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New anticancer drugs linked to increased costs, life expectancy
New anticancer drugs are often expensive and have been accompanied by large increases in the cost of medical treatment, but they also are associated with gains in life expectancy, according to an analysis of Medicare data published online.
Investigators looked at four different types of cancer – breast, kidney, lung, and chronic myeloid leukemia (CML) – over two time periods: 1996-2000 and 2007-2011. Patients treated for CML during 2007-2011 had the largest increases in both average lifetime medical cost ($142,000) and months of life gained (22.1) over those treated during 1996-2000, reported David H. Howard, PhD, of Emory University, Atlanta, and his associates.
Breast cancer patients had the next-largest increases: 13.2 months of life expectancy and $72,000 in lifetime medical cost for those who received physician-administered intravenous drugs. For breast cancer patients who received only oral drugs, the increases were 2 months of life and $9,000 in lifetime cost, they noted.
Patients with kidney cancer had an average life-expectancy increase of 7.9 months and a cost increase of $45,000, but those estimates don’t fully reflect the effect of several oral drugs that were introduced after 2007 but did not come into widespread use during the entire study period, Dr. Howard and his associates noted (Health Aff. 2016 Sep 7;35[9]:1581-7).
Lung cancer patients experienced the smallest changes between the two time periods, with an increase in life expectancy of 3.9 months for those who received physician-administered anticancer drugs and a lifetime medical cost increase of $23,000. Patients with lung cancer who did not receive such drugs had increases of 0.7 months of life expectancy and $4,000 in lifetime medical costs.
The researchers used data from the Surveillance, Epidemiology, and End Results–Medicare database, and all costs are adjusted to 2012 dollars. Data collection was supported by the California Department of Health and funding for the study was provided by Pfizer. Three of Dr. Howard’s five coinvestigators are Pfizer employees.
New anticancer drugs are often expensive and have been accompanied by large increases in the cost of medical treatment, but they also are associated with gains in life expectancy, according to an analysis of Medicare data published online.
Investigators looked at four different types of cancer – breast, kidney, lung, and chronic myeloid leukemia (CML) – over two time periods: 1996-2000 and 2007-2011. Patients treated for CML during 2007-2011 had the largest increases in both average lifetime medical cost ($142,000) and months of life gained (22.1) over those treated during 1996-2000, reported David H. Howard, PhD, of Emory University, Atlanta, and his associates.
Breast cancer patients had the next-largest increases: 13.2 months of life expectancy and $72,000 in lifetime medical cost for those who received physician-administered intravenous drugs. For breast cancer patients who received only oral drugs, the increases were 2 months of life and $9,000 in lifetime cost, they noted.
Patients with kidney cancer had an average life-expectancy increase of 7.9 months and a cost increase of $45,000, but those estimates don’t fully reflect the effect of several oral drugs that were introduced after 2007 but did not come into widespread use during the entire study period, Dr. Howard and his associates noted (Health Aff. 2016 Sep 7;35[9]:1581-7).
Lung cancer patients experienced the smallest changes between the two time periods, with an increase in life expectancy of 3.9 months for those who received physician-administered anticancer drugs and a lifetime medical cost increase of $23,000. Patients with lung cancer who did not receive such drugs had increases of 0.7 months of life expectancy and $4,000 in lifetime medical costs.
The researchers used data from the Surveillance, Epidemiology, and End Results–Medicare database, and all costs are adjusted to 2012 dollars. Data collection was supported by the California Department of Health and funding for the study was provided by Pfizer. Three of Dr. Howard’s five coinvestigators are Pfizer employees.
New anticancer drugs are often expensive and have been accompanied by large increases in the cost of medical treatment, but they also are associated with gains in life expectancy, according to an analysis of Medicare data published online.
Investigators looked at four different types of cancer – breast, kidney, lung, and chronic myeloid leukemia (CML) – over two time periods: 1996-2000 and 2007-2011. Patients treated for CML during 2007-2011 had the largest increases in both average lifetime medical cost ($142,000) and months of life gained (22.1) over those treated during 1996-2000, reported David H. Howard, PhD, of Emory University, Atlanta, and his associates.
Breast cancer patients had the next-largest increases: 13.2 months of life expectancy and $72,000 in lifetime medical cost for those who received physician-administered intravenous drugs. For breast cancer patients who received only oral drugs, the increases were 2 months of life and $9,000 in lifetime cost, they noted.
Patients with kidney cancer had an average life-expectancy increase of 7.9 months and a cost increase of $45,000, but those estimates don’t fully reflect the effect of several oral drugs that were introduced after 2007 but did not come into widespread use during the entire study period, Dr. Howard and his associates noted (Health Aff. 2016 Sep 7;35[9]:1581-7).
Lung cancer patients experienced the smallest changes between the two time periods, with an increase in life expectancy of 3.9 months for those who received physician-administered anticancer drugs and a lifetime medical cost increase of $23,000. Patients with lung cancer who did not receive such drugs had increases of 0.7 months of life expectancy and $4,000 in lifetime medical costs.
The researchers used data from the Surveillance, Epidemiology, and End Results–Medicare database, and all costs are adjusted to 2012 dollars. Data collection was supported by the California Department of Health and funding for the study was provided by Pfizer. Three of Dr. Howard’s five coinvestigators are Pfizer employees.
FROM HEALTH AFFAIRS
Rapidly Growing Scalp Nodule
Cutaneous Metastasis of Pulmonary Adenocarcinoma
Cutaneous metastasis of pulmonary adenocarcinoma (CMPA) is a rare phenomenon with an overall survival rate of less than 5 months.1,2 Often, CMPA can be the heralding feature of an aggressive systemic malignancy in 2.8% to 22% of reported cases.2-4 Clinically, CMPAs often present as fixed, violaceous, ulcerated nodules on the chest wall, scalp, or site of a prior procedure.3,5,6 Other clinical presentations have been described including zosteriform and inflammatory carcinomalike CMPA and CMPA on the tip of the nose.7 Histologically, CMPA presents as a subdermal collection of atypical glands arranged as clustered aggregates of infiltrative glands penetrating the dermal stroma (quiz image). The atypical glands have large oval nuclei with high nuclear to cytoplasm ratios with scant pale cytoplasm.
Cutaneous metastasis of pulmonary adenocarcinoma is difficult to distinguish from other metastatic or primary glandular malignancies based on histology alone. Immunohistochemical analysis can aid in the diagnosis of the primary tumor. Pulmonary adenocarcinomas are positive for cytokeratin (CK) 7 and thyroid transcription factor 1 (TTF-1), and they are negative for CK5/6 and CK20.7 The differential diagnosis for CMPA includes other internal malignancies such as invasive ductal adenocarcinoma of the breast and gastrointestinal adenocarcinomas (eg, gastric or colorectal carcinoma [CRC]). Additionally, endometriosis and primary sebaceous carcinomas can mimic cutaneous metastatic adenocarcinomas.
Endometriosis can mimic adenocarcinoma, especially when presenting as a subdermal nodule. However, the scattered dermal glands are cytologically banal and are surrounded by uterine-type stroma and extravasated hemorrhage, a classic presentation of endometriosis (Figure 1).
Invasive ductal carcinoma of the breast is one of the most common cutaneous metastases of internal malignancy.3 Clinically, these lesions present on the chest wall or abdomen as flesh-colored nodules. Histopathology generally reveals either tubular or single tumor cells infiltrating the dermis with surrounding desmoplastic fibrosis (Figure 2). Immunohistochemistry typically is positive for CK7, estrogen receptor, and mammaglobin, and negative for CK20, CK5/6, and TTF-1.
Gastrointestinal adenocarcinomas encompass a variety of primary sites that can metastasize to the skin including CRC. Clinically, cutaneous metastases of CRC present as multiple nodules on the trunk, abdomen, or umbilicus (also known as Sister Mary Joseph nodule).7,8 Distinguishing CRC as the primary site of origin can be difficult; however, there are subtle differences depending on the histologic subtype. In well-differentiated CRCs, well-defined atypical glands are haphazardly arranged within the dermis (Figure 3), while poorly differentiated lesions can present as single cells or with a signet ring-like morphology (Figure 4). For perianal lesions, extramammary Paget disease should be considered when biopsies show large, amphophilic, intraepithelial cells. These lesions often present with mucin and CK20 expression and are frequently associated with colorectal malignancies.9 Another characteristic feature of CRC is central necrosis with karyorrhectic debris, known as dirty necrosis. Immunohistochemical analysis typically shows expression of caudal type homeobox 2 and CK20 with infrequent expression of CK7 and no expression of TTF-1; however, additional clinical history (eg, history of colorectal adenocarcinoma, positive fecal occult blood test) often is the best distinguishing feature.
Primary sebaceous carcinoma also can mimic metastatic adenocarcinoma within the skin and is histologically similar to metastatic adenocarcinomas. The most distinguishing feature is sebaceous differentiation characterized by sebocytes, which have a vacuolated cytoplasm giving the nucleus a scalloped appearance, frequently with adjacent ductlike structures (Figure 5). Epidermotropism sometimes is present in sebaceous carcinomas but cannot be relied on as a distinguishing feature. Immunohistochemical analysis also is a helpful tool; these tumors typically are positive for p63 and podoplanin, distinguishing them from negative-staining metastatic adenocarcinomas.10,11
- Terashima T, Kanazawa M. Lung cancer with skin metastasis. Chest. 1994;106:1448-1450.
- Song Z, Lin B, Shao L, et al. Cutaneous metastasis as a initial presentation in advanced non-small cell lung cancer and its poor survival prognosis. J Cancer Res Clin Oncol. 2012;138:1613-1617.
- Lookingbill DP, Spangler N, Helm KF. Cutaneous metastases in patients with metastatic carcinoma: a retrospective study of 4020 patients. J Am Acad Dermatol. 1993;29(2, pt 1):228-236.
