in immunocompromised patients, since it is a live attenuated vaccine.

PI"I don't think I even had chicken pox as a child, so would the vaccine be unnecessary?"

Fully 99% of people over age 60 are seropositive, whether or not they recall staying home from school with scratchy bumps. Dr. Tyring said all people over 60 can be presumed to be at risk for shingles and therefore could potentially benefit from the vaccine.

Dr. Tyring receives research support and has served on the speakers' bureau and as a consultant to Merck, maker of both vaccines.

All people over 60 can be presumed to be at risk for shingles and therefore may benefit from Zostavax. DR. TYRING

MONTEREY, CALIF. — Melanocytic tumors of unknown malignant potential represent some of the most difficult cases in pediatric dermatology, since little agreement exists about their diagnostic criteria, management, or outcome.

"They cause everyone, including pathologists, referring dermatologists, and surgeons, to lose sleep," said Dr. Susan Swetter, director of Stanford (Calif.) University's pigmented lesion and cutaneous melanoma clinic, at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Dr. Swetter described the management of an 8-mm raised, blue-black nodule that appeared behind the right ear of an 11-year-old girl. Satellite blue-black macules appeared on the periphery of the lesion.

A partial 5-mm punch biopsy was reviewed by pathologists at Stanford; the University of California, San Francisco; and Massachusetts General Hospital, Boston. The conclusion was that the lesion was a melanocytic tumor of unknown malignant potential (MELTUMP) with decidedly mixed signals: no ulceration but a relatively high mitotic rate (4/mm2) and probable angiolymphatic invasion.

Differential diagnoses included a pigmented epithelioid melanocytoma, an agminated Spitz nevus, or a "low-grade" melanoma. The patient underwent a "fairly intuitive" comprehensive work-up, including a thorough personal and family history, a review of the timing and speed of growth of the lesion, and a total body skin examination and physical examination, including palpation of regional lymph node basins to assess for metastasis.

Melanoma experts agree that MELTUMP lesions should be completely excised, but the specifics about recommended margins remain hazy, Dr. Swetter explained. Some experts would decide to perform a wide excision in such a case, perhaps including sentinel lymph node biopsy, as if they were treating a melanoma.

At Stanford, where the patient was seen, the decision was made to take a 1-cm margin, narrower than the 2-cm margin that would be appropriate for a 3.7-mm melanoma, and to await the pathology results before deciding whether to perform a sentinel lymph node biopsy or lymph node dissection.

The histology on the wide excision specimen showed that the lesion was symmetrical and well circumscribed with a polypoid proliferation of darkly pigmented melanocytes and a mitotic rate "well below 1/mm2."

Dr. Swetter described the applicable histology images as revealing "deeply pigmented epithelial spindle cells and unmistakable angiolymphatic invasion."

"Our pathologists thought this was most consistent with a melanocytoma diagnosis," and noted its rarity as well as its "uncertain biological behavior," said Dr. Swetter.

A comparative genomic hybridization study was ordered from the UCSF laboratory, but results were estimated to take 6–8 weeks, a period of time that could compromise afferent lymphatic drainage from a scalp lesion and reduce the accuracy of the sentinel node biopsy.

After extensive discussions with the child's parents, the Stanford team elected to perform a sentinel lymph node biopsy but to await the outcome of the comparative genomic hybridization studies prior to performing complete lymph node dissection in the event that the sentinel node specimen was positive. A metastatic work-up with PET/CT scanning was performed "in part … to allay some of the parental concern about metastatic disease." Parenthetically, Dr. Swetter noted that such a scan would not generally be indicated in an asymptomatic patient with no signs of metastatic disease and would not preclude the possibility of a positive sentinel node biopsy. The scans were negative.

Two sentinel lymph nodes were identified and removed in the right cervical neck. One was positive for subcapsular and parenchymal metastatic foci of pigmented epithelioid melanocytoma and stained strongly positive for S100, MelanA, and HMB45.

