Pub Date : 2024-02-07DOI: 10.1097/jova.0000000000000082
Lorna Holcroft, Maeve A. Mc Aleer, Alan D. Irvine
Lymphedema is a chronic condition characterized by the accumulation of lymphatic fluid in interstitial and fibro-adipose tissues. Primary lymphedema that arises from intrinsic defects in the lymphatic system is a rare form of lymphedema with a variable age of onset and heterogeneous presentation. Although a number of genetic variants have been identified and matched to corresponding phenotypes, a genetic cause for lymphedema is found in less than 30% of individuals with primary lymphedema. Recently, Michelini et al proposed NOTCH1 as a candidate gene for primary lymphedema, having identified missense variants in NOTCH1 in 7 of 235 patients with primary lymphedema for whom no causative gene had previously been identified. We report the case of a young female who developed bilateral primary lower limb lymphedema and on genetic testing was found to have a previously unreported heterozygous frameshift variant in the NOTCH1 gene predicting loss of function.
{"title":"A Novel Likely Pathogenic Variant in NOTCH1 Associated With Primary Lymphedema","authors":"Lorna Holcroft, Maeve A. Mc Aleer, Alan D. Irvine","doi":"10.1097/jova.0000000000000082","DOIUrl":"https://doi.org/10.1097/jova.0000000000000082","url":null,"abstract":"Lymphedema is a chronic condition characterized by the accumulation of lymphatic fluid in interstitial and fibro-adipose tissues. Primary lymphedema that arises from intrinsic defects in the lymphatic system is a rare form of lymphedema with a variable age of onset and heterogeneous presentation. Although a number of genetic variants have been identified and matched to corresponding phenotypes, a genetic cause for lymphedema is found in less than 30% of individuals with primary lymphedema. Recently, Michelini et al proposed NOTCH1 as a candidate gene for primary lymphedema, having identified missense variants in NOTCH1 in 7 of 235 patients with primary lymphedema for whom no causative gene had previously been identified. We report the case of a young female who developed bilateral primary lower limb lymphedema and on genetic testing was found to have a previously unreported heterozygous frameshift variant in the NOTCH1 gene predicting loss of function.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"53 11-12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139856932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-06DOI: 10.1097/jova.0000000000000081
Andrew Baker, Kevin Wong, Laura Gonzales-Krellwitz, Elizabeth Kim, Graham M Strub
Lymphatic malformations are vascular anomalies that often arise from congenital defects and can manifest in a variety of locations, including the abdomen. Such lesions are often targeted with sclerotherapy, which has become the first-line treatment due to the limitations of surgical intervention. Sclerotherapy is associated with side effects including local necrosis and edema, with localized tissue destruction seldom reported. Here we describe the case of a neonate female with bowel wall perforation following sclerotherapy with ethanol and doxycycline for macrocystic abdominal lymphatic malformation.
{"title":"Bowel Perforation Following Sclerotherapy of a Massive Intra-Abdominal Lymphatic Malformation","authors":"Andrew Baker, Kevin Wong, Laura Gonzales-Krellwitz, Elizabeth Kim, Graham M Strub","doi":"10.1097/jova.0000000000000081","DOIUrl":"https://doi.org/10.1097/jova.0000000000000081","url":null,"abstract":"Lymphatic malformations are vascular anomalies that often arise from congenital defects and can manifest in a variety of locations, including the abdomen. Such lesions are often targeted with sclerotherapy, which has become the first-line treatment due to the limitations of surgical intervention. Sclerotherapy is associated with side effects including local necrosis and edema, with localized tissue destruction seldom reported. Here we describe the case of a neonate female with bowel wall perforation following sclerotherapy with ethanol and doxycycline for macrocystic abdominal lymphatic malformation.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"79 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139860845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-06DOI: 10.1097/jova.0000000000000081
Andrew Baker, Kevin Wong, Laura Gonzales-Krellwitz, Elizabeth Kim, Graham M Strub
Lymphatic malformations are vascular anomalies that often arise from congenital defects and can manifest in a variety of locations, including the abdomen. Such lesions are often targeted with sclerotherapy, which has become the first-line treatment due to the limitations of surgical intervention. Sclerotherapy is associated with side effects including local necrosis and edema, with localized tissue destruction seldom reported. Here we describe the case of a neonate female with bowel wall perforation following sclerotherapy with ethanol and doxycycline for macrocystic abdominal lymphatic malformation.
