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Qiu T, Xiang S, Zhou J, Yang M, Lan Y, Zhang X, Gong X, Zhang Z, Ji Y. Sirolimus for kaposiform hemangioendothelioma: Potential mechanisms of action and resistance. Int J Cancer 2025; 156:689-699. [PMID: 39369447 DOI: 10.1002/ijc.35207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 09/19/2024] [Accepted: 09/24/2024] [Indexed: 10/08/2024]
Abstract
Kaposiform hemangioendotheliomas (KHEs) are vascular tumors that are considered borderline or locally aggressive and may lead to lethal outcomes. Traditional therapies, such as surgery and embolization, may be insufficient or technically impossible for patients with KHE. Sirolimus (or rapamycin), a specific inhibitor of mechanistic target of rapamycin, has recently been demonstrated to be very useful in the treatment of KHEs. Here, we highlight recent substantial progress regarding the effects of sirolimus on KHEs and discuss the potential mechanisms of action of sirolimus in treating this disease. The prevention of platelet activation and inflammation, along with antiangiogenic effects, the inhibition of lymphangiogenesis, the attenuation of fibrosis, or a combination of all these effects, may be responsible for the therapeutic effects of sirolimus. In addition, the mechanism of sirolimus resistance in some KHE patients is discussed. Finally, we review the somatic mutations that have recently been identified in KEH lesions, and discuss the potential of novel therapeutic targets based on these further understandings of the cellular and molecular pathogenesis of KHE.
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Affiliation(s)
- Tong Qiu
- Division of Oncology, Department of Pediatric Surgery and Med-X Center for Informatics, West China Hospital of Sichuan University, Chengdu, China
| | - Shanshan Xiang
- Division of Oncology, Department of Pediatric Surgery and Med-X Center for Informatics, West China Hospital of Sichuan University, Chengdu, China
| | - Jiangyuan Zhou
- Division of Oncology, Department of Pediatric Surgery and Med-X Center for Informatics, West China Hospital of Sichuan University, Chengdu, China
| | - Min Yang
- Division of Oncology, Department of Pediatric Surgery and Med-X Center for Informatics, West China Hospital of Sichuan University, Chengdu, China
| | - Yuru Lan
- Division of Oncology, Department of Pediatric Surgery and Med-X Center for Informatics, West China Hospital of Sichuan University, Chengdu, China
| | - Xuepeng Zhang
- Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Xue Gong
- Division of Oncology, Department of Pediatric Surgery and Med-X Center for Informatics, West China Hospital of Sichuan University, Chengdu, China
| | - Zixin Zhang
- Division of Oncology, Department of Pediatric Surgery and Med-X Center for Informatics, West China Hospital of Sichuan University, Chengdu, China
| | - Yi Ji
- Division of Oncology, Department of Pediatric Surgery and Med-X Center for Informatics, West China Hospital of Sichuan University, Chengdu, China
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Zhang Y, Qiu T, Yang C, Zhou J, Yang M, Gong X, Zhang Z, Lan Y, Zhang X, Chen S, Ji Y. Similarities and differences in the clinical features and management of primary lymphedema and kaposiform hemangioendothelioma associated with lymphedema in children. Front Pediatr 2025; 13:1480213. [PMID: 40026487 PMCID: PMC11869848 DOI: 10.3389/fped.2025.1480213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 01/23/2025] [Indexed: 03/05/2025] Open
Abstract
Background Primary lymphedema (PLE) and kaposiform hemangioendothelioma-related lymphedema (KLE) are rare vascular anomalies (VAs). This study aimed to examine the clinical features, management, and prognosis of PLE and KLE. Method The clinical features, imaging, treatments, and outcomes of 12 patients with PLE and 12 patients with KLE were retrospectively reviewed. Results The mean age at which signs/symptoms were diagnosed was 68.2 months for PLE patients and 25 months for KLE patients. In PLE, the involvement of multiple sites is common, whereas in KLE, it typically affects a single site. Morbid obesity, which is common in adult patients, is rare in pediatric PLE and KLE patients. Imaging agent accumulation was observed in KLE but not in PLE via lymphoscintigraphy. In contrast, complications of PLE primarily involve skin and soft tissue, whereas musculoskeletal system complications are more common in KLE. Regarding prognosis, most patients stabilize or even experience lesion regression after standard treatment. Conclusion PLE and KLE share clinical symptoms. PLE often involves multiple sites, whereas KLE typically presents unilaterally with local lymphatic stasis. Standardized treatment enables the majority of children with lymphedema to control the disease without progression, with KLE showing potential reversibility. Given their rarity, a multidisciplinary approach is crucial for diagnosis and management.
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Affiliation(s)
- Yujia Zhang
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Tong Qiu
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China
- Med-X Center for Informatics, Sichuan University, Chengdu, China
| | - Congxia Yang
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jiangyuan Zhou
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China
- Med-X Center for Informatics, Sichuan University, Chengdu, China
| | - Min Yang
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xue Gong
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zixin Zhang
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China
- Med-X Center for Informatics, Sichuan University, Chengdu, China
| | - Yuru Lan
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xuepeng Zhang
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Siyuan Chen
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Ji
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China
- Med-X Center for Informatics, Sichuan University, Chengdu, China
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Tariq AT, Kazmi SMH, Riyaz S, Ali Z. Angiosarcoma associated with Kasabach-Merritt syndrome presenting with typical signs and symptoms of pulmonary tuberculosis: a case report. J Med Case Rep 2024; 18:623. [PMID: 39719629 DOI: 10.1186/s13256-024-04895-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Accepted: 09/16/2024] [Indexed: 12/26/2024] Open
Abstract
BACKGROUND Angiosarcoma is a rapidly proliferating vascular tumor that originates in endothelial cells of vessels. Rarely, it can be associated with consumptive coagulopathy due to disseminated intravascular coagulation eventually leading to thrombocytopenia and microangiopathic hemolytic anemia. This specific manifestation is termed Kasabach-Merritt syndrome. Patients usually present with manifestations related to the primary diagnosis of angiosarcoma depending on the organ it is involving. However, if Kasabach-Merritt syndrome has occurred, it will present with manifestations such as bleeding and thromboembolic phenomenon. To date, no favorable outcomes have been documented, and the overall prognosis remains grim. CASE PRESENTATION A 44-year-old male patient of Afghan origin developed typical signs and symptoms of pulmonary tuberculosis, that is, fever, cough, hemoptysis, weight loss, and night sweats. He was initially managed in an Afghan medical facility where workup for tuberculosis was done but came back negative. He empirically received anti-tuberculous therapy owing to typical presentation and tuberculosis being endemic in the area. The condition of the patient worsened, and he presented to our facility (Shifa International Hospital, Islamabad, Pakistan). Workup led to the diagnosis of a metastatic vascular neoplasm, which was further complicated with consumptive coagulopathy, and microangiopathic hemolytic anemia. This presentation is known as Kasabach-Merritt syndrome. Multidisciplinary team discussion was called, and it was decided to proceed with palliative chemotherapy with paclitaxel. CONCLUSION Although a patient may present with typical signs and symptoms of, but negative workup for, TB, if there is a high index of suspicion and the patient is receiving empirical treatment for pulmonary tuberculosis, clinical worsening should alert to think about differential diagnosis. In our case, histopathological analysis of lymph node and radiological findings led us to the diagnosis.
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Affiliation(s)
- Ahmad Talha Tariq
- Shifa International Hospital/Shifa Tameer e Millat University, Islamabad, Pakistan.
| | | | - Shahzad Riyaz
- Shifa International Hospital/Shifa Tameer e Millat University, Islamabad, Pakistan
| | - Zafar Ali
- Shifa International Hospital/Shifa Tameer e Millat University, Islamabad, Pakistan
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Ahmed S, Dilawar B, Moeen S, Dilawar S, Sheikh H, Arain MA. Abdominal kaposiform hemangioendothelioma presenting as volvulus and recurring intestinal obstruction in a neonate: a case report. J Med Case Rep 2024; 18:619. [PMID: 39709514 DOI: 10.1186/s13256-024-04976-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 11/12/2024] [Indexed: 12/23/2024] Open
Abstract
BACKGROUND Kaposiform hemangioendothelioma is a rare vascular tumor primarily occurring in infants and children. The most common sites for kaposiform hemangioendothelioma are extremities, with very few cases of abdominal kaposiform hemangioendothelioma reported in neonates. Making a diagnosis of Kaposiform hemangioendothelioma can be challenging when the patient presents with generalized symptoms such as bilious vomiting and constipation that can be attributed to other more common causes of intestinal obstruction. CASE PRESENTATION A 28-day-old Pakistani baby girl presented with bilious vomiting and constipation. The abdomen was distended, and scans showed generalized dilation of bowel loops. A preliminary diagnosis of intestinal obstruction due to volvulus was made, and the patient underwent an exploratory laparotomy. Postoperatively, the patient remained unwell with profuse aspirates in nasogastric and no improvement in ileus. Repeat scans were again suggestive of midgut volvulus, which was initially managed conservatively, but later redo surgery was done. Ischemic bowel was resected with histopathology showing kaposiform hemangioendothelioma. In the meantime, the baby developed an abdominal collection, infection, and short gut syndrome due to resection of the bowel. The family was counseled regarding the prognosis, and the patient was transferred from hospital to home upon request. The baby passed away 2 days later. CONCLUSION While extremely rare, abdominal kaposiform hemangioendothelioma can be an important and potentially lifesaving differential diagnosis to consider in neonates and infants with recurring and nonresolving intestinal obstruction. The management is complex, and prognosis can be poor in diffuse, congested lesions involving a large part of the gut.
