Melanoma

SAN ANTONIO — The use of total body photography as a surveillance tool for melanoma has great potential to reduce the number of unnecessary biopsies, Dr. Allan C. Halpern said at the annual meeting of the American Academy of Dermatology.

When used appropriately in conjunction with self-examination and regular follow-up, total body photography (TBP) can also increase the likelihood of detecting thinner melanomas, said Dr. Halpern, chief of dermatology at Memorial Sloan-Kettering Cancer Center, New York.

Although it does have some disadvantages—namely the possibility of raising the threshold for removal of lesions in favor of follow-up in patients who may not return for follow-up—it also has a number of possible advantages for both patients and physicians, he said.

The key is to use TBP cautiously. The first visit is not the time to raise the threshold for removing a suspicious lesion in anticipation of using TBP for surveillance. Instead, build a relationship before relying on the patient to perform self-evaluations and come in for routine follow-up visits. Once a relationship is established and the patient is compliant, TBP can be a great tool for engaging patients in their own care and increasing patient satisfaction, he noted.

The sensitivity and specificity of TBP for melanoma are increased in those who do come back. Studies have shown that patients who are engaged in their care because they receive copies of the photos and are asked to do monthly self-examinations by comparing lesions with the photos are more likely to do self-examinations and are more likely to be effective when performing self-examinations than are patients who do not receive photos, Dr. Halpern said.

As a result, the use of TBP is increasing. A survey of AAD members showed 63% of 105 residency programs use TBP and 49% of AAD members use it at least some of the time in patients with dysplastic nevi. Furthermore, 83% of programs with specialized pigmented lesions clinics and 49% of those without such a clinic are using TBP.

Those who don't use TBP cite perceived logistical difficulties, financial constraints, and doubt about its benefits as reasons for not using it, he said.

The use of TBP requires only a digital camera of at least 6–12 megapixels (although he uses one with 40 megapixels), a computer, and a space with good lighting and the availability of a blue or black backdrop, Dr. Halpern explained, also noting that a CPT code for TBP exists.

As for benefits, one small study showed no difference in detection of melanoma for those who used and didn't use TBP. It did show an increase in sensitivity and specificity for detection of nonmelanomas, and another showed that twice as many patients who received photos were compliant with recommended care, including self-examination, than those who were not.

The actual taking of the photographs can be uncomfortable for the patient, so it is a good idea to perform a physical examination first. Dr. Halpern always starts with the patient facing away from him to allow the patient time to acclimate to the discomfort of the situation and to allow himself time to regain composure before facing the patient should he encounter an alarming lesion.

Photos can be taken by the physician, a specially trained nurse, or a medical photographer. Some practices have a photographer on staff, and hospitals may employ photographers and be accommodating when it comes to TBP services. "You can achieve very high-quality pictures if you nail down a system and use it in a sufficiently standardized fashion," Dr. Halpern said, noting that there are papers in the literature to provide guidance for using TBP.

Basically, as much of the body surface as possible should be photographed, and positioning should be chosen to allow this.

Side-by-side (photos and patient) examinations can then be conducted at follow-up visits. He recommended examining patients while they are standing, which makes it easier to compare lesions against those in the photos.

Patient privacy needs to be carefully protected, so photos kept on office computers should be encrypted, he said.

Patients should be provided with hard copies and a compact disk along with a photo-marking pen that they can use to mark the photographs if they find something of concern on their monthly self-examination.

It is important to inform patients that their role in performing self-examinations is not meant to be anxiety provoking; rather it should be an exercise in becoming familiar with the big picture so they can recognize obvious changes and fast-growing lesions that might be of concern.

Dr. Halpern used a night-sky analogy to describe how patients should view their photos. If they become familiar with their own "constellations," they will notice when something new appears in the field, or if something other than the North Star is shining brightest. The patient's job is to notice the obvious changes; the physician's job is to find the subtle changes, he said.

As for which patients are the best candidates for TBP, he suggested using it for those with dysplastic nevi who have undergone many excisions and those with a familial or personal history of melanoma. No prospective data exist to guide how often patients should be seen, but every 6 months has been a good interval in Dr. Halpern's experience. "We do find the vast majority of melanomas in surveillance with these patients. … This is one of the major reasons for doing total body photograph."

Patients who receive copies of their photos, and are asked to do monthly self-exams, are more likely to do the exams and be effective in doing so, said Dr. Allan C. Halpern. Daphne Demas/MSKCC Dermatology

SAN ANTONIO — The use of total body photography as a surveillance tool for melanoma has great potential to reduce the number of unnecessary biopsies, Dr. Allan C. Halpern said at the annual meeting of the American Academy of Dermatology.

When used appropriately in conjunction with self-examination and regular follow-up, total body photography (TBP) can also increase the likelihood of detecting thinner melanomas, said Dr. Halpern, chief of dermatology at Memorial Sloan-Kettering Cancer Center, New York.

Although it does have some disadvantages—namely the possibility of raising the threshold for removal of lesions in favor of follow-up in patients who may not return for follow-up—it also has a number of possible advantages for both patients and physicians, he said.

The key is to use TBP cautiously. The first visit is not the time to raise the threshold for removing a suspicious lesion in anticipation of using TBP for surveillance. Instead, build a relationship before relying on the patient to perform self-evaluations and come in for routine follow-up visits. Once a relationship is established and the patient is compliant, TBP can be a great tool for engaging patients in their own care and increasing patient satisfaction, he noted.

The sensitivity and specificity of TBP for melanoma are increased in those who do come back. Studies have shown that patients who are engaged in their care because they receive copies of the photos and are asked to do monthly self-examinations by comparing lesions with the photos are more likely to do self-examinations and are more likely to be effective when performing self-examinations than are patients who do not receive photos, Dr. Halpern said.

As a result, the use of TBP is increasing. A survey of AAD members showed 63% of 105 residency programs use TBP and 49% of AAD members use it at least some of the time in patients with dysplastic nevi. Furthermore, 83% of programs with specialized pigmented lesions clinics and 49% of those without such a clinic are using TBP.

Those who don't use TBP cite perceived logistical difficulties, financial constraints, and doubt about its benefits as reasons for not using it, he said.

The use of TBP requires only a digital camera of at least 6–12 megapixels (although he uses one with 40 megapixels), a computer, and a space with good lighting and the availability of a blue or black backdrop, Dr. Halpern explained, also noting that a CPT code for TBP exists.

As for benefits, one small study showed no difference in detection of melanoma for those who used and didn't use TBP. It did show an increase in sensitivity and specificity for detection of nonmelanomas, and another showed that twice as many patients who received photos were compliant with recommended care, including self-examination, than those who were not.

The actual taking of the photographs can be uncomfortable for the patient, so it is a good idea to perform a physical examination first. Dr. Halpern always starts with the patient facing away from him to allow the patient time to acclimate to the discomfort of the situation and to allow himself time to regain composure before facing the patient should he encounter an alarming lesion.

Photos can be taken by the physician, a specially trained nurse, or a medical photographer. Some practices have a photographer on staff, and hospitals may employ photographers and be accommodating when it comes to TBP services. "You can achieve very high-quality pictures if you nail down a system and use it in a sufficiently standardized fashion," Dr. Halpern said, noting that there are papers in the literature to provide guidance for using TBP.

Basically, as much of the body surface as possible should be photographed, and positioning should be chosen to allow this.

Side-by-side (photos and patient) examinations can then be conducted at follow-up visits. He recommended examining patients while they are standing, which makes it easier to compare lesions against those in the photos.

Patient privacy needs to be carefully protected, so photos kept on office computers should be encrypted, he said.

Patients should be provided with hard copies and a compact disk along with a photo-marking pen that they can use to mark the photographs if they find something of concern on their monthly self-examination.

It is important to inform patients that their role in performing self-examinations is not meant to be anxiety provoking; rather it should be an exercise in becoming familiar with the big picture so they can recognize obvious changes and fast-growing lesions that might be of concern.

Dr. Halpern used a night-sky analogy to describe how patients should view their photos. If they become familiar with their own "constellations," they will notice when something new appears in the field, or if something other than the North Star is shining brightest. The patient's job is to notice the obvious changes; the physician's job is to find the subtle changes, he said.

As for which patients are the best candidates for TBP, he suggested using it for those with dysplastic nevi who have undergone many excisions and those with a familial or personal history of melanoma. No prospective data exist to guide how often patients should be seen, but every 6 months has been a good interval in Dr. Halpern's experience. "We do find the vast majority of melanomas in surveillance with these patients. … This is one of the major reasons for doing total body photograph."

Patients who receive copies of their photos, and are asked to do monthly self-exams, are more likely to do the exams and be effective in doing so, said Dr. Allan C. Halpern. Daphne Demas/MSKCC Dermatology

SAN ANTONIO — The use of total body photography as a surveillance tool for melanoma has great potential to reduce the number of unnecessary biopsies, Dr. Allan C. Halpern said at the annual meeting of the American Academy of Dermatology.

When used appropriately in conjunction with self-examination and regular follow-up, total body photography (TBP) can also increase the likelihood of detecting thinner melanomas, said Dr. Halpern, chief of dermatology at Memorial Sloan-Kettering Cancer Center, New York.