- Saeed S, Keehn CA, Morgan MB. Cutaneous metastasis: a clinical, pathological, and immunohistochemical appraisal. J Cutan Pathol. 2004;31:419-430.
- Chang SE, Choi JC, Moon KC. A papillary carcinoma: cutaneous metastases from lung cancer. J Dermatol. 2001;28:110-111.
- Snow S, Madjar D, Reizner G, et al. Renal cell carcinoma metastatic to the scalp: case report and review of the literature. Dermatol Surg. 2001;27:192-194.
- Alcaraz I, Cerroni L, Rutten A, et al. Cutaneous metastases from internal malignancies: a clinicopathologic and immunohistochemical review. Am J Dermatopathol. 2012;34:347-393.
- Schwartz IS. Sister (Mary?) Joseph's nodule. N Engl J Med. 1987;316:1348-1349.
- Goldblum J, Hart W. Perianal Paget's disease: a histologic and immunohistochemical study of 11 cases with and without associated rectal adenocarcinoma. Am J Surg Pathol. 1998;22:170-179.
- Ivan D, Nash J, Preito V, et al. Use of p63 expression in distinguishing primary and metastatic cutaneous adnexal neoplasms from metastatic adenocarcinoma to skin. J Cutan Pathol. 2006;34:474-480.
- Liang H, Wu H, Giorgadze T, et al. Podoplanin is a highly sensitive and specific marker to distinguish primary skin adnexal carcinomas from adenocarcinomas metastatic to skin. Am J Surg Pathol. 2007;31:304-310.
Cutaneous Metastasis of Pulmonary Adenocarcinoma
Cutaneous metastasis of pulmonary adenocarcinoma (CMPA) is a rare phenomenon with an overall survival rate of less than 5 months.1,2 Often, CMPA can be the heralding feature of an aggressive systemic malignancy in 2.8% to 22% of reported cases.2-4 Clinically, CMPAs often present as fixed, violaceous, ulcerated nodules on the chest wall, scalp, or site of a prior procedure.3,5,6 Other clinical presentations have been described including zosteriform and inflammatory carcinomalike CMPA and CMPA on the tip of the nose.7 Histologically, CMPA presents as a subdermal collection of atypical glands arranged as clustered aggregates of infiltrative glands penetrating the dermal stroma (quiz image). The atypical glands have large oval nuclei with high nuclear to cytoplasm ratios with scant pale cytoplasm.
Cutaneous metastasis of pulmonary adenocarcinoma is difficult to distinguish from other metastatic or primary glandular malignancies based on histology alone. Immunohistochemical analysis can aid in the diagnosis of the primary tumor. Pulmonary adenocarcinomas are positive for cytokeratin (CK) 7 and thyroid transcription factor 1 (TTF-1), and they are negative for CK5/6 and CK20.7 The differential diagnosis for CMPA includes other internal malignancies such as invasive ductal adenocarcinoma of the breast and gastrointestinal adenocarcinomas (eg, gastric or colorectal carcinoma [CRC]). Additionally, endometriosis and primary sebaceous carcinomas can mimic cutaneous metastatic adenocarcinomas.
Endometriosis can mimic adenocarcinoma, especially when presenting as a subdermal nodule. However, the scattered dermal glands are cytologically banal and are surrounded by uterine-type stroma and extravasated hemorrhage, a classic presentation of endometriosis (Figure 1).
Invasive ductal carcinoma of the breast is one of the most common cutaneous metastases of internal malignancy.3 Clinically, these lesions present on the chest wall or abdomen as flesh-colored nodules. Histopathology generally reveals either tubular or single tumor cells infiltrating the dermis with surrounding desmoplastic fibrosis (Figure 2). Immunohistochemistry typically is positive for CK7, estrogen receptor, and mammaglobin, and negative for CK20, CK5/6, and TTF-1.
Gastrointestinal adenocarcinomas encompass a variety of primary sites that can metastasize to the skin including CRC. Clinically, cutaneous metastases of CRC present as multiple nodules on the trunk, abdomen, or umbilicus (also known as Sister Mary Joseph nodule).7,8 Distinguishing CRC as the primary site of origin can be difficult; however, there are subtle differences depending on the histologic subtype. In well-differentiated CRCs, well-defined atypical glands are haphazardly arranged within the dermis (Figure 3), while poorly differentiated lesions can present as single cells or with a signet ring-like morphology (Figure 4). For perianal lesions, extramammary Paget disease should be considered when biopsies show large, amphophilic, intraepithelial cells. These lesions often present with mucin and CK20 expression and are frequently associated with colorectal malignancies.9 Another characteristic feature of CRC is central necrosis with karyorrhectic debris, known as dirty necrosis. Immunohistochemical analysis typically shows expression of caudal type homeobox 2 and CK20 with infrequent expression of CK7 and no expression of TTF-1; however, additional clinical history (eg, history of colorectal adenocarcinoma, positive fecal occult blood test) often is the best distinguishing feature.
Primary sebaceous carcinoma also can mimic metastatic adenocarcinoma within the skin and is histologically similar to metastatic adenocarcinomas. The most distinguishing feature is sebaceous differentiation characterized by sebocytes, which have a vacuolated cytoplasm giving the nucleus a scalloped appearance, frequently with adjacent ductlike structures (Figure 5). Epidermotropism sometimes is present in sebaceous carcinomas but cannot be relied on as a distinguishing feature. Immunohistochemical analysis also is a helpful tool; these tumors typically are positive for p63 and podoplanin, distinguishing them from negative-staining metastatic adenocarcinomas.10,11
Cutaneous Metastasis of Pulmonary Adenocarcinoma
Cutaneous metastasis of pulmonary adenocarcinoma (CMPA) is a rare phenomenon with an overall survival rate of less than 5 months.1,2 Often, CMPA can be the heralding feature of an aggressive systemic malignancy in 2.8% to 22% of reported cases.2-4 Clinically, CMPAs often present as fixed, violaceous, ulcerated nodules on the chest wall, scalp, or site of a prior procedure.3,5,6 Other clinical presentations have been described including zosteriform and inflammatory carcinomalike CMPA and CMPA on the tip of the nose.7 Histologically, CMPA presents as a subdermal collection of atypical glands arranged as clustered aggregates of infiltrative glands penetrating the dermal stroma (quiz image). The atypical glands have large oval nuclei with high nuclear to cytoplasm ratios with scant pale cytoplasm.
Cutaneous metastasis of pulmonary adenocarcinoma is difficult to distinguish from other metastatic or primary glandular malignancies based on histology alone. Immunohistochemical analysis can aid in the diagnosis of the primary tumor. Pulmonary adenocarcinomas are positive for cytokeratin (CK) 7 and thyroid transcription factor 1 (TTF-1), and they are negative for CK5/6 and CK20.7 The differential diagnosis for CMPA includes other internal malignancies such as invasive ductal adenocarcinoma of the breast and gastrointestinal adenocarcinomas (eg, gastric or colorectal carcinoma [CRC]). Additionally, endometriosis and primary sebaceous carcinomas can mimic cutaneous metastatic adenocarcinomas.
Endometriosis can mimic adenocarcinoma, especially when presenting as a subdermal nodule. However, the scattered dermal glands are cytologically banal and are surrounded by uterine-type stroma and extravasated hemorrhage, a classic presentation of endometriosis (Figure 1).
Invasive ductal carcinoma of the breast is one of the most common cutaneous metastases of internal malignancy.3 Clinically, these lesions present on the chest wall or abdomen as flesh-colored nodules. Histopathology generally reveals either tubular or single tumor cells infiltrating the dermis with surrounding desmoplastic fibrosis (Figure 2). Immunohistochemistry typically is positive for CK7, estrogen receptor, and mammaglobin, and negative for CK20, CK5/6, and TTF-1.
Gastrointestinal adenocarcinomas encompass a variety of primary sites that can metastasize to the skin including CRC. Clinically, cutaneous metastases of CRC present as multiple nodules on the trunk, abdomen, or umbilicus (also known as Sister Mary Joseph nodule).7,8 Distinguishing CRC as the primary site of origin can be difficult; however, there are subtle differences depending on the histologic subtype. In well-differentiated CRCs, well-defined atypical glands are haphazardly arranged within the dermis (Figure 3), while poorly differentiated lesions can present as single cells or with a signet ring-like morphology (Figure 4). For perianal lesions, extramammary Paget disease should be considered when biopsies show large, amphophilic, intraepithelial cells. These lesions often present with mucin and CK20 expression and are frequently associated with colorectal malignancies.9 Another characteristic feature of CRC is central necrosis with karyorrhectic debris, known as dirty necrosis. Immunohistochemical analysis typically shows expression of caudal type homeobox 2 and CK20 with infrequent expression of CK7 and no expression of TTF-1; however, additional clinical history (eg, history of colorectal adenocarcinoma, positive fecal occult blood test) often is the best distinguishing feature.
Primary sebaceous carcinoma also can mimic metastatic adenocarcinoma within the skin and is histologically similar to metastatic adenocarcinomas. The most distinguishing feature is sebaceous differentiation characterized by sebocytes, which have a vacuolated cytoplasm giving the nucleus a scalloped appearance, frequently with adjacent ductlike structures (Figure 5). Epidermotropism sometimes is present in sebaceous carcinomas but cannot be relied on as a distinguishing feature. Immunohistochemical analysis also is a helpful tool; these tumors typically are positive for p63 and podoplanin, distinguishing them from negative-staining metastatic adenocarcinomas.10,11
- Terashima T, Kanazawa M. Lung cancer with skin metastasis. Chest. 1994;106:1448-1450.