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Affiliation(s)
- Salaar Ahmed
- Medical College, Aga Khan University, Stadium Road, Karachi, 74800, Pakistan.
| | | | - Sarosh Moeen
- Department of Pathology, Aga Khan University, Karachi, Pakistan
| | | | - Hafsa Sheikh
- Department of Surgery, Aga Khan University, Karachi, Pakistan
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Peralta-Amaro AL, Cadena-Corona CU, Domínguez-Valdez LF, Cobos-Quevedo ODJ, Vera-Lastra OL, Cruz-Domínguez MDP, Acosta-Jiménez E, González-González KL. Kasabach-Merritt syndrome associated with infiltrating giant colonic hemangioma in a pregnant woman: Report of a fatal case. Obstet Med 2024; 17:226-229. [PMID: 39640953 PMCID: PMC11615977 DOI: 10.1177/1753495x231172618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 04/11/2023] [Indexed: 12/07/2024] Open
Abstract
Kasabach-Merritt syndrome (KMS) is a coagulopathy characterized by thrombocytopenia and hypofibrinogenemia associated with large vascular tumors. KMS can lead to disseminated intravascular coagulation which, if not treated promptly, can be life-threatening. There are few reported cases of this syndrome and its evolution in pregnant women.
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Affiliation(s)
- Ana Lilia Peralta-Amaro
- Internal Medicine Department, Hospital de Especialidades Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social, Mexico City, Mexico
- Division of Postgraduate Studies, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Carlos Ublester Cadena-Corona
- Internal Medicine Department, Hospital de Especialidades Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social, Mexico City, Mexico
- Division of Postgraduate Studies, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Luis Fernando Domínguez-Valdez
- Internal Medicine Department, Hospital de Especialidades Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social, Mexico City, Mexico
- Division of Postgraduate Studies, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Orestes de Jesús Cobos-Quevedo
- Internal Medicine Department, Hospital de Especialidades Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social, Mexico City, Mexico
- Division of Postgraduate Studies, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Olga Lidia Vera-Lastra
- Internal Medicine Department, Hospital de Especialidades Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social, Mexico City, Mexico
- Division of Postgraduate Studies, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - María del Pilar Cruz-Domínguez
- Internal Medicine Department, Hospital de Especialidades Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social, Mexico City, Mexico
- Division of Postgraduate Studies, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Elsa Acosta-Jiménez
- Division of Postgraduate Studies, Universidad Nacional Autónoma de México, Mexico City, Mexico
- Patology Department, Hospital de Especialidades Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Karla Lourdes González-González
- Hematology Department, Hospital de Especialidades Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social, Mexico City, Mexico
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White MH, Hawkins CM. The Role of Medical Management in Vascular Anomalies. Semin Intervent Radiol 2024; 41:404-412. [PMID: 39524237 PMCID: PMC11543096 DOI: 10.1055/s-0044-1791538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Historically, the care for patients with vascular anomalies has been challenging due to the complex nature and diversity of these anomalies with a wide array of symptomatology. In the recent past, most therapies for vascular anomalies focused on surgical, procedural, and supportive care measures to treat local symptoms, but many patients still experienced significant disease with excess morbidity and mortality. Today, the pharmacotherapeutic options available for treating vascular anomalies have greatly expanded due to the increased understanding of the genetic and molecular pathways causing these anomalies, with the subsequent development of more targeted pharmacotherapies. In addition to the growth in targeted medications available to treat patients with vascular anomalies, there has been an improved understanding of the hematologic abnormalities related to these diseases and how to manage them. While interventional radiologists do not typically primarily manage systemic medications to treat vascular anomalies, a baseline understanding of the medical management of these diseases is essential to ensuring that a contemporary, multidisciplinary, multimodal approach to treatment is pursued when appropriate. Ultimately, patients are now benefitting from having multiple modalities of treatments available to them and are experiencing improved quality of life and less morbidity.
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Affiliation(s)
- Michael H. White
- Address for correspondence Michael H. White, MD, MSc Division of Pediatrics, Department of Pediatric Hematology and Oncology, Emory School of Medicine, Aflac Cancer and Blood Disorders Center, Children's Healthcare of AtlantaAtlantaGA 30322
| | - C. Matthew Hawkins
- Children's Healthcare of Atlanta, Vascular Anomalies Clinic, Atlanta, Georgia
- Division of Pediatric Radiology, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia
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Gayou E, Chau A, Josephs S. Imaging of Vascular Anomalies. Semin Intervent Radiol 2024; 41:339-349. [PMID: 39524243 PMCID: PMC11543108 DOI: 10.1055/s-0044-1791205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Vascular anomalies (VAs) are a heterogeneous group of vascular malformations and tumors that are frequently encountered in daily practice. While most are benign, malignant vascular tumors exist, as do other nonvascular soft-tissue malignancies that may masquerade as a benign VA. The subtleties of arriving at an accurate diagnosis can be intimidating, as new entities are described and names of conditions have been modified. Therefore, the goal of this article is to describe the classic imaging findings of VAs so that the interventional radiologist can confidently and competently contribute to management decisions, with special attention to ominous imaging features that should prompt biopsy or further imaging workup.
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Affiliation(s)
- Edward Gayou
- Department of Radiology, Texas Children's Hospital North Austin Campus, Austin, Texas
| | - Alex Chau
- Department of Radiology, Texas Children's Hospital North Austin Campus, Austin, Texas
| | - Shellie Josephs
- Department of Radiology, Texas Children's Hospital North Austin Campus, Austin, Texas
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8
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Frenette C, Mendiratta-Lala M, Salgia R, Wong RJ, Sauer BG, Pillai A. ACG Clinical Guideline: Focal Liver Lesions. Am J Gastroenterol 2024; 119:1235-1271. [PMID: 38958301 DOI: 10.14309/ajg.0000000000002857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 04/25/2024] [Indexed: 07/04/2024]
Abstract
Focal liver lesions (FLLs) have become an increasingly common finding on abdominal imaging, especially asymptomatic and incidental liver lesions. Gastroenterologists and hepatologists often see these patients in consultation and make recommendations for management of multiple types of liver lesions, including hepatocellular adenoma, focal nodular hyperplasia, hemangioma, and hepatic cystic lesions including polycystic liver disease. Malignancy is important to consider in the differential diagnosis of FLLs, and healthcare providers must be familiar with the diagnosis and management of FLLs. This American College of Gastroenterology practice guideline uses the best evidence available to make diagnosis and management recommendations for the most common FLLs.
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Affiliation(s)
| | | | - Reena Salgia
- Department of Gastroenterology/Hepatology, Henry Ford Health, Detroit, Michigan, USA
| | - Robert J Wong
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System and Stanford University School of Medicine, Palo Alto, California, USA
| | - Bryan G Sauer
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Anjana Pillai
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Chicago Medical Center, University of Chicago, Chicago, Illinois, USA
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Jung R, Trivedi CM. Congenital Vascular and Lymphatic Diseases. Circ Res 2024; 135:159-173. [PMID: 38900856 PMCID: PMC11192239 DOI: 10.1161/circresaha.124.323181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/22/2024]
Abstract
Over the past several centuries, the integration of contemporary medical techniques and innovative technologies, like genetic sequencing, have played a pivotal role in enhancing our comprehension of congenital vascular and lymphatic disorders. Nonetheless, the uncommon and complex characteristics of these disorders, especially considering their formation during the intrauterine stage, present significant obstacles in diagnosis and treatment. Here, we review the intricacies of these congenital abnormalities, offering an in-depth examination of key diagnostic approaches, genetic factors, and therapeutic methods.
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Affiliation(s)
- Roy Jung
- Division of Cardiovascular Medicine, UMass Chan Medical School, Worcester, MA 01605 USA
- Department of Medicine, UMass Chan Medical School, Worcester, MA 01605 USA
- Translational Science Program, Morningside Graduate School of Biomedical Sciences, UMass Chan Medical School, Worcester, MA 01605 USA
| | - Chinmay M. Trivedi
- Division of Cardiovascular Medicine, UMass Chan Medical School, Worcester, MA 01605 USA
- Department of Medicine, UMass Chan Medical School, Worcester, MA 01605 USA
- Translational Science Program, Morningside Graduate School of Biomedical Sciences, UMass Chan Medical School, Worcester, MA 01605 USA
- Department of Molecular, Cell, and Cancer Biology, UMass Chan Medical School; Worcester, MA 01605 USA
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Le M, Wenke K, Herrmann J, Singer D, Lange M. [A Uncommon Case: Kasabach-Merritt syndrome with VACTERL Association]. Z Geburtshilfe Neonatol 2024; 228:298-302. [PMID: 38428835 DOI: 10.1055/a-2262-8607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/03/2024]
Abstract
The Kasabach-Merrit syndrome is characterized as the association of a vascular tumor, typically a caposiform hemangioendothelioma and rarely a tufted hemangioma, and a severe consumptive coagulopathy with potentially life-threatening thrombocytopenia. The severe coagulopathy with increased bleeding tendency must be considered before invasive procedures and often requires repeated platelet concentrate substitutions. We present a case of a mature male neonate with Kasabach-Merritt- Syndrome as well as VACTERL association. The VACTERL association describes a group of malformations. Our patient presented with anal atresia combined with tethered cord, and left renal agenesis. The VACTERL association as well as Kasabach-Merritt syndrome were found to be independent pathologies within this patient. A common occurrence or an association with each other has not been described in the literature so far. The challenging coagulation setting due to severe thrombocytopenia complicated the surgical management so far. Finally, mTOR-inhibitor sirolimus was successful in terms of tumor reduction and especially reduction of platelet consumption.
