Associations of migraine severity and presence of associated features with inhibitory control varied by body mass index (BMI) in overweight/obese women with migraine, according to a recent study. These findings, therefore, warrant consideration of weight status in clarifying the role of migraine in executive functioning. Women (n=124) aged 18–50 years with overweight/obesity BMI=35.1 ± 6.4 kg/m² and migraine completed a 28-day smartphone-based headache diary assessing migraine headache severity (attack frequency, pain intensity) and frequency of associated features (aura, photophobia, phonophobia, nausea). They then completed computerized measures of inhibitory control during an interictal (headache-free) period. Researchers found:

• Participants with higher migraine attack frequency performed worse on the Flanker test (accuracy and reaction time).
• Migraine attack frequency and pain intensity interacted with BMI to predict slower Stroop and/or Flanker Reaction Time (RT).
• More frequent photophobia, phonophobia, and aura were independently related to slower RT on the Stroop and/or Flanker tests, and BMI moderated the relationship between the occurrence of aura and Stroop RT.

The role of migraine headache severity, associated features and interactions with overweight/obesity in inhibitory control. Int J Neurosci. 2018;128(1):63-70. doi:10.1080/00207454.2017.1366474.

Associations of migraine severity and presence of associated features with inhibitory control varied by body mass index (BMI) in overweight/obese women with migraine, according to a recent study. These findings, therefore, warrant consideration of weight status in clarifying the role of migraine in executive functioning. Women (n=124) aged 18–50 years with overweight/obesity BMI=35.1 ± 6.4 kg/m² and migraine completed a 28-day smartphone-based headache diary assessing migraine headache severity (attack frequency, pain intensity) and frequency of associated features (aura, photophobia, phonophobia, nausea). They then completed computerized measures of inhibitory control during an interictal (headache-free) period. Researchers found:

• Participants with higher migraine attack frequency performed worse on the Flanker test (accuracy and reaction time).
• Migraine attack frequency and pain intensity interacted with BMI to predict slower Stroop and/or Flanker Reaction Time (RT).
• More frequent photophobia, phonophobia, and aura were independently related to slower RT on the Stroop and/or Flanker tests, and BMI moderated the relationship between the occurrence of aura and Stroop RT.

The role of migraine headache severity, associated features and interactions with overweight/obesity in inhibitory control. Int J Neurosci. 2018;128(1):63-70. doi:10.1080/00207454.2017.1366474.

Associations of migraine severity and presence of associated features with inhibitory control varied by body mass index (BMI) in overweight/obese women with migraine, according to a recent study. These findings, therefore, warrant consideration of weight status in clarifying the role of migraine in executive functioning. Women (n=124) aged 18–50 years with overweight/obesity BMI=35.1 ± 6.4 kg/m² and migraine completed a 28-day smartphone-based headache diary assessing migraine headache severity (attack frequency, pain intensity) and frequency of associated features (aura, photophobia, phonophobia, nausea). They then completed computerized measures of inhibitory control during an interictal (headache-free) period. Researchers found:

• Participants with higher migraine attack frequency performed worse on the Flanker test (accuracy and reaction time).
• Migraine attack frequency and pain intensity interacted with BMI to predict slower Stroop and/or Flanker Reaction Time (RT).
• More frequent photophobia, phonophobia, and aura were independently related to slower RT on the Stroop and/or Flanker tests, and BMI moderated the relationship between the occurrence of aura and Stroop RT.

The role of migraine headache severity, associated features and interactions with overweight/obesity in inhibitory control. Int J Neurosci. 2018;128(1):63-70. doi:10.1080/00207454.2017.1366474.

To the Editor:

A 40-year-old woman with a history of stage IIIC ovarian cancer presented with progressing abdominal erythema and pain of 1 month’s duration. She had been diagnosed 4 years prior with grade 3, poorly differentiated papillary serous carcinoma involving the bilateral ovaries, uterine tubes, uterus, and omentum with lymphovascular invasion. She underwent tumor resection and debulking followed by paclitaxel plus platinum-based chemotherapy. The cancer recurred 2 years later with carcinomatous ascites. She declined chemotherapy but underwent therapeutic paracentesis.

One month prior to presentation, the patient developed a small, tender, erythematous patch on the abdomen. Her primary physician started her on cephalexin for presumed cellulitis without improvement. The erythema continued to spread on the abdomen with worsening pain, which prompted her presentation to the emergency department. She was admitted and started on intravenous vancomycin.

On admission to the hospital, the patient was cachexic and afebrile with a white blood cell count of 10,400/µL (reference range, 4500–11,000/µL). Physical examination revealed a well-demarcated, 15×20-cm, erythematous, blanchable, indurated plaque in the periumbilical region (Figure 1). The plaque was tender to palpation with guarding but no increased warmth. Punch biopsies of the abdominal skin revealed carcinoma within the lymphatic channels in the deep dermis and dilated lymphatics throughout the overlying dermis (Figure 2). These findings were diagnostic for carcinoma erysipeloides. Tissue and blood cultures were negative for bacterial, fungal, or mycobacterial growth. Vancomycin was discontinued, and she was discharged with pain medication. She declined chemotherapy due to the potential side effects and elected to continue symptomatic management with palliative paracentesis. After she was discharged, she underwent a tunneled pleural catheterization for recurrent malignant pleural effusions.

Carcinoma erysipeloides is a rare cutaneous metastasis secondary to internal malignancy that presents as well-demarcated areas of erythema and is sometimes misdiagnosed as cellulitis or erysipelas. Histology is notable for lymphovascular congestion without inflammation. Carcinoma erysipeloides most commonly is associated with breast cancer, but it also has been described in cancers of the prostate, larynx, stomach, lungs, thyroid, parotid gland, fallopian tubes, cervix, pancreas, and metastatic melanoma.^1-5 While the pathogenesis of carcinoma erysipeloides is poorly understood, it is thought to occur by direct spread of tumor cells from the lymph nodes to the cutaneous lymphatics, causing obstruction and edema.

Ovarian cancer has the highest mortality of all gynecologic cancers and often is associated with delayed diagnosis. Cutaneous metastasis is a late manifestation often presenting as subcutaneous nodules.^6,7 Carcinoma erysipeloides is an even rarer presentation of ovarian cancer, with a poor prognosis and a median survival of 18 months.⁸ A PubMed search of articles indexed for MEDLINE using the term carcinoma erysipeloides revealed 9 cases of carcinoma erysipeloides from ovarian cancer: 1 describing erythematous papules, plaques, and zosteriform vesicles on the upper thighs to the lower abdomen,⁹ and 8 describing erythematous plaques on the breasts.^8,10 We report a case of carcinoma erysipeloides associated with stage IIIc ovarian cancer localized to the abdominal wall mimicking cellulitis. Our report reminds clinicians of this important diagnosis in ovarian cancer and of the importance of a skin biopsy to expedite a definitive diagnosis. Immunohistochemistry using ovarian tumor markers (eg, paired-box gene 8, cancer antigen 125) is an additional tool to accurately identify malignant cells in skin biopsy.^8,10 Once diagnosed, primary treatment for carcinoma erysipeloides is treatment of the underlying malignancy.

To the Editor:

A 40-year-old woman with a history of stage IIIC ovarian cancer presented with progressing abdominal erythema and pain of 1 month’s duration. She had been diagnosed 4 years prior with grade 3, poorly differentiated papillary serous carcinoma involving the bilateral ovaries, uterine tubes, uterus, and omentum with lymphovascular invasion. She underwent tumor resection and debulking followed by paclitaxel plus platinum-based chemotherapy. The cancer recurred 2 years later with carcinomatous ascites. She declined chemotherapy but underwent therapeutic paracentesis.

One month prior to presentation, the patient developed a small, tender, erythematous patch on the abdomen. Her primary physician started her on cephalexin for presumed cellulitis without improvement. The erythema continued to spread on the abdomen with worsening pain, which prompted her presentation to the emergency department. She was admitted and started on intravenous vancomycin.

On admission to the hospital, the patient was cachexic and afebrile with a white blood cell count of 10,400/µL (reference range, 4500–11,000/µL). Physical examination revealed a well-demarcated, 15×20-cm, erythematous, blanchable, indurated plaque in the periumbilical region (Figure 1). The plaque was tender to palpation with guarding but no increased warmth. Punch biopsies of the abdominal skin revealed carcinoma within the lymphatic channels in the deep dermis and dilated lymphatics throughout the overlying dermis (Figure 2). These findings were diagnostic for carcinoma erysipeloides. Tissue and blood cultures were negative for bacterial, fungal, or mycobacterial growth. Vancomycin was discontinued, and she was discharged with pain medication. She declined chemotherapy due to the potential side effects and elected to continue symptomatic management with palliative paracentesis. After she was discharged, she underwent a tunneled pleural catheterization for recurrent malignant pleural effusions.

Carcinoma erysipeloides is a rare cutaneous metastasis secondary to internal malignancy that presents as well-demarcated areas of erythema and is sometimes misdiagnosed as cellulitis or erysipelas. Histology is notable for lymphovascular congestion without inflammation. Carcinoma erysipeloides most commonly is associated with breast cancer, but it also has been described in cancers of the prostate, larynx, stomach, lungs, thyroid, parotid gland, fallopian tubes, cervix, pancreas, and metastatic melanoma.^1-5 While the pathogenesis of carcinoma erysipeloides is poorly understood, it is thought to occur by direct spread of tumor cells from the lymph nodes to the cutaneous lymphatics, causing obstruction and edema.