{"title":"Bowel Perforation Following Sclerotherapy of a Massive Intra-Abdominal Lymphatic Malformation","authors":"Andrew Baker, Kevin Wong, Laura Gonzales-Krellwitz, Elizabeth Kim, Graham M Strub","doi":"10.1097/jova.0000000000000081","DOIUrl":"https://doi.org/10.1097/jova.0000000000000081","url":null,"abstract":"Lymphatic malformations are vascular anomalies that often arise from congenital defects and can manifest in a variety of locations, including the abdomen. Such lesions are often targeted with sclerotherapy, which has become the first-line treatment due to the limitations of surgical intervention. Sclerotherapy is associated with side effects including local necrosis and edema, with localized tissue destruction seldom reported. Here we describe the case of a neonate female with bowel wall perforation following sclerotherapy with ethanol and doxycycline for macrocystic abdominal lymphatic malformation.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"15 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139801090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-10DOI: 10.1097/jova.0000000000000083
Anna M. Kerr, Christine Bereitschaft, Jessica Goldberg, Bryan A. Sisk
The goal of the current study was to gain a deeper understanding of the significant experiences that characterize care for vascular anomalies (VAs). A total of 166 adult patients and 88 caregivers (N = 254) completed an anonymous online cross-sectional survey about their experiences seeking care for their (or their child’s) vascular anomaly. We used thematic analysis to analyze participants’ responses to 3 open-ended questions asking about the biggest challenges, most memorable positive experiences, and any other significant experiences. Participants reported significant healthcare experiences representing 5 primary areas: diagnosis and treatment, healthcare system and logistics, psychosocial consequences, physical consequences, and clinical relationships. The availability of clinical knowledge and information was identified as an overarching theme affecting all 5 categories. The most common negative experiences related to healthcare system and logistics (n = 100). Clinical relationships were commonly identified in both positive (n = 100) and negative (n = 86) experiences. Their responses highlighted the value of a well-organized system of care that promotes productive interactions with expert clinicians and connects patients with support organizations. Unfortunately, VA patients and caregivers often experience long diagnostic journeys, fragmented care, and nonproductive interactions with clinicians due to the pervasive lack of information about VAs. The results indicate the need for systemic changes to address these barriers to care for patients with rare diseases.
{"title":"Significant Experiences Caring for Vascular Anomalies: A Survey of Caregivers and Adult Patients","authors":"Anna M. Kerr, Christine Bereitschaft, Jessica Goldberg, Bryan A. Sisk","doi":"10.1097/jova.0000000000000083","DOIUrl":"https://doi.org/10.1097/jova.0000000000000083","url":null,"abstract":"\u0000 \u0000 The goal of the current study was to gain a deeper understanding of the significant experiences that characterize care for vascular anomalies (VAs).\u0000 \u0000 \u0000 \u0000 A total of 166 adult patients and 88 caregivers (N = 254) completed an anonymous online cross-sectional survey about their experiences seeking care for their (or their child’s) vascular anomaly. We used thematic analysis to analyze participants’ responses to 3 open-ended questions asking about the biggest challenges, most memorable positive experiences, and any other significant experiences.\u0000 \u0000 \u0000 \u0000 Participants reported significant healthcare experiences representing 5 primary areas: diagnosis and treatment, healthcare system and logistics, psychosocial consequences, physical consequences, and clinical relationships. The availability of clinical knowledge and information was identified as an overarching theme affecting all 5 categories. The most common negative experiences related to healthcare system and logistics (n = 100). Clinical relationships were commonly identified in both positive (n = 100) and negative (n = 86) experiences.\u0000 \u0000 \u0000 \u0000 Their responses highlighted the value of a well-organized system of care that promotes productive interactions with expert clinicians and connects patients with support organizations. Unfortunately, VA patients and caregivers often experience long diagnostic journeys, fragmented care, and nonproductive interactions with clinicians due to the pervasive lack of information about VAs. The results indicate the need for systemic changes to address these barriers to care for patients with rare diseases.\u0000","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"6 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139439569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-08DOI: 10.1097/jova.0000000000000079
Bryan A. Sisk, Christine Bereitschaft, Jessica Goldberg, Anna M. Kerr