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Affiliation(s)
- Melanie Le
- Klinik und Poliklinik für Kinderchirurgie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Katharina Wenke
- Klinik und Poliklinik für Kinderchirurgie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Jochen Herrmann
- Abteilung für Kinderradiologie, Klinik und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Dominique Singer
- Neonatologie und Pädiatrische Intensivmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Mario Lange
- Neonatologie und Pädiatrische Intensivmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
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Cheng J, Zou Y, Fu R, Jin P, Huang M, Wu Z, Bai H, Huang X, Yuan H. Sirolimus combined with glucocorticoids in the treatment of Kasabach-Merritt phenomenon in a neonate: A case report. Medicine (Baltimore) 2024; 103:e37706. [PMID: 38579031 PMCID: PMC10994472 DOI: 10.1097/md.0000000000037706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 03/04/2024] [Indexed: 04/07/2024] Open
Abstract
RATIONALE Kaposiform hemangioendothelioma is an aggressive vascular tumor that is often associated with life-threatening coagulopathies and Kasabach-Merritt phenomenon. Pathologic biopsies can provide a good basis for diagnosis and treatment. Therapy with srolimus combined with glucocorticoids may offer patients a favorable prognosis. PATIENT CONCERNS A large purplish-red mass on the knee of a child with extremely progressive thrombocytopenia and refractory coagulation abnormalities. Conventional doses of glucocorticoids alone failed to improve coagulation abnormalities and the child developed large cutaneous petechiae and scalp hematomas. DIAGNOSIS Kaposiform hemangioendothelioma combined with Kasabach-Merritt phenomenon. INTERVENTIONS The patient received prednisolone 2.0 mg/kg*d for 4 days. Blood products were transfused to ensure vital signs and to complete the pathologic biopsy. Sirolimus combined with prednisolone was given after clarifying the diagnosis of Kaposiform hemangioendothelioma. OUTCOMES The tumor basically disappeared on examination and the ultrasound showed a subcutaneous hyperechoic mass with normal blood flow. LESSONS Sirolimus combined with glucocorticoids is effective in controlling Kasabach-Merritt phenomenon and pathologic biopsy is important for definitive diagnosis.
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Affiliation(s)
- Jun Cheng
- Department of Plastic Surgery, Jiangxi Provincial Children’s Hospital, Nanchang, China
| | - Yun Zou
- Department of Plastic Surgery, Jiangxi Provincial Children’s Hospital, Nanchang, China
| | - Ronghua Fu
- Department of Plastic Surgery, Jiangxi Provincial Children’s Hospital, Nanchang, China
| | - Pingliang Jin
- Department of Plastic Surgery, Jiangxi Provincial Children’s Hospital, Nanchang, China
| | - Mengyu Huang
- Department of Plastic Surgery, Jiangxi Provincial Children’s Hospital, Nanchang, China
| | - Zhiping Wu
- Department of Plastic Surgery, Jiangxi Provincial Children’s Hospital, Nanchang, China
| | - Hanxiang Bai
- Department of Plastic Surgery, Jiangxi Provincial Children’s Hospital, Nanchang, China
| | - Xiangqun Huang
- Department of Plastic Surgery, Jiangxi Provincial Children’s Hospital, Nanchang, China
| | - Hua Yuan
- Department of Plastic Surgery, Jiangxi Provincial Children’s Hospital, Nanchang, China
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12
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Borst AJ, Eng W, Griffin M, Ricci KW, Engel E, Adams DM, Dayneka J, Cohen-Cutler SJ, Andreoli SM, Wu MD, Wheeler AP, Heym KM, Crary SE, Nakano TA, Schulte RR, Setty BA, McLean TW, Pahl KS, Intzes S, Pateva I, Teitelbaum M, Zong Z, Li Y, Jeng MR. Treatment practices and response in kaposiform hemangioendothelioma: A multicenter cohort study. Pediatr Blood Cancer 2024; 71:e30779. [PMID: 38073018 DOI: 10.1002/pbc.30779] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 10/24/2023] [Accepted: 11/08/2023] [Indexed: 01/24/2024]
Abstract
BACKGROUND AND OBJECTIVES Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors in children historically associated with significant morbidity and mortality. This study was conducted to determine first-line therapy in the absence of available prospective clinical trials. METHODS Patients from 17 institutions diagnosed with KHE/TA between 2005 and 2020 with more than 6 months of follow-up were included. Response rates to sirolimus and vincristine were compared at 3 and 6 months. Durability of response and response to other treatment modalities were also evaluated. RESULTS Of 159 unique KHE/TA subjects, Kasabach-Merritt phenomenon (KMP) was present in 64 (40.3%), and only two patients were deceased (1.3%). Over 60% (n = 96) demonstrated treatment response at 3 months, and more than 70% (n = 114) by 6 months (no significant difference across groups). The vincristine group had higher radiologic response at 3 months compared to sirolimus (72.7% vs. 20%, p = .03), but there were no differences between these groups at 6 months. There were no differences in rates of recurrent or progressive disease between vincristine and sirolimus. CONCLUSIONS In this large, multicenter cohort of 159 patients with KHE/TA, rates of KMP were consistent with historical literature, but the mortality rate (1.3%) was much lower. Overall treatment response rates were high (>70%), and there was no significant difference in treatment response or durability of disease comparing sirolimus to vincristine. Our results support individualized treatment decision plans depending on clinical scenario and patient/physician preferences. Response criteria and response rates reported here will be useful for guiding future treatment protocols for vascular tumors.
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Affiliation(s)
- Alexandra J Borst
- Perelman School of Medicine at the University of Pennsylvania/Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Whitney Eng
- Harvard Medical School/Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA
| | - Morgan Griffin
- Harvard Medical School/Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA
| | - Kiersten W Ricci
- The University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Elissa Engel
- The University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Denise M Adams
- Perelman School of Medicine at the University of Pennsylvania/Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Jillian Dayneka
- Perelman School of Medicine at the University of Pennsylvania/Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
- Tulane School of Medicine/Children's Hospital New Orleans, New Orleans, Louisiana, USA
| | - Sally J Cohen-Cutler
- Perelman School of Medicine at the University of Pennsylvania/Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
- Keck School of Medicine of University of Southern California/Children's Hospital Los Angeles, Los Angeles, California, USA
| | - Steven M Andreoli
- University of Florida College of Medicine-Jacksonville/Nemours Children's Specialty Care, Jacksonville, Florida, USA
| | - Melinda D Wu
- Oregon Health & Science University, Doernbecher Children's Hospital, Portland, Oregon, USA
| | - Allison P Wheeler
- Vanderbilt University School of Medicine/Monroe Carell Jr Children's Hospital, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | | | - Shelley E Crary
- University of Arkansas for Medical Sciences/Arkansas Children's Hospital, Little Rock, Arkansas, USA
| | - Taizo A Nakano
- University of Colorado School of Medicine/Children's Hospital Colorado, Aurora, Colorado, USA
| | - Rachael R Schulte
- Indiana University School of Medicine/Riley Children's Hospital, Indianapolis, Indiana, USA
| | - Bhuvana A Setty
- Ohio State University College of Medicine/Nationwide Children's Hospital, Columbus, Ohio, USA
| | - Thomas W McLean
- Wake Forest University School of Medicine/Atrium Health Wake Forest Baptist, Winston-Salem, North Carolina, USA
| | - Kristy S Pahl
- Duke University School of Medicine, Duke Children's Hospital, Durham, North Carolina, USA
| | - Stefanos Intzes
- Providence Sacred Heart Medical Center and Children's Hospital, Spokane, Washington, USA
| | - Irina Pateva
- Case Western Reserve University/Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA
| | | | - Zili Zong
- Perelman School of Medicine at the University of Pennsylvania/Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Yimei Li
- Perelman School of Medicine at the University of Pennsylvania/Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Michael R Jeng
- Stanford University School of Medicine/Lucile Packard Children's Hospital, Palo Alto, California, USA
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13
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Gatts J, Chandra S, Krishnan D, Ricci K. Medical Management of Nonmalignant Vascular Tumors of the Head and Neck: Part 1. Oral Maxillofac Surg Clin North Am 2024; 36:103-113. [PMID: 37875385 DOI: 10.1016/j.coms.2023.09.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2023]
Abstract
Vascular anomalies, broadly classified as nonmalignant tumors and malformations, consist of a multitude of disorders that have a wide range of symptoms and complications as well as overlapping clinical, radiologic, and histologic findings. Although usually difficult, distinguishing between nonmalignant vascular tumors and malformations, as well as the precise diagnosis within these distinctions, is critical because prognosis, therapy, and chronicity of care vary greatly. In contrast to normal endothelial turnover in vascular malformations, vascular tumors are characterized by the abnormal proliferation of endothelial cells and aberrant blood vessels.