- Song Z, Lin B, Shao L, et al. Cutaneous metastasis as a initial presentation in advanced non-small cell lung cancer and its poor survival prognosis. J Cancer Res Clin Oncol. 2012;138:1613-1617.
- Lookingbill DP, Spangler N, Helm KF. Cutaneous metastases in patients with metastatic carcinoma: a retrospective study of 4020 patients. J Am Acad Dermatol. 1993;29(2, pt 1):228-236.
- Saeed S, Keehn CA, Morgan MB. Cutaneous metastasis: a clinical, pathological, and immunohistochemical appraisal. J Cutan Pathol. 2004;31:419-430.
- Chang SE, Choi JC, Moon KC. A papillary carcinoma: cutaneous metastases from lung cancer. J Dermatol. 2001;28:110-111.
- Snow S, Madjar D, Reizner G, et al. Renal cell carcinoma metastatic to the scalp: case report and review of the literature. Dermatol Surg. 2001;27:192-194.
- Alcaraz I, Cerroni L, Rutten A, et al. Cutaneous metastases from internal malignancies: a clinicopathologic and immunohistochemical review. Am J Dermatopathol. 2012;34:347-393.
- Schwartz IS. Sister (Mary?) Joseph's nodule. N Engl J Med. 1987;316:1348-1349.
- Goldblum J, Hart W. Perianal Paget's disease: a histologic and immunohistochemical study of 11 cases with and without associated rectal adenocarcinoma. Am J Surg Pathol. 1998;22:170-179.
- Ivan D, Nash J, Preito V, et al. Use of p63 expression in distinguishing primary and metastatic cutaneous adnexal neoplasms from metastatic adenocarcinoma to skin. J Cutan Pathol. 2006;34:474-480.
- Liang H, Wu H, Giorgadze T, et al. Podoplanin is a highly sensitive and specific marker to distinguish primary skin adnexal carcinomas from adenocarcinomas metastatic to skin. Am J Surg Pathol. 2007;31:304-310.
- Terashima T, Kanazawa M. Lung cancer with skin metastasis. Chest. 1994;106:1448-1450.
- Song Z, Lin B, Shao L, et al. Cutaneous metastasis as a initial presentation in advanced non-small cell lung cancer and its poor survival prognosis. J Cancer Res Clin Oncol. 2012;138:1613-1617.
- Lookingbill DP, Spangler N, Helm KF. Cutaneous metastases in patients with metastatic carcinoma: a retrospective study of 4020 patients. J Am Acad Dermatol. 1993;29(2, pt 1):228-236.
- Saeed S, Keehn CA, Morgan MB. Cutaneous metastasis: a clinical, pathological, and immunohistochemical appraisal. J Cutan Pathol. 2004;31:419-430.
- Chang SE, Choi JC, Moon KC. A papillary carcinoma: cutaneous metastases from lung cancer. J Dermatol. 2001;28:110-111.
- Snow S, Madjar D, Reizner G, et al. Renal cell carcinoma metastatic to the scalp: case report and review of the literature. Dermatol Surg. 2001;27:192-194.
- Alcaraz I, Cerroni L, Rutten A, et al. Cutaneous metastases from internal malignancies: a clinicopathologic and immunohistochemical review. Am J Dermatopathol. 2012;34:347-393.
- Schwartz IS. Sister (Mary?) Joseph's nodule. N Engl J Med. 1987;316:1348-1349.
- Goldblum J, Hart W. Perianal Paget's disease: a histologic and immunohistochemical study of 11 cases with and without associated rectal adenocarcinoma. Am J Surg Pathol. 1998;22:170-179.
- Ivan D, Nash J, Preito V, et al. Use of p63 expression in distinguishing primary and metastatic cutaneous adnexal neoplasms from metastatic adenocarcinoma to skin. J Cutan Pathol. 2006;34:474-480.
- Liang H, Wu H, Giorgadze T, et al. Podoplanin is a highly sensitive and specific marker to distinguish primary skin adnexal carcinomas from adenocarcinomas metastatic to skin. Am J Surg Pathol. 2007;31:304-310.
A 67-year-old woman with no history of malignancy presented with a scalp nodule. The photomicrograph showed atypical glands forming a subepidermal nodule with pleomorphic cells characterized by scant eosinophilic cytoplasm and large prominent nucleoli. Immunohistochemical analysis revealed diffuse thyroid transcription factor 1 and cytokeratin 7 positivity.
SVS Member Vice Chair of ABS
SVS member Dr. Spence M. Taylor has been elected vice chair of the American Board of Surgery for 2017-18. He will serve as chair in 2018-19. Dr. Taylor joined the ABS as a director in 2011, representing the Southern Surgical Association.
He is a member of the ABS Vascular Surgery Board and Credentials Committee.
For more information, read the ABS summer newsletter.
SVS member Dr. Spence M. Taylor has been elected vice chair of the American Board of Surgery for 2017-18. He will serve as chair in 2018-19. Dr. Taylor joined the ABS as a director in 2011, representing the Southern Surgical Association.
He is a member of the ABS Vascular Surgery Board and Credentials Committee.
For more information, read the ABS summer newsletter.
SVS member Dr. Spence M. Taylor has been elected vice chair of the American Board of Surgery for 2017-18. He will serve as chair in 2018-19. Dr. Taylor joined the ABS as a director in 2011, representing the Southern Surgical Association.
He is a member of the ABS Vascular Surgery Board and Credentials Committee.
For more information, read the ABS summer newsletter.
Submit Proposals for VAM 2017
All SVS members may submit proposals for invited sessions for the 2017 Vascular Annual Meeting, set for May 31 to June 3 (plenaries and exhibits are June 1 to 3) in San Diego, Calif.
Previously, the process was open only to SVS committees; planners opened the process to all members this year, with any and all ideas for sessions to be reviewed for further development.
Invited sessions include postgraduate courses, breakfast and concurrent sessions and workshops. Initial submissions are due Sept. 16.
All SVS members may submit proposals for invited sessions for the 2017 Vascular Annual Meeting, set for May 31 to June 3 (plenaries and exhibits are June 1 to 3) in San Diego, Calif.
Previously, the process was open only to SVS committees; planners opened the process to all members this year, with any and all ideas for sessions to be reviewed for further development.
Invited sessions include postgraduate courses, breakfast and concurrent sessions and workshops. Initial submissions are due Sept. 16.
All SVS members may submit proposals for invited sessions for the 2017 Vascular Annual Meeting, set for May 31 to June 3 (plenaries and exhibits are June 1 to 3) in San Diego, Calif.
Previously, the process was open only to SVS committees; planners opened the process to all members this year, with any and all ideas for sessions to be reviewed for further development.
Invited sessions include postgraduate courses, breakfast and concurrent sessions and workshops. Initial submissions are due Sept. 16.
Review Course Recordings Available
Just in time for the September recertification exam! Recordings of the 2015 Comprehensive Vascular Review Course are available for purchase. The 2015 intensive two-day course was led by vascular surgeons with extensive expertise in their respective fields.
The recordings include didactic lectures and review of essential VESAP questions. The recordings also provide a comprehensive update in all areas of vascular surgery.
No CME credit is available.
Purchase the recordings here.
Just in time for the September recertification exam! Recordings of the 2015 Comprehensive Vascular Review Course are available for purchase. The 2015 intensive two-day course was led by vascular surgeons with extensive expertise in their respective fields.
The recordings include didactic lectures and review of essential VESAP questions. The recordings also provide a comprehensive update in all areas of vascular surgery.
No CME credit is available.
Purchase the recordings here.
Just in time for the September recertification exam! Recordings of the 2015 Comprehensive Vascular Review Course are available for purchase. The 2015 intensive two-day course was led by vascular surgeons with extensive expertise in their respective fields.
The recordings include didactic lectures and review of essential VESAP questions. The recordings also provide a comprehensive update in all areas of vascular surgery.
No CME credit is available.
Purchase the recordings here.
Are You Up for the ‘Cardio’ Challenge?
SVS members who are researchers and clinicians have an opportunity to win $5,000 for study hypotheses in cardiovascular research.
The American Heart Association and PCORI (Patient-Centered Outcomes Research Institute) have announced a ‘crowdsourcing’ challenge, asking researchers and clinicians to suggest research questions that address difficult challenges identified by patients with cardiovascular diseases. Proposals should focus on questions that can be answered through comparative clinical effectiveness research with a precision medicine approach.
Submissions are due by Oct. 6. Four winners will each receive a $5,000 cash prize.
SVS members who are researchers and clinicians have an opportunity to win $5,000 for study hypotheses in cardiovascular research.
The American Heart Association and PCORI (Patient-Centered Outcomes Research Institute) have announced a ‘crowdsourcing’ challenge, asking researchers and clinicians to suggest research questions that address difficult challenges identified by patients with cardiovascular diseases. Proposals should focus on questions that can be answered through comparative clinical effectiveness research with a precision medicine approach.
Submissions are due by Oct. 6. Four winners will each receive a $5,000 cash prize.
SVS members who are researchers and clinicians have an opportunity to win $5,000 for study hypotheses in cardiovascular research.
The American Heart Association and PCORI (Patient-Centered Outcomes Research Institute) have announced a ‘crowdsourcing’ challenge, asking researchers and clinicians to suggest research questions that address difficult challenges identified by patients with cardiovascular diseases. Proposals should focus on questions that can be answered through comparative clinical effectiveness research with a precision medicine approach.
Submissions are due by Oct. 6. Four winners will each receive a $5,000 cash prize.
Highlights From the 2016 AHS Meeting
Click here to download the digital edition.
Click here to download the digital edition.
Click here to download the digital edition.
Should clopidogrel be discontinued prior to open vascular procedures?