Ovarian cancer has the highest mortality of all gynecologic cancers and often is associated with delayed diagnosis. Cutaneous metastasis is a late manifestation often presenting as subcutaneous nodules.^6,7 Carcinoma erysipeloides is an even rarer presentation of ovarian cancer, with a poor prognosis and a median survival of 18 months.⁸ A PubMed search of articles indexed for MEDLINE using the term carcinoma erysipeloides revealed 9 cases of carcinoma erysipeloides from ovarian cancer: 1 describing erythematous papules, plaques, and zosteriform vesicles on the upper thighs to the lower abdomen,⁹ and 8 describing erythematous plaques on the breasts.^8,10 We report a case of carcinoma erysipeloides associated with stage IIIc ovarian cancer localized to the abdominal wall mimicking cellulitis. Our report reminds clinicians of this important diagnosis in ovarian cancer and of the importance of a skin biopsy to expedite a definitive diagnosis. Immunohistochemistry using ovarian tumor markers (eg, paired-box gene 8, cancer antigen 125) is an additional tool to accurately identify malignant cells in skin biopsy.^8,10 Once diagnosed, primary treatment for carcinoma erysipeloides is treatment of the underlying malignancy.

To the Editor:

A 40-year-old woman with a history of stage IIIC ovarian cancer presented with progressing abdominal erythema and pain of 1 month’s duration. She had been diagnosed 4 years prior with grade 3, poorly differentiated papillary serous carcinoma involving the bilateral ovaries, uterine tubes, uterus, and omentum with lymphovascular invasion. She underwent tumor resection and debulking followed by paclitaxel plus platinum-based chemotherapy. The cancer recurred 2 years later with carcinomatous ascites. She declined chemotherapy but underwent therapeutic paracentesis.

One month prior to presentation, the patient developed a small, tender, erythematous patch on the abdomen. Her primary physician started her on cephalexin for presumed cellulitis without improvement. The erythema continued to spread on the abdomen with worsening pain, which prompted her presentation to the emergency department. She was admitted and started on intravenous vancomycin.

On admission to the hospital, the patient was cachexic and afebrile with a white blood cell count of 10,400/µL (reference range, 4500–11,000/µL). Physical examination revealed a well-demarcated, 15×20-cm, erythematous, blanchable, indurated plaque in the periumbilical region (Figure 1). The plaque was tender to palpation with guarding but no increased warmth. Punch biopsies of the abdominal skin revealed carcinoma within the lymphatic channels in the deep dermis and dilated lymphatics throughout the overlying dermis (Figure 2). These findings were diagnostic for carcinoma erysipeloides. Tissue and blood cultures were negative for bacterial, fungal, or mycobacterial growth. Vancomycin was discontinued, and she was discharged with pain medication. She declined chemotherapy due to the potential side effects and elected to continue symptomatic management with palliative paracentesis. After she was discharged, she underwent a tunneled pleural catheterization for recurrent malignant pleural effusions.

Carcinoma erysipeloides is a rare cutaneous metastasis secondary to internal malignancy that presents as well-demarcated areas of erythema and is sometimes misdiagnosed as cellulitis or erysipelas. Histology is notable for lymphovascular congestion without inflammation. Carcinoma erysipeloides most commonly is associated with breast cancer, but it also has been described in cancers of the prostate, larynx, stomach, lungs, thyroid, parotid gland, fallopian tubes, cervix, pancreas, and metastatic melanoma.^1-5 While the pathogenesis of carcinoma erysipeloides is poorly understood, it is thought to occur by direct spread of tumor cells from the lymph nodes to the cutaneous lymphatics, causing obstruction and edema.

Ovarian cancer has the highest mortality of all gynecologic cancers and often is associated with delayed diagnosis. Cutaneous metastasis is a late manifestation often presenting as subcutaneous nodules.^6,7 Carcinoma erysipeloides is an even rarer presentation of ovarian cancer, with a poor prognosis and a median survival of 18 months.⁸ A PubMed search of articles indexed for MEDLINE using the term carcinoma erysipeloides revealed 9 cases of carcinoma erysipeloides from ovarian cancer: 1 describing erythematous papules, plaques, and zosteriform vesicles on the upper thighs to the lower abdomen,⁹ and 8 describing erythematous plaques on the breasts.^8,10 We report a case of carcinoma erysipeloides associated with stage IIIc ovarian cancer localized to the abdominal wall mimicking cellulitis. Our report reminds clinicians of this important diagnosis in ovarian cancer and of the importance of a skin biopsy to expedite a definitive diagnosis. Immunohistochemistry using ovarian tumor markers (eg, paired-box gene 8, cancer antigen 125) is an additional tool to accurately identify malignant cells in skin biopsy.^8,10 Once diagnosed, primary treatment for carcinoma erysipeloides is treatment of the underlying malignancy.

To the Editor:

Sentinel lymph node (SLN) biopsies routinely are performed to detect regional metastases in a variety of malignancies, including breast cancer, squamous cell carcinoma, Merkel cell carcinoma, and melanoma. Histologic examination of an SLN occasionally enables detection of other unsuspected underlying diseases that typically are inflammatory in nature. Although concomitant hematolymphoid malignancy, particularly chronic lymphocytic leukemia, has been reported in SLNs, collision of 2 different solid tumors in the same SLN is rare.^1,2 We report a unique case documenting collision of both metastatic melanoma and prostatic adenocarcinoma detected in an SLN to raise awareness of the diagnostic challenges occurring in patients with coexisting malignancies.

A 71-year-old man with a history of metastatic prostatic adenocarcinoma to the bone presented for treatment of a melanoma that was newly diagnosed by an outside dermatologist. The patient’s medical history was notable for radical prostatectomy performed 15 years prior for treatment of a prostatic adenocarcinoma (Gleason score unknown) followed by bilateral orchiectomy performed 7 years later after his serum prostate-specific antigen (PSA) level began to rise, with no response to goserelin (a gonadotropin-releasing hormone agonist) therapy. Two years prior to the diagnosis of metastatic disease, his PSA level started to rise again and the patient received bicalutamide with little improvement, followed by 8 cycles of docetaxel. His PSA level improved and he most recently was being treated with abiraterone acetate. The patient’s latest computed tomography scan showed that the bony metastases secondary to prostatic adenocarcinoma had progressed. His serum PSA level was 105 ng/mL (reference range, <4.0 ng/mL) at the current presentation, elevated from 64 ng/mL one year prior.

Recently, the patient had noted a changing pigmented skin lesion on the left side of the flank. The patient described the lesion as a “black mole” first appearing 2 years prior, which had begun to ooze, change shape, and become darker and more nodular. A shave biopsy revealed a primary cutaneous malignant melanoma at least 3.4 mm in depth with ulceration and a mitotic rate of 15/mm². No molecular studies were performed on the melanoma. Standard treatment via wide local excision and sentinel lymphadenectomy was planned.

Lymphoscintigraphy revealed 3 left draining axillary lymph nodes. The patient was treated with wide local excision and left axillary SLN biopsy. Five SLNs and 3 non-SLNs were excised. Per protocol, all SLNs were examined pathologically with serial sections: 2 hematoxylin and eosin–stained levels, S-100, and melan-A immunohistochemical stains. No residual melanoma was identified in the wide-excision specimen. Examination of the left axillary SLNs revealed metastatic melanoma in 3 of 5 SLNs. Two SLNs demonstrated total replacement by metastatic melanoma. A third SLN revealed a metastatic malignant neoplasm occupying 75% of the nodal area (Figure, A). S-100 and melan-A immunohistochemical staining were negative in this nodule but revealed small aggregates and isolated tumor cells distinct from this nodule that were diagnostic of micrometastatic melanoma (Figures, B and C). The tumor cells in the large nodule were histologically distinct from the melanoma and were instead composed of nests of epithelioid cells with clear cytoplasm (Figure, D). Upon further immunohistochemical staining, this tumor was strongly positive for AE1/AE3 keratin and PIN4 cocktail (cytokeratin 5, cytokeratin 15, p63, and p504s/alpha-methylacyl-CoA-racemase)(Figure, E) with focal positivity for PSA and prostatic acid phosphatase, diagnostic of metastatic adenocarcinoma of prostate origin.

A positron emission tomography scan performed a few days after the discovery of metastatic prostatic adenocarcinoma in the SLNs showed expected postoperative changes (eg, increased activity from procedure-related inflammation) in the left side of the flank and axilla as well as moderately hypermetabolic left supraclavicular lymph nodes suspicious for viable metastatic disease. Subsequent fine-needle aspiration of the aforementioned lymph nodes revealed metastatic prostatic adenocarcinoma. The preoperative lymphoscintigraphy at the time of SLN biopsy did not show drainage to the left supraclavicular nodal basin.