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Affiliation(s)
- Jorie Gatts
- Hemangioma and Vascular Malformation Center, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7015, Cincinnati, OH 45229, USA
| | - Srinivasa Chandra
- Department of Oral and Maxillofacial Surgery-Head and Neck Oncology and Microvascular Reconstruction, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
| | - Deepak Krishnan
- Department of Surgery, Section of Oral & Maxillofacial Surgery, University of Cincinnati, 200 Albert Sabin Way, ML 0461, Cincinnati, OH 45219, USA; University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0558, USA
| | - Kiersten Ricci
- Hemangioma and Vascular Malformation Center, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7015, Cincinnati, OH 45229, USA; University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0558, USA.
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14
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Liu L, Gu W, Teng L, Xu Y, Zheng F, Hu M, Lu M, Xu X. Kaposiform hemangioendothelioma presented with raynaud phenomenon: a case report. BMC Pediatr 2023; 23:574. [PMID: 37978357 PMCID: PMC10655467 DOI: 10.1186/s12887-023-04407-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 11/06/2023] [Indexed: 11/19/2023] Open
Abstract
BACKGROUND Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm affecting infants or young children. KHE includes a spectrum of lesions, ranging from small and superficial tumors to large and invasive lesions with Kasabach-Merritt phenomenon (KMP). Currently, no published studies have reported a KHE presenting as thrombocytopenia and Raynaud phenomenon. CASE PRESENTATION A 2-year-old boy with right hand swelling and thrombocytopenia was admitted to our hospital. His right hand turned swelling and red, even occasionally cyanotic. This condition became worse in response to cool environments and improved with warming, and platelet counts were between 50 ~ 80 × 10^9/L. Physical examination on admission revealed the swelling and frostbite-like rash of the right-hand fingers, and the skin temperature of the right hand was lower than the left. On day 3 of admission, chest CT results showed an irregular mass on the right side of the spine. The puncture biopsy demonstrated positive CD31, D2-40, and FLI1 immunohistochemical staining, but negative GLUT1 staining, confirming the diagnosis of KHE. Furthermore, endothelin-1 (ET1) expression levels significantly increased, and eNOS and A20 expression levels significantly decreased comparing with control patients. The patient received methylprednisolone and sirolimus treatments, and his condition gradually improved during the follow-up. CONCLUSIONS We reported the first case of KHE presenting with thrombocytopenia and Raynaud phenomenon. The development of Raynaud phenomenon could be associated with increased ET-1 and reduced eNOS and A20 expressions. Careful differential diagnosis of hidden KHE should be considered in children with thrombocytopenia and Raynaud phenomenon.
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Affiliation(s)
- Lingke Liu
- Department of Rheumatology Immunology & Allergy, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Binsheng Rd 3333, Binjiang District, Hangzhou, 310052, P.R. China
- Pediatrics, The Affiliated Hospital of Shaoxing University, Shaoxing, 312000, PR China
| | - Weizhong Gu
- Pathology, National Clinical Research Center for Child Health, Hangzhou, 310003, PR China
| | - Liping Teng
- Department of Rheumatology Immunology & Allergy, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Binsheng Rd 3333, Binjiang District, Hangzhou, 310052, P.R. China
| | - Yiping Xu
- Department of Rheumatology Immunology & Allergy, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Binsheng Rd 3333, Binjiang District, Hangzhou, 310052, P.R. China
| | - Fei Zheng
- Department of Rheumatology Immunology & Allergy, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Binsheng Rd 3333, Binjiang District, Hangzhou, 310052, P.R. China
| | - Minfei Hu
- Department of Rheumatology Immunology & Allergy, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Binsheng Rd 3333, Binjiang District, Hangzhou, 310052, P.R. China
| | - Meiping Lu
- Department of Rheumatology Immunology & Allergy, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Binsheng Rd 3333, Binjiang District, Hangzhou, 310052, P.R. China
| | - Xuefeng Xu
- Department of Rheumatology Immunology & Allergy, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Binsheng Rd 3333, Binjiang District, Hangzhou, 310052, P.R. China.
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15
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Martyanov AA, Tesakov IP, Khachatryan LA, An OI, Boldova AE, Ignatova AA, Koltsova EM, Korobkin JJD, Podoplelova NA, Svidelskaya GS, Yushkova E, Novichkova GA, Eble JA, Panteleev MA, Kalinin DV, Sveshnikova AN. Platelet functional abnormalities in pediatric patients with kaposiform hemangioendothelioma/Kasabach-Merritt phenomenon. Blood Adv 2023; 7:4936-4949. [PMID: 37307200 PMCID: PMC10463204 DOI: 10.1182/bloodadvances.2022009590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 05/05/2023] [Accepted: 05/21/2023] [Indexed: 06/14/2023] Open
Abstract
Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy that is commonly associated with a life-threatening thrombocytopenic condition, Kasabach-Merritt phenomenon (KMP). Platelet CLEC-2, tumor podoplanin interaction is considered the key mechanism of platelet clearance in these patients. Here, we aimed to assess platelet functionality in such patients. Three groups of 6 to 9 children were enrolled: group A with KHE/KMP without hematologic response (HR) to therapy; group B with KHE/KMP with HR; and group C with healthy children. Platelet functionality was assessed by continuous and end point flow cytometry, low-angle light scattering analysis (LaSca), fluorescent microscopy of blood smears, and ex vivo thrombi formation. Platelet integrin activation in response to a combination of CRP (GPVI agonist) and TRAP-6 (PAR1 agonist), as well as calcium mobilization and integrin activation in response to CRP or rhodocytin (CLEC-2 agonist) alone, were significantly diminished in groups A and B. At the same time, platelet responses to ADP with or without TRAP-6 were unaltered. Thrombi formation from collagen in parallel plate flow chambers was also noticeably decreased in groups A and B. In silico analysis of these results predicted diminished amounts of CLEC-2 on the platelet surface of patients, which was further confirmed by immunofluorescence microscopy and flow cytometry. In addition, we also noted a decrease in GPVI levels on platelets from group A. In KHE/KMP, platelet responses induced by CLEC-2 or GPVI activation are impaired because of the diminished number of receptors on the platelet surface. This impairment correlates with the severity of the disease and resolves as the patient recovers.
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Affiliation(s)
- Alexey A. Martyanov
- Dmitry Rogachev National Medical Research Centеr of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
| | - Ivan P. Tesakov
- Dmitry Rogachev National Medical Research Centеr of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
| | - Lili A. Khachatryan
- Dmitry Rogachev National Medical Research Centеr of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
| | - Olga I. An
- Center for Theoretical Problems of Physico-Сhemical Pharmacology, Russian Academy of Sciences, Moscow, Russia
| | - Anna E. Boldova
- Center for Theoretical Problems of Physico-Сhemical Pharmacology, Russian Academy of Sciences, Moscow, Russia
| | - Anastasia A. Ignatova
- Dmitry Rogachev National Medical Research Centеr of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
- Center for Theoretical Problems of Physico-Сhemical Pharmacology, Russian Academy of Sciences, Moscow, Russia
| | - Ekaterina M. Koltsova
- Dmitry Rogachev National Medical Research Centеr of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
- Center for Theoretical Problems of Physico-Сhemical Pharmacology, Russian Academy of Sciences, Moscow, Russia
| | - Julia-Jessica D. Korobkin
- Center for Theoretical Problems of Physico-Сhemical Pharmacology, Russian Academy of Sciences, Moscow, Russia
| | - Nadezhda A. Podoplelova
- Dmitry Rogachev National Medical Research Centеr of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
- Center for Theoretical Problems of Physico-Сhemical Pharmacology, Russian Academy of Sciences, Moscow, Russia
| | - Galina S. Svidelskaya
- Dmitry Rogachev National Medical Research Centеr of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
- Center for Theoretical Problems of Physico-Сhemical Pharmacology, Russian Academy of Sciences, Moscow, Russia
| | - Eugenia Yushkova
- Center for Theoretical Problems of Physico-Сhemical Pharmacology, Russian Academy of Sciences, Moscow, Russia
| | - Galina A. Novichkova
- Dmitry Rogachev National Medical Research Centеr of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
| | - Johannes A. Eble
- Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany
| | - Mikhail A. Panteleev
- Dmitry Rogachev National Medical Research Centеr of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
- Center for Theoretical Problems of Physico-Сhemical Pharmacology, Russian Academy of Sciences, Moscow, Russia
- Lomonosov Moscow State University, Moscow, Russia
| | - Dmitrii V. Kalinin
- Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Münster, Germany
| | - Anastasia N. Sveshnikova
- Dmitry Rogachev National Medical Research Centеr of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
- Center for Theoretical Problems of Physico-Сhemical Pharmacology, Russian Academy of Sciences, Moscow, Russia
- Lomonosov Moscow State University, Moscow, Russia
- Sechenov First Moscow State Medical University, Moscow, Russia
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16
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Lan Y, Zhou J, Qiu T, Gong X, Ji Y. Refractory kaposiform lymphangiomatosis relieved by splenectomy. Front Pediatr 2023; 11:1203336. [PMID: 37664553 PMCID: PMC10469894 DOI: 10.3389/fped.2023.1203336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 08/02/2023] [Indexed: 09/05/2023] Open
Abstract
INTRODUCTION Kaposiform lymphangiomatosis (KLA) is a rare and complex lymphatic anomaly with a poor prognosis. There is no standard treatment, and drug therapies are the most common therapeutic method. However, some patients' symptoms become gradually aggravated despite medical treatment. Splenectomy may be an alternative option when pharmacological therapies are ineffective. MATERIALS AND METHODS We reviewed and evaluated the cases of 3 patients with KLA who ultimately underwent splenectomy. Results: The lesions were diffusely distributed and involved the lungs and spleens of the 3 patients. Laboratory examinations revealed that all three patients had thrombocytopenia and reduced fibrinogen levels. All patients underwent symptomatic splenectomy after the medication failed. Surprisingly, their symptoms greatly improved. Histopathological investigation of the splenic lesions of the three patients confirmed the diagnosis of KLA. Immunohistochemical staining showed positivity for CD31, CD34, podoplanin, Prox-1 and angiopoietin 2 (Ang-2). DISCUSSION This study aimed to review the features of KLA patients treated by splenectomy and explore the underlying link between splenectomy and prognosis. The reason for the improvement after splenectomy may be related to increased Ang-2 levels and platelet activation in patients with KLA. Future research should seek to develop more targeted drugs based on molecular findings, which may give new hope for the treatment of KLA.