The continued use of perioperative clopidogrel is appropriate
Surgeons have always worried about bleeding risks for procedures we do. Complex vascular procedures are further complicated by the myriad of available antiplatelet agents designed to reduce ischemic events from cardiovascular disease burden at the expense of potential bleeding complications if antiplatelet medications are continued. Rather than relying on anecdotal reports by historical vignettes, let’s look at the evidence.
There probably is no other drug available in our vascular toolbox which has been studied more in the last 20 years than clopidogrel. Multiple randomized and double blinded studies such as CASPAR1 and CHARISMA2 have amplified what was known since the early CAPRIE trial in the 1990’s and that is that clopidogrel is safe when used as a single medication or as a dual agent with aspirin (duel antiplatelet therapy [DAPT]).
But not all our patients need DAPT. There is no level 1 evidence demonstrating the need for any antiplatelet therapy in the primary prevention of cardiovascular events for patients deemed at low or moderate risk of cardiovascular disease from a large meta-analysis review of six primary prevention trials encompassing over 95,000 patients.3
If our patients do present with vascular disease, current ACCP guidelines recommend single-agent antiplatelet medication (either ASA or clopidogrel) for symptomatic peripheral arterial disease (PAD) whether planning LE revascularization with bypass or via endovascular means with grade 1A evidence.4 This works fine for single-focus vascular disease and each antiplatelet agent have proponents but either works well.
That’s great, but what about all those sick cardiac patients we see the most of? First, CHARISMA subgroup analysis of patients with preexisting coronary and/or cerebrovascular disease demonstrate a 7.1% risk reduction in MI, cerebrovascular events, and cardiac ischemic deaths when continuing DAPT over aspirin alone, and similar risk reduction is found in PAD patients for endpoints of MI and ischemic cardiovascular events. Second, there was no significant difference in severe, fatal, or moderate bleeding in those receiving DAPT vs. aspirin alone with only minor bleeding increased using DAPT. Third, real-life practice echoes multiple trial experiences such as the Vascular Study Group of New England study group confirmed in reviewing 16 centers and 66 surgeons with more than 10,000 patients. Approximately 39% underwent major aortic or lower extremity bypass operations.
No statistical difference could be found for reoperation (P = .74), transfusion (P = .1) or operative type between DAPT or aspirin use alone.5 This is rediscovered once again by Saadeh and Sfeir in their prospective study of 647 major arterial procedures over 7 years finding no significant difference in reoperation for bleeding or bleeding mortality between DAPT vs. aspirin alone.6
So can we stop bashing clopidogrel as an evil agent of bleeding as Dr. Dalsing wishes to do? After all, he has been on record as stating, “I don’t know if our bleeding risk is worse or better … something we have to do to keep our grafts going.” Evidence tells us the benefits for continuing DAPT as seen in risk reduction in primary cardiovascular outcomes far outweigh the risk of minor bleeding associated with continued use.
Let the science dictate practice. Patients with low or moderate risk for cardiovascular disease need no antiplatelet medication unless undergoing PAD treatment where a single agent, either aspirin or clopidogrel alone, is sufficient. In those patients having a large cardiovascular burden of disease, combination of aspirin and clopidogrel improves survival benefit and reduces ischemic events without a significant risk of reoperation, transfusion, or bleeding-related mortality. As many of our patients require DAPT for drug eluting coronary stents, withholding clopidogrel preoperatively increases overall risk beyond acceptable limits. Improving surgical skills and paying attention to hemostasis during the operation will allow naysayers to achieve improved patient survival without fear of bleeding when continuing best medical therapy such as DAPT.
Gary Lemmon, MD, is professor of vascular surgery at Indiana University, Indianapolis, and chief, vascular surgery, Indianapolis VA Medical Center. He reported no relevant conflicts.
References
1. J Vasc Surg. 2010;52:825-33
2. Eur Heart J. 2009;30:192-201
3. Lancet. 2009;373:1849-604. Chest. 2012;141:e669s-90s
5. J Vasc Surg. 2011;54: 779-84
6. J Vasc Surg. 2013;58: 1586-92
The continued use of perioperative clopidogrel is debatable!
There are cases in which clopidogrel should not be discontinued for a needed vascular intervention. Delaying operation or maintaining clopidogrel during operation if your patient required a recent coronary stent is warranted unless you are willing to accept an acute coronary thrombosis.
However, in other cases, for example infrainguinal grafts, the risk of potential increased bleeding when adding clopidogrel to aspirin may outweigh potential improvements in graft patency. This is especially true of below-knee vein bypass grafts where data do not support improved patency. However, in the CASPAR trial, prosthetic graft patency did appear to be beneficial, but only in subgroup analysis.1
It is true that severe bleeding was not increased (intracranial hemorrhage, or hemodynamic compromise: 1 vs 2.7%, P = NS) but moderate bleeding (transfusion required: 0.7 vs 3.7%, P = .012) and mild bleeding (5.4 vs 12.1%, P = .004) was increased when this agent was used especially in vein graft surgery. This risk of bleeding was present even when clopidogrel was begun 2 or more days after surgery.1
To complicate this decision, a Cochrane review did not consider subgroup analysis as statistically valid and so the authors considered infrainguinal graft patency as not improved with clopidogrel but bleeding risk was increased. One might even question the use of acetylsalicylic acid (ASA) for vein graft bypasses based on the results of this metanalysis.2 Carotid endarterectomy is a common vascular surgery procedure in which antiplatelet use has been evaluated in the real-world situation and with large cohorts. As is always the case when dealing with patient issues, the addition of one agent does not tell the entire story and patient demographics can have a significant influence on the outcome. A report from the Vascular Quality Initiative (VQI) database controlled for patient differences by propensity matching with more than 4,500 patients in each of the two groups; ASA vs. ASA + clopidogrel; demonstrated that major bleeding, defined as return to the OR for bleeding, was statistically more common with dual therapy (1.3% vs. 0.7%, P = .004).3
The addition of clopidogrel did statistically decrease the risk of ipsilateral TIA or stroke (0.8% vs. 1.2%, P = .02) but not the risk of death (0.2% vs. 0.3%, P = .3) or postoperative MI (1% vs. 0.8%, P = .4). Reoperation for bleeding is not inconsequential since in patients requiring this intervention, there is a significantly worse outcome in regard to stroke (3.7% vs. 0.8%, P = .001), MI (6.2% vs. 0.8%, P = .001), and death (2.5% vs. 0.2%,P = .001). Further drill down involving propensity score–matched analysis stratified by symptom status (asymptomatic vs. symptomatic) was quite interesting in that in only asymptomatic patients did the addition of clopidogrel actually demonstrate a statistically significant reduction in TIA or stroke, any stroke, or composite stroke/death. Symptomatic patients taking dual therapy demonstrated a slight reduction in TIA or stroke (1.4% vs. 1.7%, P = .6), any stroke (1.1% vs. 1.2%, P = .9) and composite stroke/death (1.2% vs. 1.5%, P = .5) but in no instance was statistical significance reached. The use of protamine did help to decrease the risk of bleeding.
Regarding the use of dual therapy during open aortic operations, an earlier report of the VQI database demonstrated no significant difference in bleeding risk statistically, but if one delves deeper the data indicate something different. In the majority of cases, vascular surgeons do not feel comfortable preforming this extensive dissection on dual therapy. Of the cases reported, 1,074 were preformed either free of either drug or only on ASA while 42 were on dual therapy and only 12 on clopidogrel only. In fact, in the conclusions, the authors note that they do not believe that conclusions regarding clopidogrel use in patient undergoing open abdominal aortic aneurysm repair can be drawn based on their results since the potential for a type II error was too great.4
It may be that our current level of sophistication is not sufficiently mature to determine the actual effect that clopidogrel is having on our patients. Clopidogrel, a thienopyridine, inhibits platelet activation by blocking the ADP-binding site for the P2Y12 receptor. Over 85% of ingested drug is metabolized into inactive metabolites while 15% is metabolized by the liver via a two-step oxidative process into the active thiol metabolite. Inter-individual variability in the antiplatelet response to thienopyridines is noted and partially caused by genetic mutations in the CP isoenzymes. Platelet reactivity testing is possible but most of the work has been conducted for those patients requiring coronary artery revascularization. Results of tailoring intervention to maximize therapeutic benefit and decrease the risk of bleeding have been inconsistent but, in some studies, appear to be promising.5 This approach may ultimately be found superior to determining how effective clopidogrel actually is in a particular case with some insight into the bleeding risk as well. With this determination, whether or not to hold clopidogrel perioperatively can be made with some science behind the decision.
Clearly, a blanket statement that the risk of bleeding should be accepted or ignored because of the demonstrated benefits of clopidogrel in patients requiring vascular surgery is not accurate. In some cases, there is no clear benefit, so eliminating the bleeding risk may well be the appropriate decision. The astute vascular surgeon understands the details of the written word in order to make an educated decision and understands that new information such as determining platelet reactivity may provide more clarity to such decisions in the future.
Michael C. Dalsing, MD, is chief of vascular surgery at Indiana University, Indianapolis. He reported no relevant conflicts.
References
1. J Vasc Surg. 2010;52:825-33
2. Cochrane Database Syst Rev. 2015, Issue 2. Art. No.: CD000535
The continued use of perioperative clopidogrel is appropriate
Surgeons have always worried about bleeding risks for procedures we do. Complex vascular procedures are further complicated by the myriad of available antiplatelet agents designed to reduce ischemic events from cardiovascular disease burden at the expense of potential bleeding complications if antiplatelet medications are continued. Rather than relying on anecdotal reports by historical vignettes, let’s look at the evidence.
There probably is no other drug available in our vascular toolbox which has been studied more in the last 20 years than clopidogrel. Multiple randomized and double blinded studies such as CASPAR1 and CHARISMA2 have amplified what was known since the early CAPRIE trial in the 1990’s and that is that clopidogrel is safe when used as a single medication or as a dual agent with aspirin (duel antiplatelet therapy [DAPT]).