Based on a discussion of the patient’s case during a multidisciplinary tumor board consultation, the benefit of performing completion lymph node dissection for melanoma management did not outweigh the risks. Accordingly, the patient received adjuvant radiation therapy to the axillary nodal basin. He was started on ketoconazole and zoledronic acid therapy for metastatic prostate adenocarcinoma and was alive with disease at 6-month follow-up. The finding of both metastatic melanoma and prostate adenocarcinoma detected in an SLN after wide excision and SLN biopsy for cutaneous melanoma is a unique report of collision of these 2 tumors. Rare cases of collision between 2 solid tumors occurring in the same lymph node have involved prostate adenocarcinoma as one of the solid tumor components.^1,3 Detection of tumor collision on lymph node biopsy between prostatic adenocarcinoma and urothelial carcinoma has been documented in 2 separate cases.¹ Three additional cases of concurrent prostatic adenocarcinoma and colorectal adenocarcinoma identified on lymph node biopsy have been reported.^1,3 Although never proven statistically, it is likely that these concurrent diagnoses are due to the high incidences of prostate and colorectal adenocarcinomas in the general US population; they are ranked first and third, respectively, for cancer incidence in US males.⁴

As demonstrated in the current case and the available literature, immunohistochemical stains play a vital role in the detection of tumor collision phenomena as well as identification of histologic source of the metastases. Furthermore, thorough histopathologic examination of biopsy specimens in the context of a patient’s clinical history remains paramount in obtaining an accurate diagnosis. Earlier identification of second malignancies in SLNs can alert the clinician to the presence of relapse of a known concurrent malignancy before it is clinically apparent, enhancing the possibility of more effective treatment of earlier disease. As has been demonstrated for lymphoma and melanoma, in rare cases awareness of the possibility of a second malignancy in the SLN can result in earlier initial diagnosis of undiscovered malignancy.²

To the Editor:

Sentinel lymph node (SLN) biopsies routinely are performed to detect regional metastases in a variety of malignancies, including breast cancer, squamous cell carcinoma, Merkel cell carcinoma, and melanoma. Histologic examination of an SLN occasionally enables detection of other unsuspected underlying diseases that typically are inflammatory in nature. Although concomitant hematolymphoid malignancy, particularly chronic lymphocytic leukemia, has been reported in SLNs, collision of 2 different solid tumors in the same SLN is rare.^1,2 We report a unique case documenting collision of both metastatic melanoma and prostatic adenocarcinoma detected in an SLN to raise awareness of the diagnostic challenges occurring in patients with coexisting malignancies.

A 71-year-old man with a history of metastatic prostatic adenocarcinoma to the bone presented for treatment of a melanoma that was newly diagnosed by an outside dermatologist. The patient’s medical history was notable for radical prostatectomy performed 15 years prior for treatment of a prostatic adenocarcinoma (Gleason score unknown) followed by bilateral orchiectomy performed 7 years later after his serum prostate-specific antigen (PSA) level began to rise, with no response to goserelin (a gonadotropin-releasing hormone agonist) therapy. Two years prior to the diagnosis of metastatic disease, his PSA level started to rise again and the patient received bicalutamide with little improvement, followed by 8 cycles of docetaxel. His PSA level improved and he most recently was being treated with abiraterone acetate. The patient’s latest computed tomography scan showed that the bony metastases secondary to prostatic adenocarcinoma had progressed. His serum PSA level was 105 ng/mL (reference range, <4.0 ng/mL) at the current presentation, elevated from 64 ng/mL one year prior.

Recently, the patient had noted a changing pigmented skin lesion on the left side of the flank. The patient described the lesion as a “black mole” first appearing 2 years prior, which had begun to ooze, change shape, and become darker and more nodular. A shave biopsy revealed a primary cutaneous malignant melanoma at least 3.4 mm in depth with ulceration and a mitotic rate of 15/mm². No molecular studies were performed on the melanoma. Standard treatment via wide local excision and sentinel lymphadenectomy was planned.

Lymphoscintigraphy revealed 3 left draining axillary lymph nodes. The patient was treated with wide local excision and left axillary SLN biopsy. Five SLNs and 3 non-SLNs were excised. Per protocol, all SLNs were examined pathologically with serial sections: 2 hematoxylin and eosin–stained levels, S-100, and melan-A immunohistochemical stains. No residual melanoma was identified in the wide-excision specimen. Examination of the left axillary SLNs revealed metastatic melanoma in 3 of 5 SLNs. Two SLNs demonstrated total replacement by metastatic melanoma. A third SLN revealed a metastatic malignant neoplasm occupying 75% of the nodal area (Figure, A). S-100 and melan-A immunohistochemical staining were negative in this nodule but revealed small aggregates and isolated tumor cells distinct from this nodule that were diagnostic of micrometastatic melanoma (Figures, B and C). The tumor cells in the large nodule were histologically distinct from the melanoma and were instead composed of nests of epithelioid cells with clear cytoplasm (Figure, D). Upon further immunohistochemical staining, this tumor was strongly positive for AE1/AE3 keratin and PIN4 cocktail (cytokeratin 5, cytokeratin 15, p63, and p504s/alpha-methylacyl-CoA-racemase)(Figure, E) with focal positivity for PSA and prostatic acid phosphatase, diagnostic of metastatic adenocarcinoma of prostate origin.

A positron emission tomography scan performed a few days after the discovery of metastatic prostatic adenocarcinoma in the SLNs showed expected postoperative changes (eg, increased activity from procedure-related inflammation) in the left side of the flank and axilla as well as moderately hypermetabolic left supraclavicular lymph nodes suspicious for viable metastatic disease. Subsequent fine-needle aspiration of the aforementioned lymph nodes revealed metastatic prostatic adenocarcinoma. The preoperative lymphoscintigraphy at the time of SLN biopsy did not show drainage to the left supraclavicular nodal basin.

Based on a discussion of the patient’s case during a multidisciplinary tumor board consultation, the benefit of performing completion lymph node dissection for melanoma management did not outweigh the risks. Accordingly, the patient received adjuvant radiation therapy to the axillary nodal basin. He was started on ketoconazole and zoledronic acid therapy for metastatic prostate adenocarcinoma and was alive with disease at 6-month follow-up. The finding of both metastatic melanoma and prostate adenocarcinoma detected in an SLN after wide excision and SLN biopsy for cutaneous melanoma is a unique report of collision of these 2 tumors. Rare cases of collision between 2 solid tumors occurring in the same lymph node have involved prostate adenocarcinoma as one of the solid tumor components.^1,3 Detection of tumor collision on lymph node biopsy between prostatic adenocarcinoma and urothelial carcinoma has been documented in 2 separate cases.¹ Three additional cases of concurrent prostatic adenocarcinoma and colorectal adenocarcinoma identified on lymph node biopsy have been reported.^1,3 Although never proven statistically, it is likely that these concurrent diagnoses are due to the high incidences of prostate and colorectal adenocarcinomas in the general US population; they are ranked first and third, respectively, for cancer incidence in US males.⁴

As demonstrated in the current case and the available literature, immunohistochemical stains play a vital role in the detection of tumor collision phenomena as well as identification of histologic source of the metastases. Furthermore, thorough histopathologic examination of biopsy specimens in the context of a patient’s clinical history remains paramount in obtaining an accurate diagnosis. Earlier identification of second malignancies in SLNs can alert the clinician to the presence of relapse of a known concurrent malignancy before it is clinically apparent, enhancing the possibility of more effective treatment of earlier disease. As has been demonstrated for lymphoma and melanoma, in rare cases awareness of the possibility of a second malignancy in the SLN can result in earlier initial diagnosis of undiscovered malignancy.²

To the Editor:

Sentinel lymph node (SLN) biopsies routinely are performed to detect regional metastases in a variety of malignancies, including breast cancer, squamous cell carcinoma, Merkel cell carcinoma, and melanoma. Histologic examination of an SLN occasionally enables detection of other unsuspected underlying diseases that typically are inflammatory in nature. Although concomitant hematolymphoid malignancy, particularly chronic lymphocytic leukemia, has been reported in SLNs, collision of 2 different solid tumors in the same SLN is rare.^1,2 We report a unique case documenting collision of both metastatic melanoma and prostatic adenocarcinoma detected in an SLN to raise awareness of the diagnostic challenges occurring in patients with coexisting malignancies.

A 71-year-old man with a history of metastatic prostatic adenocarcinoma to the bone presented for treatment of a melanoma that was newly diagnosed by an outside dermatologist. The patient’s medical history was notable for radical prostatectomy performed 15 years prior for treatment of a prostatic adenocarcinoma (Gleason score unknown) followed by bilateral orchiectomy performed 7 years later after his serum prostate-specific antigen (PSA) level began to rise, with no response to goserelin (a gonadotropin-releasing hormone agonist) therapy. Two years prior to the diagnosis of metastatic disease, his PSA level started to rise again and the patient received bicalutamide with little improvement, followed by 8 cycles of docetaxel. His PSA level improved and he most recently was being treated with abiraterone acetate. The patient’s latest computed tomography scan showed that the bony metastases secondary to prostatic adenocarcinoma had progressed. His serum PSA level was 105 ng/mL (reference range, <4.0 ng/mL) at the current presentation, elevated from 64 ng/mL one year prior.

Recently, the patient had noted a changing pigmented skin lesion on the left side of the flank. The patient described the lesion as a “black mole” first appearing 2 years prior, which had begun to ooze, change shape, and become darker and more nodular. A shave biopsy revealed a primary cutaneous malignant melanoma at least 3.4 mm in depth with ulceration and a mitotic rate of 15/mm². No molecular studies were performed on the melanoma. Standard treatment via wide local excision and sentinel lymphadenectomy was planned.