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Affiliation(s)
| | | | | | | | - Yi Ji
- Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
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17
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Dhabhar JB, Mehta V. Recurrent metastatic angiosarcoma presenting as Kasabach-Merritt syndrome. BMJ Case Rep 2023; 16:e255134. [PMID: 37500188 PMCID: PMC10387657 DOI: 10.1136/bcr-2023-255134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/29/2023] Open
Abstract
Angiosarcoma is an incredibly rare type of malignancy, accounting for only 1%-2% of all soft-tissue sarcomas globally. It is clinically, pathologically and radiologically difficult to diagnose angiosarcoma owing to its varied presentation with little or no well-defined imaging findings.Kasabach-Merritt syndrome is also a lesser-heard entity which carries extremely poor prognosis. It is primarily seen in infants with vascular malformations and in kaposiform haemangioendothelioma. It is a condition of consumptive coagulopathy and only few of the cases have been reported so far in the adults with a background of angiosarcoma.This report presents the case of a male in his 70s who was diagnosed with metastatic angiosarcoma and experienced a complicated disease course due to Kasabach-Merritt syndrome.
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Affiliation(s)
- Jeyhan Boman Dhabhar
- Medical Oncology, PD Hinduja National Hospital and Medical Research Centre, Mumbai, India
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18
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Zhou J, Lan Y, Qiu T, Gong X, Zhang Z, He C, Peng Q, Hu F, Zhang X, Lu G, Qiu L, Kong F, Zhang Y, Chen S, Ji Y. Impact of age and tumor size on the development of the Kasabach-Merritt phenomenon in patients with kaposiform hemangioendothelioma: a retrospective cohort study. PRECISION CLINICAL MEDICINE 2023; 6:pbad008. [PMID: 37305527 PMCID: PMC10249050 DOI: 10.1093/pcmedi/pbad008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 05/17/2023] [Indexed: 06/13/2023] Open
Abstract
INTRODUCTION The Kasabach-Merritt phenomenon (KMP) is a severe complication of kaposiform hemangioendothelioma (KHE). The risk factors for KMP need further investigation. METHODS The medical records of patients with KHE were reviewed. Univariate and multivariate logistic regression models were used for the risk factors for KMP, and the area under the receiver operator characteristic (ROC) curve was used to assess the predictive power of risk factors. RESULTS A total of 338 patients with KHE were enrolled. The incidence of KMP was 45.9%. Age of onset (P < 0.001, odds ratio [OR] 0.939; 95% confidence interval [CI] 0.914-0.966), lesion size (P < 0.001, OR 1.944; 95% CI 1.646-2.296), mixed type (P = 0.030, OR 2.428; 95% CI 1.092-5.397), deep type (P = 0.010, OR 4.006; 95% CI 1.389-11.556), and mediastinal or retroperitoneal lesion location (P = 0.019, OR 11.864; 95% CI 1.497-94.003) were correlated with KMP occurrence through multivariate logistic regression. ROC curve analysis revealed that the optimal cutoffs were 4.75 months for the age of onset (P < 0.001, OR 7.206, 95% CI 4.073-12.749) and a lesion diameter of 5.35 cm (P < 0.001, OR 11.817, 95% CI 7.084-19.714). Bounded by a lesion size of 5.35 cm, we found significant differences in tumor morphology, age of onset, treatments, and hematological parameters. Using an onset age of 4.75 months as a cutoff, we found significant differences in tumor morphology, lesion size, hematological parameters, and prognosis. CONCLUSION For KHE patients with an onset age <4.75 months and/or lesion diameter >5.35 cm, clinicians should be wary of the occurrence of KMP. Active management is recommended to improve the prognosis.
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Affiliation(s)
- Jiangyuan Zhou
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Yuru Lan
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Tong Qiu
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Xue Gong
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Zixin Zhang
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Chunshui He
- Department of Vascular Surgery, University Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610032, China
| | - Qiang Peng
- Department of Pediatric Surgery, Chengdu Women and Children's Central Hospital, Chengdu 610073, China
| | - Fan Hu
- Department of Vascular & Interventional Radiology, West China Second University Hospital, Sichuan University, Chengdu 610044, China
| | - Xuepeng Zhang
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Guoyan Lu
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610044, China
| | - Liqing Qiu
- Department of Pediatric Surgery, Chengdu Shangjin Nanfu Hospital, Chengdu 611730, China
| | - Feiteng Kong
- Department of Pediatric Surgery, Sichuan Women and Children's Hospital, Chengdu 610036, China
| | - Yongbo Zhang
- Department of Pediatric Surgery, Chengdu Women and Children's Central Hospital, Chengdu 610073, China
| | - Siyuan Chen
- Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Yi Ji
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
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19
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Andreoti TAA, Berg S, Holm A, Angerer M, Oberlin M, Foeldi E, Baumgartner I, Niemeyer CM, Rössler J, Kapp FG. Complex Lymphatic Anomalies: Report on a Patient Registry Using the Latest Diagnostic Guidelines. Lymphat Res Biol 2023. [PMID: 36706428 DOI: 10.1089/lrb.2022.0041] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Objective: Generalized lymphatic anomaly (GLA), Gorham-Stout disease (GSD), kaposiform lymphangiomatosis (KLA), and central conducting lymphatic anomaly (CCLA) are rare, multisystem lymphatic disorders, referred to as complex lymphatic anomalies (CLAs). Their etiology remains poorly understood; however, somatic activating mutations have recently been discovered, and the results of targeted treatments are promising. This study aimed to elaborate on the phenotypic description of CLA. Methods: Thirty-six consecutive patients were recruited for the "GLA/GSD Registry" of the University Hospital of Freiburg, Germany (2015-2021). Clinical data were prospectively collected provided that a signed informed consent form was obtained. The latest proposed diagnostic guidelines were retrospectively applied. Results: Thirty-two patients (38% males) were included in the study; 15 GLA, 10 GSD, 3 KLA, and 4 CCLA patients were identified. Eighty-four percent already had symptoms by the age of 15 years. Osteolysis and periosseous soft-tissue infiltration were associated with GSD (p < 0.001 and p = 0.011, respectively), ascites and protein-losing enteropathy with CCLA (p = 0.007 and p = 0.004, respectively), and consumption coagulopathy with KLA (p = 0.006). No statistically significant differences were found in organ involvement, distribution of osteolytic lesions, number of affected bones and fractures. Twenty-five patients had complications; one patient with GLA died despite multimodal treatment. Spontaneous regression was seen in one patient with untreated KLA. Conclusions: CLA are rare, and their overlapping clinical presentations make differential diagnosis difficult. The characterization of our case series contributes to the phenotypic description and differentiation of these four clinical entities. A further understanding of their pathogenesis is crucial for evaluating targeted therapies and optimizing medical care.