But not all our patients need DAPT. There is no level 1 evidence demonstrating the need for any antiplatelet therapy in the primary prevention of cardiovascular events for patients deemed at low or moderate risk of cardiovascular disease from a large meta-analysis review of six primary prevention trials encompassing over 95,000 patients.3
If our patients do present with vascular disease, current ACCP guidelines recommend single-agent antiplatelet medication (either ASA or clopidogrel) for symptomatic peripheral arterial disease (PAD) whether planning LE revascularization with bypass or via endovascular means with grade 1A evidence.4 This works fine for single-focus vascular disease and each antiplatelet agent have proponents but either works well.
That’s great, but what about all those sick cardiac patients we see the most of? First, CHARISMA subgroup analysis of patients with preexisting coronary and/or cerebrovascular disease demonstrate a 7.1% risk reduction in MI, cerebrovascular events, and cardiac ischemic deaths when continuing DAPT over aspirin alone, and similar risk reduction is found in PAD patients for endpoints of MI and ischemic cardiovascular events. Second, there was no significant difference in severe, fatal, or moderate bleeding in those receiving DAPT vs. aspirin alone with only minor bleeding increased using DAPT. Third, real-life practice echoes multiple trial experiences such as the Vascular Study Group of New England study group confirmed in reviewing 16 centers and 66 surgeons with more than 10,000 patients. Approximately 39% underwent major aortic or lower extremity bypass operations.
No statistical difference could be found for reoperation (P = .74), transfusion (P = .1) or operative type between DAPT or aspirin use alone.5 This is rediscovered once again by Saadeh and Sfeir in their prospective study of 647 major arterial procedures over 7 years finding no significant difference in reoperation for bleeding or bleeding mortality between DAPT vs. aspirin alone.6
So can we stop bashing clopidogrel as an evil agent of bleeding as Dr. Dalsing wishes to do? After all, he has been on record as stating, “I don’t know if our bleeding risk is worse or better … something we have to do to keep our grafts going.” Evidence tells us the benefits for continuing DAPT as seen in risk reduction in primary cardiovascular outcomes far outweigh the risk of minor bleeding associated with continued use.
Let the science dictate practice. Patients with low or moderate risk for cardiovascular disease need no antiplatelet medication unless undergoing PAD treatment where a single agent, either aspirin or clopidogrel alone, is sufficient. In those patients having a large cardiovascular burden of disease, combination of aspirin and clopidogrel improves survival benefit and reduces ischemic events without a significant risk of reoperation, transfusion, or bleeding-related mortality. As many of our patients require DAPT for drug eluting coronary stents, withholding clopidogrel preoperatively increases overall risk beyond acceptable limits. Improving surgical skills and paying attention to hemostasis during the operation will allow naysayers to achieve improved patient survival without fear of bleeding when continuing best medical therapy such as DAPT.
Gary Lemmon, MD, is professor of vascular surgery at Indiana University, Indianapolis, and chief, vascular surgery, Indianapolis VA Medical Center. He reported no relevant conflicts.
References
1. J Vasc Surg. 2010;52:825-33
2. Eur Heart J. 2009;30:192-201
3. Lancet. 2009;373:1849-604. Chest. 2012;141:e669s-90s
5. J Vasc Surg. 2011;54: 779-84
6. J Vasc Surg. 2013;58: 1586-92
The continued use of perioperative clopidogrel is debatable!
There are cases in which clopidogrel should not be discontinued for a needed vascular intervention. Delaying operation or maintaining clopidogrel during operation if your patient required a recent coronary stent is warranted unless you are willing to accept an acute coronary thrombosis.
However, in other cases, for example infrainguinal grafts, the risk of potential increased bleeding when adding clopidogrel to aspirin may outweigh potential improvements in graft patency. This is especially true of below-knee vein bypass grafts where data do not support improved patency. However, in the CASPAR trial, prosthetic graft patency did appear to be beneficial, but only in subgroup analysis.1
It is true that severe bleeding was not increased (intracranial hemorrhage, or hemodynamic compromise: 1 vs 2.7%, P = NS) but moderate bleeding (transfusion required: 0.7 vs 3.7%, P = .012) and mild bleeding (5.4 vs 12.1%, P = .004) was increased when this agent was used especially in vein graft surgery. This risk of bleeding was present even when clopidogrel was begun 2 or more days after surgery.1
To complicate this decision, a Cochrane review did not consider subgroup analysis as statistically valid and so the authors considered infrainguinal graft patency as not improved with clopidogrel but bleeding risk was increased. One might even question the use of acetylsalicylic acid (ASA) for vein graft bypasses based on the results of this metanalysis.2 Carotid endarterectomy is a common vascular surgery procedure in which antiplatelet use has been evaluated in the real-world situation and with large cohorts. As is always the case when dealing with patient issues, the addition of one agent does not tell the entire story and patient demographics can have a significant influence on the outcome. A report from the Vascular Quality Initiative (VQI) database controlled for patient differences by propensity matching with more than 4,500 patients in each of the two groups; ASA vs. ASA + clopidogrel; demonstrated that major bleeding, defined as return to the OR for bleeding, was statistically more common with dual therapy (1.3% vs. 0.7%, P = .004).3
The addition of clopidogrel did statistically decrease the risk of ipsilateral TIA or stroke (0.8% vs. 1.2%, P = .02) but not the risk of death (0.2% vs. 0.3%, P = .3) or postoperative MI (1% vs. 0.8%, P = .4). Reoperation for bleeding is not inconsequential since in patients requiring this intervention, there is a significantly worse outcome in regard to stroke (3.7% vs. 0.8%, P = .001), MI (6.2% vs. 0.8%, P = .001), and death (2.5% vs. 0.2%,P = .001). Further drill down involving propensity score–matched analysis stratified by symptom status (asymptomatic vs. symptomatic) was quite interesting in that in only asymptomatic patients did the addition of clopidogrel actually demonstrate a statistically significant reduction in TIA or stroke, any stroke, or composite stroke/death. Symptomatic patients taking dual therapy demonstrated a slight reduction in TIA or stroke (1.4% vs. 1.7%, P = .6), any stroke (1.1% vs. 1.2%, P = .9) and composite stroke/death (1.2% vs. 1.5%, P = .5) but in no instance was statistical significance reached. The use of protamine did help to decrease the risk of bleeding.
Regarding the use of dual therapy during open aortic operations, an earlier report of the VQI database demonstrated no significant difference in bleeding risk statistically, but if one delves deeper the data indicate something different. In the majority of cases, vascular surgeons do not feel comfortable preforming this extensive dissection on dual therapy. Of the cases reported, 1,074 were preformed either free of either drug or only on ASA while 42 were on dual therapy and only 12 on clopidogrel only. In fact, in the conclusions, the authors note that they do not believe that conclusions regarding clopidogrel use in patient undergoing open abdominal aortic aneurysm repair can be drawn based on their results since the potential for a type II error was too great.4
It may be that our current level of sophistication is not sufficiently mature to determine the actual effect that clopidogrel is having on our patients. Clopidogrel, a thienopyridine, inhibits platelet activation by blocking the ADP-binding site for the P2Y12 receptor. Over 85% of ingested drug is metabolized into inactive metabolites while 15% is metabolized by the liver via a two-step oxidative process into the active thiol metabolite. Inter-individual variability in the antiplatelet response to thienopyridines is noted and partially caused by genetic mutations in the CP isoenzymes. Platelet reactivity testing is possible but most of the work has been conducted for those patients requiring coronary artery revascularization. Results of tailoring intervention to maximize therapeutic benefit and decrease the risk of bleeding have been inconsistent but, in some studies, appear to be promising.5 This approach may ultimately be found superior to determining how effective clopidogrel actually is in a particular case with some insight into the bleeding risk as well. With this determination, whether or not to hold clopidogrel perioperatively can be made with some science behind the decision.
Clearly, a blanket statement that the risk of bleeding should be accepted or ignored because of the demonstrated benefits of clopidogrel in patients requiring vascular surgery is not accurate. In some cases, there is no clear benefit, so eliminating the bleeding risk may well be the appropriate decision. The astute vascular surgeon understands the details of the written word in order to make an educated decision and understands that new information such as determining platelet reactivity may provide more clarity to such decisions in the future.
Michael C. Dalsing, MD, is chief of vascular surgery at Indiana University, Indianapolis. He reported no relevant conflicts.
References
1. J Vasc Surg. 2010;52:825-33
2. Cochrane Database Syst Rev. 2015, Issue 2. Art. No.: CD000535
The continued use of perioperative clopidogrel is appropriate
Surgeons have always worried about bleeding risks for procedures we do. Complex vascular procedures are further complicated by the myriad of available antiplatelet agents designed to reduce ischemic events from cardiovascular disease burden at the expense of potential bleeding complications if antiplatelet medications are continued. Rather than relying on anecdotal reports by historical vignettes, let’s look at the evidence.
There probably is no other drug available in our vascular toolbox which has been studied more in the last 20 years than clopidogrel. Multiple randomized and double blinded studies such as CASPAR1 and CHARISMA2 have amplified what was known since the early CAPRIE trial in the 1990’s and that is that clopidogrel is safe when used as a single medication or as a dual agent with aspirin (duel antiplatelet therapy [DAPT]).
But not all our patients need DAPT. There is no level 1 evidence demonstrating the need for any antiplatelet therapy in the primary prevention of cardiovascular events for patients deemed at low or moderate risk of cardiovascular disease from a large meta-analysis review of six primary prevention trials encompassing over 95,000 patients.3
If our patients do present with vascular disease, current ACCP guidelines recommend single-agent antiplatelet medication (either ASA or clopidogrel) for symptomatic peripheral arterial disease (PAD) whether planning LE revascularization with bypass or via endovascular means with grade 1A evidence.4 This works fine for single-focus vascular disease and each antiplatelet agent have proponents but either works well.
