Michele G. Sullivan

EXPERT ANALYSIS FROM THE ACMS ANNUAL MEETING

ORLANDO – An alternating schedule of ibuprofen and acetaminophen every 3 hours is an excellent method of managing postoperative pain associated with Mohs surgery, especially if the initial dose is taken at the start of the procedure.

By starting with ibuprofen, the regimen capitalizes on the drug’s anti-inflammatory component to reduce overall postoperative analgesic requirement, Dr. Bryan Carroll said at the annual meeting of the American College of Mohs Surgery.

“This combination has even been shown to be superior to narcotics, both alone and in combination,” said Dr. Carroll, director of dermatologic surgery at Eastern Virginia Medical School, Norfolk. “This finding has been reinforced in the Mohs literature,” he added, citing a study that found the combination of acetaminophen and ibuprofen was more effective than acetaminophen alone or acetaminophen with codeine in controlling pain after Mohs surgery and reconstruction (Dermatol Surg. 2011 Jul;37[7]:1007-13).

Alternately layering the analgesics allows both to build to a maximum concentration in the blood without any nadirs where pain can get a foothold, an important concept in pain management, Dr. Carroll said.

And having two medications on board allows simultaneous targeting of different portions of the pain signaling pathway, he added. Ibuprofen works at the points of transduction and transmission, while acetaminophen works at the points of transmission and perception.

Dr. Carroll’s regimen starts at the time of surgery, when patients receive 400 mg ibuprofen. Three hours later, they receive 1 gram of acetaminophen; this dose should be adjusted for patients older than 60 years, who should not get more than 3 grams in 24 hours, and for those with liver failure, who should be limited to 2 grams over 24 hours.

This alternating dose is repeated every 3 hours. By the time of discharge, most patients have had at least two doses. This schedule is usually sufficient for patients at moderate to high risk of uncontrolled pain, who can then manage their discomfort with either drug the next day, he said.

Patients at higher risk of uncontrolled pain can use the regimen for the first day, and then titrate off according to their comfort. Some of these patients, however, may benefit from oxycodone, with the addition of laxative and an antiemetic, he noted.

The layering technique provides consistent postoperative pain relief that’s effective for most patients – even those who undergo substantial reconstruction, Dr. Carroll said in an interview. “This schedule is sufficient for all of our procedures, including larger reconstructions such as forehead flaps and cervicofacial rotation flaps. But additional interventions are indicated for patients with a high risk of uncontrolled pain. It’s the patient, not the procedure, which determines need for escalation.”

Teasing out those patients who may need more assertive pain management should be done in a preoperative assessment, Dr. Carroll said. A patient’s expectations of pain and history of chronic pain are some of the biggest factors in predicting a patient who will have uncontrolled pain.

“The experience of pain in Mohs surgery has limited studies,” he said. “Only a handful of investigations have looked at predictors that could help us plan. But of these, two things do stand out: a patient’s expectation of pain and a patient’s history of chronic pain.”

Surprisingly, he said, studies have determined that even a modestly elevated expectation of pain is enough to tip patients into a high-risk category. “If a patient predicted that his pain would be a 4 on a 1-10 scale, that was correlated with a lack of pain control during the operative experience. Maybe we’d expect this correlation if the expectation was an 8 or a 10, but a 4 was surprising. If a patient has even that amount of concern, I start thinking about additional interventions I can provide to maximize comfort.”

A patient’s past experience with pain is also a very large factor in how that person will experience postoperative pain. “Chronic pain does correlate with uncontrolled pain during surgery. I always ask about it. And this talk also helps drive your conversation about what you will be doing to keep them comfortable.”

That chat should include an explanation of how chronic and acute pain differ, Dr. Carroll said. “Chronic and acute pain involve different pathways and need different interventions. If the patient expresses fear, saying something like, ‘Tylenol is like water to me,’ believe him. It is like water for chronic pain. But you can also tell that patient that chronic pain is different from acute pain, and that acetaminophen will be a part of successfully managing it.”

Dr. Carroll had no financial disclosures.

[email protected]

EXPERT ANALYSIS FROM THE ACMS ANNUAL MEETING

ORLANDO – An alternating schedule of ibuprofen and acetaminophen every 3 hours is an excellent method of managing postoperative pain associated with Mohs surgery, especially if the initial dose is taken at the start of the procedure.

By starting with ibuprofen, the regimen capitalizes on the drug’s anti-inflammatory component to reduce overall postoperative analgesic requirement, Dr. Bryan Carroll said at the annual meeting of the American College of Mohs Surgery.

“This combination has even been shown to be superior to narcotics, both alone and in combination,” said Dr. Carroll, director of dermatologic surgery at Eastern Virginia Medical School, Norfolk. “This finding has been reinforced in the Mohs literature,” he added, citing a study that found the combination of acetaminophen and ibuprofen was more effective than acetaminophen alone or acetaminophen with codeine in controlling pain after Mohs surgery and reconstruction (Dermatol Surg. 2011 Jul;37[7]:1007-13).

Alternately layering the analgesics allows both to build to a maximum concentration in the blood without any nadirs where pain can get a foothold, an important concept in pain management, Dr. Carroll said.

And having two medications on board allows simultaneous targeting of different portions of the pain signaling pathway, he added. Ibuprofen works at the points of transduction and transmission, while acetaminophen works at the points of transmission and perception.

Dr. Carroll’s regimen starts at the time of surgery, when patients receive 400 mg ibuprofen. Three hours later, they receive 1 gram of acetaminophen; this dose should be adjusted for patients older than 60 years, who should not get more than 3 grams in 24 hours, and for those with liver failure, who should be limited to 2 grams over 24 hours.

This alternating dose is repeated every 3 hours. By the time of discharge, most patients have had at least two doses. This schedule is usually sufficient for patients at moderate to high risk of uncontrolled pain, who can then manage their discomfort with either drug the next day, he said.

Patients at higher risk of uncontrolled pain can use the regimen for the first day, and then titrate off according to their comfort. Some of these patients, however, may benefit from oxycodone, with the addition of laxative and an antiemetic, he noted.