Ironically, MELTUMP lesions have been associated with a very high rate of sentinel lymph node positivity in the two largest retrospective studies to date (44%–50%, compared with approximately 20% for typical melanomas with Breslow thickness greater than 1 mm).

However, the picture is confusing, because studies also associate atypical Spitz tumors with a very high survival rate despite apparent micrometastases.

In the case of Dr. Swetter's patient, a comparative genomic hybridization offered what appeared to be optimistic information, since the lesion contained aberrations on chromosome 11, a finding that has been exclusively associated with Spitz nevi in comparative studies with other benign nevi and melanomas. No complete lymph node dissection was performed and the patient has been followed for more than a year without evidence of recurrent disease.

Fatal outcomes have resulted in cases where several pathologists concurred with a diagnosis of Spitz nevus or atypical Spitzoid tumors, suggesting that these cases represented unrecognized melanoma, although this scenario does not appear to be the norm. The lesions should be completely excised, and treated similarly to melanomas when they are characterized by frank atypia or uncertain biologic behavior.

Until more information can be gathered from the national pediatric melanoma and melanocytic neoplasms database organized by Dr. Bruce Overbook at Case Western Reserve University in Cleveland, Dr. Swetter urged open and frank discussions among medical professionals and families about the diagnostic uncertainty regarding these lesions.

An 8-mm raised, blue-black nodule on an 11-year-old raised uncertainty among Stanford University specialists. Stanford University Departments of Dermatology and Pathology and the Melanoma Care Coalition, Pharmadura, LLC

MONTEREY, CALIF. — Melanocytic tumors of unknown malignant potential represent some of the most difficult cases in pediatric dermatology, since little agreement exists about their diagnostic criteria, management, or outcome.

"They cause everyone, including pathologists, referring dermatologists, and surgeons, to lose sleep," said Dr. Susan Swetter, director of Stanford (Calif.) University's pigmented lesion and cutaneous melanoma clinic, at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Dr. Swetter described the management of an 8-mm raised, blue-black nodule that appeared behind the right ear of an 11-year-old girl. Satellite blue-black macules appeared on the periphery of the lesion.

A partial 5-mm punch biopsy was reviewed by pathologists at Stanford; the University of California, San Francisco; and Massachusetts General Hospital, Boston. The conclusion was that the lesion was a melanocytic tumor of unknown malignant potential (MELTUMP) with decidedly mixed signals: no ulceration but a relatively high mitotic rate (4/mm2) and probable angiolymphatic invasion.

Differential diagnoses included a pigmented epithelioid melanocytoma, an agminated Spitz nevus, or a "low-grade" melanoma. The patient underwent a "fairly intuitive" comprehensive work-up, including a thorough personal and family history, a review of the timing and speed of growth of the lesion, and a total body skin examination and physical examination, including palpation of regional lymph node basins to assess for metastasis.

Melanoma experts agree that MELTUMP lesions should be completely excised, but the specifics about recommended margins remain hazy, Dr. Swetter explained. Some experts would decide to perform a wide excision in such a case, perhaps including sentinel lymph node biopsy, as if they were treating a melanoma.

At Stanford, where the patient was seen, the decision was made to take a 1-cm margin, narrower than the 2-cm margin that would be appropriate for a 3.7-mm melanoma, and to await the pathology results before deciding whether to perform a sentinel lymph node biopsy or lymph node dissection.

The histology on the wide excision specimen showed that the lesion was symmetrical and well circumscribed with a polypoid proliferation of darkly pigmented melanocytes and a mitotic rate "well below 1/mm2."

Dr. Swetter described the applicable histology images as revealing "deeply pigmented epithelial spindle cells and unmistakable angiolymphatic invasion."

"Our pathologists thought this was most consistent with a melanocytoma diagnosis," and noted its rarity as well as its "uncertain biological behavior," said Dr. Swetter.

A comparative genomic hybridization study was ordered from the UCSF laboratory, but results were estimated to take 6–8 weeks, a period of time that could compromise afferent lymphatic drainage from a scalp lesion and reduce the accuracy of the sentinel node biopsy.