That’s great, but what about all those sick cardiac patients we see the most of? First, CHARISMA subgroup analysis of patients with preexisting coronary and/or cerebrovascular disease demonstrate a 7.1% risk reduction in MI, cerebrovascular events, and cardiac ischemic deaths when continuing DAPT over aspirin alone, and similar risk reduction is found in PAD patients for endpoints of MI and ischemic cardiovascular events. Second, there was no significant difference in severe, fatal, or moderate bleeding in those receiving DAPT vs. aspirin alone with only minor bleeding increased using DAPT. Third, real-life practice echoes multiple trial experiences such as the Vascular Study Group of New England study group confirmed in reviewing 16 centers and 66 surgeons with more than 10,000 patients. Approximately 39% underwent major aortic or lower extremity bypass operations.
No statistical difference could be found for reoperation (P = .74), transfusion (P = .1) or operative type between DAPT or aspirin use alone.5 This is rediscovered once again by Saadeh and Sfeir in their prospective study of 647 major arterial procedures over 7 years finding no significant difference in reoperation for bleeding or bleeding mortality between DAPT vs. aspirin alone.6
So can we stop bashing clopidogrel as an evil agent of bleeding as Dr. Dalsing wishes to do? After all, he has been on record as stating, “I don’t know if our bleeding risk is worse or better … something we have to do to keep our grafts going.” Evidence tells us the benefits for continuing DAPT as seen in risk reduction in primary cardiovascular outcomes far outweigh the risk of minor bleeding associated with continued use.
Let the science dictate practice. Patients with low or moderate risk for cardiovascular disease need no antiplatelet medication unless undergoing PAD treatment where a single agent, either aspirin or clopidogrel alone, is sufficient. In those patients having a large cardiovascular burden of disease, combination of aspirin and clopidogrel improves survival benefit and reduces ischemic events without a significant risk of reoperation, transfusion, or bleeding-related mortality. As many of our patients require DAPT for drug eluting coronary stents, withholding clopidogrel preoperatively increases overall risk beyond acceptable limits. Improving surgical skills and paying attention to hemostasis during the operation will allow naysayers to achieve improved patient survival without fear of bleeding when continuing best medical therapy such as DAPT.
Gary Lemmon, MD, is professor of vascular surgery at Indiana University, Indianapolis, and chief, vascular surgery, Indianapolis VA Medical Center. He reported no relevant conflicts.
References
1. J Vasc Surg. 2010;52:825-33
2. Eur Heart J. 2009;30:192-201
3. Lancet. 2009;373:1849-604. Chest. 2012;141:e669s-90s
5. J Vasc Surg. 2011;54: 779-84
6. J Vasc Surg. 2013;58: 1586-92
The continued use of perioperative clopidogrel is debatable!
There are cases in which clopidogrel should not be discontinued for a needed vascular intervention. Delaying operation or maintaining clopidogrel during operation if your patient required a recent coronary stent is warranted unless you are willing to accept an acute coronary thrombosis.
However, in other cases, for example infrainguinal grafts, the risk of potential increased bleeding when adding clopidogrel to aspirin may outweigh potential improvements in graft patency. This is especially true of below-knee vein bypass grafts where data do not support improved patency. However, in the CASPAR trial, prosthetic graft patency did appear to be beneficial, but only in subgroup analysis.1
It is true that severe bleeding was not increased (intracranial hemorrhage, or hemodynamic compromise: 1 vs 2.7%, P = NS) but moderate bleeding (transfusion required: 0.7 vs 3.7%, P = .012) and mild bleeding (5.4 vs 12.1%, P = .004) was increased when this agent was used especially in vein graft surgery. This risk of bleeding was present even when clopidogrel was begun 2 or more days after surgery.1
To complicate this decision, a Cochrane review did not consider subgroup analysis as statistically valid and so the authors considered infrainguinal graft patency as not improved with clopidogrel but bleeding risk was increased. One might even question the use of acetylsalicylic acid (ASA) for vein graft bypasses based on the results of this metanalysis.2 Carotid endarterectomy is a common vascular surgery procedure in which antiplatelet use has been evaluated in the real-world situation and with large cohorts. As is always the case when dealing with patient issues, the addition of one agent does not tell the entire story and patient demographics can have a significant influence on the outcome. A report from the Vascular Quality Initiative (VQI) database controlled for patient differences by propensity matching with more than 4,500 patients in each of the two groups; ASA vs. ASA + clopidogrel; demonstrated that major bleeding, defined as return to the OR for bleeding, was statistically more common with dual therapy (1.3% vs. 0.7%, P = .004).3
The addition of clopidogrel did statistically decrease the risk of ipsilateral TIA or stroke (0.8% vs. 1.2%, P = .02) but not the risk of death (0.2% vs. 0.3%, P = .3) or postoperative MI (1% vs. 0.8%, P = .4). Reoperation for bleeding is not inconsequential since in patients requiring this intervention, there is a significantly worse outcome in regard to stroke (3.7% vs. 0.8%, P = .001), MI (6.2% vs. 0.8%, P = .001), and death (2.5% vs. 0.2%,P = .001). Further drill down involving propensity score–matched analysis stratified by symptom status (asymptomatic vs. symptomatic) was quite interesting in that in only asymptomatic patients did the addition of clopidogrel actually demonstrate a statistically significant reduction in TIA or stroke, any stroke, or composite stroke/death. Symptomatic patients taking dual therapy demonstrated a slight reduction in TIA or stroke (1.4% vs. 1.7%, P = .6), any stroke (1.1% vs. 1.2%, P = .9) and composite stroke/death (1.2% vs. 1.5%, P = .5) but in no instance was statistical significance reached. The use of protamine did help to decrease the risk of bleeding.
Regarding the use of dual therapy during open aortic operations, an earlier report of the VQI database demonstrated no significant difference in bleeding risk statistically, but if one delves deeper the data indicate something different. In the majority of cases, vascular surgeons do not feel comfortable preforming this extensive dissection on dual therapy. Of the cases reported, 1,074 were preformed either free of either drug or only on ASA while 42 were on dual therapy and only 12 on clopidogrel only. In fact, in the conclusions, the authors note that they do not believe that conclusions regarding clopidogrel use in patient undergoing open abdominal aortic aneurysm repair can be drawn based on their results since the potential for a type II error was too great.4
It may be that our current level of sophistication is not sufficiently mature to determine the actual effect that clopidogrel is having on our patients. Clopidogrel, a thienopyridine, inhibits platelet activation by blocking the ADP-binding site for the P2Y12 receptor. Over 85% of ingested drug is metabolized into inactive metabolites while 15% is metabolized by the liver via a two-step oxidative process into the active thiol metabolite. Inter-individual variability in the antiplatelet response to thienopyridines is noted and partially caused by genetic mutations in the CP isoenzymes. Platelet reactivity testing is possible but most of the work has been conducted for those patients requiring coronary artery revascularization. Results of tailoring intervention to maximize therapeutic benefit and decrease the risk of bleeding have been inconsistent but, in some studies, appear to be promising.5 This approach may ultimately be found superior to determining how effective clopidogrel actually is in a particular case with some insight into the bleeding risk as well. With this determination, whether or not to hold clopidogrel perioperatively can be made with some science behind the decision.
Clearly, a blanket statement that the risk of bleeding should be accepted or ignored because of the demonstrated benefits of clopidogrel in patients requiring vascular surgery is not accurate. In some cases, there is no clear benefit, so eliminating the bleeding risk may well be the appropriate decision. The astute vascular surgeon understands the details of the written word in order to make an educated decision and understands that new information such as determining platelet reactivity may provide more clarity to such decisions in the future.
Michael C. Dalsing, MD, is chief of vascular surgery at Indiana University, Indianapolis. He reported no relevant conflicts.
References
1. J Vasc Surg. 2010;52:825-33
2. Cochrane Database Syst Rev. 2015, Issue 2. Art. No.: CD000535
Painful Purple Toes
The Diagnosis: Blue Toe Syndrome
The clinical manifestation suggested blue toe syndrome. A variety of causes for blue toe syndrome are known such as embolism, thrombosis, vasoconstrictive disorders, infectious and noninfectious inflammation, extensive venous thrombosis, and abnormal circulating blood.1 Among them, only emboli from atherosclerotic plaques give rise to typical cholesterol clefts on skin biopsy (Figure 1). Such atheroemboli often are an iatrogenic complication, especially those caused by invasive percutaneous procedures or damage to the arterial walls from vascular surgery. However, spontaneous plaque hemorrhage or shearing forces of the circulating blood can disrupt atheromatous plaques and cause embolization of the cholesterol crystals, which was likely to be the case in our patient because no preceding trigger events were noted.
Other clinical features also are seen in atheroembolism. Approximately half of patients with atheroembolism develop clinical kidney disease.2 Almost all iatrogenic cases have acute or subacute reduction in glomerular filtration rate of at least to 50% level, whereas the spontaneous cases present as stable chronic renal failure.3 Approximately 20% of patients with atheroembolism also have involvement of digestive organs.4,5 Abdominal pain, diarrhea, and gastrointestinal blood loss are common features; bowel infarction and perforation occasionally occur.5 Pancreatitis is another common complication, and serum amylase levels are raised in approximately 50% of patients.6 Atheroemboli may reach the eyes and brain. They occasionally can cause loss of vision,7 as well as transient ischemic attacks, strokes, and gradual deterioration in cerebral function.3 Blood eosinophilia, which occurs in approximately 60% of patients, is an important finding.3,8
Although there is no specific therapy for atheroembolism, the use of antiplatelet agents is considered reasonable because they are beneficial in preventing myocardial infarction in patients with atherosclerosis.9 In our case, the livedo reticularis cleared, as did the coldness on the affected toes after 2 weeks of sarpogrelate hydrochloride administration; however, development of necrotic change was noted (Figure 2). Necrotic change on the hallux disappeared after 2 weeks.