The layering technique provides consistent postoperative pain relief that’s effective for most patients – even those who undergo substantial reconstruction, Dr. Carroll said in an interview. “This schedule is sufficient for all of our procedures, including larger reconstructions such as forehead flaps and cervicofacial rotation flaps. But additional interventions are indicated for patients with a high risk of uncontrolled pain. It’s the patient, not the procedure, which determines need for escalation.”

Teasing out those patients who may need more assertive pain management should be done in a preoperative assessment, Dr. Carroll said. A patient’s expectations of pain and history of chronic pain are some of the biggest factors in predicting a patient who will have uncontrolled pain.

“The experience of pain in Mohs surgery has limited studies,” he said. “Only a handful of investigations have looked at predictors that could help us plan. But of these, two things do stand out: a patient’s expectation of pain and a patient’s history of chronic pain.”

Surprisingly, he said, studies have determined that even a modestly elevated expectation of pain is enough to tip patients into a high-risk category. “If a patient predicted that his pain would be a 4 on a 1-10 scale, that was correlated with a lack of pain control during the operative experience. Maybe we’d expect this correlation if the expectation was an 8 or a 10, but a 4 was surprising. If a patient has even that amount of concern, I start thinking about additional interventions I can provide to maximize comfort.”

A patient’s past experience with pain is also a very large factor in how that person will experience postoperative pain. “Chronic pain does correlate with uncontrolled pain during surgery. I always ask about it. And this talk also helps drive your conversation about what you will be doing to keep them comfortable.”

That chat should include an explanation of how chronic and acute pain differ, Dr. Carroll said. “Chronic and acute pain involve different pathways and need different interventions. If the patient expresses fear, saying something like, ‘Tylenol is like water to me,’ believe him. It is like water for chronic pain. But you can also tell that patient that chronic pain is different from acute pain, and that acetaminophen will be a part of successfully managing it.”

Dr. Carroll had no financial disclosures.

[email protected]

EXPERT ANALYSIS FROM THE ACMS ANNUAL MEETING

ORLANDO – An alternating schedule of ibuprofen and acetaminophen every 3 hours is an excellent method of managing postoperative pain associated with Mohs surgery, especially if the initial dose is taken at the start of the procedure.

By starting with ibuprofen, the regimen capitalizes on the drug’s anti-inflammatory component to reduce overall postoperative analgesic requirement, Dr. Bryan Carroll said at the annual meeting of the American College of Mohs Surgery.

“This combination has even been shown to be superior to narcotics, both alone and in combination,” said Dr. Carroll, director of dermatologic surgery at Eastern Virginia Medical School, Norfolk. “This finding has been reinforced in the Mohs literature,” he added, citing a study that found the combination of acetaminophen and ibuprofen was more effective than acetaminophen alone or acetaminophen with codeine in controlling pain after Mohs surgery and reconstruction (Dermatol Surg. 2011 Jul;37[7]:1007-13).

Alternately layering the analgesics allows both to build to a maximum concentration in the blood without any nadirs where pain can get a foothold, an important concept in pain management, Dr. Carroll said.

And having two medications on board allows simultaneous targeting of different portions of the pain signaling pathway, he added. Ibuprofen works at the points of transduction and transmission, while acetaminophen works at the points of transmission and perception.

Dr. Carroll’s regimen starts at the time of surgery, when patients receive 400 mg ibuprofen. Three hours later, they receive 1 gram of acetaminophen; this dose should be adjusted for patients older than 60 years, who should not get more than 3 grams in 24 hours, and for those with liver failure, who should be limited to 2 grams over 24 hours.

This alternating dose is repeated every 3 hours. By the time of discharge, most patients have had at least two doses. This schedule is usually sufficient for patients at moderate to high risk of uncontrolled pain, who can then manage their discomfort with either drug the next day, he said.

Patients at higher risk of uncontrolled pain can use the regimen for the first day, and then titrate off according to their comfort. Some of these patients, however, may benefit from oxycodone, with the addition of laxative and an antiemetic, he noted.

The layering technique provides consistent postoperative pain relief that’s effective for most patients – even those who undergo substantial reconstruction, Dr. Carroll said in an interview. “This schedule is sufficient for all of our procedures, including larger reconstructions such as forehead flaps and cervicofacial rotation flaps. But additional interventions are indicated for patients with a high risk of uncontrolled pain. It’s the patient, not the procedure, which determines need for escalation.”

Teasing out those patients who may need more assertive pain management should be done in a preoperative assessment, Dr. Carroll said. A patient’s expectations of pain and history of chronic pain are some of the biggest factors in predicting a patient who will have uncontrolled pain.

“The experience of pain in Mohs surgery has limited studies,” he said. “Only a handful of investigations have looked at predictors that could help us plan. But of these, two things do stand out: a patient’s expectation of pain and a patient’s history of chronic pain.”

Surprisingly, he said, studies have determined that even a modestly elevated expectation of pain is enough to tip patients into a high-risk category. “If a patient predicted that his pain would be a 4 on a 1-10 scale, that was correlated with a lack of pain control during the operative experience. Maybe we’d expect this correlation if the expectation was an 8 or a 10, but a 4 was surprising. If a patient has even that amount of concern, I start thinking about additional interventions I can provide to maximize comfort.”

A patient’s past experience with pain is also a very large factor in how that person will experience postoperative pain. “Chronic pain does correlate with uncontrolled pain during surgery. I always ask about it. And this talk also helps drive your conversation about what you will be doing to keep them comfortable.”

That chat should include an explanation of how chronic and acute pain differ, Dr. Carroll said. “Chronic and acute pain involve different pathways and need different interventions. If the patient expresses fear, saying something like, ‘Tylenol is like water to me,’ believe him. It is like water for chronic pain. But you can also tell that patient that chronic pain is different from acute pain, and that acetaminophen will be a part of successfully managing it.”

Dr. Carroll had no financial disclosures.

[email protected]

ORLANDO – Sentinel node biopsies may be a useful staging tool for patients with cutaneous squamous cell carcinomas of the head and neck.

These patients – especially those with compromised immune systems – appear to be at sufficiently high risk of metastasis to justify the procedure, Dr. Jonathan Lopez said at the annual meeting of the American College of Mohs Surgery.