After extensive discussions with the child's parents, the Stanford team elected to perform a sentinel lymph node biopsy but to await the outcome of the comparative genomic hybridization studies prior to performing complete lymph node dissection in the event that the sentinel node specimen was positive. A metastatic work-up with PET/CT scanning was performed "in part … to allay some of the parental concern about metastatic disease." Parenthetically, Dr. Swetter noted that such a scan would not generally be indicated in an asymptomatic patient with no signs of metastatic disease and would not preclude the possibility of a positive sentinel node biopsy. The scans were negative.

Two sentinel lymph nodes were identified and removed in the right cervical neck. One was positive for subcapsular and parenchymal metastatic foci of pigmented epithelioid melanocytoma and stained strongly positive for S100, MelanA, and HMB45.

Ironically, MELTUMP lesions have been associated with a very high rate of sentinel lymph node positivity in the two largest retrospective studies to date (44%–50%, compared with approximately 20% for typical melanomas with Breslow thickness greater than 1 mm).

However, the picture is confusing, because studies also associate atypical Spitz tumors with a very high survival rate despite apparent micrometastases.

In the case of Dr. Swetter's patient, a comparative genomic hybridization offered what appeared to be optimistic information, since the lesion contained aberrations on chromosome 11, a finding that has been exclusively associated with Spitz nevi in comparative studies with other benign nevi and melanomas. No complete lymph node dissection was performed and the patient has been followed for more than a year without evidence of recurrent disease.

Fatal outcomes have resulted in cases where several pathologists concurred with a diagnosis of Spitz nevus or atypical Spitzoid tumors, suggesting that these cases represented unrecognized melanoma, although this scenario does not appear to be the norm. The lesions should be completely excised, and treated similarly to melanomas when they are characterized by frank atypia or uncertain biologic behavior.

Until more information can be gathered from the national pediatric melanoma and melanocytic neoplasms database organized by Dr. Bruce Overbook at Case Western Reserve University in Cleveland, Dr. Swetter urged open and frank discussions among medical professionals and families about the diagnostic uncertainty regarding these lesions.

An 8-mm raised, blue-black nodule on an 11-year-old raised uncertainty among Stanford University specialists. Stanford University Departments of Dermatology and Pathology and the Melanoma Care Coalition, Pharmadura, LLC

MONTEREY, CALIF. — Melanocytic tumors of unknown malignant potential represent some of the most difficult cases in pediatric dermatology, since little agreement exists about their diagnostic criteria, management, or outcome.

"They cause everyone, including pathologists, referring dermatologists, and surgeons, to lose sleep," said Dr. Susan Swetter, director of Stanford (Calif.) University's pigmented lesion and cutaneous melanoma clinic, at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Dr. Swetter described the management of an 8-mm raised, blue-black nodule that appeared behind the right ear of an 11-year-old girl. Satellite blue-black macules appeared on the periphery of the lesion.

A partial 5-mm punch biopsy was reviewed by pathologists at Stanford; the University of California, San Francisco; and Massachusetts General Hospital, Boston. The conclusion was that the lesion was a melanocytic tumor of unknown malignant potential (MELTUMP) with decidedly mixed signals: no ulceration but a relatively high mitotic rate (4/mm2) and probable angiolymphatic invasion.

Differential diagnoses included a pigmented epithelioid melanocytoma, an agminated Spitz nevus, or a "low-grade" melanoma. The patient underwent a "fairly intuitive" comprehensive work-up, including a thorough personal and family history, a review of the timing and speed of growth of the lesion, and a total body skin examination and physical examination, including palpation of regional lymph node basins to assess for metastasis.

Melanoma experts agree that MELTUMP lesions should be completely excised, but the specifics about recommended margins remain hazy, Dr. Swetter explained. Some experts would decide to perform a wide excision in such a case, perhaps including sentinel lymph node biopsy, as if they were treating a melanoma.