Although it does have some disadvantages—namely the possibility of raising the threshold for removal of lesions in favor of follow-up in patients who may not return for follow-up—it also has a number of possible advantages for both patients and physicians, he said.

The key is to use TBP cautiously. The first visit is not the time to raise the threshold for removing a suspicious lesion in anticipation of using TBP for surveillance. Instead, build a relationship before relying on the patient to perform self-evaluations and come in for routine follow-up visits. Once a relationship is established and the patient is compliant, TBP can be a great tool for engaging patients in their own care and increasing patient satisfaction, he noted.

The sensitivity and specificity of TBP for melanoma are increased in those who do come back. Studies have shown that patients who are engaged in their care because they receive copies of the photos and are asked to do monthly self-examinations by comparing lesions with the photos are more likely to do self-examinations and are more likely to be effective when performing self-examinations than are patients who do not receive photos, Dr. Halpern said.

As a result, the use of TBP is increasing. A survey of AAD members showed 63% of 105 residency programs use TBP and 49% of AAD members use it at least some of the time in patients with dysplastic nevi. Furthermore, 83% of programs with specialized pigmented lesions clinics and 49% of those without such a clinic are using TBP.

Those who don't use TBP cite perceived logistical difficulties, financial constraints, and doubt about its benefits as reasons for not using it, he said.

The use of TBP requires only a digital camera of at least 6–12 megapixels (although he uses one with 40 megapixels), a computer, and a space with good lighting and the availability of a blue or black backdrop, Dr. Halpern explained, also noting that a CPT code for TBP exists.

As for benefits, one small study showed no difference in detection of melanoma for those who used and didn't use TBP. It did show an increase in sensitivity and specificity for detection of nonmelanomas, and another showed that twice as many patients who received photos were compliant with recommended care, including self-examination, than those who were not.

The actual taking of the photographs can be uncomfortable for the patient, so it is a good idea to perform a physical examination first. Dr. Halpern always starts with the patient facing away from him to allow the patient time to acclimate to the discomfort of the situation and to allow himself time to regain composure before facing the patient should he encounter an alarming lesion.

Photos can be taken by the physician, a specially trained nurse, or a medical photographer. Some practices have a photographer on staff, and hospitals may employ photographers and be accommodating when it comes to TBP services. "You can achieve very high-quality pictures if you nail down a system and use it in a sufficiently standardized fashion," Dr. Halpern said, noting that there are papers in the literature to provide guidance for using TBP.

Basically, as much of the body surface as possible should be photographed, and positioning should be chosen to allow this.

Side-by-side (photos and patient) examinations can then be conducted at follow-up visits. He recommended examining patients while they are standing, which makes it easier to compare lesions against those in the photos.

Patient privacy needs to be carefully protected, so photos kept on office computers should be encrypted, he said.

Patients should be provided with hard copies and a compact disk along with a photo-marking pen that they can use to mark the photographs if they find something of concern on their monthly self-examination.

It is important to inform patients that their role in performing self-examinations is not meant to be anxiety provoking; rather it should be an exercise in becoming familiar with the big picture so they can recognize obvious changes and fast-growing lesions that might be of concern.

Dr. Halpern used a night-sky analogy to describe how patients should view their photos. If they become familiar with their own "constellations," they will notice when something new appears in the field, or if something other than the North Star is shining brightest. The patient's job is to notice the obvious changes; the physician's job is to find the subtle changes, he said.

As for which patients are the best candidates for TBP, he suggested using it for those with dysplastic nevi who have undergone many excisions and those with a familial or personal history of melanoma. No prospective data exist to guide how often patients should be seen, but every 6 months has been a good interval in Dr. Halpern's experience. "We do find the vast majority of melanomas in surveillance with these patients. … This is one of the major reasons for doing total body photograph."

Patients who receive copies of their photos, and are asked to do monthly self-exams, are more likely to do the exams and be effective in doing so, said Dr. Allan C. Halpern. Daphne Demas/MSKCC Dermatology

SAN DIEGO — Extracutaneous melanomas are rare—they make up only 15% of all melanomas—but small primary lesions can be easily overlooked during a routine skin exam, according to one expert.

Sites that require close inspection include the scalp, nail beds, interdigital folds, and perianal skin. These areas "are easily accessible to clinical exam and can make a big difference for your patients," Dr. Terence C. O'Grady said at an update on melanoma sponsored by the Scripps Clinic.

The most commonly affected sites for extracutaneous melanoma include the ocular or juxtacutaneous mucosal membranes, said Dr. O'Grady, who directs the dermatology residency program at the University of California, San Diego.

The three most common metastatic locations include the lungs (70%), the liver (68%), and the bowels (58%). Other sites include the pancreas (50%), the adrenal gland (50%), the heart (49%), kidneys (45%), brain (39%), thyroid (39%), and spleen (36%), he said.

Melanoma can metastasize to these sites in a number of ways. A melanoma could have been completely removed without histologic examination.

"You could also have a completely regressed melanoma at another site that was not treated," he said.

"This can be a real problem because there is no evidence of a pre-existing lesion. In our clinic, if we don't see a primary lesion we do a Wood's light exam and look for hypopigmented areas that may represent previously regressed lesions. Unfortunately, when you biopsy these regressed areas, the only thing you usually see is pigment incontinence on the histology, so there's no evidence that the melanoma was ever there," Dr. O'Grady said.

Because it's rare to find primary melanomas in these locations, he continued, "it's more probable that these lesions are metastatic to that site rather than being a primary lesion."

The five most common locations of primary extracutaneous melanoma include the eye (79%), the vulva (7%), soft tissues (3%), anorectum (2%), and the vagina (2%), according to Dr. O'Grady. "Many of us loathe to do an exam of the genitalia, but [lesions in this area] do occur," he said. "I usually tell patients that have had a melanoma or are at high risk for melanoma to bring this point up with other physicians they [may see], so they can have those areas examined."

Dr. O'Grady said that he begins his skin examinations at the scalp and works his way down to the feet.

"I always tell patients who wear nail polish to have that removed for the exam so I can see the nail bed," he said. "I look at the interdigital folds and at the bottom of the feet. Patients always wonder, 'What are you looking for in between my toes?' I tell them, 'You can get pigmented lesions in those areas. You can also get melanomas in those areas.'"

He also emphasized the importance of biopsying lesions detected in subungual areas. "These lesions can be impossible to diagnose without a biopsy, but a lot of [clinicians] don't feel comfortably doing a nail biopsy," said Dr. O'Grady.

"Not only is that a problem, but when you send it to pathology and you don't have someone who knows how to handle nail specimens, you're going to end up with a very nondiagnostic specimen. You want to see the skin on top of the nail, the nail plate, and the subungual tissue," he said.

SAN DIEGO — Extracutaneous melanomas are rare—they make up only 15% of all melanomas—but small primary lesions can be easily overlooked during a routine skin exam, according to one expert.

Sites that require close inspection include the scalp, nail beds, interdigital folds, and perianal skin. These areas "are easily accessible to clinical exam and can make a big difference for your patients," Dr. Terence C. O'Grady said at an update on melanoma sponsored by the Scripps Clinic.

The most commonly affected sites for extracutaneous melanoma include the ocular or juxtacutaneous mucosal membranes, said Dr. O'Grady, who directs the dermatology residency program at the University of California, San Diego.

The three most common metastatic locations include the lungs (70%), the liver (68%), and the bowels (58%). Other sites include the pancreas (50%), the adrenal gland (50%), the heart (49%), kidneys (45%), brain (39%), thyroid (39%), and spleen (36%), he said.

Melanoma can metastasize to these sites in a number of ways. A melanoma could have been completely removed without histologic examination.

"You could also have a completely regressed melanoma at another site that was not treated," he said.

"This can be a real problem because there is no evidence of a pre-existing lesion. In our clinic, if we don't see a primary lesion we do a Wood's light exam and look for hypopigmented areas that may represent previously regressed lesions. Unfortunately, when you biopsy these regressed areas, the only thing you usually see is pigment incontinence on the histology, so there's no evidence that the melanoma was ever there," Dr. O'Grady said.

Because it's rare to find primary melanomas in these locations, he continued, "it's more probable that these lesions are metastatic to that site rather than being a primary lesion."

The five most common locations of primary extracutaneous melanoma include the eye (79%), the vulva (7%), soft tissues (3%), anorectum (2%), and the vagina (2%), according to Dr. O'Grady. "Many of us loathe to do an exam of the genitalia, but [lesions in this area] do occur," he said. "I usually tell patients that have had a melanoma or are at high risk for melanoma to bring this point up with other physicians they [may see], so they can have those areas examined."

Dr. O'Grady said that he begins his skin examinations at the scalp and works his way down to the feet.

"I always tell patients who wear nail polish to have that removed for the exam so I can see the nail bed," he said. "I look at the interdigital folds and at the bottom of the feet. Patients always wonder, 'What are you looking for in between my toes?' I tell them, 'You can get pigmented lesions in those areas. You can also get melanomas in those areas.'"

He also emphasized the importance of biopsying lesions detected in subungual areas. "These lesions can be impossible to diagnose without a biopsy, but a lot of [clinicians] don't feel comfortably doing a nail biopsy," said Dr. O'Grady.