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Affiliation(s)
- Themis-Areti A Andreoti
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Inselspital-University Hospital of Bern, University of Bern, Bern, Switzerland.,Graduate School for Health Sciences, University of Bern, Bern, Switzerland
| | - Sebastian Berg
- Division of Pediatric Radiology, Department of Radiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany
| | - Annegret Holm
- VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany.,Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Marina Angerer
- VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany.,Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Michael Oberlin
- VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany.,Foeldiclinic, Hinterzarten, Germany
| | - Etelka Foeldi
- VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany.,Foeldiclinic, Hinterzarten, Germany
| | - Iris Baumgartner
- Division of Angiology, Swiss Cardiovascular Center, Inselspital-University Hospital of Bern, University of Bern, Bern, Switzerland
| | - Charlotte M Niemeyer
- VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany.,Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Jochen Rössler
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Inselspital-University Hospital of Bern, University of Bern, Bern, Switzerland.,VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany.,Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Friedrich G Kapp
- VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany.,Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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20
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Ai C, Qiu T, Zhou J, Wang C, Song J, Pu S, Jin S. Case Report: Pancreatic and hepatic kaposiform hemangioendothelioma presenting as consumptive coagulopathy and right hepatic atrophy. Front Oncol 2023; 13:1097997. [PMID: 37205203 PMCID: PMC10187787 DOI: 10.3389/fonc.2023.1097997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 04/07/2023] [Indexed: 05/21/2023] Open
Abstract
Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor that causes progressive angiogenesis and lymphangiogenesis, which often occurs in the skin or soft tissue, with an acute onset and rapid progression. A 4-year-old girl was admitted to our hospital with a 2-year history of thrombocytopenia, combined with right hepatic atrophy and pancreatic lesion for 3 months. At the age of two, she developed purpura and thrombocytopenia was detected, after treatment with gamma globulin and corticosteroids, the platelet count normalized, but it dropped immediately at lower doses. One year after the cessation of corticosteroids therapy, the patient presented with abdominal pain and abnormal liver function and the magnetic resonance imaging (MRI) revealed right hepatic atrophy and pancreatic occupancy, but the first liver biopsy did not reveal any positive pathological results. By analyzing the clinical manifestations in conjunction with MRI and abnormal coagulation, we considered that the patient might be diagnosed as KHE with Kasabach-Merritt phenomenon, however, sirolimus treatment was ineffective and pancreatic biopsy only showed a tendency for tumors of vascular origin. Finally, we performed a Whipple operation after the right hepatic artery embolization, histological and immunohistochemical examination suggested KHE. Three months postoperatively, the patient's liver function, pancreatic enzymes and blood clotting function gradually returned to normal. KHEs may result in significant blood loss with worsening of the coagulopathy and functional impairment, timely surgical intervention for KHE is necessary when non-invasive or minimally invasive treatment is ineffective, or the symptoms of tumor compression are obvious.
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21
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Ying H, Qiao C, Wang L, Lin X. Progressive kaposiform hemangioendothelioma and sirolimus-related severe thrombocytopenia. Indian J Dermatol Venereol Leprol 2023; 89:54-59. [PMID: 36688881 DOI: 10.25259/ijdvl_799_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Accepted: 04/01/2020] [Indexed: 12/15/2022]
Abstract
Kaposiform hemangioendothelioma is a locally invasive tumor and we were unable to find any previous reports of multifocal progression. Sirolimus, a mammalian target of rapamycin inhibitor, has been widely used to treat kaposiform hemangioendothelioma. Herein, we report a case of multifocal progressive kaposiform hemangioendothelioma, wherein sirolimus treatment caused severe thrombocytopenia. A 12-year-old East Asian girl presented with indurated dark-purple masses on her back. The patient had received three surgical interventions following the first appearance of the masses in 2012 and subsequent reappearances in 2014 and 2016. Kaposiform hemangioendothelioma was diagnosed based on radiological and pathological findings. Two more masses appeared in the following year. The patient was treated with oral sirolimus (2.5 mg/ m2/day) and developed grade 3 thrombocytopenia 8 days later. The patient was uneventfully relieved 5 days later after the withdrawal of sirolimus and the administration of appropriate medications. This rare case indicated that kaposiform hemangioendothelioma could be progressive with local metastatic characteristics in children. Besides, the severe sirolimus-induced complication highlights the importance of serum drug level monitoring during treatment. Physicians should be extremely cautious while treating kaposiform hemangioendothelioma patients with sirolimus.
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Affiliation(s)
- Hanru Ying
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Congzhen Qiao
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lizhen Wang
- Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoxi Lin
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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22
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Pompili M, Ardito F, Brunetti E, Cabibbo G, Calliada F, Cillo U, de Sio I, Golfieri R, Grova M, Gruttadauria S, Guido M, Iavarone M, Manciulli T, Pagano D, Pettinari I, Santopaolo F, Soresi M, Colli A. Benign liver lesions 2022: Guideline for clinical practice of Associazione Italiana Studio del Fegato (AISF), Società Italiana di Radiologia Medica e Interventistica (SIRM), Società Italiana di Chirurgia (SIC), Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB), Associazione Italiana di Chirurgia Epatobilio-Pancreatica (AICEP), Società Italiana Trapianti d'Organo (SITO), Società Italiana di Anatomia Patologica e Citologia Diagnostica (SIAPEC-IAP) - Part II - Solid lesions. Dig Liver Dis 2022; 54:1614-1622. [PMID: 36089523 DOI: 10.1016/j.dld.2022.08.031] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/11/2022] [Accepted: 08/18/2022] [Indexed: 12/30/2022]
Abstract
Benign liver lesions are increasingly diagnosed in daily clinical practice due to the growing use of imaging techniques for the study of the abdomen in patients who have non-specific symptoms and do not have an increased risk of hepatic malignancy. They include simple or parasitic hepatic cysts and solid benign tumors which differ widely in terms of prevalence, clinical relevance, symptoms and natural history and often lead to significant clinical problems relating to diagnosis and clinical management. Following the need to have updated guidelines on the management of benign focal liver lesions, the Scientific Societies mainly involved in their management have promoted the drafting of a new dedicated document. This document was drawn up according to the present Italian rules and methodologies necessary to produce clinical, diagnostic, and therapeutic guidelines based on evidence. Here we present the second part of the guideline, concerning the diagnosis and clinical management of hemangioma, focal nodular hyperplasia, and hepatocellular adenoma.
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Affiliation(s)
- Maurizio Pompili
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Gemelli, Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia, "Agostino Gemelli", Largo A. Gemelli, 8, Roma 00168, Italy.
| | - Francesco Ardito
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Gemelli, Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia, "Agostino Gemelli", Largo A. Gemelli, 8, Roma 00168, Italy
| | - Enrico Brunetti
- Dipartimento di Scienze Cliniche, Chirurgiche, Diagnostiche e Pediatriche, Università di Pavia. Unità di Malattie Infettive e Immunologia, IRCCS Fondazione Ospedale San Matteo, Pavia, Italy
| | - Giuseppe Cabibbo
- Sezione di Gastroenterologia e Epatologia, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro" (PROMISE) Università di Palermo, Italy
| | - Fabrizio Calliada
- Dipartimento di Radiologia, Fondazione Policlinico San Matteo IRCCS, Università di Pavia, Italy
| | - Umberto Cillo
- Chirurgia Epatobiliare e Trapianto di Fegato, Ospedale Universitario di Padova, Italy
| | - Ilario de Sio
- Epatogastroenterologia, Università della Campania Luigi Vanvitelli, Facoltà di Medicina e Chirurgia, Napoli, Italy
| | - Rita Golfieri
- Dipartimento di Radiologia, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
| | - Mauro Grova
- Sezione di Gastroenterologia e Epatologia, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro" (PROMISE) Università di Palermo, Italy
| | - Salvatore Gruttadauria
- Dipartimento per la cura e lo studio delle Patologie Addominali e dei Trapianti Addominali, Dipartimento di Chirurgia e Specialità Medico-Chirurgiche, IRCCS-ISMETT-UPMCI, Palermo, Università di Catania, Italy
| | - Maria Guido
- Dipartimento di Anatomia Patologica, Azienda ULSS2 Marca Trevigiana, Treviso, Italy; Dipartimento di Medicina - DIMED, Università di Padova, Italy
| | - Massimo Iavarone
- Divisione di Gastroenterologia ed Epatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Tommaso Manciulli
- Dipartimento di Medicina Sperimentale e Clinica - Università degli Studi, Firenze, Italy
| | - Duilio Pagano
- Dipartimento per la cura e lo studio delle Patologie Addominali e dei Trapianti Addominali, IRCCS-ISMETT-UPMC, Palermo, Italy
| | - Irene Pettinari
- Dipartimento di Radiologia, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
| | - Francesco Santopaolo
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Gemelli, Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia, "Agostino Gemelli", Largo A. Gemelli, 8, Roma 00168, Italy
| | - Maurizio Soresi
- Medicina Interna, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro" (PROMISE) Università di Palermo, Italy
| | - Agostino Colli
- Dipartimento di Medicina Trasfusionale ed Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
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23
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Li L, Xu L, Wang P, Liu F, Wei Y, Xu M, Zhang M, Li B. Advantages of laparoscopic hepatic hemangioma surgery in quality of life: a prospective study. Surg Endosc 2022; 36:8967-8974. [PMID: 35701674 DOI: 10.1007/s00464-022-09348-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 05/20/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Surgical intervention is the most accurate method for the treatment of hepatic hemangioma. The advantages of laparoscopic surgery on quality of life should be clarified by prospective studies. METHODS The sample sizes of the laparoscopic and open surgery groups were calculated based on previous retrospective literature. Intraoperative and postoperative parameters were prospectively collected and analyzed. Quality of life in both groups was predicted by a mixed linear model. RESULTS Sixty patients were enrolled in the laparoscopic surgery group and open surgery group. The laparoscopic group had a longer operation time (P = 0.040) and more hospitalization expenses (P = 0.001); however, the Clavien-Dindo classification and comprehensive complication index suggested a lower incidence of surgical complications in the laparoscopic group, with P values of 0.049 and 0.002, respectively. After mixed linear model prediction, between-group analysis indicated that the laparoscopic group had little impact on role-physical functioning and role-emotional functioning; in addition, within-group analysis showed a rapid recovery time on role-physical functioning and role-emotional functioning in the laparoscopic group. Quality of life in both groups recovered to the preoperative level within 1 year after the operation. CONCLUSION The advantages of laparoscopic hepatectomy for hepatic hemangioma were fewer postoperative complications, lower impact on quality of life and faster recovery from affected quality of life.