“We found that sentinel lymph node biopsy in our clinic had a 91% negative predictive value for local recurrence, nodal recurrence, and disease-specific death. It provides valuable prognostic information for patients at increased risk of nodal metastasis,” said Dr. Lopez, a dermatology resident at the Mayo Clinic, Rochester, Minn.

He and his associates conducted a chart review of 24 patients treated at the Mayo Clinic from 2000 to 2014 for a cutaneous squamous cell carcinoma (SCC) of the head or neck. Of these, 11 patients were immunosuppressed. Five had undergone a kidney transplant and three a lung transplant. One patient had Hodgkin’s lymphoma, one had cutaneous lymphocytic leukemia, and one, metastatic urothelial carcinoma.

Before sentinel node biopsy, eight patients had a wide local excision; 12 were treated with Mohs micrographic surgery only; and four had a Mohs procedure followed by resection for better margins.

The biopsies identified two patients with nodal disease, but failed to identify a third who had it, Dr. Lopez said.

Patient No. 1 had a primary SCC on the nasal tip that was stage 2, according to the American Joint Committee on Cancer (AJCC) staging system, and 2b according to the Brigham and Women’s Hospital (BWH) system. He had undergone a prior double lung transplant and his lymph node dissection showed no nodal metastasis. He declined radiotherapy and died within 2 months of the biopsy, of unclear causes that were not related to his skin cancer.

Patient No. 2 had a primary lesion on the right cheek, and a history of kidney transplant. His cancer was stage 2 by the AJCC system and 2b by the BWH system. His lymph node dissection of the right parotid and neck was negative. At last follow-up of 3.5 years, he was cancer free. However, Dr. Lopez noted, the patient died at 4 years’ follow-up of unknown causes.

The final patient had a primary lesion on the right conchal bowl. It was a stage 2 cancer by the AJCC system and 2a by the BWH system. His sentinel node biopsy was negative. However, the otolaryngologist who performed the biopsy also took seven superficial parotid nodes and one of those was positive. This patient had no recurrence at the last visit, 1.5 years after the biopsy.

The sentinel node biopsies were negative in the 21 other patients. Of these, 14 had no evidence of recurrence at a mean of 3 years’ follow-up after the sentinel lymph node biopsy. Two developed local recurrence and two others, both of whom had a history of multiple squamous cell carcinomas, developed nodal spread and died of metastatic disease. Three have died of causes unrelated to their cancer.

Dr. Lopez had no financial disclosures.

[email protected]

ORLANDO – Sentinel node biopsies may be a useful staging tool for patients with cutaneous squamous cell carcinomas of the head and neck.

These patients – especially those with compromised immune systems – appear to be at sufficiently high risk of metastasis to justify the procedure, Dr. Jonathan Lopez said at the annual meeting of the American College of Mohs Surgery.

“We found that sentinel lymph node biopsy in our clinic had a 91% negative predictive value for local recurrence, nodal recurrence, and disease-specific death. It provides valuable prognostic information for patients at increased risk of nodal metastasis,” said Dr. Lopez, a dermatology resident at the Mayo Clinic, Rochester, Minn.

He and his associates conducted a chart review of 24 patients treated at the Mayo Clinic from 2000 to 2014 for a cutaneous squamous cell carcinoma (SCC) of the head or neck. Of these, 11 patients were immunosuppressed. Five had undergone a kidney transplant and three a lung transplant. One patient had Hodgkin’s lymphoma, one had cutaneous lymphocytic leukemia, and one, metastatic urothelial carcinoma.

Before sentinel node biopsy, eight patients had a wide local excision; 12 were treated with Mohs micrographic surgery only; and four had a Mohs procedure followed by resection for better margins.

The biopsies identified two patients with nodal disease, but failed to identify a third who had it, Dr. Lopez said.

Patient No. 1 had a primary SCC on the nasal tip that was stage 2, according to the American Joint Committee on Cancer (AJCC) staging system, and 2b according to the Brigham and Women’s Hospital (BWH) system. He had undergone a prior double lung transplant and his lymph node dissection showed no nodal metastasis. He declined radiotherapy and died within 2 months of the biopsy, of unclear causes that were not related to his skin cancer.

Patient No. 2 had a primary lesion on the right cheek, and a history of kidney transplant. His cancer was stage 2 by the AJCC system and 2b by the BWH system. His lymph node dissection of the right parotid and neck was negative. At last follow-up of 3.5 years, he was cancer free. However, Dr. Lopez noted, the patient died at 4 years’ follow-up of unknown causes.

The final patient had a primary lesion on the right conchal bowl. It was a stage 2 cancer by the AJCC system and 2a by the BWH system. His sentinel node biopsy was negative. However, the otolaryngologist who performed the biopsy also took seven superficial parotid nodes and one of those was positive. This patient had no recurrence at the last visit, 1.5 years after the biopsy.

The sentinel node biopsies were negative in the 21 other patients. Of these, 14 had no evidence of recurrence at a mean of 3 years’ follow-up after the sentinel lymph node biopsy. Two developed local recurrence and two others, both of whom had a history of multiple squamous cell carcinomas, developed nodal spread and died of metastatic disease. Three have died of causes unrelated to their cancer.

Dr. Lopez had no financial disclosures.

[email protected]

ORLANDO – Sentinel node biopsies may be a useful staging tool for patients with cutaneous squamous cell carcinomas of the head and neck.

These patients – especially those with compromised immune systems – appear to be at sufficiently high risk of metastasis to justify the procedure, Dr. Jonathan Lopez said at the annual meeting of the American College of Mohs Surgery.

“We found that sentinel lymph node biopsy in our clinic had a 91% negative predictive value for local recurrence, nodal recurrence, and disease-specific death. It provides valuable prognostic information for patients at increased risk of nodal metastasis,” said Dr. Lopez, a dermatology resident at the Mayo Clinic, Rochester, Minn.

He and his associates conducted a chart review of 24 patients treated at the Mayo Clinic from 2000 to 2014 for a cutaneous squamous cell carcinoma (SCC) of the head or neck. Of these, 11 patients were immunosuppressed. Five had undergone a kidney transplant and three a lung transplant. One patient had Hodgkin’s lymphoma, one had cutaneous lymphocytic leukemia, and one, metastatic urothelial carcinoma.