"Not only is that a problem, but when you send it to pathology and you don't have someone who knows how to handle nail specimens, you're going to end up with a very nondiagnostic specimen. You want to see the skin on top of the nail, the nail plate, and the subungual tissue," he said.

SAN DIEGO — Extracutaneous melanomas are rare—they make up only 15% of all melanomas—but small primary lesions can be easily overlooked during a routine skin exam, according to one expert.

Sites that require close inspection include the scalp, nail beds, interdigital folds, and perianal skin. These areas "are easily accessible to clinical exam and can make a big difference for your patients," Dr. Terence C. O'Grady said at an update on melanoma sponsored by the Scripps Clinic.

The most commonly affected sites for extracutaneous melanoma include the ocular or juxtacutaneous mucosal membranes, said Dr. O'Grady, who directs the dermatology residency program at the University of California, San Diego.

The three most common metastatic locations include the lungs (70%), the liver (68%), and the bowels (58%). Other sites include the pancreas (50%), the adrenal gland (50%), the heart (49%), kidneys (45%), brain (39%), thyroid (39%), and spleen (36%), he said.

Melanoma can metastasize to these sites in a number of ways. A melanoma could have been completely removed without histologic examination.

"You could also have a completely regressed melanoma at another site that was not treated," he said.

"This can be a real problem because there is no evidence of a pre-existing lesion. In our clinic, if we don't see a primary lesion we do a Wood's light exam and look for hypopigmented areas that may represent previously regressed lesions. Unfortunately, when you biopsy these regressed areas, the only thing you usually see is pigment incontinence on the histology, so there's no evidence that the melanoma was ever there," Dr. O'Grady said.

Because it's rare to find primary melanomas in these locations, he continued, "it's more probable that these lesions are metastatic to that site rather than being a primary lesion."

The five most common locations of primary extracutaneous melanoma include the eye (79%), the vulva (7%), soft tissues (3%), anorectum (2%), and the vagina (2%), according to Dr. O'Grady. "Many of us loathe to do an exam of the genitalia, but [lesions in this area] do occur," he said. "I usually tell patients that have had a melanoma or are at high risk for melanoma to bring this point up with other physicians they [may see], so they can have those areas examined."

Dr. O'Grady said that he begins his skin examinations at the scalp and works his way down to the feet.

"I always tell patients who wear nail polish to have that removed for the exam so I can see the nail bed," he said. "I look at the interdigital folds and at the bottom of the feet. Patients always wonder, 'What are you looking for in between my toes?' I tell them, 'You can get pigmented lesions in those areas. You can also get melanomas in those areas.'"

He also emphasized the importance of biopsying lesions detected in subungual areas. "These lesions can be impossible to diagnose without a biopsy, but a lot of [clinicians] don't feel comfortably doing a nail biopsy," said Dr. O'Grady.

"Not only is that a problem, but when you send it to pathology and you don't have someone who knows how to handle nail specimens, you're going to end up with a very nondiagnostic specimen. You want to see the skin on top of the nail, the nail plate, and the subungual tissue," he said.

WAIKOLOA, HAWAII — Dermatologic surveillance following diagnosis of a primary melanoma is often overly intensive, Dr. Daniel G. Coit asserted at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

"The key recommendation for melanoma patients is that they ought to go on lifetime dermatologic surveillance. But I'm here to help you, not to hurt you. We find a lot of patients who are fairly low risk undergoing dermatologic surveillance every 3 months for the rest of their lives. I think this needlessly imposes an unreasonable burden on the shoulders of my teammates in dermatology," noted Dr. Coit, a surgeon who is coleader of the melanoma disease management team at Memorial Sloan-Kettering Cancer Center in New York and a member of the American Joint Committee on Cancer melanoma staging committee.

"You don't need to follow up everybody three or four times a year," he emphasized. Indeed, annual skin surveillance is entirely appropriate in melanoma patients who are not in a subgroup at elevated risk for another primary melanoma, he said.

And who are these high-risk subgroups? Most notably, melanoma patients who have dysplastic nevi, who have a positive family history for melanoma, or who have already been diagnosed with a second primary tumor, Dr. Coit continued.

Several years ago he and his Sloan-Kettering colleagues examined this issue of second primary melanomas in detail. They reported on 4,484 patients with primary melanoma followed prospectively at the tertiary cancer center; 8.6% went on to have two or more primary melanomas. Patients with more than one primary melanoma averaged 2.3.

The estimated cumulative 5-year risk of a second primary melanoma was 11.4%. Fifty-nine percent of patients presented with their second primary tumor within 1 year of their first. After that first year, the incidence in patients without a family history of dysplastic nevi leveled off at about 0.3% per year, less than many physicians might expect. Interestingly, that low long-term annual rate was quite similar to the figure reported in an earlier analysis of the Duke University (Durham, N.C.) melanoma database, Dr. Coit noted (Surgery 1993;113:330–9).

Not only were the majority of second primary melanomas detected during the first year of surveillance in the Sloan-Kettering series, but most of those diagnosed in the first year were found at the time the initial primary was diagnosed.

"With the heightened awareness created by finding a primary melanoma, these patients undergo a complete and very thorough review, and other suspicious lesions are biopsied. After that the slope of the curve [of incident second primary melanoma] is actually pretty flat," according to Dr. Coit.

This was not the case, however, in the high-risk subgroups. In such patients, a case can be made for lifetime dermatologic surveillance more often than annually, he said.

In the Sloan-Kettering study, the subgroup of melanoma patients at highest risk of another primary tumor consisted of patients who had already been diagnosed with a second primary melanoma; they had a 15.6% incidence of a third primary tumor within 1 year of their second and a 31% probability of developing a third primary within 5 years (JAMA 2005;294:1647–54).

Forty-nine percent of patients had their second primary melanoma on the same body site as their first. The greatest site concordance was 60% for lesions on the extremities.

Dr. Keith T. Flaherty observed that the risk over time is not linear. It depends, instead, upon the stage of the first primary melanoma. The risk is greatest early on for those with high-risk disease and much more spread out over time in patients with early-stage disease.

"That needs to inform our surveillance," said Dr. Flaherty, who is a medical oncologist at the University of Pennsylvania in Philadelphia.

Dr. Coit concurred. "I'd go so far as to say that almost no one with early-stage disease recurs early, and almost no one with late-stage disease recurs late," he added.

Skin Disease Education Foundation and this news organization are wholly owned subsidiaries of Elsevier.

WAIKOLOA, HAWAII — Dermatologic surveillance following diagnosis of a primary melanoma is often overly intensive, Dr. Daniel G. Coit asserted at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

"The key recommendation for melanoma patients is that they ought to go on lifetime dermatologic surveillance. But I'm here to help you, not to hurt you. We find a lot of patients who are fairly low risk undergoing dermatologic surveillance every 3 months for the rest of their lives. I think this needlessly imposes an unreasonable burden on the shoulders of my teammates in dermatology," noted Dr. Coit, a surgeon who is coleader of the melanoma disease management team at Memorial Sloan-Kettering Cancer Center in New York and a member of the American Joint Committee on Cancer melanoma staging committee.

"You don't need to follow up everybody three or four times a year," he emphasized. Indeed, annual skin surveillance is entirely appropriate in melanoma patients who are not in a subgroup at elevated risk for another primary melanoma, he said.

And who are these high-risk subgroups? Most notably, melanoma patients who have dysplastic nevi, who have a positive family history for melanoma, or who have already been diagnosed with a second primary tumor, Dr. Coit continued.

Several years ago he and his Sloan-Kettering colleagues examined this issue of second primary melanomas in detail. They reported on 4,484 patients with primary melanoma followed prospectively at the tertiary cancer center; 8.6% went on to have two or more primary melanomas. Patients with more than one primary melanoma averaged 2.3.

The estimated cumulative 5-year risk of a second primary melanoma was 11.4%. Fifty-nine percent of patients presented with their second primary tumor within 1 year of their first. After that first year, the incidence in patients without a family history of dysplastic nevi leveled off at about 0.3% per year, less than many physicians might expect. Interestingly, that low long-term annual rate was quite similar to the figure reported in an earlier analysis of the Duke University (Durham, N.C.) melanoma database, Dr. Coit noted (Surgery 1993;113:330–9).

Not only were the majority of second primary melanomas detected during the first year of surveillance in the Sloan-Kettering series, but most of those diagnosed in the first year were found at the time the initial primary was diagnosed.

"With the heightened awareness created by finding a primary melanoma, these patients undergo a complete and very thorough review, and other suspicious lesions are biopsied. After that the slope of the curve [of incident second primary melanoma] is actually pretty flat," according to Dr. Coit.

This was not the case, however, in the high-risk subgroups. In such patients, a case can be made for lifetime dermatologic surveillance more often than annually, he said.

In the Sloan-Kettering study, the subgroup of melanoma patients at highest risk of another primary tumor consisted of patients who had already been diagnosed with a second primary melanoma; they had a 15.6% incidence of a third primary tumor within 1 year of their second and a 31% probability of developing a third primary within 5 years (JAMA 2005;294:1647–54).

Forty-nine percent of patients had their second primary melanoma on the same body site as their first. The greatest site concordance was 60% for lesions on the extremities.