At Stanford, where the patient was seen, the decision was made to take a 1-cm margin, narrower than the 2-cm margin that would be appropriate for a 3.7-mm melanoma, and to await the pathology results before deciding whether to perform a sentinel lymph node biopsy or lymph node dissection.

The histology on the wide excision specimen showed that the lesion was symmetrical and well circumscribed with a polypoid proliferation of darkly pigmented melanocytes and a mitotic rate "well below 1/mm2."

Dr. Swetter described the applicable histology images as revealing "deeply pigmented epithelial spindle cells and unmistakable angiolymphatic invasion."

"Our pathologists thought this was most consistent with a melanocytoma diagnosis," and noted its rarity as well as its "uncertain biological behavior," said Dr. Swetter.

A comparative genomic hybridization study was ordered from the UCSF laboratory, but results were estimated to take 6–8 weeks, a period of time that could compromise afferent lymphatic drainage from a scalp lesion and reduce the accuracy of the sentinel node biopsy.

After extensive discussions with the child's parents, the Stanford team elected to perform a sentinel lymph node biopsy but to await the outcome of the comparative genomic hybridization studies prior to performing complete lymph node dissection in the event that the sentinel node specimen was positive. A metastatic work-up with PET/CT scanning was performed "in part … to allay some of the parental concern about metastatic disease." Parenthetically, Dr. Swetter noted that such a scan would not generally be indicated in an asymptomatic patient with no signs of metastatic disease and would not preclude the possibility of a positive sentinel node biopsy. The scans were negative.

Two sentinel lymph nodes were identified and removed in the right cervical neck. One was positive for subcapsular and parenchymal metastatic foci of pigmented epithelioid melanocytoma and stained strongly positive for S100, MelanA, and HMB45.

Ironically, MELTUMP lesions have been associated with a very high rate of sentinel lymph node positivity in the two largest retrospective studies to date (44%–50%, compared with approximately 20% for typical melanomas with Breslow thickness greater than 1 mm).

However, the picture is confusing, because studies also associate atypical Spitz tumors with a very high survival rate despite apparent micrometastases.

In the case of Dr. Swetter's patient, a comparative genomic hybridization offered what appeared to be optimistic information, since the lesion contained aberrations on chromosome 11, a finding that has been exclusively associated with Spitz nevi in comparative studies with other benign nevi and melanomas. No complete lymph node dissection was performed and the patient has been followed for more than a year without evidence of recurrent disease.

Fatal outcomes have resulted in cases where several pathologists concurred with a diagnosis of Spitz nevus or atypical Spitzoid tumors, suggesting that these cases represented unrecognized melanoma, although this scenario does not appear to be the norm. The lesions should be completely excised, and treated similarly to melanomas when they are characterized by frank atypia or uncertain biologic behavior.

Until more information can be gathered from the national pediatric melanoma and melanocytic neoplasms database organized by Dr. Bruce Overbook at Case Western Reserve University in Cleveland, Dr. Swetter urged open and frank discussions among medical professionals and families about the diagnostic uncertainty regarding these lesions.

An 8-mm raised, blue-black nodule on an 11-year-old raised uncertainty among Stanford University specialists. Stanford University Departments of Dermatology and Pathology and the Melanoma Care Coalition, Pharmadura, LLC

Controversy is a fact of life for pharmaceutical companies and the Food and Drug Administration but the saga of an investigative immunotherapeutic agent for advanced prostate cancer has been unusually contentious.

The struggle to gain FDA approval for sipuleucel-T, to be marketed as Provenge by Dendreon Corp., has included a raucous FDA meeting, picketing in Washington, congressional lobbying, and a lawsuit.

A final decision about whether to approve the drug now awaits interim findings from a 500-patient phase III trial, but in the meantime, the dispute has ignited activism reminiscent of the efforts to get HIV drugs “fast tracked” in the 1980s.

The dispute has raised questions about whether biologic agents can be judged by the same efficacy standards as traditional drugs, particularly when the goal is to treat terminal patients with few alternatives.