To characterize the experiences of patients with vascular malformations (VMs) when seeking care for acute or emergent health needs. Semistructured qualitative interviews and survey study. National recruitment through patient advocacy groups and multidisciplinary vascular anomaly clinics. Adult patients and parents of children with self-reported VM. We interviewed 25 young adult patients and 34 parents. We received survey responses from 138 adult patients and 73 parents who answered all items of interest (analytic cohort = 211). Interview participants described negative experiences with emergency care related to 4 themes: (1) delayed or inadequate care, (2) lack of competent, knowledgeable clinicians, (3) lack of collegial collaboration, and (4) insufficient trust of clinicians in parent’s or patient’s knowledge. Patients and parents reported an average of 1.7 and 2.6 VM-related health problems requiring emergent management in the prior year, respectively. In multivariable logistic regression, having at least one acute or emergent problem in the prior year was associated with household income ≥$100 000 (odds ratio = 0.34, 95% confidence interval, 0.17–0.70), but not gender, race, and ethnicity, age, having a VM specialist, or primary care doctor’s knowledge of VMs. Many patients with VMs require emergent or acute care for complications of their VM. Patients with lower household incomes are more likely to experience these emergent events. Negative experiences often focused on nonsupportive clinician behaviors. Future studies should develop tools to empower patient self-advocacy and provide high-yield information to nonspecialist clinicians.
{"title":"Emergency Care for Pediatric and Adult Patients Affected by Complex Vascular Malformations","authors":"Bryan A. Sisk, Christine Bereitschaft, Jessica Goldberg, Anna M. Kerr","doi":"10.1097/jova.0000000000000079","DOIUrl":"https://doi.org/10.1097/jova.0000000000000079","url":null,"abstract":"\u0000 \u0000 To characterize the experiences of patients with vascular malformations (VMs) when seeking care for acute or emergent health needs.\u0000 \u0000 \u0000 \u0000 Semistructured qualitative interviews and survey study.\u0000 \u0000 \u0000 \u0000 National recruitment through patient advocacy groups and multidisciplinary vascular anomaly clinics.\u0000 \u0000 \u0000 \u0000 Adult patients and parents of children with self-reported VM.\u0000 \u0000 \u0000 \u0000 We interviewed 25 young adult patients and 34 parents. We received survey responses from 138 adult patients and 73 parents who answered all items of interest (analytic cohort = 211). Interview participants described negative experiences with emergency care related to 4 themes: (1) delayed or inadequate care, (2) lack of competent, knowledgeable clinicians, (3) lack of collegial collaboration, and (4) insufficient trust of clinicians in parent’s or patient’s knowledge. Patients and parents reported an average of 1.7 and 2.6 VM-related health problems requiring emergent management in the prior year, respectively. In multivariable logistic regression, having at least one acute or emergent problem in the prior year was associated with household income ≥$100 000 (odds ratio = 0.34, 95% confidence interval, 0.17–0.70), but not gender, race, and ethnicity, age, having a VM specialist, or primary care doctor’s knowledge of VMs.\u0000 \u0000 \u0000 \u0000 Many patients with VMs require emergent or acute care for complications of their VM. Patients with lower household incomes are more likely to experience these emergent events. Negative experiences often focused on nonsupportive clinician behaviors. Future studies should develop tools to empower patient self-advocacy and provide high-yield information to nonspecialist clinicians.\u0000","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"26 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139445945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-08DOI: 10.1097/jova.0000000000000077
{"title":"Erratum to Parkes Weber Syndrome: Contribution of the Genotype to the Diagnosis","authors":"","doi":"10.1097/jova.0000000000000077","DOIUrl":"https://doi.org/10.1097/jova.0000000000000077","url":null,"abstract":"","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"38 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139446223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-05DOI: 10.1097/jova.0000000000000073
Michal Ad, A. Greene
Primary lymphedema most commonly affects the lower extremities, is progressive, and is not curable. The condition is associated with mutations in approximately 30 genes. Patients usually present with edema during infancy or adolescence. Four of 364 (1%) patients with primary lymphedema in our database were diagnosed by prenatal imaging. Three children did not exhibit lymphedema after birth, 2 had a VEGFC mutation, and 2 exhibited normal lymphatic function by lymphoscintigraphy. Lymphedema identified prenatally is associated with a VEGFC mutation and can resolve postnatally.