Lymphoscintigraphy revealed 3 left draining axillary lymph nodes. The patient was treated with wide local excision and left axillary SLN biopsy. Five SLNs and 3 non-SLNs were excised. Per protocol, all SLNs were examined pathologically with serial sections: 2 hematoxylin and eosin–stained levels, S-100, and melan-A immunohistochemical stains. No residual melanoma was identified in the wide-excision specimen. Examination of the left axillary SLNs revealed metastatic melanoma in 3 of 5 SLNs. Two SLNs demonstrated total replacement by metastatic melanoma. A third SLN revealed a metastatic malignant neoplasm occupying 75% of the nodal area (Figure, A). S-100 and melan-A immunohistochemical staining were negative in this nodule but revealed small aggregates and isolated tumor cells distinct from this nodule that were diagnostic of micrometastatic melanoma (Figures, B and C). The tumor cells in the large nodule were histologically distinct from the melanoma and were instead composed of nests of epithelioid cells with clear cytoplasm (Figure, D). Upon further immunohistochemical staining, this tumor was strongly positive for AE1/AE3 keratin and PIN4 cocktail (cytokeratin 5, cytokeratin 15, p63, and p504s/alpha-methylacyl-CoA-racemase)(Figure, E) with focal positivity for PSA and prostatic acid phosphatase, diagnostic of metastatic adenocarcinoma of prostate origin.

A positron emission tomography scan performed a few days after the discovery of metastatic prostatic adenocarcinoma in the SLNs showed expected postoperative changes (eg, increased activity from procedure-related inflammation) in the left side of the flank and axilla as well as moderately hypermetabolic left supraclavicular lymph nodes suspicious for viable metastatic disease. Subsequent fine-needle aspiration of the aforementioned lymph nodes revealed metastatic prostatic adenocarcinoma. The preoperative lymphoscintigraphy at the time of SLN biopsy did not show drainage to the left supraclavicular nodal basin.

Based on a discussion of the patient’s case during a multidisciplinary tumor board consultation, the benefit of performing completion lymph node dissection for melanoma management did not outweigh the risks. Accordingly, the patient received adjuvant radiation therapy to the axillary nodal basin. He was started on ketoconazole and zoledronic acid therapy for metastatic prostate adenocarcinoma and was alive with disease at 6-month follow-up. The finding of both metastatic melanoma and prostate adenocarcinoma detected in an SLN after wide excision and SLN biopsy for cutaneous melanoma is a unique report of collision of these 2 tumors. Rare cases of collision between 2 solid tumors occurring in the same lymph node have involved prostate adenocarcinoma as one of the solid tumor components.^1,3 Detection of tumor collision on lymph node biopsy between prostatic adenocarcinoma and urothelial carcinoma has been documented in 2 separate cases.¹ Three additional cases of concurrent prostatic adenocarcinoma and colorectal adenocarcinoma identified on lymph node biopsy have been reported.^1,3 Although never proven statistically, it is likely that these concurrent diagnoses are due to the high incidences of prostate and colorectal adenocarcinomas in the general US population; they are ranked first and third, respectively, for cancer incidence in US males.⁴

As demonstrated in the current case and the available literature, immunohistochemical stains play a vital role in the detection of tumor collision phenomena as well as identification of histologic source of the metastases. Furthermore, thorough histopathologic examination of biopsy specimens in the context of a patient’s clinical history remains paramount in obtaining an accurate diagnosis. Earlier identification of second malignancies in SLNs can alert the clinician to the presence of relapse of a known concurrent malignancy before it is clinically apparent, enhancing the possibility of more effective treatment of earlier disease. As has been demonstrated for lymphoma and melanoma, in rare cases awareness of the possibility of a second malignancy in the SLN can result in earlier initial diagnosis of undiscovered malignancy.²

As we providers begin to gain a better understanding of the complexities of gender identity and expression, studies examining the health of transgender and gender-nonconforming (TGNC) youth are emerging. Multiple studies have demonstrated the mental health disparities that TGNC youth face, but more studies examining other health risks and disparities are needed.

Prevalence of TGNC students higher than expected

The 2.7% prevalence of TGNC youth in this sample is higher than previously reported. Previous studies looking at prevalence rates of TGNC youth often dichotomized gender identities into binary (masculine or feminine) groups and were not inclusive of nonbinary and questioning identities. This may have led to underestimation of the size of this population.^2,3 This study assessed for TGNC identities by asking, “Do you consider yourself transgender, genderqueer, gender fluid, or unsure about your gender identity?” Given the prevalence of TGNC identities in this sample, it is likely that TGNC youth will be encountered in general pediatric practice. As such, it is important that we as providers continue to build our competency in working with this population.
 

Statistically significant differences in health status were identified

Almost two-thirds (62%) of TGNC youth identified their health as poor, fair, or good as opposed to very good or excellent, compared with one-third (33.1%) of cisgender youth. Over half (52%) of TGNC youth reported staying home from school because of illness at least once in the past month, compared with 43% of cisgender youth. About 60% of TGNC youth reported a preventive medical check-up in the past year, compared with 65% of cisgender youth. In terms of long-term health problems, TGNC youth reported higher rates of long-term physical (25% vs. 15%) and mental health (59% vs. 17%) problems than did their cisgender peers.

Role of perceived gender expression

A unique aspect of this study was that it sought to examine the effect of perceived gender expression (the way others interpret a person’s gender presentation; their appearance, style, dress, or the way they walk or talk) on health status and care utilization. Categories of perceived gender expression included very or mostly feminine, somewhat feminine, equally feminine and masculine, somewhat masculine, or very or mostly masculine. The prevalence of TGNC adolescents with an equally feminine and masculine gender expression was highest for both those assigned male (29%) and assigned female (41%) at birth, compared with other perceived gender presentations.

TGNC youth who were perceived to have a gender expression that was incongruent with the sex assigned at birth were at higher risk of reporting poor health status. For example, in TGNC participants who were assigned male at birth, those perceived as equally feminine and masculine (49%) or somewhat masculine (58%) were significantly more likely to report having poorer general health than those with a very masculine perceived gender expression (32%).
 

Suggestions for providers

The authors of the study and the accompanying commentary by Daniel Shumer, MD, MPH, suggest that there are things we as health care providers can do to address these barriers.

• Recognize that health disparities exist in this population. Individuals perceived as gender nonconforming may be vulnerable to discrimination and have difficulty accessing and receiving heath care, compared with their cisgender peers.
• Screen for health risks and identify barriers to care for TGNC youth while promoting and bolstering wellness within this community.
• Continue to promote access to gender affirming care. Data suggest that children who receive gender affirming care achieve mental health status similar to that of their cisgender peers.^3,4,5
• Continue to develop an understanding of how youth understand and express gender.
• Nonbinary youth face unique barriers when accessing health affirming services because of fears that their gender identity may be misunderstood. These barriers lead to delays in seeking health care services, which may lead to poorer outcomes. As providers, educating ourselves about these diverse identities and being respectful of all patients’ identities can help reduce these barriers.

Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at Ohio State University, both in Columbus. She said she had no relevant financial disclosures. Email her at [email protected].

References

1. Pediatrics. 2018 Feb 5. doi: 10.1542/peds.2017-1683.

2. J Adolesc Health. 2017 Oct;61(4):521-6.

3. Pediatrics. 2018. doi: 10.1542/peds.2017-4079.

4. Pediatrics. 2014 Oct;134(4):696-704.

5. Pediatrics. 2016 Mar;137(3):e20153223.

As we providers begin to gain a better understanding of the complexities of gender identity and expression, studies examining the health of transgender and gender-nonconforming (TGNC) youth are emerging. Multiple studies have demonstrated the mental health disparities that TGNC youth face, but more studies examining other health risks and disparities are needed.

Prevalence of TGNC students higher than expected

The 2.7% prevalence of TGNC youth in this sample is higher than previously reported. Previous studies looking at prevalence rates of TGNC youth often dichotomized gender identities into binary (masculine or feminine) groups and were not inclusive of nonbinary and questioning identities. This may have led to underestimation of the size of this population.^2,3 This study assessed for TGNC identities by asking, “Do you consider yourself transgender, genderqueer, gender fluid, or unsure about your gender identity?” Given the prevalence of TGNC identities in this sample, it is likely that TGNC youth will be encountered in general pediatric practice. As such, it is important that we as providers continue to build our competency in working with this population.
 

Statistically significant differences in health status were identified

Almost two-thirds (62%) of TGNC youth identified their health as poor, fair, or good as opposed to very good or excellent, compared with one-third (33.1%) of cisgender youth. Over half (52%) of TGNC youth reported staying home from school because of illness at least once in the past month, compared with 43% of cisgender youth. About 60% of TGNC youth reported a preventive medical check-up in the past year, compared with 65% of cisgender youth. In terms of long-term health problems, TGNC youth reported higher rates of long-term physical (25% vs. 15%) and mental health (59% vs. 17%) problems than did their cisgender peers.

Role of perceived gender expression

A unique aspect of this study was that it sought to examine the effect of perceived gender expression (the way others interpret a person’s gender presentation; their appearance, style, dress, or the way they walk or talk) on health status and care utilization. Categories of perceived gender expression included very or mostly feminine, somewhat feminine, equally feminine and masculine, somewhat masculine, or very or mostly masculine. The prevalence of TGNC adolescents with an equally feminine and masculine gender expression was highest for both those assigned male (29%) and assigned female (41%) at birth, compared with other perceived gender presentations.