It has also generated concern in some scientists about the increasing influence of “antiscience” voices in American life. And finally, it has highlighted media pressure on the scientific community to justify established principles guiding medical policy decisions in the face of tearful families and angry investor campaigns.

It began March 29, when officials of the Seattle-based biotech firm presented to the FDA's Cellular, Tissue, and Gene Therapies Advisory Committee the results of two fast-tracked, phase III parallel studies of their biologic agent in a total of 225 men with asymptomatic, hormone-refractory, metastatic prostate cancer.

Sipuleucel-T would be the first oncologic drug in a new class, designed to stimulate a patient's immune system with a “vaccine” made from his own peripheral blood mononuclear cells, including antigen-presenting cells. The cells would be extracted by plasmapheresis and flown to a centralized laboratory, where they are activated with a recombinant fusion protein containing prostate antigen fused to GM-CSF, an immune cell activator. Within 3 days of collection, the cells are reinfused into the patient in an outpatient procedure.

After the March meeting, at least two committee members, oncologist Howard I. Scher of Memorial Sloan-Kettering Cancer Center, New York, and Dr. Maha Hussain, professor of internal medicine and urology at the University of Michigan, Ann Arbor, wrote to the FDA to express concern about the implications of approving the drug based on the evidence. The letters were leaked and reprinted, first in The Cancer Letter, then online.

Dr. Scher said inconsistent trial data “do not constitute 'proof' of benefit or justify a conclusion that they are 'reasonably likely' to predict benefit. … The only conclusion is that the survival difference observed may have occurred by chance alone.”

The company had argued that the survival results were “clinically meaningful, significantly persuasive, and internally consistent in the intent-to-treat population.”

A 4.5-month survival benefit from a drug with few side effects is urgently needed by prostate cancer patients, who now gain only about a 2-month survival advantage from docetaxel (Taxotere), a drug with side effects that many patients find debilitating.

On May 9, the FDA rejected the committee suggestion to approve sipuleucel-T, requesting more data from Dendreon.

The decision sparked a debate about whether the FDA's restraint represented a scientifically valid concern about the efficacy of a treatment that failed to pass muster in clinical trials, or a risk-averse philosophy depriving patients of treatments that offer them their only hope of prolonged survival.

Within the month, Dr. David Penson of the University of Southern California, Los Angeles, presided over a press briefing at the annual meeting of the American Urological Association marked by frustration about the decision. He listed three reasons the FDA might reject a recommendation to approve a drug: safety, efficacy, and politics. “[We] were really hoping this would be approved, because these patients have so few other options,” he said.

After the July 30 filing of a federal lawsuit by Care to Live, an Ohio nonprofit organization seeking an emergency injunction that would make the drug available to cancer patients, an FDA spokeswoman said the agency could no longer comment on the issue. A U.S. Court of Appeals, District of Columbia Circuit, in early August ruled that patients do not have a constitutional right to unapproved drugs, in a suit brought by the Abigail Alliance for Better Access to Developmental Drugs. The Alliance has vowed to appeal.

Dendreon announced that the FDA had decided to accept either a positive interim or final analysis of survival from its ongoing, phase III, 500-patient IMPACT study as the basis for amending the Biologics License Application that was filed on a fast-track basis in early 2007, possibly paving the way for approval as soon as 2008.

Activists demand FDA approval of Provenge during a Sept. 18 protest in front of the agency's offices in Rockville, Md. Sheri Mattes/Elsevier Global Medical News

Controversy is a fact of life for pharmaceutical companies and the Food and Drug Administration but the saga of an investigative immunotherapeutic agent for advanced prostate cancer has been unusually contentious.

The struggle to gain FDA approval for sipuleucel-T, to be marketed as Provenge by Dendreon Corp., has included a raucous FDA meeting, picketing in Washington, congressional lobbying, and a lawsuit.