{"title":"Prenatal Lymphedema: A Genotype-Phenotype Analysis","authors":"Michal Ad, A. Greene","doi":"10.1097/jova.0000000000000073","DOIUrl":"https://doi.org/10.1097/jova.0000000000000073","url":null,"abstract":"Primary lymphedema most commonly affects the lower extremities, is progressive, and is not curable. The condition is associated with mutations in approximately 30 genes. Patients usually present with edema during infancy or adolescence. Four of 364 (1%) patients with primary lymphedema in our database were diagnosed by prenatal imaging. Three children did not exhibit lymphedema after birth, 2 had a VEGFC mutation, and 2 exhibited normal lymphatic function by lymphoscintigraphy. Lymphedema identified prenatally is associated with a VEGFC mutation and can resolve postnatally.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139383991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-22DOI: 10.1097/jova.0000000000000071
Lana Bricknell, Christopher M. Richmond, Romi Das Gupta, Diane Payton, Yun Phua, Roy M. Kimble
Eccrine angiomatous hamartoma (EAH) is a rare vascular anomaly with mixed eccrine and vascular components, typically identified in children. While benign, EAH can cause significant morbidity and be difficult to treat. The aims of this case series were to identify all patients with EAH that have been seen at the Queensland Children’s Hospital and describe their phenotypic and somatic genotypic details, in an effort to contribute to the limiting understanding and literature surrounding this condition. Individuals with EAH were retrospectively identified through engagement in a multidisciplinary vascular anomaly clinic in a tertiary Australian children’s hospital. All individuals had a previous histological diagnosis of EAH. High-read-depth sequencing of a panel of 27 genes known to be associated with vascular anomalies was undertaken on affected tissue. Samples were rereviewed by a senior pathologist and geneticist for this study. Five cases of EAH were identified. All were associated with 1 of 3 somatic PIK3CA variants (c.1633G>A;p.Glu545Lys, c.1624G>A;p.Glu542Lys, and c.3140A>G;p.Histo1047Arg) in low allele fractions. These variants have previously been reported in a range of tumors and vascular anomalies, including PIK3CA-related overgrowth spectrum, but not in EAH. Occurrence of somatic PIK3CA variants in EAH provides evidence for a novel gene-disease association and is plausibly the cause of EAH in some individuals. This finding expands the phenotypic spectrum of PIK3CA, contributes to understanding of the pathophysiology of this rare condition, and may avail molecularly targeted therapy in the future.
{"title":"Somatic PIK3CA Variants Are Associated With Eccrine Angiomatous Hamartomas","authors":"Lana Bricknell, Christopher M. Richmond, Romi Das Gupta, Diane Payton, Yun Phua, Roy M. Kimble","doi":"10.1097/jova.0000000000000071","DOIUrl":"https://doi.org/10.1097/jova.0000000000000071","url":null,"abstract":"Eccrine angiomatous hamartoma (EAH) is a rare vascular anomaly with mixed eccrine and vascular components, typically identified in children. While benign, EAH can cause significant morbidity and be difficult to treat. The aims of this case series were to identify all patients with EAH that have been seen at the Queensland Children’s Hospital and describe their phenotypic and somatic genotypic details, in an effort to contribute to the limiting understanding and literature surrounding this condition. Individuals with EAH were retrospectively identified through engagement in a multidisciplinary vascular anomaly clinic in a tertiary Australian children’s hospital. All individuals had a previous histological diagnosis of EAH. High-read-depth sequencing of a panel of 27 genes known to be associated with vascular anomalies was undertaken on affected tissue. Samples were rereviewed by a senior pathologist and geneticist for this study. Five cases of EAH were identified. All were associated with 1 of 3 somatic PIK3CA variants (c.1633G>A;p.Glu545Lys, c.1624G>A;p.Glu542Lys, and c.3140A>G;p.Histo1047Arg) in low allele fractions. These variants have previously been reported in a range of tumors and vascular anomalies, including PIK3CA-related overgrowth spectrum, but not in EAH. Occurrence of somatic PIK3CA variants in EAH provides evidence for a novel gene-disease association and is plausibly the cause of EAH in some individuals. This finding expands the phenotypic spectrum of PIK3CA, contributes to understanding of the pathophysiology of this rare condition, and may avail molecularly targeted therapy in the future.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"265 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139250090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-15DOI: 10.1097/jova.0000000000000070