Dr. Keith T. Flaherty observed that the risk over time is not linear. It depends, instead, upon the stage of the first primary melanoma. The risk is greatest early on for those with high-risk disease and much more spread out over time in patients with early-stage disease.

"That needs to inform our surveillance," said Dr. Flaherty, who is a medical oncologist at the University of Pennsylvania in Philadelphia.

Dr. Coit concurred. "I'd go so far as to say that almost no one with early-stage disease recurs early, and almost no one with late-stage disease recurs late," he added.

Skin Disease Education Foundation and this news organization are wholly owned subsidiaries of Elsevier.

WAIKOLOA, HAWAII — Dermatologic surveillance following diagnosis of a primary melanoma is often overly intensive, Dr. Daniel G. Coit asserted at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

"The key recommendation for melanoma patients is that they ought to go on lifetime dermatologic surveillance. But I'm here to help you, not to hurt you. We find a lot of patients who are fairly low risk undergoing dermatologic surveillance every 3 months for the rest of their lives. I think this needlessly imposes an unreasonable burden on the shoulders of my teammates in dermatology," noted Dr. Coit, a surgeon who is coleader of the melanoma disease management team at Memorial Sloan-Kettering Cancer Center in New York and a member of the American Joint Committee on Cancer melanoma staging committee.

"You don't need to follow up everybody three or four times a year," he emphasized. Indeed, annual skin surveillance is entirely appropriate in melanoma patients who are not in a subgroup at elevated risk for another primary melanoma, he said.

And who are these high-risk subgroups? Most notably, melanoma patients who have dysplastic nevi, who have a positive family history for melanoma, or who have already been diagnosed with a second primary tumor, Dr. Coit continued.

Several years ago he and his Sloan-Kettering colleagues examined this issue of second primary melanomas in detail. They reported on 4,484 patients with primary melanoma followed prospectively at the tertiary cancer center; 8.6% went on to have two or more primary melanomas. Patients with more than one primary melanoma averaged 2.3.

The estimated cumulative 5-year risk of a second primary melanoma was 11.4%. Fifty-nine percent of patients presented with their second primary tumor within 1 year of their first. After that first year, the incidence in patients without a family history of dysplastic nevi leveled off at about 0.3% per year, less than many physicians might expect. Interestingly, that low long-term annual rate was quite similar to the figure reported in an earlier analysis of the Duke University (Durham, N.C.) melanoma database, Dr. Coit noted (Surgery 1993;113:330–9).

Not only were the majority of second primary melanomas detected during the first year of surveillance in the Sloan-Kettering series, but most of those diagnosed in the first year were found at the time the initial primary was diagnosed.

"With the heightened awareness created by finding a primary melanoma, these patients undergo a complete and very thorough review, and other suspicious lesions are biopsied. After that the slope of the curve [of incident second primary melanoma] is actually pretty flat," according to Dr. Coit.

This was not the case, however, in the high-risk subgroups. In such patients, a case can be made for lifetime dermatologic surveillance more often than annually, he said.

In the Sloan-Kettering study, the subgroup of melanoma patients at highest risk of another primary tumor consisted of patients who had already been diagnosed with a second primary melanoma; they had a 15.6% incidence of a third primary tumor within 1 year of their second and a 31% probability of developing a third primary within 5 years (JAMA 2005;294:1647–54).

Forty-nine percent of patients had their second primary melanoma on the same body site as their first. The greatest site concordance was 60% for lesions on the extremities.

Dr. Keith T. Flaherty observed that the risk over time is not linear. It depends, instead, upon the stage of the first primary melanoma. The risk is greatest early on for those with high-risk disease and much more spread out over time in patients with early-stage disease.

"That needs to inform our surveillance," said Dr. Flaherty, who is a medical oncologist at the University of Pennsylvania in Philadelphia.

Dr. Coit concurred. "I'd go so far as to say that almost no one with early-stage disease recurs early, and almost no one with late-stage disease recurs late," he added.

Skin Disease Education Foundation and this news organization are wholly owned subsidiaries of Elsevier.

Azadeh Esmaeili, MS, IV, Alon Scope, MD, Allan C. Halpern, MD, and Ashfaq A. Marghoob, MD

The ability to detect early melanoma remains of paramount importance in our efforts to curtail deaths related to this malignancy. Fortunately, our clinical skills at recognizing the varied clinical presentation of early melanomas are continuously improving. Our enhanced clinical acumen together with improved awareness of the danger signs of melanoma has resulted in a greater proportion of thin melanomas being diagnosed today as compared to the past. The implementation and utilization of in vivo imaging technologies in clinical practice promises to further enhance our ability to detect melanoma while this cancer is still thin and easily curable. This article describes the utility and application of the in vivo imaging technologies that are currently in clinical use today including dermoscopy, total body photography, individual lesion photography, and reflectance confocal microscopy.

*For a PDF of the full article, click on the link to the left of this introduction.

Azadeh Esmaeili, MS, IV, Alon Scope, MD, Allan C. Halpern, MD, and Ashfaq A. Marghoob, MD

The ability to detect early melanoma remains of paramount importance in our efforts to curtail deaths related to this malignancy. Fortunately, our clinical skills at recognizing the varied clinical presentation of early melanomas are continuously improving. Our enhanced clinical acumen together with improved awareness of the danger signs of melanoma has resulted in a greater proportion of thin melanomas being diagnosed today as compared to the past. The implementation and utilization of in vivo imaging technologies in clinical practice promises to further enhance our ability to detect melanoma while this cancer is still thin and easily curable. This article describes the utility and application of the in vivo imaging technologies that are currently in clinical use today including dermoscopy, total body photography, individual lesion photography, and reflectance confocal microscopy.

*For a PDF of the full article, click on the link to the left of this introduction.

Azadeh Esmaeili, MS, IV, Alon Scope, MD, Allan C. Halpern, MD, and Ashfaq A. Marghoob, MD

The ability to detect early melanoma remains of paramount importance in our efforts to curtail deaths related to this malignancy. Fortunately, our clinical skills at recognizing the varied clinical presentation of early melanomas are continuously improving. Our enhanced clinical acumen together with improved awareness of the danger signs of melanoma has resulted in a greater proportion of thin melanomas being diagnosed today as compared to the past. The implementation and utilization of in vivo imaging technologies in clinical practice promises to further enhance our ability to detect melanoma while this cancer is still thin and easily curable. This article describes the utility and application of the in vivo imaging technologies that are currently in clinical use today including dermoscopy, total body photography, individual lesion photography, and reflectance confocal microscopy.

*For a PDF of the full article, click on the link to the left of this introduction.

Andreas Blum, MD, Iris Zalaudek, MD, and Giuseppe Argenziano, MD

Between 1987 and 2007, different groups developed digital image analysis systems for the diagnosis of benign and malignant skin tumors. As the result of significant differences in the technical devices, the number, the nature and benign/malignant ratio of included skin tumors, different variables and statistical methods any comparison of these different systems and their results is difficult. For the use and comparison of the diagnostic performance of different digital image analysis systems in the future, some principle basic conditions are required: All used systems should have a standardized recording system and calibration. First, melanocytic and nonmelanocytic lesions should be included for the development of the diagnostic algorithms. Critical analyses of the results should answer the question if in future only melanocytic lesions should be analyzed or all pigmented and nonpigmented lesions. This will also lead to the answer if only dermatologists or all specialities of medical doctors will use such a system. All artifacts (eg, hairs, air bubbles) should be removed. The number of variables should be chosen according to the number of included melanomas. A high number of benign skin lesions should be included. Of all lesions only 10% or better less should be invasive melanomas. Each system should be developed by a training-set and controlled by an independent test-set. Each system should be controlled by the user with the final decision and responsibility and tested by independent users without any conflict of financial interest.

*For a PDF of the full article, click on the link to the left of this introduction.

Andreas Blum, MD, Iris Zalaudek, MD, and Giuseppe Argenziano, MD

Between 1987 and 2007, different groups developed digital image analysis systems for the diagnosis of benign and malignant skin tumors. As the result of significant differences in the technical devices, the number, the nature and benign/malignant ratio of included skin tumors, different variables and statistical methods any comparison of these different systems and their results is difficult. For the use and comparison of the diagnostic performance of different digital image analysis systems in the future, some principle basic conditions are required: All used systems should have a standardized recording system and calibration. First, melanocytic and nonmelanocytic lesions should be included for the development of the diagnostic algorithms. Critical analyses of the results should answer the question if in future only melanocytic lesions should be analyzed or all pigmented and nonpigmented lesions. This will also lead to the answer if only dermatologists or all specialities of medical doctors will use such a system. All artifacts (eg, hairs, air bubbles) should be removed. The number of variables should be chosen according to the number of included melanomas. A high number of benign skin lesions should be included. Of all lesions only 10% or better less should be invasive melanomas. Each system should be developed by a training-set and controlled by an independent test-set. Each system should be controlled by the user with the final decision and responsibility and tested by independent users without any conflict of financial interest.

*For a PDF of the full article, click on the link to the left of this introduction.