TGNC youth who were perceived to have a gender expression that was incongruent with the sex assigned at birth were at higher risk of reporting poor health status. For example, in TGNC participants who were assigned male at birth, those perceived as equally feminine and masculine (49%) or somewhat masculine (58%) were significantly more likely to report having poorer general health than those with a very masculine perceived gender expression (32%).
 

Suggestions for providers

The authors of the study and the accompanying commentary by Daniel Shumer, MD, MPH, suggest that there are things we as health care providers can do to address these barriers.

• Recognize that health disparities exist in this population. Individuals perceived as gender nonconforming may be vulnerable to discrimination and have difficulty accessing and receiving heath care, compared with their cisgender peers.
• Screen for health risks and identify barriers to care for TGNC youth while promoting and bolstering wellness within this community.
• Continue to promote access to gender affirming care. Data suggest that children who receive gender affirming care achieve mental health status similar to that of their cisgender peers.^3,4,5
• Continue to develop an understanding of how youth understand and express gender.
• Nonbinary youth face unique barriers when accessing health affirming services because of fears that their gender identity may be misunderstood. These barriers lead to delays in seeking health care services, which may lead to poorer outcomes. As providers, educating ourselves about these diverse identities and being respectful of all patients’ identities can help reduce these barriers.

Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at Ohio State University, both in Columbus. She said she had no relevant financial disclosures. Email her at [email protected].

References

1. Pediatrics. 2018 Feb 5. doi: 10.1542/peds.2017-1683.

2. J Adolesc Health. 2017 Oct;61(4):521-6.

3. Pediatrics. 2018. doi: 10.1542/peds.2017-4079.

4. Pediatrics. 2014 Oct;134(4):696-704.

5. Pediatrics. 2016 Mar;137(3):e20153223.

As we providers begin to gain a better understanding of the complexities of gender identity and expression, studies examining the health of transgender and gender-nonconforming (TGNC) youth are emerging. Multiple studies have demonstrated the mental health disparities that TGNC youth face, but more studies examining other health risks and disparities are needed.

Prevalence of TGNC students higher than expected

The 2.7% prevalence of TGNC youth in this sample is higher than previously reported. Previous studies looking at prevalence rates of TGNC youth often dichotomized gender identities into binary (masculine or feminine) groups and were not inclusive of nonbinary and questioning identities. This may have led to underestimation of the size of this population.^2,3 This study assessed for TGNC identities by asking, “Do you consider yourself transgender, genderqueer, gender fluid, or unsure about your gender identity?” Given the prevalence of TGNC identities in this sample, it is likely that TGNC youth will be encountered in general pediatric practice. As such, it is important that we as providers continue to build our competency in working with this population.
 

Statistically significant differences in health status were identified

Almost two-thirds (62%) of TGNC youth identified their health as poor, fair, or good as opposed to very good or excellent, compared with one-third (33.1%) of cisgender youth. Over half (52%) of TGNC youth reported staying home from school because of illness at least once in the past month, compared with 43% of cisgender youth. About 60% of TGNC youth reported a preventive medical check-up in the past year, compared with 65% of cisgender youth. In terms of long-term health problems, TGNC youth reported higher rates of long-term physical (25% vs. 15%) and mental health (59% vs. 17%) problems than did their cisgender peers.

Role of perceived gender expression

A unique aspect of this study was that it sought to examine the effect of perceived gender expression (the way others interpret a person’s gender presentation; their appearance, style, dress, or the way they walk or talk) on health status and care utilization. Categories of perceived gender expression included very or mostly feminine, somewhat feminine, equally feminine and masculine, somewhat masculine, or very or mostly masculine. The prevalence of TGNC adolescents with an equally feminine and masculine gender expression was highest for both those assigned male (29%) and assigned female (41%) at birth, compared with other perceived gender presentations.

TGNC youth who were perceived to have a gender expression that was incongruent with the sex assigned at birth were at higher risk of reporting poor health status. For example, in TGNC participants who were assigned male at birth, those perceived as equally feminine and masculine (49%) or somewhat masculine (58%) were significantly more likely to report having poorer general health than those with a very masculine perceived gender expression (32%).
 

Suggestions for providers

The authors of the study and the accompanying commentary by Daniel Shumer, MD, MPH, suggest that there are things we as health care providers can do to address these barriers.

• Recognize that health disparities exist in this population. Individuals perceived as gender nonconforming may be vulnerable to discrimination and have difficulty accessing and receiving heath care, compared with their cisgender peers.
• Screen for health risks and identify barriers to care for TGNC youth while promoting and bolstering wellness within this community.
• Continue to promote access to gender affirming care. Data suggest that children who receive gender affirming care achieve mental health status similar to that of their cisgender peers.^3,4,5
• Continue to develop an understanding of how youth understand and express gender.
• Nonbinary youth face unique barriers when accessing health affirming services because of fears that their gender identity may be misunderstood. These barriers lead to delays in seeking health care services, which may lead to poorer outcomes. As providers, educating ourselves about these diverse identities and being respectful of all patients’ identities can help reduce these barriers.

Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at Ohio State University, both in Columbus. She said she had no relevant financial disclosures. Email her at [email protected].

References

1. Pediatrics. 2018 Feb 5. doi: 10.1542/peds.2017-1683.

2. J Adolesc Health. 2017 Oct;61(4):521-6.

3. Pediatrics. 2018. doi: 10.1542/peds.2017-4079.

4. Pediatrics. 2014 Oct;134(4):696-704.

5. Pediatrics. 2016 Mar;137(3):e20153223.

For patients with refractory epilepsy who receive vagus nerve stimulation (VNS) therapy, the risk of sudden unexpected death in epilepsy (SUDEP) decreases significantly during long-term follow-up, according to research published online ahead of print January 16 in Epilepsia. This finding “has not been previously reported in the literature and would be of value for patients at risk of SUDEP,” said the authors.

Long-Term Data Are Lacking

Most epidemiologic studies of SUDEP have had cross-sectional designs. Consequently, neurologists have lacked information about potential changes in the rate of SUDEP over time. Cyberonics, a Houston-based company, records information about implantation of its VNS device when the implanting facilities provide this information to it. To understand the evolution of SUDEP risk over time, Philippe Ryvlin, MD, Head of the Department of Clinical Neurosciences at Vaud University Hospital in Lausanne, Switzerland, and colleagues analyzed information from the company’s database.

For their study, the authors examined patients who underwent device implantation for epilepsy between November 16, 1988, and December 31, 2012. Eligible participants were US citizens or residents at the time of implantation and had a Social Security Number and a known date of birth. To ascertain patients’ vital status and cause of death, Dr. Ryvlin and colleagues submitted data to the Centers for Disease Control and Prevention’s National Death Index (NDI). The NDI included an underlying cause and as many as 20 contributory causes for each death.

The investigators defined SUDEP according to the criteria published by Annegers in 1997. To adjudicate SUDEP, they examined NDI data and death reports that Cyberonics recorded in a subset of patients. For patients for whom a death report was unavailable, the investigators performed adjudication by extrapolation.

Rate of SUDEP Decreased by One-Fourth

According to the database, 57,551 patients underwent implantation with the VNS device during the study period. A total of 40,443 (70%) participants met the researchers’ inclusion criteria. Patients’ average age at implantation was 30.8, and 15% of patients were under age 12. Half of participants were male.

The median duration of follow-up was 7.6 years. In all, 2,864 (7%) participants underwent explantation or had their devices turned off before the cutoff date, and 3,689 (9%) patients died during the study period.

A total of 953 (25.8%) of the deaths were associated with underlying and contributory causes considered compatible with SUDEP. Adjudication per protocol resulted in 632 (66.3%) cases of definite, probable, and possible SUDEP. The consensus conclusion among investigators resulted in 638 (66.9%) SUDEP cases. Adjudication by extrapolation resulted in 667 (70.0%) SUDEP cases and 286 (30.0%) non-SUDEP cases.

The crude and age-adjusted rates of SUDEP during years 3 to 10 of follow-up (2.10/1,000 patient years and 1.68/1,000 patient years, respectively) were significantly lower than those observed during the first two years of follow-up (2.74/1,000 patient years and 2.47/1,000 patient years, respectively). The crude rate ratio of SUDEP was 0.77, and the age-adjusted rate ratio of SUDEP was 0.68.

Biomarkers of SUDEP Would Aid Research

Because the study did not include a control group, and the database did not have preimplantation baseline information or data about individual responses to VNS therapy, the analysis does not clarify the role of VNS in the rate of SUDEP. Factors such as attrition, natural evolution, aging, or changes in medications or medical practice over time could explain the study findings, said Dr. Ryvlin.

The reasons for which SUDEP risk decreases over time should be investigated further, said the authors. A three-year randomized controlled trial would require at least 28,000 patients in each arm to compare adjunctive VNS treatment and standard treatment, but this level of enrollment is not feasible. “Novel biomarkers highly predictive of SUDEP will be needed to make prospective studies of SUDEP prevention feasible in an enriched population,” said Dr. Ryvlin. “Until then, only large retrospective cohorts, such as the study presented here, can help us make progress in SUDEP prevention, an issue that one should acknowledge when weighing the limitations and value of currently available data.”