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Affiliation(s)
- Lian Li
- Department of Liver Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China
| | - Liangliang Xu
- Department of Liver Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China
| | - Peng Wang
- Department of Liver Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China
| | - Fei Liu
- Department of Liver Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China
| | - Yonggang Wei
- Department of Liver Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China
| | - Mingqing Xu
- Department of Liver Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China
| | - Ming Zhang
- Department of Liver Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China.
| | - Bo Li
- Department of Liver Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China.
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24
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Ning J. A rare case of retroperitoneal kaposiform haemangioendothelioma with Kasabach-Merritt phenomenon. Asian J Surg 2022; 46:1904-1905. [PMID: 36347741 DOI: 10.1016/j.asjsur.2022.10.093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 10/27/2022] [Indexed: 11/06/2022] Open
Affiliation(s)
- Junjie Ning
- Department of Pediatrics, First People's Hospital of Zigong City, Sichuan Province, Zigong, 643000, China.
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25
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Zhang L, Liu L, Luo H, Xu W, Chen H, Yan M, Wang Y. Combination therapy for pediatric patients with Kasabach-Merritt phenomenon: A single-center retrospective study. Medicine (Baltimore) 2022; 101:e30296. [PMID: 36042656 PMCID: PMC9410585 DOI: 10.1097/md.0000000000030296] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
This study aimed to in the management of Kasabach-Merritt phenomenon (KMP), a severe thrombocytopenic coagulopathy that occurs in the presence of an enlarging vascular tumor. Here, we retrospectively evaluated 12 patients with KMP in Guangzhou Women and Children's Medical Center, Guangzhou Medical University, from 2017 to 2021. 12 patients, including 7 females and 5 males, were identified. Tumors were located in the leg (n = 4), neck (n = 1), face (n = 3), chest wall (n = 1), back (n = 2), and retroperitoneum (n = 1). A plaque-like lesion with ecchymosis was the most common cutaneous manifestation. All the patients underwent embolization therapy. Nine patients received steroid treatment and 7 patients were administered with sirolimus. The mean duration of treatment was 1.6 months. All the patients reported in this study were alive when discharged. Embolization combined with steroid and sirolimus appears effective in patients with KMP, as well as in those who experienced disease recurrence. However, a long-term follow-up of the children cured of KMP will be necessary to monitor its recurrence and improve the outcome.
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Affiliation(s)
- Li Zhang
- Department of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Lang Liu
- Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Huanmin Luo
- The Third Clinical School of Guangzhou Medical University, Guangzhou, China
| | - Wenbiao Xu
- Department of Radiology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Huishan Chen
- Department of Allergy, Immunology and Rheumatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Muxia Yan
- Department of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Yiqian Wang
- Department of Biochemistry and Molecular Biology, GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China
- *Correspondence: Yiqian Wang, Department of Biochemistry and Molecular Biology, GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, 511436, China (e-mail: )
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26
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Qiu Y, Chen Z, Yang Q, Huang W, Song L, Fan Y, Kang L. Case report: A rare case of retroperitoneal kaposiform hemangioendothelioma with spinal involvement without abnormal platelet count in 18F-FDG PET/CT. Front Med (Lausanne) 2022; 9:946477. [PMID: 36035391 PMCID: PMC9403054 DOI: 10.3389/fmed.2022.946477] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 07/18/2022] [Indexed: 11/20/2022] Open
Abstract
Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm that mostly appears in infancy or early childhood. Most KHE occurred on the limbs and trunk with cutaneous lesions. Approximately 12% of KHE patients manifested as deep masses and spinal involvement is extremely rare. KHE may develop into life-threatening thrombocytopenia and consumptive coagulopathy, known as the Kasabach-Merritt phenomenon (KMP), especially in patients with retroperitoneal involvement. The thrombocytopenia is usually severe, with a median platelet count of 21 × 109/L at the initial presentation of KMP. Here, firstly we described a case of a 13-month-old girl with KHE who presented the movement limitation of the lower extremity caused by spinal involvement with a normal platelet count. 18F-fluorodeoxyglucose-positron emission tomography/CT (18F-FDG PET/CT) showed mildly elevated metabolism in the lesion, suggesting a probably low-grade malignant tumor. Then the patient was diagnosed with KHE by biopsy. After 6-month sirolimus monotherapy, the size of the retroperitoneal lesion was reduced significantly and the patient showed improvement in clinical symptoms. This case demonstrated the advantage of 18F-FDG PET/CT in the evaluation of disease activity in KHE and the possibility of using 18F-FDG PET/CT to guide therapy and prognostication.
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27
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Liang Z, Lan M, Xu X, Liu F, Tao B, Chen Z, Zeng J. Management of pancreatic kaposiform hemangioendothelioma with sirolimus in a pediatric patient: a case report and literature review. Transl Pediatr 2022; 11:1422-1430. [PMID: 36072541 PMCID: PMC9442215 DOI: 10.21037/tp-22-38] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 06/22/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Kaposiform hemangioendothelioma (KHE) is a rare locally aggressive vascular tumor. The pancreas is not a common site of KHE, especially in pediatric patients. Given that no guidelines are available for the treatment of KHE, management is currently based on expert opinions and clinical experiences. Here, we report a case of pancreatic KHE with obstructive jaundice, which was treated successfully with oral sirolimus instead of radical surgery. Additionally, a literature review on pancreatic KHE was performed to summarize prior clinical experiences and the available treatments. CASE DESCRIPTION A 10-month-old Chinese male infant presented with obstructive jaundice without any signs of fever, abdominal pain, or distention. A detailed consultation revealed an uneventful history. The obstructive jaundice worsened significantly during 3 weeks of conservative therapy. A pancreatic mass was identified via radiological evidence, and a laparoscopic biopsy of the tumor was performed, which confirmed the diagnosis of pancreatic KHE based on histological findings. Oral sirolimus 0.8 mg/m2 twice daily was administered at a steady serum concentration of 5-15 ng/mL, which led to a shrinkage in tumor size and resolution of jaundice. The patient showed no evidence of recurrence after 1 year of follow-up and is still on sirolimus treatment, which has been tolerated well up to the time of this report. CONCLUSIONS The pancreas is a rare location of KHE, which is a locally aggressive vascular tumor. Diagnosis is based on histological findings, and therapy should be multidisciplinary and individualized. Although sirolimus has been very successful in the treatment of KHE even without radical surgery, the possible risks of tumor recurrence and adverse effects warrant some caution.
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Affiliation(s)
- Zijian Liang
- Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Menglong Lan
- Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Xiaogang Xu
- Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Fei Liu
- Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Boyuan Tao
- Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Zhen Chen
- Department of Radiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Jixiao Zeng
- Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
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28
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Mack JM, Crary SE. How we approach coagulopathy with vascular anomalies. Pediatr Blood Cancer 2022; 69 Suppl 3:e29353. [PMID: 36070211 DOI: 10.1002/pbc.29353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 08/14/2021] [Accepted: 08/31/2021] [Indexed: 01/19/2023]
Abstract
Some vascular anomalies can present with challenging hematologic aberrations. Kaposiform hemangioendothelioma (KHE) may be complicated with Kasabach-Merritt phenomenon (KMP) and stagnant blood flow in slow-flow malformations can promote activation and consumption of coagulation factors, which results in bleeding and clotting known as localized intravascular coagulopathy (LIC). These patients can experience significant morbidity secondary to pain due to thrombosis and are at higher risk of hematologic complications during surgical procedures. No standard of care has been established to prevent or manage these complications. This review focuses on the management of coagulopathy in children and adults with vascular anomalies.