Before sentinel node biopsy, eight patients had a wide local excision; 12 were treated with Mohs micrographic surgery only; and four had a Mohs procedure followed by resection for better margins.

The biopsies identified two patients with nodal disease, but failed to identify a third who had it, Dr. Lopez said.

Patient No. 1 had a primary SCC on the nasal tip that was stage 2, according to the American Joint Committee on Cancer (AJCC) staging system, and 2b according to the Brigham and Women’s Hospital (BWH) system. He had undergone a prior double lung transplant and his lymph node dissection showed no nodal metastasis. He declined radiotherapy and died within 2 months of the biopsy, of unclear causes that were not related to his skin cancer.

Patient No. 2 had a primary lesion on the right cheek, and a history of kidney transplant. His cancer was stage 2 by the AJCC system and 2b by the BWH system. His lymph node dissection of the right parotid and neck was negative. At last follow-up of 3.5 years, he was cancer free. However, Dr. Lopez noted, the patient died at 4 years’ follow-up of unknown causes.

The final patient had a primary lesion on the right conchal bowl. It was a stage 2 cancer by the AJCC system and 2a by the BWH system. His sentinel node biopsy was negative. However, the otolaryngologist who performed the biopsy also took seven superficial parotid nodes and one of those was positive. This patient had no recurrence at the last visit, 1.5 years after the biopsy.

The sentinel node biopsies were negative in the 21 other patients. Of these, 14 had no evidence of recurrence at a mean of 3 years’ follow-up after the sentinel lymph node biopsy. Two developed local recurrence and two others, both of whom had a history of multiple squamous cell carcinomas, developed nodal spread and died of metastatic disease. Three have died of causes unrelated to their cancer.

Dr. Lopez had no financial disclosures.

[email protected]

ORLANDO – Matrilin-2 – a matrix protein found in peritumoral stroma – reliably distinguished invasive basal cell carcinoma from the often difficult-to-distinguish basaloid follicular hamartoma (BFH), in a study that evaluated the protein as a marker in this setting.

The protein marked 41 of 42 cancers and none of the hamartomas, Dr. Renato Goreshi reported at the annual meeting of the American College of Mohs Surgery. The one cancer it failed to identify was a superficial basal cell tumor – a finding that makes sense, since dermal fibroblasts appear to secrete matrilin-2 as a response to invasive skin tumors, said Dr. Goreshi of the Roger Williams Cancer Center, Providence, R.I.

Mohs surgery typically employs hematoxylin and eosin staining to delineate tumor boundary. But, Dr. Goreshi said, that stain doesn’t always reliably differentiate adnexal tumors from basal cell carcinomas. “Basaloid follicular hamartoma can be particularly difficult to distinguish from basal cell carcinoma,” he said.

BFH typically presents as individual or linearly arranged, small skin-colored to brown papules or plaques, or as multiple lesions in a generalized distribution on the face, scalp, and occasionally, the trunk (Arch Pathol Lab Med. 2010 Aug;134[8]:1215-9). These are often stable for many years. The differential diagnosis includes basal cell carcinoma and trichoepithelioma.

BFH sometimes occurs near a BCC, although there are no data on how often this happens.

Dr. Goreshi cited a 2007 case report of a young woman that illustrates this problem. The patient presented with a basal cell carcinoma on the side of her nose. The adjacent BFH was unrecognized, however. She underwent a multiple-stage Mohs that was unnecessarily extended because tumor margins included sections of the BFH.

“The lesion was interpreted as malignancy by both the Mohs surgeon and the dermatopathologist, but was later determined to have been a hamartoma. This highlights the importance of finding an effective marker,” Dr. Goreshi said.

He and his fellowship director, Dr. Satori Iwamoto, chief of Mohs micrographic surgery at Roger Williams, looked for a reliable way to differentiate these tumors, capitalizing on the invasive nature of BCC. The peritumoral stroma plays a role in tumor growth and invasion. It involves fibroblasts, inflammatory and endothelial cells, and extracellular matrix proteins. Matrilin-2, which is involved in the formation of filamentous networks, was a promising candidate and the initial investigations looked good, said Dr. Goreshi said.

Their confirmatory study comprised 42 BCC and seven BFH sections that were obtained during Mohs surgery. All were stained for matrilin-2 and scored for location and intensity of staining by two reviewers. The investigators also conducted flow cytometry to determine the source of the protein.

The BCC set consisted of 11 morpheaform/infiltrative BCCs, 25 nodular BCCs, and 6 superficial BCCs. With the exception of one superficial lesion, all of these stained positive for matrilin-2 in the peritumoral stroma. None of the BFH sections stained positive for the protein, however. Flow cytometry determined that the protein was coming from dermal fibroblasts in the stroma.

This is actually a key point, Dr. Goreshi noted. “Matrilin-2 is not acting as a conventional tumor marker would, but as a marker of invasion.”

This was again played out in the variation of staining intensity in the tumor subtypes. It was most intense around the infiltrative subtypes. There was also adnexal staining, but it was significantly less than what was seen in the peritumoral stroma. There was virtually no staining in or around the hamartoma.

Staining was not as intense around the superficial BCC subtypes. In fact, it was not significantly different from what was seen in the adnexal structures. Again, however, there was no staining in or around the hamartoma.

“Now we are looking at the staining patterns of other lesions, including melanoma and squamous cell carcinoma, and trying to figure out why the dermal fibroblasts are secreting matrilin-2,” Dr. Goreshi said.

The study was the winner of the 2016 Theodore Tromovitch Award, presented for original research conducted by a fellow-in-training during his or her year of training.

Neither Dr. Goreshi nor Dr. Iwamoto had any relevant financial disclosures.

[email protected]

ORLANDO – Matrilin-2 – a matrix protein found in peritumoral stroma – reliably distinguished invasive basal cell carcinoma from the often difficult-to-distinguish basaloid follicular hamartoma (BFH), in a study that evaluated the protein as a marker in this setting.

The protein marked 41 of 42 cancers and none of the hamartomas, Dr. Renato Goreshi reported at the annual meeting of the American College of Mohs Surgery. The one cancer it failed to identify was a superficial basal cell tumor – a finding that makes sense, since dermal fibroblasts appear to secrete matrilin-2 as a response to invasive skin tumors, said Dr. Goreshi of the Roger Williams Cancer Center, Providence, R.I.