—Erik Greb

Suggested Reading

Ryvlin P, So EL, Gordon CM, et al. Long-term surveillance of SUDEP in drug-resistant epilepsy patients treated with VNS therapy. Epilepsia. 2018 Jan 16 [Epub ahead of print].

For patients with refractory epilepsy who receive vagus nerve stimulation (VNS) therapy, the risk of sudden unexpected death in epilepsy (SUDEP) decreases significantly during long-term follow-up, according to research published online ahead of print January 16 in Epilepsia. This finding “has not been previously reported in the literature and would be of value for patients at risk of SUDEP,” said the authors.

Long-Term Data Are Lacking

Most epidemiologic studies of SUDEP have had cross-sectional designs. Consequently, neurologists have lacked information about potential changes in the rate of SUDEP over time. Cyberonics, a Houston-based company, records information about implantation of its VNS device when the implanting facilities provide this information to it. To understand the evolution of SUDEP risk over time, Philippe Ryvlin, MD, Head of the Department of Clinical Neurosciences at Vaud University Hospital in Lausanne, Switzerland, and colleagues analyzed information from the company’s database.

For their study, the authors examined patients who underwent device implantation for epilepsy between November 16, 1988, and December 31, 2012. Eligible participants were US citizens or residents at the time of implantation and had a Social Security Number and a known date of birth. To ascertain patients’ vital status and cause of death, Dr. Ryvlin and colleagues submitted data to the Centers for Disease Control and Prevention’s National Death Index (NDI). The NDI included an underlying cause and as many as 20 contributory causes for each death.

The investigators defined SUDEP according to the criteria published by Annegers in 1997. To adjudicate SUDEP, they examined NDI data and death reports that Cyberonics recorded in a subset of patients. For patients for whom a death report was unavailable, the investigators performed adjudication by extrapolation.

Rate of SUDEP Decreased by One-Fourth

According to the database, 57,551 patients underwent implantation with the VNS device during the study period. A total of 40,443 (70%) participants met the researchers’ inclusion criteria. Patients’ average age at implantation was 30.8, and 15% of patients were under age 12. Half of participants were male.

The median duration of follow-up was 7.6 years. In all, 2,864 (7%) participants underwent explantation or had their devices turned off before the cutoff date, and 3,689 (9%) patients died during the study period.

A total of 953 (25.8%) of the deaths were associated with underlying and contributory causes considered compatible with SUDEP. Adjudication per protocol resulted in 632 (66.3%) cases of definite, probable, and possible SUDEP. The consensus conclusion among investigators resulted in 638 (66.9%) SUDEP cases. Adjudication by extrapolation resulted in 667 (70.0%) SUDEP cases and 286 (30.0%) non-SUDEP cases.

The crude and age-adjusted rates of SUDEP during years 3 to 10 of follow-up (2.10/1,000 patient years and 1.68/1,000 patient years, respectively) were significantly lower than those observed during the first two years of follow-up (2.74/1,000 patient years and 2.47/1,000 patient years, respectively). The crude rate ratio of SUDEP was 0.77, and the age-adjusted rate ratio of SUDEP was 0.68.

Biomarkers of SUDEP Would Aid Research

Because the study did not include a control group, and the database did not have preimplantation baseline information or data about individual responses to VNS therapy, the analysis does not clarify the role of VNS in the rate of SUDEP. Factors such as attrition, natural evolution, aging, or changes in medications or medical practice over time could explain the study findings, said Dr. Ryvlin.

The reasons for which SUDEP risk decreases over time should be investigated further, said the authors. A three-year randomized controlled trial would require at least 28,000 patients in each arm to compare adjunctive VNS treatment and standard treatment, but this level of enrollment is not feasible. “Novel biomarkers highly predictive of SUDEP will be needed to make prospective studies of SUDEP prevention feasible in an enriched population,” said Dr. Ryvlin. “Until then, only large retrospective cohorts, such as the study presented here, can help us make progress in SUDEP prevention, an issue that one should acknowledge when weighing the limitations and value of currently available data.”

—Erik Greb

Suggested Reading

Ryvlin P, So EL, Gordon CM, et al. Long-term surveillance of SUDEP in drug-resistant epilepsy patients treated with VNS therapy. Epilepsia. 2018 Jan 16 [Epub ahead of print].

For patients with refractory epilepsy who receive vagus nerve stimulation (VNS) therapy, the risk of sudden unexpected death in epilepsy (SUDEP) decreases significantly during long-term follow-up, according to research published online ahead of print January 16 in Epilepsia. This finding “has not been previously reported in the literature and would be of value for patients at risk of SUDEP,” said the authors.

Long-Term Data Are Lacking

Most epidemiologic studies of SUDEP have had cross-sectional designs. Consequently, neurologists have lacked information about potential changes in the rate of SUDEP over time. Cyberonics, a Houston-based company, records information about implantation of its VNS device when the implanting facilities provide this information to it. To understand the evolution of SUDEP risk over time, Philippe Ryvlin, MD, Head of the Department of Clinical Neurosciences at Vaud University Hospital in Lausanne, Switzerland, and colleagues analyzed information from the company’s database.

For their study, the authors examined patients who underwent device implantation for epilepsy between November 16, 1988, and December 31, 2012. Eligible participants were US citizens or residents at the time of implantation and had a Social Security Number and a known date of birth. To ascertain patients’ vital status and cause of death, Dr. Ryvlin and colleagues submitted data to the Centers for Disease Control and Prevention’s National Death Index (NDI). The NDI included an underlying cause and as many as 20 contributory causes for each death.

The investigators defined SUDEP according to the criteria published by Annegers in 1997. To adjudicate SUDEP, they examined NDI data and death reports that Cyberonics recorded in a subset of patients. For patients for whom a death report was unavailable, the investigators performed adjudication by extrapolation.

Rate of SUDEP Decreased by One-Fourth

According to the database, 57,551 patients underwent implantation with the VNS device during the study period. A total of 40,443 (70%) participants met the researchers’ inclusion criteria. Patients’ average age at implantation was 30.8, and 15% of patients were under age 12. Half of participants were male.

The median duration of follow-up was 7.6 years. In all, 2,864 (7%) participants underwent explantation or had their devices turned off before the cutoff date, and 3,689 (9%) patients died during the study period.

A total of 953 (25.8%) of the deaths were associated with underlying and contributory causes considered compatible with SUDEP. Adjudication per protocol resulted in 632 (66.3%) cases of definite, probable, and possible SUDEP. The consensus conclusion among investigators resulted in 638 (66.9%) SUDEP cases. Adjudication by extrapolation resulted in 667 (70.0%) SUDEP cases and 286 (30.0%) non-SUDEP cases.

The crude and age-adjusted rates of SUDEP during years 3 to 10 of follow-up (2.10/1,000 patient years and 1.68/1,000 patient years, respectively) were significantly lower than those observed during the first two years of follow-up (2.74/1,000 patient years and 2.47/1,000 patient years, respectively). The crude rate ratio of SUDEP was 0.77, and the age-adjusted rate ratio of SUDEP was 0.68.

Biomarkers of SUDEP Would Aid Research

Because the study did not include a control group, and the database did not have preimplantation baseline information or data about individual responses to VNS therapy, the analysis does not clarify the role of VNS in the rate of SUDEP. Factors such as attrition, natural evolution, aging, or changes in medications or medical practice over time could explain the study findings, said Dr. Ryvlin.

The reasons for which SUDEP risk decreases over time should be investigated further, said the authors. A three-year randomized controlled trial would require at least 28,000 patients in each arm to compare adjunctive VNS treatment and standard treatment, but this level of enrollment is not feasible. “Novel biomarkers highly predictive of SUDEP will be needed to make prospective studies of SUDEP prevention feasible in an enriched population,” said Dr. Ryvlin. “Until then, only large retrospective cohorts, such as the study presented here, can help us make progress in SUDEP prevention, an issue that one should acknowledge when weighing the limitations and value of currently available data.”

—Erik Greb

Suggested Reading

Ryvlin P, So EL, Gordon CM, et al. Long-term surveillance of SUDEP in drug-resistant epilepsy patients treated with VNS therapy. Epilepsia. 2018 Jan 16 [Epub ahead of print].