Anna L. McCarter, M. Dellinger
Gorham-Stout disease (GSD) is a rare lymphatic anomaly that can be caused by somatic activating mutations in KRAS. This discovery has led investigators to suggest that MEK inhibitors could be a novel treatment for GSD. However, the effect of MEK inhibitors on bone disease in animal models of GSD has not been investigated. We recently reported that Osx-tTA;TetO-Vegfc mice exhibit a phenotype that resembles GSD. Osx-tTA;TetO-Vegfc mice overexpress vascular endothelial growth factor-C (VEGF-C) in bone, which stimulates the development of lymphatic vessels in bone and the gradual loss of cortical bone. The objective of this study was to characterize the effect of trametinib, an FDA-approved MEK1/2 inhibitor, on lymphangiogenesis and osteolysis in Osx-tTA;TetO-Vegfc mice. Immunoblotting was performed to assess the effect of trametinib on VEGF-C-induced phosphorylation of ERK1/2, AKT, and S6 in primary human lymphatic endothelial cells. Prevention and intervention experiments were performed to determine the effect of trametinib on lymphangiogenesis and osteolysis in Osx-tTA;TetO-Vegfc mice. We found that trametinib blocked VEGF-C-induced phosphorylation of ERK1/2 in primary human lymphatic endothelial cells. We also found that trametinib prevented VEGF-C-induced lymphatic invasion of bone and cortical bone loss in Osx-tTA;TetO-Vegfc mice. Additionally, trametinib slowed the progression of disease in Osx-tTA;TetO-Vegfc mice with established disease. However, it did not reverse disease in Osx-tTA;TetO-Vegfc mice. Our results show trametinib impacts bone disease in Osx-tTA;TetO-Vegfc mice. These findings further support the testing of MEK inhibitors in patients with GSD and other RAS pathway-driven complex lymphatic anomalies with bone involvement.
{"title":"Trametinib Inhibits Lymphatic Vessel Invasion of Bone in a Mouse Model of Gorham-Stout Disease","authors":"Anna L. McCarter, M. Dellinger","doi":"10.1097/jova.0000000000000070","DOIUrl":"https://doi.org/10.1097/jova.0000000000000070","url":null,"abstract":"Gorham-Stout disease (GSD) is a rare lymphatic anomaly that can be caused by somatic activating mutations in KRAS. This discovery has led investigators to suggest that MEK inhibitors could be a novel treatment for GSD. However, the effect of MEK inhibitors on bone disease in animal models of GSD has not been investigated. We recently reported that Osx-tTA;TetO-Vegfc mice exhibit a phenotype that resembles GSD. Osx-tTA;TetO-Vegfc mice overexpress vascular endothelial growth factor-C (VEGF-C) in bone, which stimulates the development of lymphatic vessels in bone and the gradual loss of cortical bone. The objective of this study was to characterize the effect of trametinib, an FDA-approved MEK1/2 inhibitor, on lymphangiogenesis and osteolysis in Osx-tTA;TetO-Vegfc mice. Immunoblotting was performed to assess the effect of trametinib on VEGF-C-induced phosphorylation of ERK1/2, AKT, and S6 in primary human lymphatic endothelial cells. Prevention and intervention experiments were performed to determine the effect of trametinib on lymphangiogenesis and osteolysis in Osx-tTA;TetO-Vegfc mice. We found that trametinib blocked VEGF-C-induced phosphorylation of ERK1/2 in primary human lymphatic endothelial cells. We also found that trametinib prevented VEGF-C-induced lymphatic invasion of bone and cortical bone loss in Osx-tTA;TetO-Vegfc mice. Additionally, trametinib slowed the progression of disease in Osx-tTA;TetO-Vegfc mice with established disease. However, it did not reverse disease in Osx-tTA;TetO-Vegfc mice. Our results show trametinib impacts bone disease in Osx-tTA;TetO-Vegfc mice. These findings further support the testing of MEK inhibitors in patients with GSD and other RAS pathway-driven complex lymphatic anomalies with bone involvement.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"44 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139273498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-15DOI: 10.1097/jova.0000000000000072