A final decision about whether to approve the drug now awaits interim findings from a 500-patient phase III trial, but in the meantime, the dispute has ignited activism reminiscent of the efforts to get HIV drugs “fast tracked” in the 1980s.

The dispute has raised questions about whether biologic agents can be judged by the same efficacy standards as traditional drugs, particularly when the goal is to treat terminal patients with few alternatives.

It has also generated concern in some scientists about the increasing influence of “antiscience” voices in American life. And finally, it has highlighted media pressure on the scientific community to justify established principles guiding medical policy decisions in the face of tearful families and angry investor campaigns.

It began March 29, when officials of the Seattle-based biotech firm presented to the FDA's Cellular, Tissue, and Gene Therapies Advisory Committee the results of two fast-tracked, phase III parallel studies of their biologic agent in a total of 225 men with asymptomatic, hormone-refractory, metastatic prostate cancer.

Sipuleucel-T would be the first oncologic drug in a new class, designed to stimulate a patient's immune system with a “vaccine” made from his own peripheral blood mononuclear cells, including antigen-presenting cells. The cells would be extracted by plasmapheresis and flown to a centralized laboratory, where they are activated with a recombinant fusion protein containing prostate antigen fused to GM-CSF, an immune cell activator. Within 3 days of collection, the cells are reinfused into the patient in an outpatient procedure.

After the March meeting, at least two committee members, oncologist Howard I. Scher of Memorial Sloan-Kettering Cancer Center, New York, and Dr. Maha Hussain, professor of internal medicine and urology at the University of Michigan, Ann Arbor, wrote to the FDA to express concern about the implications of approving the drug based on the evidence. The letters were leaked and reprinted, first in The Cancer Letter, then online.

Dr. Scher said inconsistent trial data “do not constitute 'proof' of benefit or justify a conclusion that they are 'reasonably likely' to predict benefit. … The only conclusion is that the survival difference observed may have occurred by chance alone.”

The company had argued that the survival results were “clinically meaningful, significantly persuasive, and internally consistent in the intent-to-treat population.”

A 4.5-month survival benefit from a drug with few side effects is urgently needed by prostate cancer patients, who now gain only about a 2-month survival advantage from docetaxel (Taxotere), a drug with side effects that many patients find debilitating.

On May 9, the FDA rejected the committee suggestion to approve sipuleucel-T, requesting more data from Dendreon.

The decision sparked a debate about whether the FDA's restraint represented a scientifically valid concern about the efficacy of a treatment that failed to pass muster in clinical trials, or a risk-averse philosophy depriving patients of treatments that offer them their only hope of prolonged survival.

Within the month, Dr. David Penson of the University of Southern California, Los Angeles, presided over a press briefing at the annual meeting of the American Urological Association marked by frustration about the decision. He listed three reasons the FDA might reject a recommendation to approve a drug: safety, efficacy, and politics. “[We] were really hoping this would be approved, because these patients have so few other options,” he said.

After the July 30 filing of a federal lawsuit by Care to Live, an Ohio nonprofit organization seeking an emergency injunction that would make the drug available to cancer patients, an FDA spokeswoman said the agency could no longer comment on the issue. A U.S. Court of Appeals, District of Columbia Circuit, in early August ruled that patients do not have a constitutional right to unapproved drugs, in a suit brought by the Abigail Alliance for Better Access to Developmental Drugs. The Alliance has vowed to appeal.

Dendreon announced that the FDA had decided to accept either a positive interim or final analysis of survival from its ongoing, phase III, 500-patient IMPACT study as the basis for amending the Biologics License Application that was filed on a fast-track basis in early 2007, possibly paving the way for approval as soon as 2008.

Activists demand FDA approval of Provenge during a Sept. 18 protest in front of the agency's offices in Rockville, Md. Sheri Mattes/Elsevier Global Medical News

Controversy is a fact of life for pharmaceutical companies and the Food and Drug Administration but the saga of an investigative immunotherapeutic agent for advanced prostate cancer has been unusually contentious.