The American College of Obstetricians and Gynecologists (ACOG) is a nonprofit organization of women’s health care physicians advocating the highest standards of practice, continuing member education, and public awareness of women’s health care issues.¹ The organization has long recognized the impact that social media and mobile technology would have for itself as well as its membership. ACOG published a Social Media Guide in 2012, featuring a section on how to use apps in ObGyn practice and provided a list of apps for ObGyns and their patients.²

ACOG introduced its own app 4 years ago and has since updated the app several times, most recently on December 6, 2017. The ACOG app has a useful search function, a home button, and a place for users to email feedback (TABLE 1). The app most importantly contains several applets (small applications designed to perform a specific function within the main application). These applets encompass 3 types of apps for health care providers: clinical decision-making apps (Practice Bulletins, Committee Opinions, an Estimated Due Date Calculator that was featured in a prior review,³ Indicated Delivery, and Immunize) (TABLE 2), reference and information gathering apps (Today’s Headlines), and member support apps (ACOG Contacts, Careers, Annual Meeting, Districts, Council on Resident Education in Obstetrics and Gynecology [CREOG], and Website).⁴

This review will focus on the main ACOG app, which is evaluated by a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature use, and important special features).⁵ In addition, the clinical decision-making applets will be highlighted in a second table. I commend ACOG for developing these useful tools to augment their members’ practices. Of note, for the Practice Bulletins and Indicated Delivery applets, users will need to input their ACOG log-in access information.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The American College of Obstetricians and Gynecologists (ACOG) is a nonprofit organization of women’s health care physicians advocating the highest standards of practice, continuing member education, and public awareness of women’s health care issues.¹ The organization has long recognized the impact that social media and mobile technology would have for itself as well as its membership. ACOG published a Social Media Guide in 2012, featuring a section on how to use apps in ObGyn practice and provided a list of apps for ObGyns and their patients.²

ACOG introduced its own app 4 years ago and has since updated the app several times, most recently on December 6, 2017. The ACOG app has a useful search function, a home button, and a place for users to email feedback (TABLE 1). The app most importantly contains several applets (small applications designed to perform a specific function within the main application). These applets encompass 3 types of apps for health care providers: clinical decision-making apps (Practice Bulletins, Committee Opinions, an Estimated Due Date Calculator that was featured in a prior review,³ Indicated Delivery, and Immunize) (TABLE 2), reference and information gathering apps (Today’s Headlines), and member support apps (ACOG Contacts, Careers, Annual Meeting, Districts, Council on Resident Education in Obstetrics and Gynecology [CREOG], and Website).⁴

This review will focus on the main ACOG app, which is evaluated by a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature use, and important special features).⁵ In addition, the clinical decision-making applets will be highlighted in a second table. I commend ACOG for developing these useful tools to augment their members’ practices. Of note, for the Practice Bulletins and Indicated Delivery applets, users will need to input their ACOG log-in access information.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The American College of Obstetricians and Gynecologists (ACOG) is a nonprofit organization of women’s health care physicians advocating the highest standards of practice, continuing member education, and public awareness of women’s health care issues.¹ The organization has long recognized the impact that social media and mobile technology would have for itself as well as its membership. ACOG published a Social Media Guide in 2012, featuring a section on how to use apps in ObGyn practice and provided a list of apps for ObGyns and their patients.²

ACOG introduced its own app 4 years ago and has since updated the app several times, most recently on December 6, 2017. The ACOG app has a useful search function, a home button, and a place for users to email feedback (TABLE 1). The app most importantly contains several applets (small applications designed to perform a specific function within the main application). These applets encompass 3 types of apps for health care providers: clinical decision-making apps (Practice Bulletins, Committee Opinions, an Estimated Due Date Calculator that was featured in a prior review,³ Indicated Delivery, and Immunize) (TABLE 2), reference and information gathering apps (Today’s Headlines), and member support apps (ACOG Contacts, Careers, Annual Meeting, Districts, Council on Resident Education in Obstetrics and Gynecology [CREOG], and Website).⁴

This review will focus on the main ACOG app, which is evaluated by a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature use, and important special features).⁵ In addition, the clinical decision-making applets will be highlighted in a second table. I commend ACOG for developing these useful tools to augment their members’ practices. Of note, for the Practice Bulletins and Indicated Delivery applets, users will need to input their ACOG log-in access information.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Patients with reported penicillin allergies are significantly more likely to develop surgical site infections, according to a study conducted at Massachusetts General Hospital in Boston.

With new evidence reporting 90%-99% of patients with a reported allergy are not actually allergic, conducting a preoperative allergy test could improve treatment choice and decrease the risk of SSI, as well as the notable financial burden associated with it. Thus, “systematic, preoperative penicillin allergy evaluations in surgical patients may not only improve antibiotic choice but also decrease SSI risk,” according to Kimberly Blumenthal, MD, the quality director for the department of allergy and immunology at Massachusetts General Hospital, and her fellow investigators.

Thinkstock

[email protected]

SOURCE: Blumenthal K et al. Clin Infect Dis. 2018 Jan 18;66(3):329-36.

Patients with reported penicillin allergies are significantly more likely to develop surgical site infections, according to a study conducted at Massachusetts General Hospital in Boston.

With new evidence reporting 90%-99% of patients with a reported allergy are not actually allergic, conducting a preoperative allergy test could improve treatment choice and decrease the risk of SSI, as well as the notable financial burden associated with it. Thus, “systematic, preoperative penicillin allergy evaluations in surgical patients may not only improve antibiotic choice but also decrease SSI risk,” according to Kimberly Blumenthal, MD, the quality director for the department of allergy and immunology at Massachusetts General Hospital, and her fellow investigators.

Thinkstock

[email protected]

SOURCE: Blumenthal K et al. Clin Infect Dis. 2018 Jan 18;66(3):329-36.

Patients with reported penicillin allergies are significantly more likely to develop surgical site infections, according to a study conducted at Massachusetts General Hospital in Boston.

With new evidence reporting 90%-99% of patients with a reported allergy are not actually allergic, conducting a preoperative allergy test could improve treatment choice and decrease the risk of SSI, as well as the notable financial burden associated with it. Thus, “systematic, preoperative penicillin allergy evaluations in surgical patients may not only improve antibiotic choice but also decrease SSI risk,” according to Kimberly Blumenthal, MD, the quality director for the department of allergy and immunology at Massachusetts General Hospital, and her fellow investigators.

Thinkstock

[email protected]

SOURCE: Blumenthal K et al. Clin Infect Dis. 2018 Jan 18;66(3):329-36.

SAN DIEGO – Dermatologists, who served as crucial sentinels during the early years of the AIDS epidemic, should be alert for dermatologic signs and symptoms of HIV infection, according to Toby Maurer, MD, professor of clinical dermatology at the University of California, San Francisco.

“We’re now seeing a lot of HIV-infected patients presenting once again with skin symptoms,” including new-onset psoriasis, poorly controlled seborrheic dermatitis, and even Kaposi’s sarcoma, she said in a video interview at the annual meeting of the American Academy of Dermatology.

The upswing in cases of Kaposi’s sarcoma “comes as a shock to many dermatologists; they thought Kaposi’s sarcoma was a thing of the past,” added Dr. Maurer, who presented on HIV-associated skin conditions at the meeting.

“My whole plea is to remember that HIV has not gone away, that it keeps showing up, and that the skin symptoms absolutely show up,” she said. “It’s not on the radar as much as it should be.”

In her presentation, Dr. Maurer, who is also chief of dermatology at San Francisco General Hospital, said HIV and HIV medications have a variety of impacts on skin. For example, psoriasis gets worse when patients are off medication and better when they’re on it, she said, while molluscum contagiosum and herpes simplex can actually worsen when patients start HIV drugs. And, she said, a late start of AIDS drugs can worsen eczema.

In the interview, she discussed the impact of starting antiretrovirals late into the infection, when CD4 counts are low, on skin conditions, as well as possible reasons behind the increase in Kaposi’s sarcoma, and interactions between systemic dermatologic medications and some antiretrovirals.

Dr. Maurer reports no relevant disclosures.

[email protected]

SAN DIEGO – Dermatologists, who served as crucial sentinels during the early years of the AIDS epidemic, should be alert for dermatologic signs and symptoms of HIV infection, according to Toby Maurer, MD, professor of clinical dermatology at the University of California, San Francisco.

“We’re now seeing a lot of HIV-infected patients presenting once again with skin symptoms,” including new-onset psoriasis, poorly controlled seborrheic dermatitis, and even Kaposi’s sarcoma, she said in a video interview at the annual meeting of the American Academy of Dermatology.

The upswing in cases of Kaposi’s sarcoma “comes as a shock to many dermatologists; they thought Kaposi’s sarcoma was a thing of the past,” added Dr. Maurer, who presented on HIV-associated skin conditions at the meeting.

“My whole plea is to remember that HIV has not gone away, that it keeps showing up, and that the skin symptoms absolutely show up,” she said. “It’s not on the radar as much as it should be.”

In her presentation, Dr. Maurer, who is also chief of dermatology at San Francisco General Hospital, said HIV and HIV medications have a variety of impacts on skin. For example, psoriasis gets worse when patients are off medication and better when they’re on it, she said, while molluscum contagiosum and herpes simplex can actually worsen when patients start HIV drugs. And, she said, a late start of AIDS drugs can worsen eczema.

In the interview, she discussed the impact of starting antiretrovirals late into the infection, when CD4 counts are low, on skin conditions, as well as possible reasons behind the increase in Kaposi’s sarcoma, and interactions between systemic dermatologic medications and some antiretrovirals.

Dr. Maurer reports no relevant disclosures.

[email protected]

SAN DIEGO – Dermatologists, who served as crucial sentinels during the early years of the AIDS epidemic, should be alert for dermatologic signs and symptoms of HIV infection, according to Toby Maurer, MD, professor of clinical dermatology at the University of California, San Francisco.

“We’re now seeing a lot of HIV-infected patients presenting once again with skin symptoms,” including new-onset psoriasis, poorly controlled seborrheic dermatitis, and even Kaposi’s sarcoma, she said in a video interview at the annual meeting of the American Academy of Dermatology.

The upswing in cases of Kaposi’s sarcoma “comes as a shock to many dermatologists; they thought Kaposi’s sarcoma was a thing of the past,” added Dr. Maurer, who presented on HIV-associated skin conditions at the meeting.