Mohs surgery typically employs hematoxylin and eosin staining to delineate tumor boundary. But, Dr. Goreshi said, that stain doesn’t always reliably differentiate adnexal tumors from basal cell carcinomas. “Basaloid follicular hamartoma can be particularly difficult to distinguish from basal cell carcinoma,” he said.

BFH typically presents as individual or linearly arranged, small skin-colored to brown papules or plaques, or as multiple lesions in a generalized distribution on the face, scalp, and occasionally, the trunk (Arch Pathol Lab Med. 2010 Aug;134[8]:1215-9). These are often stable for many years. The differential diagnosis includes basal cell carcinoma and trichoepithelioma.

BFH sometimes occurs near a BCC, although there are no data on how often this happens.

Dr. Goreshi cited a 2007 case report of a young woman that illustrates this problem. The patient presented with a basal cell carcinoma on the side of her nose. The adjacent BFH was unrecognized, however. She underwent a multiple-stage Mohs that was unnecessarily extended because tumor margins included sections of the BFH.

“The lesion was interpreted as malignancy by both the Mohs surgeon and the dermatopathologist, but was later determined to have been a hamartoma. This highlights the importance of finding an effective marker,” Dr. Goreshi said.

He and his fellowship director, Dr. Satori Iwamoto, chief of Mohs micrographic surgery at Roger Williams, looked for a reliable way to differentiate these tumors, capitalizing on the invasive nature of BCC. The peritumoral stroma plays a role in tumor growth and invasion. It involves fibroblasts, inflammatory and endothelial cells, and extracellular matrix proteins. Matrilin-2, which is involved in the formation of filamentous networks, was a promising candidate and the initial investigations looked good, said Dr. Goreshi said.

Their confirmatory study comprised 42 BCC and seven BFH sections that were obtained during Mohs surgery. All were stained for matrilin-2 and scored for location and intensity of staining by two reviewers. The investigators also conducted flow cytometry to determine the source of the protein.

The BCC set consisted of 11 morpheaform/infiltrative BCCs, 25 nodular BCCs, and 6 superficial BCCs. With the exception of one superficial lesion, all of these stained positive for matrilin-2 in the peritumoral stroma. None of the BFH sections stained positive for the protein, however. Flow cytometry determined that the protein was coming from dermal fibroblasts in the stroma.

This is actually a key point, Dr. Goreshi noted. “Matrilin-2 is not acting as a conventional tumor marker would, but as a marker of invasion.”

This was again played out in the variation of staining intensity in the tumor subtypes. It was most intense around the infiltrative subtypes. There was also adnexal staining, but it was significantly less than what was seen in the peritumoral stroma. There was virtually no staining in or around the hamartoma.

Staining was not as intense around the superficial BCC subtypes. In fact, it was not significantly different from what was seen in the adnexal structures. Again, however, there was no staining in or around the hamartoma.

“Now we are looking at the staining patterns of other lesions, including melanoma and squamous cell carcinoma, and trying to figure out why the dermal fibroblasts are secreting matrilin-2,” Dr. Goreshi said.

The study was the winner of the 2016 Theodore Tromovitch Award, presented for original research conducted by a fellow-in-training during his or her year of training.

Neither Dr. Goreshi nor Dr. Iwamoto had any relevant financial disclosures.

[email protected]

ORLANDO – Matrilin-2 – a matrix protein found in peritumoral stroma – reliably distinguished invasive basal cell carcinoma from the often difficult-to-distinguish basaloid follicular hamartoma (BFH), in a study that evaluated the protein as a marker in this setting.

The protein marked 41 of 42 cancers and none of the hamartomas, Dr. Renato Goreshi reported at the annual meeting of the American College of Mohs Surgery. The one cancer it failed to identify was a superficial basal cell tumor – a finding that makes sense, since dermal fibroblasts appear to secrete matrilin-2 as a response to invasive skin tumors, said Dr. Goreshi of the Roger Williams Cancer Center, Providence, R.I.

Mohs surgery typically employs hematoxylin and eosin staining to delineate tumor boundary. But, Dr. Goreshi said, that stain doesn’t always reliably differentiate adnexal tumors from basal cell carcinomas. “Basaloid follicular hamartoma can be particularly difficult to distinguish from basal cell carcinoma,” he said.

BFH typically presents as individual or linearly arranged, small skin-colored to brown papules or plaques, or as multiple lesions in a generalized distribution on the face, scalp, and occasionally, the trunk (Arch Pathol Lab Med. 2010 Aug;134[8]:1215-9). These are often stable for many years. The differential diagnosis includes basal cell carcinoma and trichoepithelioma.

BFH sometimes occurs near a BCC, although there are no data on how often this happens.

Dr. Goreshi cited a 2007 case report of a young woman that illustrates this problem. The patient presented with a basal cell carcinoma on the side of her nose. The adjacent BFH was unrecognized, however. She underwent a multiple-stage Mohs that was unnecessarily extended because tumor margins included sections of the BFH.

“The lesion was interpreted as malignancy by both the Mohs surgeon and the dermatopathologist, but was later determined to have been a hamartoma. This highlights the importance of finding an effective marker,” Dr. Goreshi said.

He and his fellowship director, Dr. Satori Iwamoto, chief of Mohs micrographic surgery at Roger Williams, looked for a reliable way to differentiate these tumors, capitalizing on the invasive nature of BCC. The peritumoral stroma plays a role in tumor growth and invasion. It involves fibroblasts, inflammatory and endothelial cells, and extracellular matrix proteins. Matrilin-2, which is involved in the formation of filamentous networks, was a promising candidate and the initial investigations looked good, said Dr. Goreshi said.

Their confirmatory study comprised 42 BCC and seven BFH sections that were obtained during Mohs surgery. All were stained for matrilin-2 and scored for location and intensity of staining by two reviewers. The investigators also conducted flow cytometry to determine the source of the protein.

The BCC set consisted of 11 morpheaform/infiltrative BCCs, 25 nodular BCCs, and 6 superficial BCCs. With the exception of one superficial lesion, all of these stained positive for matrilin-2 in the peritumoral stroma. None of the BFH sections stained positive for the protein, however. Flow cytometry determined that the protein was coming from dermal fibroblasts in the stroma.