Andreas Blum, MD, Iris Zalaudek, MD, and Giuseppe Argenziano, MD

Between 1987 and 2007, different groups developed digital image analysis systems for the diagnosis of benign and malignant skin tumors. As the result of significant differences in the technical devices, the number, the nature and benign/malignant ratio of included skin tumors, different variables and statistical methods any comparison of these different systems and their results is difficult. For the use and comparison of the diagnostic performance of different digital image analysis systems in the future, some principle basic conditions are required: All used systems should have a standardized recording system and calibration. First, melanocytic and nonmelanocytic lesions should be included for the development of the diagnostic algorithms. Critical analyses of the results should answer the question if in future only melanocytic lesions should be analyzed or all pigmented and nonpigmented lesions. This will also lead to the answer if only dermatologists or all specialities of medical doctors will use such a system. All artifacts (eg, hairs, air bubbles) should be removed. The number of variables should be chosen according to the number of included melanomas. A high number of benign skin lesions should be included. Of all lesions only 10% or better less should be invasive melanomas. Each system should be developed by a training-set and controlled by an independent test-set. Each system should be controlled by the user with the final decision and responsibility and tested by independent users without any conflict of financial interest.

*For a PDF of the full article, click on the link to the left of this introduction.

Malene E. Vestergaard, MD, and Scott W. Menzies, MB, BS, PhD

The objective of this review is to report and discuss the evidence for fully automated diagnostic instruments for cutaneous melanoma tested in a real-world clinical setting directly compared with human diagnosis.  A systematic review was performed and articles excluded when studies did not report sensitivity or specificity for melanoma directly compared with humans on an independent test set.  Only 3 instruments have had their diagnostic accuracy compared with a human diagnosis in the clinical field with a meaningful sample size that could allow some generalization with the wider clinical arena.  Two of these instruments showed a significantly inferior specificity for the diagnosis of melanoma compared with specialists.  In one of these studies, the sensitivity for diagnosis, although superior to the specialist diagnosis, did not reach statistical significance. In contrast, one instrument had an equivalent specificity and trended superior but not significantly for sensitivity for the diagnosis of melanoma. Other image based non clinic studies and studies comparing clinical management as the endpoint rather than diagnosis are also reviewed.

*For a PDF of the full article, click on the link to the left of this introduction.

Malene E. Vestergaard, MD, and Scott W. Menzies, MB, BS, PhD

The objective of this review is to report and discuss the evidence for fully automated diagnostic instruments for cutaneous melanoma tested in a real-world clinical setting directly compared with human diagnosis.  A systematic review was performed and articles excluded when studies did not report sensitivity or specificity for melanoma directly compared with humans on an independent test set.  Only 3 instruments have had their diagnostic accuracy compared with a human diagnosis in the clinical field with a meaningful sample size that could allow some generalization with the wider clinical arena.  Two of these instruments showed a significantly inferior specificity for the diagnosis of melanoma compared with specialists.  In one of these studies, the sensitivity for diagnosis, although superior to the specialist diagnosis, did not reach statistical significance. In contrast, one instrument had an equivalent specificity and trended superior but not significantly for sensitivity for the diagnosis of melanoma. Other image based non clinic studies and studies comparing clinical management as the endpoint rather than diagnosis are also reviewed.

*For a PDF of the full article, click on the link to the left of this introduction.

Malene E. Vestergaard, MD, and Scott W. Menzies, MB, BS, PhD

The objective of this review is to report and discuss the evidence for fully automated diagnostic instruments for cutaneous melanoma tested in a real-world clinical setting directly compared with human diagnosis.  A systematic review was performed and articles excluded when studies did not report sensitivity or specificity for melanoma directly compared with humans on an independent test set.  Only 3 instruments have had their diagnostic accuracy compared with a human diagnosis in the clinical field with a meaningful sample size that could allow some generalization with the wider clinical arena.  Two of these instruments showed a significantly inferior specificity for the diagnosis of melanoma compared with specialists.  In one of these studies, the sensitivity for diagnosis, although superior to the specialist diagnosis, did not reach statistical significance. In contrast, one instrument had an equivalent specificity and trended superior but not significantly for sensitivity for the diagnosis of melanoma. Other image based non clinic studies and studies comparing clinical management as the endpoint rather than diagnosis are also reviewed.

*For a PDF of the full article, click on the link to the left of this introduction.

Mollie A. MacCormack, MD

Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease.

*For a PDF of the full article, click on the link to the left of this introduction.

Mollie A. MacCormack, MD

Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease.

*For a PDF of the full article, click on the link to the left of this introduction.

Mollie A. MacCormack, MD

Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease.

*For a PDF of the full article, click on the link to the left of this introduction.

Apigenin (5,7,4′-trihydroxyflavone) is a low-toxic, nonmutagenic plant flavonoid that is widely found in herbs (endive, clove, and German chamomile), fruit (apples, cherries, and grapes), beverages (tea and wine), vegetables (beans, broccoli, celery, leeks, onions, barley, parsley, and tomatoes), and propolis (Skin Pharmacol. Appl. Skin Physiol. 2002;15:297–306; Eur. J. Cancer 1996;32A:146–51; J. Cell Biochem. [Suppl.] 1997;28–9:39–48).

Apigenin shows promising chemopreventive activity against skin cancer (J. Pharm. Sci. 1997;86:721–5) and has demonstrated anti-inflammatory properties (Skin Pharmacol. Appl. Skin Physiol. 2001;14:373–85). It is also believed to be partly responsible for the soothing, antispasmodic, anxiolytic activity that has been attributed to chamomile (Planta Medica 1995;61:213–6).

 Antitumor Actions in Animals

In a series of studies conducted almost 2 decades ago, the topical application of apigenin to Sencar mice inhibited, in a dose-dependent manner, skin tumorigenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). In the first study, 48% of DMBA/TPA-treated mice developed carcinomas by 33 weeks after DMBA initiation, but no carcinomas occurred in the DMBA/apigenin/TPA-treated groups. In the second study, apigenin prolonged the latency period of papilloma formation by 3 weeks and dose dependently reduced papilloma incidence. Apigenin also significantly inhibited carcinoma incidence and reduced the number of tumors. In addition, the researchers concluded that apigenin exhibited the tendency to reduce conversion of papillomas to carcinomas (Cancer Res. 1990;50:499–502).

Several studies conducted since then established that the topical application of apigenin inhibits UV-induced skin tumorigenesis in mouse skin (Mol. Carcinog. 2002;33:36–43; Carcinogenesis 1996;17:2367–75; Mol. Carcinog. 1997;19:74–82). Apigenin also has been shown to suppress TPA-mediated tumor promotion in mouse skin, partly because of its inhibitory effects on protein kinase C and expression of c-Jun and c-Fos (Eur. J. Cancer 1996;32A:146–51).

In addition to its ability to inhibit tumors, apigenin has been noted for its in vitro antioxidant properties against the superoxide anion and peroxyl radicals. In a study performed 15 years ago, the compound demonstrated anti-inflammatory activity in rats. Intradermal application of liposomal apigenin-7-glucoside dose-dependently inhibited skin inflammation previously induced by injection of xanthine oxidase and cumene hydroperoxide (Arzneimittelforschung 1993;43:370–2).

Researchers who studied the effects of apigenin using the mouse keratinocyte 308 cell line, which contains a wild-type p53 gene, determined that the compound may exert antitumorigenic activity by stimulating the p53-p21/waf1 response pathway (Carcinogenesis 2000;21:633–9).

In another study of apigenin's inhibitory influence on skin tumorigenesis, investigators found, using DNA flow cytometric analysis, interruptions in the cell cycle. Keratinocytes cultured for 24 hours in apigenin-containing medium induced a G2/M arrest in two mouse skin-derived cell lines, C50 and 308, and in human HL-60 cells. This effect was fully reversible after an additional 24 hours in apigenin-free medium (Carcinogenesis 1996;17:2367–75).

Subsequent research from the same laboratory provided evidence that apigenin can induce G1 arrest in human diploid fibroblasts by inhibiting cyclin-dependent kinase 2 (cdk2) activity and phosphorylation of retinoblastoma protein, and by inducing the cdk inhibitor p21/waf1.

These activities, the researchers wrote, may mediate the flavonoid's in vivo chemopreventive activities (Mol. Carcinog. 1997;19:74–82).

The preponderance of research on this botanical antioxidant points toward anticarcinogenic activity. In a study evaluating 15 flavonoids for their effects on morphologic changes in soft agar and cellular growth in v-H-ras-transformed NIH3T3 cells, only apigenin, kaempferol, and genistein had a reversing effect on the transformed morphology of these cells. The researchers concluded that the suppression of protein kinase C activity and nuclear oncogene expression might contribute to the molecular mechanism of action exhibited by apigenin (as well as curcumin) in its inhibition of TPA-induced tumor promotion (J. Cell Biochem. [Suppl.] 1997;28–9:39–48).

Other authors have expressed optimistism that apigenin will show a broad spectrum of chemopreventive effects by influencing various molecular targets that affect pathways in the cell (J. Nutr. 2003;133:3800S-4S).

Alternative Sunscreen?