“My whole plea is to remember that HIV has not gone away, that it keeps showing up, and that the skin symptoms absolutely show up,” she said. “It’s not on the radar as much as it should be.”

In her presentation, Dr. Maurer, who is also chief of dermatology at San Francisco General Hospital, said HIV and HIV medications have a variety of impacts on skin. For example, psoriasis gets worse when patients are off medication and better when they’re on it, she said, while molluscum contagiosum and herpes simplex can actually worsen when patients start HIV drugs. And, she said, a late start of AIDS drugs can worsen eczema.

In the interview, she discussed the impact of starting antiretrovirals late into the infection, when CD4 counts are low, on skin conditions, as well as possible reasons behind the increase in Kaposi’s sarcoma, and interactions between systemic dermatologic medications and some antiretrovirals.

Dr. Maurer reports no relevant disclosures.

[email protected]

An either/or choice is not a good strategy for pain

I found Dr. Barbieri’s editorial on postpartum opioid use and breastfeeding interesting, but one key issue was not addressed: Following this guidance means that new mothers have to choose between breastfeeding and pain control. You may explain to a patient with 2-day cesarean delivery pain, “If you take pain medicine while breastfeeding, it can adversely affect the baby. So we will give you acetaminophen.” While some moms will deal with it, others will stop breastfeeding. With the increasing pressure to advocate for breastfeeding, this strategy is likely not realistic.

R. Lee Toler, DO
Bolivia, North Carolina

My pain management protocol

While presently in an office-based setting, back in my inpatient practice days I would order oxycodone plus acetaminophen for 1 to 2 days postoperative cesarean delivery, and only 1 day after normal spontaneous delivery if the patient had a large perineal repair or multiparous involution pain. Otherwise, it was ibuprofen 800 mg, then 400 to 600 mg on discharge home.

Gabrielle Long, CNM
Mohegan Lake, New York

Respect women’s postsurgical pain management needs

There is a real disrespect for pain control for women, such as after a cesarean delivery. I would like to see any male have major surgery through a large muscle like the uterus and not need significant pain control options!

Anne V. Hale, MD
El Paso, Texas

Dr. Barbieri responds

I agree with Ms. Long that most postpartum patients, including many who have had a cesarean delivery, can achieve adequate pain control with the use of parenteral and oral nonsteroidal anti-inflammatory drugs (NSAIDs) and oral acetaminophen. Drs. Toler and Hale are concerned that postpartum pain control might be suboptimal if opioids are underprescribed. However, in many developed countries obstetricians do not use opioid pain medicine for postpartum pain management, relying on NSAIDs and acetaminophen. Given the success of this approach, I think we can significantly reduce the use of opioids by postpartum women in the United States by optimizing our use of nonopioid medications.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

An either/or choice is not a good strategy for pain

I found Dr. Barbieri’s editorial on postpartum opioid use and breastfeeding interesting, but one key issue was not addressed: Following this guidance means that new mothers have to choose between breastfeeding and pain control. You may explain to a patient with 2-day cesarean delivery pain, “If you take pain medicine while breastfeeding, it can adversely affect the baby. So we will give you acetaminophen.” While some moms will deal with it, others will stop breastfeeding. With the increasing pressure to advocate for breastfeeding, this strategy is likely not realistic.

R. Lee Toler, DO
Bolivia, North Carolina

My pain management protocol

While presently in an office-based setting, back in my inpatient practice days I would order oxycodone plus acetaminophen for 1 to 2 days postoperative cesarean delivery, and only 1 day after normal spontaneous delivery if the patient had a large perineal repair or multiparous involution pain. Otherwise, it was ibuprofen 800 mg, then 400 to 600 mg on discharge home.

Gabrielle Long, CNM
Mohegan Lake, New York

Respect women’s postsurgical pain management needs

There is a real disrespect for pain control for women, such as after a cesarean delivery. I would like to see any male have major surgery through a large muscle like the uterus and not need significant pain control options!

Anne V. Hale, MD
El Paso, Texas

Dr. Barbieri responds

I agree with Ms. Long that most postpartum patients, including many who have had a cesarean delivery, can achieve adequate pain control with the use of parenteral and oral nonsteroidal anti-inflammatory drugs (NSAIDs) and oral acetaminophen. Drs. Toler and Hale are concerned that postpartum pain control might be suboptimal if opioids are underprescribed. However, in many developed countries obstetricians do not use opioid pain medicine for postpartum pain management, relying on NSAIDs and acetaminophen. Given the success of this approach, I think we can significantly reduce the use of opioids by postpartum women in the United States by optimizing our use of nonopioid medications.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

An either/or choice is not a good strategy for pain

I found Dr. Barbieri’s editorial on postpartum opioid use and breastfeeding interesting, but one key issue was not addressed: Following this guidance means that new mothers have to choose between breastfeeding and pain control. You may explain to a patient with 2-day cesarean delivery pain, “If you take pain medicine while breastfeeding, it can adversely affect the baby. So we will give you acetaminophen.” While some moms will deal with it, others will stop breastfeeding. With the increasing pressure to advocate for breastfeeding, this strategy is likely not realistic.

R. Lee Toler, DO
Bolivia, North Carolina

My pain management protocol

While presently in an office-based setting, back in my inpatient practice days I would order oxycodone plus acetaminophen for 1 to 2 days postoperative cesarean delivery, and only 1 day after normal spontaneous delivery if the patient had a large perineal repair or multiparous involution pain. Otherwise, it was ibuprofen 800 mg, then 400 to 600 mg on discharge home.

Gabrielle Long, CNM
Mohegan Lake, New York

Respect women’s postsurgical pain management needs

There is a real disrespect for pain control for women, such as after a cesarean delivery. I would like to see any male have major surgery through a large muscle like the uterus and not need significant pain control options!

Anne V. Hale, MD
El Paso, Texas

Dr. Barbieri responds

I agree with Ms. Long that most postpartum patients, including many who have had a cesarean delivery, can achieve adequate pain control with the use of parenteral and oral nonsteroidal anti-inflammatory drugs (NSAIDs) and oral acetaminophen. Drs. Toler and Hale are concerned that postpartum pain control might be suboptimal if opioids are underprescribed. However, in many developed countries obstetricians do not use opioid pain medicine for postpartum pain management, relying on NSAIDs and acetaminophen. Given the success of this approach, I think we can significantly reduce the use of opioids by postpartum women in the United States by optimizing our use of nonopioid medications.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Typical practices of obtaining new baselines every 2 years in the high school population can be applied to athletes with a history of special education or learning disorders (LD) and headache/migraine treatment, a recent study found. This study examined the test-retest reliability of the 4- and 2-factor structures (ie, memory and speed) of ImPACT (Immediate Post-Concussion Assessment and Cognitive Test) over a 2-year interval across multiple groups with premorbid conditions, including those with a history of special education or LDs (n=114), treatment history for headache/migraine (n=81), and a control group (n= 792).

Researchers found:

• Significant improvement on all 4 composites were observed for the control group over a 2-year interval, whereas significant differences were observed only on visual motor speed for the LD and headache/migraine treatment history groups.
• The 2-factor structure has potential to increase test-retest reliability.

Two-year test-retest reliability in high school athletes using the four- and two-factor ImPACT composite structures: The effects of learning disorders and headache/migraine treatment history. Clin Neuropsychol. 2018;33(2):256-226. doi:10.1093/arclin/acx059.

Typical practices of obtaining new baselines every 2 years in the high school population can be applied to athletes with a history of special education or learning disorders (LD) and headache/migraine treatment, a recent study found. This study examined the test-retest reliability of the 4- and 2-factor structures (ie, memory and speed) of ImPACT (Immediate Post-Concussion Assessment and Cognitive Test) over a 2-year interval across multiple groups with premorbid conditions, including those with a history of special education or LDs (n=114), treatment history for headache/migraine (n=81), and a control group (n= 792).

Researchers found:

• Significant improvement on all 4 composites were observed for the control group over a 2-year interval, whereas significant differences were observed only on visual motor speed for the LD and headache/migraine treatment history groups.
• The 2-factor structure has potential to increase test-retest reliability.

Two-year test-retest reliability in high school athletes using the four- and two-factor ImPACT composite structures: The effects of learning disorders and headache/migraine treatment history. Clin Neuropsychol. 2018;33(2):256-226. doi:10.1093/arclin/acx059.

Typical practices of obtaining new baselines every 2 years in the high school population can be applied to athletes with a history of special education or learning disorders (LD) and headache/migraine treatment, a recent study found. This study examined the test-retest reliability of the 4- and 2-factor structures (ie, memory and speed) of ImPACT (Immediate Post-Concussion Assessment and Cognitive Test) over a 2-year interval across multiple groups with premorbid conditions, including those with a history of special education or LDs (n=114), treatment history for headache/migraine (n=81), and a control group (n= 792).

Researchers found:

• Significant improvement on all 4 composites were observed for the control group over a 2-year interval, whereas significant differences were observed only on visual motor speed for the LD and headache/migraine treatment history groups.
• The 2-factor structure has potential to increase test-retest reliability.

Two-year test-retest reliability in high school athletes using the four- and two-factor ImPACT composite structures: The effects of learning disorders and headache/migraine treatment history. Clin Neuropsychol. 2018;33(2):256-226. doi:10.1093/arclin/acx059.