This is actually a key point, Dr. Goreshi noted. “Matrilin-2 is not acting as a conventional tumor marker would, but as a marker of invasion.”

This was again played out in the variation of staining intensity in the tumor subtypes. It was most intense around the infiltrative subtypes. There was also adnexal staining, but it was significantly less than what was seen in the peritumoral stroma. There was virtually no staining in or around the hamartoma.

Staining was not as intense around the superficial BCC subtypes. In fact, it was not significantly different from what was seen in the adnexal structures. Again, however, there was no staining in or around the hamartoma.

“Now we are looking at the staining patterns of other lesions, including melanoma and squamous cell carcinoma, and trying to figure out why the dermal fibroblasts are secreting matrilin-2,” Dr. Goreshi said.

The study was the winner of the 2016 Theodore Tromovitch Award, presented for original research conducted by a fellow-in-training during his or her year of training.

Neither Dr. Goreshi nor Dr. Iwamoto had any relevant financial disclosures.

[email protected]

WASHINGTON – Intraperitoneal chemotherapy may be unpleasant and interfere with daily life, but the large majority of women who received it for ovarian cancer agreed that it was the right choice for them.

A small survey of women who completed up to six cycles of the treatment found that most women did experience side effects, including fatigue, pain, and gastrointestinal issues. Despite those problems, more than 80% said they felt the regimen was “worth it,” and more than 90% said they would recommend it to another woman.

“Outpatient administration of chemotherapy appears to be feasible with acceptable toxicities and high completion rates,” Dr. Kristin Gotimer said at the annual meeting of the American College of Obstetricians and Gynecologists. “Toxicities were troublesome, and they did definitely affect quality of life; but almost none of our patients regretted being treated – even the ones who experienced recurrent disease.”

Dr. Gotimer of the Winthrop University Hospital, Mineola, N.Y., discussed a retrospective study of 98 women who underwent intraperitoneal chemotherapy for a gynecologic cancer from 2006 to 2014. Mean age of the patients was 58 years. Most women (71%) had ovarian cancer, and most cancer (70%) was stage IIIC or higher. All patients underwent cytoreductive surgery before starting chemotherapy.

Almost all women were prescribed six cycles of the regimen, which consisted of IV paclitaxel on day 1, intraperitoneal cisplatin on day 2, and intraperitoneal paclitaxel on day 8. Overall, 73% of patients completed their prescribed treatment. Among those prescribed six cycles, 71% completed all of them. Of the 26 patients who discontinued, 12 did so because of port complications, and 14 did so because of toxicities.

The most commonly reported side effects were gastrointestinal effects, fatigue, and neuropathy. Grade 3/4 toxicities were most often fatigue, neuropathy, and pain; those occurred in about 6% of patients per cycle. There were four cases of neutropenic fever; two of those resulted in treatment delays.

Seven patients had to change treatment, Dr. Gotimer said. Six switched from intraperitoneal cisplatin to intraperitoneal carboplatin, and one patient switched from IV paclitaxel to IV Abraxane. Toxicities were more likely to appear in later cycles. “The probability of starting each cycle was lower if the patient had experienced a severe toxicity in the prior cycle,” Dr. Gotimer explained.

A subset of patients (48) completed a survey about the treatment at a mean of 31 months after treatment. Of those, 92% had completed all their prescribed cycles. Disease had recurred in 21%. The three-domain survey queried the mental, physical, and social impact of the treatment.

On the physical health domain, half the group reported fatigue associated with the treatment. Others complained of pain (40%), gastrointestinal effects (37%), “chemo brain” cognitive dysfunction (29%), and alopecia (25%). A few patients experienced infections and dermatologic problems (less than 10% each).

In the mental health domain, patients most often noted stress (25%), anxiety (21%), and depression (15%) during treatment. They also said the therapy interfered with their social health, affecting work attendance (27%), housework (29%), and social interactions (19%). It also imposed a substantial time commitment, 17% of patients noted.

Despite those issues, 83% of patients endorsed intraperitoneal chemotherapy as “worth it,” and almost 90% said they would recommend it to a friend or family member considering it. Only about 5% of patients said they regretted using the treatment, although Dr. Gotimer didn’t specify what those regrets were.

Despite its small size and retrospective nature, the survey offers some clinically useful information, Dr. Gotimer noted. “We can identify modifiable side effects and develop specific interventions aimed at increasing tolerability.”

The results could also be used to “improve physician and patient understanding of realistic short- and long-term expectations to improve patient counseling,” she added.

Dr. Gotimer had no financial declarations.

[email protected]

On Twitter @Alz_Gal

WASHINGTON – Intraperitoneal chemotherapy may be unpleasant and interfere with daily life, but the large majority of women who received it for ovarian cancer agreed that it was the right choice for them.

A small survey of women who completed up to six cycles of the treatment found that most women did experience side effects, including fatigue, pain, and gastrointestinal issues. Despite those problems, more than 80% said they felt the regimen was “worth it,” and more than 90% said they would recommend it to another woman.

“Outpatient administration of chemotherapy appears to be feasible with acceptable toxicities and high completion rates,” Dr. Kristin Gotimer said at the annual meeting of the American College of Obstetricians and Gynecologists. “Toxicities were troublesome, and they did definitely affect quality of life; but almost none of our patients regretted being treated – even the ones who experienced recurrent disease.”

Dr. Gotimer of the Winthrop University Hospital, Mineola, N.Y., discussed a retrospective study of 98 women who underwent intraperitoneal chemotherapy for a gynecologic cancer from 2006 to 2014. Mean age of the patients was 58 years. Most women (71%) had ovarian cancer, and most cancer (70%) was stage IIIC or higher. All patients underwent cytoreductive surgery before starting chemotherapy.

Almost all women were prescribed six cycles of the regimen, which consisted of IV paclitaxel on day 1, intraperitoneal cisplatin on day 2, and intraperitoneal paclitaxel on day 8. Overall, 73% of patients completed their prescribed treatment. Among those prescribed six cycles, 71% completed all of them. Of the 26 patients who discontinued, 12 did so because of port complications, and 14 did so because of toxicities.