In a study aimed at ascertaining the efficacy of apigenin as a chemopreventive agent against UV-induced skin cancer as well as DNA damage in a cell-free system, investigators found that apigenin treatment from 12 hours before and until 1 hour after UVA/B exposure inhibited 25%–45% of ornithine decarboxylase activity. Further, apigenin treatment of SKH-1 mouse skin before each UVB exposure lowered cancer incidence (52% inhibition) and increased tumor-free survival, compared with control mice (Anticancer Res. 1997;17:85–91).

Of particular interest related to several promising studies is the speculation among some authors that apigenin may represent an alternative sunscreen agent for humans (Mol. Carcinog. 1997;19:74–82; Carcinogenesis 1996;17:2367–75).

For an apigenin formulation to prevent skin cancer, though, it has been determined that the apigenin must be delivered into viable epidermis (Pharm. Res. 1996;13:1710–5). In vivo skin penetration studies of the flavonoids apigenin, luteolin, and apigenin 7-O-?-glucoside demonstrated several years ago that the compounds were adsorbed at the skin surface, but also penetrated into deeper layers (Pharmazie 1994;49:509–11).

Down the Road

The stage may be set for apigenin to be included in formulations, because, in addition to the expanding body of evidence indicating its anticarcinogenic properties, recent work has shown apigenin's potential as an antiphotoaging agent.

Researchers focusing on identifying antiphotoaging compounds assessed the antioxidative activity and inhibitory effects on matrix metalloproteinase-1 (MMP-1) of the extracts of a marine plant, Zostera marina L. These extracts contained apigenin-7-O-β-D-glucoside, chrysoeriol, and luteolin. All of the compounds were found to scavenge the 1,1-diphenyl-2-picrylhydrazyl radical and the superoxide radical. These botanical constituents are deemed to have antioxidative activity and inhibitory effects on MMP-1 expression, and are considered promising targets for inclusion in antiphotoaging formulations (Arch. Pharm. Res. 2004;27:177–83).

Conclusions

The great upsurge in research and interest in plant polyphenols in recent years has been characterized by greater understanding of these compounds' potential health benefits. The body of research on the phenolic flavonoid apigenin is relatively small, with the preponderance of data accumulating in the past 15 years.

Apigenin is found in German chamomile and is most likely to be included in dermatologic products featuring chamomile. It is also an active ingredient in propolis.

With its promising research profile indicating anticarcinogenic and antiphotoaging effects, in vitro and in vivo, much more research regarding this potent antioxidant is likely and warranted.

Apigenin (5,7,4′-trihydroxyflavone) is a low-toxic, nonmutagenic plant flavonoid that is widely found in herbs (endive, clove, and German chamomile), fruit (apples, cherries, and grapes), beverages (tea and wine), vegetables (beans, broccoli, celery, leeks, onions, barley, parsley, and tomatoes), and propolis (Skin Pharmacol. Appl. Skin Physiol. 2002;15:297–306; Eur. J. Cancer 1996;32A:146–51; J. Cell Biochem. [Suppl.] 1997;28–9:39–48).

Apigenin shows promising chemopreventive activity against skin cancer (J. Pharm. Sci. 1997;86:721–5) and has demonstrated anti-inflammatory properties (Skin Pharmacol. Appl. Skin Physiol. 2001;14:373–85). It is also believed to be partly responsible for the soothing, antispasmodic, anxiolytic activity that has been attributed to chamomile (Planta Medica 1995;61:213–6).

 Antitumor Actions in Animals

In a series of studies conducted almost 2 decades ago, the topical application of apigenin to Sencar mice inhibited, in a dose-dependent manner, skin tumorigenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). In the first study, 48% of DMBA/TPA-treated mice developed carcinomas by 33 weeks after DMBA initiation, but no carcinomas occurred in the DMBA/apigenin/TPA-treated groups. In the second study, apigenin prolonged the latency period of papilloma formation by 3 weeks and dose dependently reduced papilloma incidence. Apigenin also significantly inhibited carcinoma incidence and reduced the number of tumors. In addition, the researchers concluded that apigenin exhibited the tendency to reduce conversion of papillomas to carcinomas (Cancer Res. 1990;50:499–502).

Several studies conducted since then established that the topical application of apigenin inhibits UV-induced skin tumorigenesis in mouse skin (Mol. Carcinog. 2002;33:36–43; Carcinogenesis 1996;17:2367–75; Mol. Carcinog. 1997;19:74–82). Apigenin also has been shown to suppress TPA-mediated tumor promotion in mouse skin, partly because of its inhibitory effects on protein kinase C and expression of c-Jun and c-Fos (Eur. J. Cancer 1996;32A:146–51).

In addition to its ability to inhibit tumors, apigenin has been noted for its in vitro antioxidant properties against the superoxide anion and peroxyl radicals. In a study performed 15 years ago, the compound demonstrated anti-inflammatory activity in rats. Intradermal application of liposomal apigenin-7-glucoside dose-dependently inhibited skin inflammation previously induced by injection of xanthine oxidase and cumene hydroperoxide (Arzneimittelforschung 1993;43:370–2).

Researchers who studied the effects of apigenin using the mouse keratinocyte 308 cell line, which contains a wild-type p53 gene, determined that the compound may exert antitumorigenic activity by stimulating the p53-p21/waf1 response pathway (Carcinogenesis 2000;21:633–9).

In another study of apigenin's inhibitory influence on skin tumorigenesis, investigators found, using DNA flow cytometric analysis, interruptions in the cell cycle. Keratinocytes cultured for 24 hours in apigenin-containing medium induced a G2/M arrest in two mouse skin-derived cell lines, C50 and 308, and in human HL-60 cells. This effect was fully reversible after an additional 24 hours in apigenin-free medium (Carcinogenesis 1996;17:2367–75).

Subsequent research from the same laboratory provided evidence that apigenin can induce G1 arrest in human diploid fibroblasts by inhibiting cyclin-dependent kinase 2 (cdk2) activity and phosphorylation of retinoblastoma protein, and by inducing the cdk inhibitor p21/waf1.

These activities, the researchers wrote, may mediate the flavonoid's in vivo chemopreventive activities (Mol. Carcinog. 1997;19:74–82).

The preponderance of research on this botanical antioxidant points toward anticarcinogenic activity. In a study evaluating 15 flavonoids for their effects on morphologic changes in soft agar and cellular growth in v-H-ras-transformed NIH3T3 cells, only apigenin, kaempferol, and genistein had a reversing effect on the transformed morphology of these cells. The researchers concluded that the suppression of protein kinase C activity and nuclear oncogene expression might contribute to the molecular mechanism of action exhibited by apigenin (as well as curcumin) in its inhibition of TPA-induced tumor promotion (J. Cell Biochem. [Suppl.] 1997;28–9:39–48).

Other authors have expressed optimistism that apigenin will show a broad spectrum of chemopreventive effects by influencing various molecular targets that affect pathways in the cell (J. Nutr. 2003;133:3800S-4S).

Alternative Sunscreen?

In a study aimed at ascertaining the efficacy of apigenin as a chemopreventive agent against UV-induced skin cancer as well as DNA damage in a cell-free system, investigators found that apigenin treatment from 12 hours before and until 1 hour after UVA/B exposure inhibited 25%–45% of ornithine decarboxylase activity. Further, apigenin treatment of SKH-1 mouse skin before each UVB exposure lowered cancer incidence (52% inhibition) and increased tumor-free survival, compared with control mice (Anticancer Res. 1997;17:85–91).

Of particular interest related to several promising studies is the speculation among some authors that apigenin may represent an alternative sunscreen agent for humans (Mol. Carcinog. 1997;19:74–82; Carcinogenesis 1996;17:2367–75).

For an apigenin formulation to prevent skin cancer, though, it has been determined that the apigenin must be delivered into viable epidermis (Pharm. Res. 1996;13:1710–5). In vivo skin penetration studies of the flavonoids apigenin, luteolin, and apigenin 7-O-?-glucoside demonstrated several years ago that the compounds were adsorbed at the skin surface, but also penetrated into deeper layers (Pharmazie 1994;49:509–11).

Down the Road

The stage may be set for apigenin to be included in formulations, because, in addition to the expanding body of evidence indicating its anticarcinogenic properties, recent work has shown apigenin's potential as an antiphotoaging agent.

Researchers focusing on identifying antiphotoaging compounds assessed the antioxidative activity and inhibitory effects on matrix metalloproteinase-1 (MMP-1) of the extracts of a marine plant, Zostera marina L. These extracts contained apigenin-7-O-β-D-glucoside, chrysoeriol, and luteolin. All of the compounds were found to scavenge the 1,1-diphenyl-2-picrylhydrazyl radical and the superoxide radical. These botanical constituents are deemed to have antioxidative activity and inhibitory effects on MMP-1 expression, and are considered promising targets for inclusion in antiphotoaging formulations (Arch. Pharm. Res. 2004;27:177–83).

Conclusions

The great upsurge in research and interest in plant polyphenols in recent years has been characterized by greater understanding of these compounds' potential health benefits. The body of research on the phenolic flavonoid apigenin is relatively small, with the preponderance of data accumulating in the past 15 years.

Apigenin is found in German chamomile and is most likely to be included in dermatologic products featuring chamomile. It is also an active ingredient in propolis.

With its promising research profile indicating anticarcinogenic and antiphotoaging effects, in vitro and in vivo, much more research regarding this potent antioxidant is likely and warranted.