- Hirschmann JV, Raugi GJ. Blue (or purple) toe syndrome. J Am Acad Dermatol. 2009;60:1-20; quiz 21-22.
- Scolari F, Ravani P, Gaggi R, et al. The challenge of diagnosing atheroembolic renal disease: clinical features and prognostic factors. Circulation. 2007;116:298-304.
- Scolari F, Tardanico R, Zani R, et al. Cholesterol crystal embolism: a recognizable cause of renal disease. Am J Kidney Dis. 2000;36:1089-1109.
- Moolenaar W, Lamers CB. Cholesterol crystal embolization in the Netherlands. Arch Intern Med. 1996;156:653-657.
- Ben-Horin S, Bardan E, Barshack I, et al. Cholesterol crystal embolization to the digestive system: characterization of a common, yet overlooked presentation of atheroembolism. Am J Gastroenterol. 2003;98:1471-1479.
- Mayo RR, Swartz RD. Redefining the incidence of clinically detectable atheroembolism. Am J Med. 1996;100:524-529.
- Gittinger JW Jr, Kershaw GR. Retinal cholesterol emboli in the diagnosis of renal atheroembolism. Arch Intern Med. 1998;158:1265-1267.
- Kasinath BS, Corwin HL, Bidani AK, et al. Eosinophilia in the diagnosis of atheroembolic renal disease. Am J Nephrol. 1987;7:173-177.
- Quinones A, Saric M. The cholesterol emboli syndrome in atherosclerosis. Curr Atheroscler Rep. 2013;15:315.
The Diagnosis: Blue Toe Syndrome
The clinical manifestation suggested blue toe syndrome. A variety of causes for blue toe syndrome are known such as embolism, thrombosis, vasoconstrictive disorders, infectious and noninfectious inflammation, extensive venous thrombosis, and abnormal circulating blood.1 Among them, only emboli from atherosclerotic plaques give rise to typical cholesterol clefts on skin biopsy (Figure 1). Such atheroemboli often are an iatrogenic complication, especially those caused by invasive percutaneous procedures or damage to the arterial walls from vascular surgery. However, spontaneous plaque hemorrhage or shearing forces of the circulating blood can disrupt atheromatous plaques and cause embolization of the cholesterol crystals, which was likely to be the case in our patient because no preceding trigger events were noted.
Other clinical features also are seen in atheroembolism. Approximately half of patients with atheroembolism develop clinical kidney disease.2 Almost all iatrogenic cases have acute or subacute reduction in glomerular filtration rate of at least to 50% level, whereas the spontaneous cases present as stable chronic renal failure.3 Approximately 20% of patients with atheroembolism also have involvement of digestive organs.4,5 Abdominal pain, diarrhea, and gastrointestinal blood loss are common features; bowel infarction and perforation occasionally occur.5 Pancreatitis is another common complication, and serum amylase levels are raised in approximately 50% of patients.6 Atheroemboli may reach the eyes and brain. They occasionally can cause loss of vision,7 as well as transient ischemic attacks, strokes, and gradual deterioration in cerebral function.3 Blood eosinophilia, which occurs in approximately 60% of patients, is an important finding.3,8
Although there is no specific therapy for atheroembolism, the use of antiplatelet agents is considered reasonable because they are beneficial in preventing myocardial infarction in patients with atherosclerosis.9 In our case, the livedo reticularis cleared, as did the coldness on the affected toes after 2 weeks of sarpogrelate hydrochloride administration; however, development of necrotic change was noted (Figure 2). Necrotic change on the hallux disappeared after 2 weeks.
The Diagnosis: Blue Toe Syndrome
The clinical manifestation suggested blue toe syndrome. A variety of causes for blue toe syndrome are known such as embolism, thrombosis, vasoconstrictive disorders, infectious and noninfectious inflammation, extensive venous thrombosis, and abnormal circulating blood.1 Among them, only emboli from atherosclerotic plaques give rise to typical cholesterol clefts on skin biopsy (Figure 1). Such atheroemboli often are an iatrogenic complication, especially those caused by invasive percutaneous procedures or damage to the arterial walls from vascular surgery. However, spontaneous plaque hemorrhage or shearing forces of the circulating blood can disrupt atheromatous plaques and cause embolization of the cholesterol crystals, which was likely to be the case in our patient because no preceding trigger events were noted.
Other clinical features also are seen in atheroembolism. Approximately half of patients with atheroembolism develop clinical kidney disease.2 Almost all iatrogenic cases have acute or subacute reduction in glomerular filtration rate of at least to 50% level, whereas the spontaneous cases present as stable chronic renal failure.3 Approximately 20% of patients with atheroembolism also have involvement of digestive organs.4,5 Abdominal pain, diarrhea, and gastrointestinal blood loss are common features; bowel infarction and perforation occasionally occur.5 Pancreatitis is another common complication, and serum amylase levels are raised in approximately 50% of patients.6 Atheroemboli may reach the eyes and brain. They occasionally can cause loss of vision,7 as well as transient ischemic attacks, strokes, and gradual deterioration in cerebral function.3 Blood eosinophilia, which occurs in approximately 60% of patients, is an important finding.3,8
Although there is no specific therapy for atheroembolism, the use of antiplatelet agents is considered reasonable because they are beneficial in preventing myocardial infarction in patients with atherosclerosis.9 In our case, the livedo reticularis cleared, as did the coldness on the affected toes after 2 weeks of sarpogrelate hydrochloride administration; however, development of necrotic change was noted (Figure 2). Necrotic change on the hallux disappeared after 2 weeks.
- Hirschmann JV, Raugi GJ. Blue (or purple) toe syndrome. J Am Acad Dermatol. 2009;60:1-20; quiz 21-22.
- Scolari F, Ravani P, Gaggi R, et al. The challenge of diagnosing atheroembolic renal disease: clinical features and prognostic factors. Circulation. 2007;116:298-304.
- Scolari F, Tardanico R, Zani R, et al. Cholesterol crystal embolism: a recognizable cause of renal disease. Am J Kidney Dis. 2000;36:1089-1109.
- Moolenaar W, Lamers CB. Cholesterol crystal embolization in the Netherlands. Arch Intern Med. 1996;156:653-657.
- Ben-Horin S, Bardan E, Barshack I, et al. Cholesterol crystal embolization to the digestive system: characterization of a common, yet overlooked presentation of atheroembolism. Am J Gastroenterol. 2003;98:1471-1479.
- Mayo RR, Swartz RD. Redefining the incidence of clinically detectable atheroembolism. Am J Med. 1996;100:524-529.
- Gittinger JW Jr, Kershaw GR. Retinal cholesterol emboli in the diagnosis of renal atheroembolism. Arch Intern Med. 1998;158:1265-1267.
- Kasinath BS, Corwin HL, Bidani AK, et al. Eosinophilia in the diagnosis of atheroembolic renal disease. Am J Nephrol. 1987;7:173-177.
- Quinones A, Saric M. The cholesterol emboli syndrome in atherosclerosis. Curr Atheroscler Rep. 2013;15:315.
- Hirschmann JV, Raugi GJ. Blue (or purple) toe syndrome. J Am Acad Dermatol. 2009;60:1-20; quiz 21-22.
- Scolari F, Ravani P, Gaggi R, et al. The challenge of diagnosing atheroembolic renal disease: clinical features and prognostic factors. Circulation. 2007;116:298-304.
- Scolari F, Tardanico R, Zani R, et al. Cholesterol crystal embolism: a recognizable cause of renal disease. Am J Kidney Dis. 2000;36:1089-1109.
- Moolenaar W, Lamers CB. Cholesterol crystal embolization in the Netherlands. Arch Intern Med. 1996;156:653-657.
- Ben-Horin S, Bardan E, Barshack I, et al. Cholesterol crystal embolization to the digestive system: characterization of a common, yet overlooked presentation of atheroembolism. Am J Gastroenterol. 2003;98:1471-1479.
- Mayo RR, Swartz RD. Redefining the incidence of clinically detectable atheroembolism. Am J Med. 1996;100:524-529.
- Gittinger JW Jr, Kershaw GR. Retinal cholesterol emboli in the diagnosis of renal atheroembolism. Arch Intern Med. 1998;158:1265-1267.
- Kasinath BS, Corwin HL, Bidani AK, et al. Eosinophilia in the diagnosis of atheroembolic renal disease. Am J Nephrol. 1987;7:173-177.
- Quinones A, Saric M. The cholesterol emboli syndrome in atherosclerosis. Curr Atheroscler Rep. 2013;15:315.
A 63-year-old man presented with sudden onset of severe pain in the right hallux and fifth toe of 3 days' duration. The patient had hypertension and hyperlipidemia with a 45-year history of smoking and had not undergone any vascular procedures. Physical examination revealed relatively well-defined cyanotic change with remarkable coldness on the affected toes as well as livedo reticularis on the underside of the toes. All peripheral pulses were present. Laboratory investigation revealed no remarkable changes with eosinophil counts within reference range and normal renal function. A biopsy taken from the fifth toe revealed thrombotic arterioles with cholesterol clefts.
Clinical Challenges - September 2016: Fibrolamellar-hepatocellular carcinoma
What's Your Diagnosis?