The struggle to gain FDA approval for sipuleucel-T, to be marketed as Provenge by Dendreon Corp., has included a raucous FDA meeting, picketing in Washington, congressional lobbying, and a lawsuit.

A final decision about whether to approve the drug now awaits interim findings from a 500-patient phase III trial, but in the meantime, the dispute has ignited activism reminiscent of the efforts to get HIV drugs “fast tracked” in the 1980s.

The dispute has raised questions about whether biologic agents can be judged by the same efficacy standards as traditional drugs, particularly when the goal is to treat terminal patients with few alternatives.

It has also generated concern in some scientists about the increasing influence of “antiscience” voices in American life. And finally, it has highlighted media pressure on the scientific community to justify established principles guiding medical policy decisions in the face of tearful families and angry investor campaigns.

It began March 29, when officials of the Seattle-based biotech firm presented to the FDA's Cellular, Tissue, and Gene Therapies Advisory Committee the results of two fast-tracked, phase III parallel studies of their biologic agent in a total of 225 men with asymptomatic, hormone-refractory, metastatic prostate cancer.

Sipuleucel-T would be the first oncologic drug in a new class, designed to stimulate a patient's immune system with a “vaccine” made from his own peripheral blood mononuclear cells, including antigen-presenting cells. The cells would be extracted by plasmapheresis and flown to a centralized laboratory, where they are activated with a recombinant fusion protein containing prostate antigen fused to GM-CSF, an immune cell activator. Within 3 days of collection, the cells are reinfused into the patient in an outpatient procedure.

After the March meeting, at least two committee members, oncologist Howard I. Scher of Memorial Sloan-Kettering Cancer Center, New York, and Dr. Maha Hussain, professor of internal medicine and urology at the University of Michigan, Ann Arbor, wrote to the FDA to express concern about the implications of approving the drug based on the evidence. The letters were leaked and reprinted, first in The Cancer Letter, then online.

Dr. Scher said inconsistent trial data “do not constitute 'proof' of benefit or justify a conclusion that they are 'reasonably likely' to predict benefit. … The only conclusion is that the survival difference observed may have occurred by chance alone.”

The company had argued that the survival results were “clinically meaningful, significantly persuasive, and internally consistent in the intent-to-treat population.”

A 4.5-month survival benefit from a drug with few side effects is urgently needed by prostate cancer patients, who now gain only about a 2-month survival advantage from docetaxel (Taxotere), a drug with side effects that many patients find debilitating.

On May 9, the FDA rejected the committee suggestion to approve sipuleucel-T, requesting more data from Dendreon.

The decision sparked a debate about whether the FDA's restraint represented a scientifically valid concern about the efficacy of a treatment that failed to pass muster in clinical trials, or a risk-averse philosophy depriving patients of treatments that offer them their only hope of prolonged survival.

Within the month, Dr. David Penson of the University of Southern California, Los Angeles, presided over a press briefing at the annual meeting of the American Urological Association marked by frustration about the decision. He listed three reasons the FDA might reject a recommendation to approve a drug: safety, efficacy, and politics. “[We] were really hoping this would be approved, because these patients have so few other options,” he said.

After the July 30 filing of a federal lawsuit by Care to Live, an Ohio nonprofit organization seeking an emergency injunction that would make the drug available to cancer patients, an FDA spokeswoman said the agency could no longer comment on the issue. A U.S. Court of Appeals, District of Columbia Circuit, in early August ruled that patients do not have a constitutional right to unapproved drugs, in a suit brought by the Abigail Alliance for Better Access to Developmental Drugs. The Alliance has vowed to appeal.

Dendreon announced that the FDA had decided to accept either a positive interim or final analysis of survival from its ongoing, phase III, 500-patient IMPACT study as the basis for amending the Biologics License Application that was filed on a fast-track basis in early 2007, possibly paving the way for approval as soon as 2008.

Activists demand FDA approval of Provenge during a Sept. 18 protest in front of the agency's offices in Rockville, Md. Sheri Mattes/Elsevier Global Medical News