The most commonly reported side effects were gastrointestinal effects, fatigue, and neuropathy. Grade 3/4 toxicities were most often fatigue, neuropathy, and pain; those occurred in about 6% of patients per cycle. There were four cases of neutropenic fever; two of those resulted in treatment delays.

Seven patients had to change treatment, Dr. Gotimer said. Six switched from intraperitoneal cisplatin to intraperitoneal carboplatin, and one patient switched from IV paclitaxel to IV Abraxane. Toxicities were more likely to appear in later cycles. “The probability of starting each cycle was lower if the patient had experienced a severe toxicity in the prior cycle,” Dr. Gotimer explained.

A subset of patients (48) completed a survey about the treatment at a mean of 31 months after treatment. Of those, 92% had completed all their prescribed cycles. Disease had recurred in 21%. The three-domain survey queried the mental, physical, and social impact of the treatment.

On the physical health domain, half the group reported fatigue associated with the treatment. Others complained of pain (40%), gastrointestinal effects (37%), “chemo brain” cognitive dysfunction (29%), and alopecia (25%). A few patients experienced infections and dermatologic problems (less than 10% each).

In the mental health domain, patients most often noted stress (25%), anxiety (21%), and depression (15%) during treatment. They also said the therapy interfered with their social health, affecting work attendance (27%), housework (29%), and social interactions (19%). It also imposed a substantial time commitment, 17% of patients noted.

Despite those issues, 83% of patients endorsed intraperitoneal chemotherapy as “worth it,” and almost 90% said they would recommend it to a friend or family member considering it. Only about 5% of patients said they regretted using the treatment, although Dr. Gotimer didn’t specify what those regrets were.

Despite its small size and retrospective nature, the survey offers some clinically useful information, Dr. Gotimer noted. “We can identify modifiable side effects and develop specific interventions aimed at increasing tolerability.”

The results could also be used to “improve physician and patient understanding of realistic short- and long-term expectations to improve patient counseling,” she added.

Dr. Gotimer had no financial declarations.

[email protected]

On Twitter @Alz_Gal

WASHINGTON – Intraperitoneal chemotherapy may be unpleasant and interfere with daily life, but the large majority of women who received it for ovarian cancer agreed that it was the right choice for them.

A small survey of women who completed up to six cycles of the treatment found that most women did experience side effects, including fatigue, pain, and gastrointestinal issues. Despite those problems, more than 80% said they felt the regimen was “worth it,” and more than 90% said they would recommend it to another woman.

“Outpatient administration of chemotherapy appears to be feasible with acceptable toxicities and high completion rates,” Dr. Kristin Gotimer said at the annual meeting of the American College of Obstetricians and Gynecologists. “Toxicities were troublesome, and they did definitely affect quality of life; but almost none of our patients regretted being treated – even the ones who experienced recurrent disease.”

Dr. Gotimer of the Winthrop University Hospital, Mineola, N.Y., discussed a retrospective study of 98 women who underwent intraperitoneal chemotherapy for a gynecologic cancer from 2006 to 2014. Mean age of the patients was 58 years. Most women (71%) had ovarian cancer, and most cancer (70%) was stage IIIC or higher. All patients underwent cytoreductive surgery before starting chemotherapy.

Almost all women were prescribed six cycles of the regimen, which consisted of IV paclitaxel on day 1, intraperitoneal cisplatin on day 2, and intraperitoneal paclitaxel on day 8. Overall, 73% of patients completed their prescribed treatment. Among those prescribed six cycles, 71% completed all of them. Of the 26 patients who discontinued, 12 did so because of port complications, and 14 did so because of toxicities.

The most commonly reported side effects were gastrointestinal effects, fatigue, and neuropathy. Grade 3/4 toxicities were most often fatigue, neuropathy, and pain; those occurred in about 6% of patients per cycle. There were four cases of neutropenic fever; two of those resulted in treatment delays.

Seven patients had to change treatment, Dr. Gotimer said. Six switched from intraperitoneal cisplatin to intraperitoneal carboplatin, and one patient switched from IV paclitaxel to IV Abraxane. Toxicities were more likely to appear in later cycles. “The probability of starting each cycle was lower if the patient had experienced a severe toxicity in the prior cycle,” Dr. Gotimer explained.

A subset of patients (48) completed a survey about the treatment at a mean of 31 months after treatment. Of those, 92% had completed all their prescribed cycles. Disease had recurred in 21%. The three-domain survey queried the mental, physical, and social impact of the treatment.

On the physical health domain, half the group reported fatigue associated with the treatment. Others complained of pain (40%), gastrointestinal effects (37%), “chemo brain” cognitive dysfunction (29%), and alopecia (25%). A few patients experienced infections and dermatologic problems (less than 10% each).

In the mental health domain, patients most often noted stress (25%), anxiety (21%), and depression (15%) during treatment. They also said the therapy interfered with their social health, affecting work attendance (27%), housework (29%), and social interactions (19%). It also imposed a substantial time commitment, 17% of patients noted.

Despite those issues, 83% of patients endorsed intraperitoneal chemotherapy as “worth it,” and almost 90% said they would recommend it to a friend or family member considering it. Only about 5% of patients said they regretted using the treatment, although Dr. Gotimer didn’t specify what those regrets were.

Despite its small size and retrospective nature, the survey offers some clinically useful information, Dr. Gotimer noted. “We can identify modifiable side effects and develop specific interventions aimed at increasing tolerability.”

The results could also be used to “improve physician and patient understanding of realistic short- and long-term expectations to improve patient counseling,” she added.

Dr. Gotimer had no financial declarations.

[email protected]

On Twitter @Alz_Gal

WASHINGTON – A 1-week course of tamoxifen significantly reduced unscheduled bleeding in women using an etonogestrel contraceptive implant, compared with placebo.

The selective estrogen reuptake modifier cut bleeding days by half, compared with placebo, and in some women induced at least 1 month of amenorrhea, Dr. Katharine Simmons said at the annual meeting of the American College of Obstetricians and Gynecologists.

There were no real downsides to using the drug, added Dr. Simmons, an ob.gyn. in Atlanta. There were no significant differences in adverse events between the two treatment groups.