Ricardo Rodriguez Colon, Courtney Cripps, Francine Blei, Sheel Sharma
The literature on surgical management of vascular anomalies has primarily focused on the head and neck area, while studies of anomalies on the extremities have typically included larger and more dramatic clinical presentations. In this article, we aim to present our experience with surgical management of smaller symptomatic anomalies of the extremities. We performed a retrospective review of a single surgeon’s experience at a large academic center on patients from January 2013 to March 2022. We collected data on patient demographics, past medical and surgical history, operative dictations, clinic notes, and postoperative follow-up. Included patients were required to have confirmed vascular anomalies based on final pathology reports. A total of 47 patients underwent a total of 50 procedures, with 2 patients experiencing recurrence requiring repeat operative management. Our cohort had average age (standard deviation) of 27.16 (18.67). Sixteen patients had prior history of vascular anomalies upon presentation to our institution. The majority of lesions were located in a digit of the hand, the arm, or the foot. On surgical excision, the average size (range) of the excised lesions was 3.54 cm (0.5–15.0 cm) by 2.22 cm (0.3–8.0 cm). Four required coverage with local flaps, 3 with full-thickness skin graft (FTSG) and 2 with microvascular free flap. The 2 most common pathologic diagnoses were arteriovenous malformation and hemangioma, each with 14 patients. Overall complication rate was 2%, with 1 patient experiencing wound dehiscence requiring FTSG. Follow-up ranged from 0.1 months to 46.9 months with an average of 3.86 months. In the appropriately selected patient, surgical excision of symptomatic vascular anomalies of the extremities can be successfully performed with a low complication rate. Most lesions can be appropriately treated with direct excision and direct closure, although some may require FTSG, local flap, or microvascular free flap.
{"title":"Surgical Treatment of Vascular Anomalies in the Extremities: A Single Surgeon Experience","authors":"Ricardo Rodriguez Colon, Courtney Cripps, Francine Blei, Sheel Sharma","doi":"10.1097/jova.0000000000000072","DOIUrl":"https://doi.org/10.1097/jova.0000000000000072","url":null,"abstract":"The literature on surgical management of vascular anomalies has primarily focused on the head and neck area, while studies of anomalies on the extremities have typically included larger and more dramatic clinical presentations. In this article, we aim to present our experience with surgical management of smaller symptomatic anomalies of the extremities. We performed a retrospective review of a single surgeon’s experience at a large academic center on patients from January 2013 to March 2022. We collected data on patient demographics, past medical and surgical history, operative dictations, clinic notes, and postoperative follow-up. Included patients were required to have confirmed vascular anomalies based on final pathology reports. A total of 47 patients underwent a total of 50 procedures, with 2 patients experiencing recurrence requiring repeat operative management. Our cohort had average age (standard deviation) of 27.16 (18.67). Sixteen patients had prior history of vascular anomalies upon presentation to our institution. The majority of lesions were located in a digit of the hand, the arm, or the foot. On surgical excision, the average size (range) of the excised lesions was 3.54 cm (0.5–15.0 cm) by 2.22 cm (0.3–8.0 cm). Four required coverage with local flaps, 3 with full-thickness skin graft (FTSG) and 2 with microvascular free flap. The 2 most common pathologic diagnoses were arteriovenous malformation and hemangioma, each with 14 patients. Overall complication rate was 2%, with 1 patient experiencing wound dehiscence requiring FTSG. Follow-up ranged from 0.1 months to 46.9 months with an average of 3.86 months. In the appropriately selected patient, surgical excision of symptomatic vascular anomalies of the extremities can be successfully performed with a low complication rate. Most lesions can be appropriately treated with direct excision and direct closure, although some may require FTSG, local flap, or microvascular free flap.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"59 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139272255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：