Apigenin (5,7,4′-trihydroxyflavone) is a low-toxic, nonmutagenic plant flavonoid that is widely found in herbs (endive, clove, and German chamomile), fruit (apples, cherries, and grapes), beverages (tea and wine), vegetables (beans, broccoli, celery, leeks, onions, barley, parsley, and tomatoes), and propolis (Skin Pharmacol. Appl. Skin Physiol. 2002;15:297–306; Eur. J. Cancer 1996;32A:146–51; J. Cell Biochem. [Suppl.] 1997;28–9:39–48).

Apigenin shows promising chemopreventive activity against skin cancer (J. Pharm. Sci. 1997;86:721–5) and has demonstrated anti-inflammatory properties (Skin Pharmacol. Appl. Skin Physiol. 2001;14:373–85). It is also believed to be partly responsible for the soothing, antispasmodic, anxiolytic activity that has been attributed to chamomile (Planta Medica 1995;61:213–6).

 Antitumor Actions in Animals

In a series of studies conducted almost 2 decades ago, the topical application of apigenin to Sencar mice inhibited, in a dose-dependent manner, skin tumorigenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). In the first study, 48% of DMBA/TPA-treated mice developed carcinomas by 33 weeks after DMBA initiation, but no carcinomas occurred in the DMBA/apigenin/TPA-treated groups. In the second study, apigenin prolonged the latency period of papilloma formation by 3 weeks and dose dependently reduced papilloma incidence. Apigenin also significantly inhibited carcinoma incidence and reduced the number of tumors. In addition, the researchers concluded that apigenin exhibited the tendency to reduce conversion of papillomas to carcinomas (Cancer Res. 1990;50:499–502).

Several studies conducted since then established that the topical application of apigenin inhibits UV-induced skin tumorigenesis in mouse skin (Mol. Carcinog. 2002;33:36–43; Carcinogenesis 1996;17:2367–75; Mol. Carcinog. 1997;19:74–82). Apigenin also has been shown to suppress TPA-mediated tumor promotion in mouse skin, partly because of its inhibitory effects on protein kinase C and expression of c-Jun and c-Fos (Eur. J. Cancer 1996;32A:146–51).

In addition to its ability to inhibit tumors, apigenin has been noted for its in vitro antioxidant properties against the superoxide anion and peroxyl radicals. In a study performed 15 years ago, the compound demonstrated anti-inflammatory activity in rats. Intradermal application of liposomal apigenin-7-glucoside dose-dependently inhibited skin inflammation previously induced by injection of xanthine oxidase and cumene hydroperoxide (Arzneimittelforschung 1993;43:370–2).

Researchers who studied the effects of apigenin using the mouse keratinocyte 308 cell line, which contains a wild-type p53 gene, determined that the compound may exert antitumorigenic activity by stimulating the p53-p21/waf1 response pathway (Carcinogenesis 2000;21:633–9).

In another study of apigenin's inhibitory influence on skin tumorigenesis, investigators found, using DNA flow cytometric analysis, interruptions in the cell cycle. Keratinocytes cultured for 24 hours in apigenin-containing medium induced a G2/M arrest in two mouse skin-derived cell lines, C50 and 308, and in human HL-60 cells. This effect was fully reversible after an additional 24 hours in apigenin-free medium (Carcinogenesis 1996;17:2367–75).

Subsequent research from the same laboratory provided evidence that apigenin can induce G1 arrest in human diploid fibroblasts by inhibiting cyclin-dependent kinase 2 (cdk2) activity and phosphorylation of retinoblastoma protein, and by inducing the cdk inhibitor p21/waf1.

These activities, the researchers wrote, may mediate the flavonoid's in vivo chemopreventive activities (Mol. Carcinog. 1997;19:74–82).

The preponderance of research on this botanical antioxidant points toward anticarcinogenic activity. In a study evaluating 15 flavonoids for their effects on morphologic changes in soft agar and cellular growth in v-H-ras-transformed NIH3T3 cells, only apigenin, kaempferol, and genistein had a reversing effect on the transformed morphology of these cells. The researchers concluded that the suppression of protein kinase C activity and nuclear oncogene expression might contribute to the molecular mechanism of action exhibited by apigenin (as well as curcumin) in its inhibition of TPA-induced tumor promotion (J. Cell Biochem. [Suppl.] 1997;28–9:39–48).

Other authors have expressed optimistism that apigenin will show a broad spectrum of chemopreventive effects by influencing various molecular targets that affect pathways in the cell (J. Nutr. 2003;133:3800S-4S).

Alternative Sunscreen?

In a study aimed at ascertaining the efficacy of apigenin as a chemopreventive agent against UV-induced skin cancer as well as DNA damage in a cell-free system, investigators found that apigenin treatment from 12 hours before and until 1 hour after UVA/B exposure inhibited 25%–45% of ornithine decarboxylase activity. Further, apigenin treatment of SKH-1 mouse skin before each UVB exposure lowered cancer incidence (52% inhibition) and increased tumor-free survival, compared with control mice (Anticancer Res. 1997;17:85–91).

Of particular interest related to several promising studies is the speculation among some authors that apigenin may represent an alternative sunscreen agent for humans (Mol. Carcinog. 1997;19:74–82; Carcinogenesis 1996;17:2367–75).

For an apigenin formulation to prevent skin cancer, though, it has been determined that the apigenin must be delivered into viable epidermis (Pharm. Res. 1996;13:1710–5). In vivo skin penetration studies of the flavonoids apigenin, luteolin, and apigenin 7-O-?-glucoside demonstrated several years ago that the compounds were adsorbed at the skin surface, but also penetrated into deeper layers (Pharmazie 1994;49:509–11).

Down the Road

The stage may be set for apigenin to be included in formulations, because, in addition to the expanding body of evidence indicating its anticarcinogenic properties, recent work has shown apigenin's potential as an antiphotoaging agent.

Researchers focusing on identifying antiphotoaging compounds assessed the antioxidative activity and inhibitory effects on matrix metalloproteinase-1 (MMP-1) of the extracts of a marine plant, Zostera marina L. These extracts contained apigenin-7-O-β-D-glucoside, chrysoeriol, and luteolin. All of the compounds were found to scavenge the 1,1-diphenyl-2-picrylhydrazyl radical and the superoxide radical. These botanical constituents are deemed to have antioxidative activity and inhibitory effects on MMP-1 expression, and are considered promising targets for inclusion in antiphotoaging formulations (Arch. Pharm. Res. 2004;27:177–83).

Conclusions

The great upsurge in research and interest in plant polyphenols in recent years has been characterized by greater understanding of these compounds' potential health benefits. The body of research on the phenolic flavonoid apigenin is relatively small, with the preponderance of data accumulating in the past 15 years.

Apigenin is found in German chamomile and is most likely to be included in dermatologic products featuring chamomile. It is also an active ingredient in propolis.

With its promising research profile indicating anticarcinogenic and antiphotoaging effects, in vitro and in vivo, much more research regarding this potent antioxidant is likely and warranted.

SAN DIEGO — When Dr. Michael Swann advises patients to apply sunscreen to protect against melanoma, the suggestion sometimes falls on deaf ears.

"Patients who don't want to wear sunscreen will say, 'I don't wear sunscreen because it's never been shown to protect against melanoma,'" he said in an update on melanoma sponsored by the Scripps Clinic. "There are a lot of arguments against using it. People will believe what they want to believe."

He acknowledges that retrospective studies have not shown a clear benefit or detriment to using sunscreen to reduce the risk of melanoma but points his patients to other evidence. In Hawaii, where residents apply more sunscreen regularly than in other states, melanoma rates are declining.

The same goes for Australia, where an estimated 74% of residents use sunscreen regularly.

He goes on to tell them that the sunscreens studied over the past 20 years lacked any appreciable UVA protection, which may be important in melanoma. In recent years, though, sunscreens have hit the market with effective protection against UVA. For everyday protection, Dr. Swann recommends Anthelios SX by L'Oréal La Roche-Possay, which contains the sun filter Mexoryl SX.

"At this point, it is only approved as an SPF 15, so it's not really a good one for being on the golf course all day," said Dr. Swann of the Scripps Clinic, La Jolla, Calif.

For periods of longer exposure, he recommends Neutrogena sunscreens with Helioplex, which contain stable avobenzone.

He said that he has no conflict of interest with either manufacturer.

SAN DIEGO — When Dr. Michael Swann advises patients to apply sunscreen to protect against melanoma, the suggestion sometimes falls on deaf ears.

"Patients who don't want to wear sunscreen will say, 'I don't wear sunscreen because it's never been shown to protect against melanoma,'" he said in an update on melanoma sponsored by the Scripps Clinic. "There are a lot of arguments against using it. People will believe what they want to believe."

He acknowledges that retrospective studies have not shown a clear benefit or detriment to using sunscreen to reduce the risk of melanoma but points his patients to other evidence. In Hawaii, where residents apply more sunscreen regularly than in other states, melanoma rates are declining.

The same goes for Australia, where an estimated 74% of residents use sunscreen regularly.

He goes on to tell them that the sunscreens studied over the past 20 years lacked any appreciable UVA protection, which may be important in melanoma. In recent years, though, sunscreens have hit the market with effective protection against UVA. For everyday protection, Dr. Swann recommends Anthelios SX by L'Oréal La Roche-Possay, which contains the sun filter Mexoryl SX.