The 6-month study randomized 56 women to 10 mg tamoxifen twice daily or placebo for 7 days. Women were instructed to begin treatment on the third day of any period of unscheduled bleeding. They could use the drug once each month, for up to three cycles during the study period. Every day, the women had to complete a short bleeding diary. This was administered by a daily text message, which asked them to rate the strength of any bleeding over the last 24 hours, and whether or not they had taken the study drug on that day.

The women were young (mean age 25 years), and most were white (about 80%). More than 60% were nulliparous. They had been using the implant for a mean of 275 days. Upon randomization, those in the tamoxifen group reported more unscheduled bleeding days than did those in the placebo group (mean 23 vs. 20 per 30 days). Ten women in the tamoxifen group reported bleeding almost every day of the prior month.

Thirty days after taking the study drug, bleeding days were significantly reduced in the tamoxifen group, compared with the placebo group. Four of 28 women taking the drug experienced complete amenorrhea; 9 reported 5 days of bleeding. The tamoxifen group reported a median of 6 bleeding days after treatment, compared with 12 days in the placebo group.

The effect was sustained, Dr. Simmons said, with a median of 30 days before bleeding resumed in the tamoxifen group, compared with 8 days in the placebo group. Women taking the drug reported significantly greater levels of satisfaction than did those taking placebo. They also were less likely to discontinue the treatment (18% vs. 36%).

There were no significant differences in side effects. Headache was the most common, with 12 women in each group reporting it. Mood changes occurred in 7 taking tamoxifen and in 12 women taking placebo. Hot flashes were slightly more common in the tamoxifen group (6 vs. 4). Reports of nausea, weight gain, and fluid retention were similar.

Dr. Simmons conducted the study during her time at Oregon Health & Science University in Portland. She had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

WASHINGTON – A 1-week course of tamoxifen significantly reduced unscheduled bleeding in women using an etonogestrel contraceptive implant, compared with placebo.

The selective estrogen reuptake modifier cut bleeding days by half, compared with placebo, and in some women induced at least 1 month of amenorrhea, Dr. Katharine Simmons said at the annual meeting of the American College of Obstetricians and Gynecologists.

There were no real downsides to using the drug, added Dr. Simmons, an ob.gyn. in Atlanta. There were no significant differences in adverse events between the two treatment groups.

The 6-month study randomized 56 women to 10 mg tamoxifen twice daily or placebo for 7 days. Women were instructed to begin treatment on the third day of any period of unscheduled bleeding. They could use the drug once each month, for up to three cycles during the study period. Every day, the women had to complete a short bleeding diary. This was administered by a daily text message, which asked them to rate the strength of any bleeding over the last 24 hours, and whether or not they had taken the study drug on that day.

The women were young (mean age 25 years), and most were white (about 80%). More than 60% were nulliparous. They had been using the implant for a mean of 275 days. Upon randomization, those in the tamoxifen group reported more unscheduled bleeding days than did those in the placebo group (mean 23 vs. 20 per 30 days). Ten women in the tamoxifen group reported bleeding almost every day of the prior month.

Thirty days after taking the study drug, bleeding days were significantly reduced in the tamoxifen group, compared with the placebo group. Four of 28 women taking the drug experienced complete amenorrhea; 9 reported 5 days of bleeding. The tamoxifen group reported a median of 6 bleeding days after treatment, compared with 12 days in the placebo group.

The effect was sustained, Dr. Simmons said, with a median of 30 days before bleeding resumed in the tamoxifen group, compared with 8 days in the placebo group. Women taking the drug reported significantly greater levels of satisfaction than did those taking placebo. They also were less likely to discontinue the treatment (18% vs. 36%).

There were no significant differences in side effects. Headache was the most common, with 12 women in each group reporting it. Mood changes occurred in 7 taking tamoxifen and in 12 women taking placebo. Hot flashes were slightly more common in the tamoxifen group (6 vs. 4). Reports of nausea, weight gain, and fluid retention were similar.

Dr. Simmons conducted the study during her time at Oregon Health & Science University in Portland. She had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

WASHINGTON – A 1-week course of tamoxifen significantly reduced unscheduled bleeding in women using an etonogestrel contraceptive implant, compared with placebo.

The selective estrogen reuptake modifier cut bleeding days by half, compared with placebo, and in some women induced at least 1 month of amenorrhea, Dr. Katharine Simmons said at the annual meeting of the American College of Obstetricians and Gynecologists.

There were no real downsides to using the drug, added Dr. Simmons, an ob.gyn. in Atlanta. There were no significant differences in adverse events between the two treatment groups.

The 6-month study randomized 56 women to 10 mg tamoxifen twice daily or placebo for 7 days. Women were instructed to begin treatment on the third day of any period of unscheduled bleeding. They could use the drug once each month, for up to three cycles during the study period. Every day, the women had to complete a short bleeding diary. This was administered by a daily text message, which asked them to rate the strength of any bleeding over the last 24 hours, and whether or not they had taken the study drug on that day.

The women were young (mean age 25 years), and most were white (about 80%). More than 60% were nulliparous. They had been using the implant for a mean of 275 days. Upon randomization, those in the tamoxifen group reported more unscheduled bleeding days than did those in the placebo group (mean 23 vs. 20 per 30 days). Ten women in the tamoxifen group reported bleeding almost every day of the prior month.

Thirty days after taking the study drug, bleeding days were significantly reduced in the tamoxifen group, compared with the placebo group. Four of 28 women taking the drug experienced complete amenorrhea; 9 reported 5 days of bleeding. The tamoxifen group reported a median of 6 bleeding days after treatment, compared with 12 days in the placebo group.

The effect was sustained, Dr. Simmons said, with a median of 30 days before bleeding resumed in the tamoxifen group, compared with 8 days in the placebo group. Women taking the drug reported significantly greater levels of satisfaction than did those taking placebo. They also were less likely to discontinue the treatment (18% vs. 36%).

There were no significant differences in side effects. Headache was the most common, with 12 women in each group reporting it. Mood changes occurred in 7 taking tamoxifen and in 12 women taking placebo. Hot flashes were slightly more common in the tamoxifen group (6 vs. 4). Reports of nausea, weight gain, and fluid retention were similar.

Dr. Simmons conducted the study during her time at Oregon Health & Science University in Portland. She had no financial disclosures.

[email protected]

On Twitter @Alz_Gal