The diagnosis
Histologic analysis was consistent with a fibrolamellar-hepatocellular carcinoma (HCC). The patient developed decerebrate posturing without cerebral edema on CT of the head. The patient was treated with mannitol, hyperventilation, and therapeutic hypothermia, as well as lactulose, rifaximin, hemodialysis, and “empiric” sodium benzoate/sodium phenylacetate (Ammonul, Ucyclyd Pharma, Scottsdale, Ariz.) for the possibility of a urea cycle disorder. In hopes of decreasing blood flow to the tumor, the patient underwent embolization of the right hepatic artery with no clinical improvement. Given the persistently elevated ammonia level, a work-up for an underlying urea cycle disorder was performed, revealing trace citrulline and increased urine orotic acids and uracil, suggesting an ornithine transcarbamylase (OTC) deficiency. She was started on parenteral nutrition with arginine supplementation, after which her ammonia level normalized with subsequent improvement in her mental status.
Fibrolamellar-HCC is a rare, malignant, primary liver tumor predominantly affecting young adults with no underlying liver disease. This hypervascular tumor is radiographically characterized by a central scar.1 Most patients experience vague abdominal pain, weight loss, and fatigue. Fibrolamellar-HCC carries a better prognosis than HCC; in surgically resectable cases, the 5-year survival rates range between 37% and 76% vs. 12-14 months in nonresectable cases.2 Systemic chemotherapy has been used in case reports and the role of sorafenib remains unexplored and ill defined.
This is the second reported case of metastatic fibrolamellar-HCC with hyperammonemia.3 Although urea cycle disorders are more commonly diagnosed in newborns and infants, patients with partial enzyme deficiencies may present later in life and manifest in the setting of metabolic decompensation or stress. Our patient’s initial evaluation was consistent with a urea cycle deficiency, but OTC sequencing from the blood was negative. We hypothesize that the patient exhibited a “functional” OTC deficiency as a result of a combination of the massive tumor burden and portal vein thrombus, leading to a decreased expression of the OTC gene and insufficient enzyme production. The patient is doing well 3 months post resection and is being considered for a phase I clinical trial with a telomerase inhibitor, imetelstat.
References
1. Ichikawa, T., Federle, M.P., Grazioli, L., et al. Fibrolamellar hepatocellular carcinoma: Imaging and pathologic findings in 31 recent cases. Radiology. 1999;213(2):352-61.
2. Ward, S.C. Waxman, S. Fibrolamellar carcinoma: A review with focus on genetics and comparison to other malignant primary liver tumors. Semin Liver Dis. 2011;31(1):61-70.
3. Sethi, S., Tageja, N., Singh, J., et al. Hyperammonemic encephalopathy: A rare presentation of fibrolamellar hepatocellular carcinoma. Am J Med Sci. 2009;338(6):522-4.
The diagnosis
Histologic analysis was consistent with a fibrolamellar-hepatocellular carcinoma (HCC). The patient developed decerebrate posturing without cerebral edema on CT of the head. The patient was treated with mannitol, hyperventilation, and therapeutic hypothermia, as well as lactulose, rifaximin, hemodialysis, and “empiric” sodium benzoate/sodium phenylacetate (Ammonul, Ucyclyd Pharma, Scottsdale, Ariz.) for the possibility of a urea cycle disorder. In hopes of decreasing blood flow to the tumor, the patient underwent embolization of the right hepatic artery with no clinical improvement. Given the persistently elevated ammonia level, a work-up for an underlying urea cycle disorder was performed, revealing trace citrulline and increased urine orotic acids and uracil, suggesting an ornithine transcarbamylase (OTC) deficiency. She was started on parenteral nutrition with arginine supplementation, after which her ammonia level normalized with subsequent improvement in her mental status.
Fibrolamellar-HCC is a rare, malignant, primary liver tumor predominantly affecting young adults with no underlying liver disease. This hypervascular tumor is radiographically characterized by a central scar.1 Most patients experience vague abdominal pain, weight loss, and fatigue. Fibrolamellar-HCC carries a better prognosis than HCC; in surgically resectable cases, the 5-year survival rates range between 37% and 76% vs. 12-14 months in nonresectable cases.2 Systemic chemotherapy has been used in case reports and the role of sorafenib remains unexplored and ill defined.
This is the second reported case of metastatic fibrolamellar-HCC with hyperammonemia.3 Although urea cycle disorders are more commonly diagnosed in newborns and infants, patients with partial enzyme deficiencies may present later in life and manifest in the setting of metabolic decompensation or stress. Our patient’s initial evaluation was consistent with a urea cycle deficiency, but OTC sequencing from the blood was negative. We hypothesize that the patient exhibited a “functional” OTC deficiency as a result of a combination of the massive tumor burden and portal vein thrombus, leading to a decreased expression of the OTC gene and insufficient enzyme production. The patient is doing well 3 months post resection and is being considered for a phase I clinical trial with a telomerase inhibitor, imetelstat.
References
1. Ichikawa, T., Federle, M.P., Grazioli, L., et al. Fibrolamellar hepatocellular carcinoma: Imaging and pathologic findings in 31 recent cases. Radiology. 1999;213(2):352-61.
2. Ward, S.C. Waxman, S. Fibrolamellar carcinoma: A review with focus on genetics and comparison to other malignant primary liver tumors. Semin Liver Dis. 2011;31(1):61-70.
3. Sethi, S., Tageja, N., Singh, J., et al. Hyperammonemic encephalopathy: A rare presentation of fibrolamellar hepatocellular carcinoma. Am J Med Sci. 2009;338(6):522-4.
The diagnosis
Histologic analysis was consistent with a fibrolamellar-hepatocellular carcinoma (HCC). The patient developed decerebrate posturing without cerebral edema on CT of the head. The patient was treated with mannitol, hyperventilation, and therapeutic hypothermia, as well as lactulose, rifaximin, hemodialysis, and “empiric” sodium benzoate/sodium phenylacetate (Ammonul, Ucyclyd Pharma, Scottsdale, Ariz.) for the possibility of a urea cycle disorder. In hopes of decreasing blood flow to the tumor, the patient underwent embolization of the right hepatic artery with no clinical improvement. Given the persistently elevated ammonia level, a work-up for an underlying urea cycle disorder was performed, revealing trace citrulline and increased urine orotic acids and uracil, suggesting an ornithine transcarbamylase (OTC) deficiency. She was started on parenteral nutrition with arginine supplementation, after which her ammonia level normalized with subsequent improvement in her mental status.
Fibrolamellar-HCC is a rare, malignant, primary liver tumor predominantly affecting young adults with no underlying liver disease. This hypervascular tumor is radiographically characterized by a central scar.1 Most patients experience vague abdominal pain, weight loss, and fatigue. Fibrolamellar-HCC carries a better prognosis than HCC; in surgically resectable cases, the 5-year survival rates range between 37% and 76% vs. 12-14 months in nonresectable cases.2 Systemic chemotherapy has been used in case reports and the role of sorafenib remains unexplored and ill defined.
This is the second reported case of metastatic fibrolamellar-HCC with hyperammonemia.3 Although urea cycle disorders are more commonly diagnosed in newborns and infants, patients with partial enzyme deficiencies may present later in life and manifest in the setting of metabolic decompensation or stress. Our patient’s initial evaluation was consistent with a urea cycle deficiency, but OTC sequencing from the blood was negative. We hypothesize that the patient exhibited a “functional” OTC deficiency as a result of a combination of the massive tumor burden and portal vein thrombus, leading to a decreased expression of the OTC gene and insufficient enzyme production. The patient is doing well 3 months post resection and is being considered for a phase I clinical trial with a telomerase inhibitor, imetelstat.
References
1. Ichikawa, T., Federle, M.P., Grazioli, L., et al. Fibrolamellar hepatocellular carcinoma: Imaging and pathologic findings in 31 recent cases. Radiology. 1999;213(2):352-61.
2. Ward, S.C. Waxman, S. Fibrolamellar carcinoma: A review with focus on genetics and comparison to other malignant primary liver tumors. Semin Liver Dis. 2011;31(1):61-70.
3. Sethi, S., Tageja, N., Singh, J., et al. Hyperammonemic encephalopathy: A rare presentation of fibrolamellar hepatocellular carcinoma. Am J Med Sci. 2009;338(6):522-4.
What's Your Diagnosis?
What's Your Diagnosis?
By Jana G. Hashash, MD, Kavitha Thudi, MD, and Shahid M. Malik, MD. Published previously in Gastroenterology (2012;143[5]:1157, 1401-2).
An 18-year-old white woman with no significant medical history was in good health until 2 days before admission, when she developed nausea, vomiting, and confusion. She was awake but lethargic and disoriented with asterixis. The remainder of her neurologic examination was nonfocal.
Laboratory data revealed white blood cell count of 13,000/L, hemoglobin of 13 g, and a platelet count of 300,000/L. A serum venous ammonia level was 342 micromol/L (normal range, 9-33). A urine drug screen was negative, as were her serum acetaminophen and aminosalicylic acid levels. Infectious work-up was unrevealing. Work-up for underlying chronic liver disease, including viral hepatitis serologies, autoimmune serologies, ceruloplasmin level, alpha-1 antitrypsin level, as well as hemochromatosis gene testing, was negative. An electroencephalography revealed burst suppression but no seizure activity. A lumbar puncture was negative.
An abdominal contrast-enhanced CT revealed an 11 × 15-cm heterogeneous, hypervascular mass replacing the majority of the right hepatic lobe (Figure A), right portal vein thrombosis, an enlarged hypervascular portocaval node measuring 2.0 × 2.0 cm, and an 8-mm left lower lobe lung lesion concerning for metastatic disease. Her liver was mildly enlarged, but was noncirrhotic. There was no radiologic evidence of portal hypertension or varices. There was no evidence of extrahepatic portosystemic shunting. Serum tumor markers, including alpha-fetoprotein, were within normal limits (1 ng/mL).
What is the cause of this young patient’s acute hepatic encephalopathy?