"At this point, it is only approved as an SPF 15, so it's not really a good one for being on the golf course all day," said Dr. Swann of the Scripps Clinic, La Jolla, Calif.

For periods of longer exposure, he recommends Neutrogena sunscreens with Helioplex, which contain stable avobenzone.

He said that he has no conflict of interest with either manufacturer.

SAN DIEGO — When Dr. Michael Swann advises patients to apply sunscreen to protect against melanoma, the suggestion sometimes falls on deaf ears.

"Patients who don't want to wear sunscreen will say, 'I don't wear sunscreen because it's never been shown to protect against melanoma,'" he said in an update on melanoma sponsored by the Scripps Clinic. "There are a lot of arguments against using it. People will believe what they want to believe."

He acknowledges that retrospective studies have not shown a clear benefit or detriment to using sunscreen to reduce the risk of melanoma but points his patients to other evidence. In Hawaii, where residents apply more sunscreen regularly than in other states, melanoma rates are declining.

The same goes for Australia, where an estimated 74% of residents use sunscreen regularly.

He goes on to tell them that the sunscreens studied over the past 20 years lacked any appreciable UVA protection, which may be important in melanoma. In recent years, though, sunscreens have hit the market with effective protection against UVA. For everyday protection, Dr. Swann recommends Anthelios SX by L'Oréal La Roche-Possay, which contains the sun filter Mexoryl SX.

"At this point, it is only approved as an SPF 15, so it's not really a good one for being on the golf course all day," said Dr. Swann of the Scripps Clinic, La Jolla, Calif.

For periods of longer exposure, he recommends Neutrogena sunscreens with Helioplex, which contain stable avobenzone.

He said that he has no conflict of interest with either manufacturer.

SAN DIEGO — When it comes to follow-up surveillance of melanoma patients, history and physical examination remain the cornerstone of good care, with little solid evidence to support anything else.

"The literature on this aspect of melanoma management is incomplete, mainly because there are very few prospective studies," Dr. Peter R. Shumaker said at a melanoma update sponsored by the Scripps Clinic.

He discussed several goals for the postoperative follow-up of melanoma patients:

▸ Earliest possible detection of treatable recurrence. About one-quarter of patients with local disease and 60%–70% of patients with in-transit [and] nodal disease will develop recurrence, said Dr. Shumaker, clinical fellow in procedural dermatology at the Scripps Clinic in La Jolla, Calif.

One study that reviewed the rate of first recurrence after treatment for malignant melanoma among 250 Australian patients found that 52% of recurrences were in the regional lymph nodes, 17% were local, 8% were in-transit, and 23% were visceral (Plast. Reconstr. Surg. 1993;91:94–8).

"The majority of recurrences occur within the first couple of years," Dr. Shumaker said.

▸ Detection of other primary skin cancers. "These patients are at high risk for a second primary melanoma," he said.

▸ Patient education, emotional support, and reassurance. Most studies report that at least half of recurrences are found by the patients themselves, despite being in a structured follow-up program. "So these follow-ups, in addition to providing an opportunity to inspect and palpate lesions, also provide an opportunity to educate patients," Dr. Shumaker said.

▸ Quality assurance. By this Dr. Shumaker meant the collection of data to improve future treatment and surveillance, such as blood tests and imaging techniques.

Chest x-rays and blood tests are frequently used in the routine follow-up of melanoma patients, "but they offer little benefit in terms of cost effectiveness," Dr. Shumaker said. They generally provide low sensitivity and a high rate of false positives.

Dr. Shumaker considers

Ultrasound "appears to be more sensitive than physical exam in detecting tumor recurrence in in-transit routes and regional nodal basins," he said. "There is an increased likelihood of survival benefit from asymptomatic detection in these areas."

He noted that ultrasound can be combined with fine-needle aspiration to diagnose recurrent or metastatic disease, but there appears to be no role for abdominal ultrasound in routine follow-up.

At Scripps, Dr. Shumaker and his associates perform a comprehensive history and physical exam in melanoma patients every 3 months for 3 years, then every 6 months for life. "This includes baseline and an annual chest x-ray and lab tests," he said.

Most studies report that at least half of recurrences are found bythe patients themselves. DR. SHUMAKER

SAN DIEGO — When it comes to follow-up surveillance of melanoma patients, history and physical examination remain the cornerstone of good care, with little solid evidence to support anything else.

"The literature on this aspect of melanoma management is incomplete, mainly because there are very few prospective studies," Dr. Peter R. Shumaker said at a melanoma update sponsored by the Scripps Clinic.

He discussed several goals for the postoperative follow-up of melanoma patients:

▸ Earliest possible detection of treatable recurrence. About one-quarter of patients with local disease and 60%–70% of patients with in-transit [and] nodal disease will develop recurrence, said Dr. Shumaker, clinical fellow in procedural dermatology at the Scripps Clinic in La Jolla, Calif.

One study that reviewed the rate of first recurrence after treatment for malignant melanoma among 250 Australian patients found that 52% of recurrences were in the regional lymph nodes, 17% were local, 8% were in-transit, and 23% were visceral (Plast. Reconstr. Surg. 1993;91:94–8).

"The majority of recurrences occur within the first couple of years," Dr. Shumaker said.

▸ Detection of other primary skin cancers. "These patients are at high risk for a second primary melanoma," he said.

▸ Patient education, emotional support, and reassurance. Most studies report that at least half of recurrences are found by the patients themselves, despite being in a structured follow-up program. "So these follow-ups, in addition to providing an opportunity to inspect and palpate lesions, also provide an opportunity to educate patients," Dr. Shumaker said.

▸ Quality assurance. By this Dr. Shumaker meant the collection of data to improve future treatment and surveillance, such as blood tests and imaging techniques.

Chest x-rays and blood tests are frequently used in the routine follow-up of melanoma patients, "but they offer little benefit in terms of cost effectiveness," Dr. Shumaker said. They generally provide low sensitivity and a high rate of false positives.

Dr. Shumaker considers

Ultrasound "appears to be more sensitive than physical exam in detecting tumor recurrence in in-transit routes and regional nodal basins," he said. "There is an increased likelihood of survival benefit from asymptomatic detection in these areas."

He noted that ultrasound can be combined with fine-needle aspiration to diagnose recurrent or metastatic disease, but there appears to be no role for abdominal ultrasound in routine follow-up.

At Scripps, Dr. Shumaker and his associates perform a comprehensive history and physical exam in melanoma patients every 3 months for 3 years, then every 6 months for life. "This includes baseline and an annual chest x-ray and lab tests," he said.

Most studies report that at least half of recurrences are found bythe patients themselves. DR. SHUMAKER

SAN DIEGO — When it comes to follow-up surveillance of melanoma patients, history and physical examination remain the cornerstone of good care, with little solid evidence to support anything else.

"The literature on this aspect of melanoma management is incomplete, mainly because there are very few prospective studies," Dr. Peter R. Shumaker said at a melanoma update sponsored by the Scripps Clinic.

He discussed several goals for the postoperative follow-up of melanoma patients:

▸ Earliest possible detection of treatable recurrence. About one-quarter of patients with local disease and 60%–70% of patients with in-transit [and] nodal disease will develop recurrence, said Dr. Shumaker, clinical fellow in procedural dermatology at the Scripps Clinic in La Jolla, Calif.

One study that reviewed the rate of first recurrence after treatment for malignant melanoma among 250 Australian patients found that 52% of recurrences were in the regional lymph nodes, 17% were local, 8% were in-transit, and 23% were visceral (Plast. Reconstr. Surg. 1993;91:94–8).

"The majority of recurrences occur within the first couple of years," Dr. Shumaker said.

▸ Detection of other primary skin cancers. "These patients are at high risk for a second primary melanoma," he said.

▸ Patient education, emotional support, and reassurance. Most studies report that at least half of recurrences are found by the patients themselves, despite being in a structured follow-up program. "So these follow-ups, in addition to providing an opportunity to inspect and palpate lesions, also provide an opportunity to educate patients," Dr. Shumaker said.

▸ Quality assurance. By this Dr. Shumaker meant the collection of data to improve future treatment and surveillance, such as blood tests and imaging techniques.

Chest x-rays and blood tests are frequently used in the routine follow-up of melanoma patients, "but they offer little benefit in terms of cost effectiveness," Dr. Shumaker said. They generally provide low sensitivity and a high rate of false positives.

Dr. Shumaker considers

Ultrasound "appears to be more sensitive than physical exam in detecting tumor recurrence in in-transit routes and regional nodal basins," he said. "There is an increased likelihood of survival benefit from asymptomatic detection in these areas."

He noted that ultrasound can be combined with fine-needle aspiration to diagnose recurrent or metastatic disease, but there appears to be no role for abdominal ultrasound in routine follow-up.

At Scripps, Dr. Shumaker and his associates perform a comprehensive history and physical exam in melanoma patients every 3 months for 3 years, then every 6 months for life. "This includes baseline and an annual chest x-ray and lab tests," he said.

Most studies report that at least half of recurrences are found bythe patients themselves. DR. SHUMAKER