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Affiliation(s)
- Joana M Mack
- Department of Pediatrics, Division of Hematology/Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.,Arkansas Children's Hospital, Little Rock, Arkansas, USA
| | - Shelley E Crary
- Department of Pediatrics, Division of Hematology/Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.,Arkansas Children's Hospital, Little Rock, Arkansas, USA
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29
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Maruyama S, Matono T, Koda M. Prevalence and Characteristics of Hepatic Hemangioma Associated with Coagulopathy and Its Predictive Risk Factors. J Clin Med 2022; 11:jcm11154347. [PMID: 35893437 PMCID: PMC9368925 DOI: 10.3390/jcm11154347] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 07/24/2022] [Accepted: 07/24/2022] [Indexed: 12/10/2022] Open
Abstract
Background: Knowledge of the relationships between hepatic hemangiomas and coagulopathy and the risk factors for hemangiomas is lacking. The aim of this study was to investigate the prevalence and characteristics of hepatic hemangiomas associated with coagulopathy, elucidate the causes of coagulopathy, and identify the predictive factors for hemangioma-related complications. Methods: In 281 consecutive patients with hepatic hemangiomas, we performed ultrasonography and conducted serum laboratory tests for liver function and six coagulation factors, i.e., platelets, as well as five coagulation fibrinolytic markers (prothrombin time (PT), fibrinogen, thrombin-antithrombin III complex (TAT), d-dimer, and fibrin and fibrinogen degradation products (FDP)) as indicators of coagulation disorder. Results: Among 281 patients, 56 (19.9%) had abnormal coagulation factors. Abnormal values of d-dimer were most frequently found among the six coagulation factors. The number of abnormal coagulation factors was significantly correlated with tumor size, M2BPGi, and HDL cholesterol, among which tumor size was the most significant independent predictor of the number of abnormal coagulation factors. Conclusions: The prevalence of hepatic hemangiomas associated with coagulopathy was relatively high and became more frequent with increases in tumor size. Predictive factors of hemangioma-related complications were found to be a tumor size of >5 cm in diameter and coagulopathy, especially the elevation of d-dimer.
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Affiliation(s)
- Shigeo Maruyama
- Maruyama Medical Clinic, Aioimacho 3921, Hamada 697-0034, Shimane, Japan;
| | | | - Masahiko Koda
- Hino Hospital, Nota 332, Hino 689-4504, Tottori, Japan
- Correspondence: ; Tel.: +81-859-72-0351; Fax: +81-859-72-0089
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30
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Ji Y, Chen S, Zhou J, Yang K, Zhang X, Xiang B, Qiu T, Gong X, Zhang Z, Lan Y, Hu F, Kong F, Qiu Q, Zhang Y. Sirolimus plus prednisolone vs sirolimus monotherapy for kaposiform hemangioendothelioma: a randomized clinical trial. Blood 2022; 139:1619-1630. [PMID: 35030255 DOI: 10.1182/blood.2021014027] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 12/21/2021] [Indexed: 02/05/2023] Open
Abstract
The Kasabach-Merritt phenomenon (KMP) in kaposiform hemangioendothelioma (KHE) is characterized by life-threatening thrombocytopenia and consumptive coagulopathy. This study compared the efficacy and safety of sirolimus plus prednisolone vs sirolimus monotherapy as treatment strategies for KHE with KMP in the largest cohort to date. Participants were randomized to receive either sirolimus in combination with a short course of prednisolone or sirolimus monotherapy for at least 12 months. The primary outcome was defined as achievement of a durable platelet response (platelet count >100 × 109/L) at week 4. Participants completed efficacy assessments 2 years after the initial treatment. At week 4, a durable platelet response was achieved by 35 of 37 patients given sirolimus and prednisolone compared with 24 of 36 patients given sirolimus monotherapy (difference 27.9%; 95% confidence interval, 10.0-44.7). Compared with the sirolimus monotherapy group, the combination treatment group showed improvements in terms of measures of durable platelet responses at all points during the initial 3-week treatment period, median platelet counts during weeks 1 to 4, increased numbers of patients achieving fibrinogen stabilization at week 4, and objective lesion responses at month 12. Patients receiving combination therapy had fewer blood transfusions and a lower total incidence of disease sequelae than patients receiving sirolimus alone. The frequencies of total adverse events and grade 3-4 adverse events during treatment were similar in both groups. The responses seen in patients with KHE with KMP were profound and encouraging, suggesting that sirolimus plus prednisolone should be considered a valid treatment of KHE with KMP. This trial was registered at www.clinicaltrials.gov as #NCT03188068.
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Affiliation(s)
- Yi Ji
- Division of Oncology, Department of Pediatric Surgery and
| | - Siyuan Chen
- Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Jiangyuan Zhou
- Division of Oncology, Department of Pediatric Surgery and
| | - Kaiying Yang
- Division of Oncology, Department of Pediatric Surgery and
| | - Xuepeng Zhang
- Division of Oncology, Department of Pediatric Surgery and
| | - Bo Xiang
- Division of Oncology, Department of Pediatric Surgery and
| | - Tong Qiu
- Division of Oncology, Department of Pediatric Surgery and
| | - Xue Gong
- Division of Oncology, Department of Pediatric Surgery and
| | - Zixin Zhang
- Division of Oncology, Department of Pediatric Surgery and
| | - Yuru Lan
- Division of Oncology, Department of Pediatric Surgery and
| | - Fan Hu
- Department of Vascular & Interventional Radiology, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Feiteng Kong
- Department of Pediatric Surgery, Sichuan Women and Children's Hospital, Chengdu, China
| | - Qingxia Qiu
- Department of Pediatric Surgery, Chengdu Shangjin Nanfu Hospital, Chengdu, China; and
| | - Yongbo Zhang
- Department of Pediatric Surgery, Chengdu Women and Children's Central Hospital, Chengdu, China
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31
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Targeting inflammation-induced Kasabach-Merritt phenomenon. Blood 2022; 139:1603-1605. [PMID: 35298606 DOI: 10.1182/blood.2022015412] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 01/18/2022] [Indexed: 12/19/2022] Open
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32
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Dai S, Yang K, Qiu T, Zhou J, Zhang X, Chen S, Li L, Ji Y. Health-Related Quality of Life in Children With Kaposiform Hemangioendothelioma. Front Pediatr 2022; 10:720611. [PMID: 35281237 PMCID: PMC8907831 DOI: 10.3389/fped.2022.720611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 01/31/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND AND OBJECTIVE Kaposiform hemangioendothelioma (KHE) is a rare, aggressive and borderline vascular tumor mainly occurring in infants and children. The aim of this study was to determine the health-related quality of life (HRQOL) in children with KHE. MEASURES A total of 91 children with KHE participated in this cross-sectional study. The HRQOL was assessed by the age-specific Pediatric Quality of Life Inventory Version 4.0 (PedsQL™ 4.0) Infant Scales, Family Information Form (FIF), Family Impact Module (FIM) and Generic Core Scales (GCS). For comparison, demographically matched healthy children were recruited as a control group. The main outcome measure of HRQOL was analyzed in the two groups. We determined related factors that influenced the HRQOL in children with KHE and their parents by using a stepwise multiple regression analysis. RESULTS The study found that the scores of each item in the family impact module (FIM) were lower than 75, which suggesting that KHE can make the parents of patients in a state of poor quality of life. The scores of physiological and psychosocial domains in all age groups of patients with KHE were lower than those of normal children (P < 0.01). Activity dysfunction is the factor influencing the physiological function score of all-age patients. KMP is the factor influencing the psychosocial function score of all-age patients. CONCLUSIONS The findings presented here suggest that patients with KHE have a poor HRQOL. KMP and activity dysfunction are risk factors for poor HRQOL in patients with KHE. However, lesion size, lesion location and education level of the mother and father were not related to the HRQOL.
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Affiliation(s)
- Shiyi Dai
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Kaiying Yang
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Tong Qiu
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Jiangyuan Zhou
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Xuepeng Zhang
- Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Siyuan Chen
- Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Lizhi Li
- Department of Pediatric Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Yi Ji
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
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Wang Y, Wang S, Wang L, Bi S, Zhang J, Zha P, Dai L. Transarterial Embolization in Neonatal Kasabach-Merritt Syndrome. Front Pediatr 2021; 9:788120. [PMID: 34926356 PMCID: PMC8671612 DOI: 10.3389/fped.2021.788120] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 10/29/2021] [Indexed: 01/07/2023] Open
Abstract
Background: Kasabach-Merritt syndrome (KMS) is characterized by large hemangiomas and persistent thrombocytopenia, which may result in visceral hemorrhage and disseminated intravascular coagulation. This study aimed to evaluate the value of transarterial embolization (TAE) in neonatal KMS patients. Patients and Methods: The clinical course of 11 neonates with KMS who underwent TAE in the Department of Neonatology, Anhui Provincal Children's Hospital, Anhui Medical University, China, were reviewed retrospectively. Results: Eleven neonates with KMS (nine male and two female) were admitted to our hospital between the age of 1 h and 6 days. All were born with progressively enlarged hemangiomas and persistent thrombocytopenia. The largest lesion had its maximum size reached at 15 × 8 × 8 cm. Eight patients had cutaneous hemangiomas (1 right face, one oropharynx, one left upper arm, two back, one left lumbar, one right lower leg, and one right thigh), and three patients had liver hemangiomas. All 11 patients underwent TAE. Nine patients underwent two TAEs, and two patients underwent only one embolization procedure. They all obtained >80% devascularization of their lesions without a major complication. The platelet count increased at 2-5 days after treatment and reached normal count and coagulation profile at 18-28 days after the TAE. Conclusions: TAE is a safe and effective alternative therapy for neonatal KMS patients.
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Affiliation(s)
- Yinghao Wang
- Department of Neonatology, Anhui Provincial Children's Hospital, Anhui Medical University, Hefei, China
| | - Song Wang
- Department of Radiology, Anhui Provincial Children's Hospital, Anhui Medical University, Hefei, China
| | - Lili Wang
- Department of Neonatology, Anhui Provincial Children's Hospital, Anhui Medical University, Hefei, China
| | - Shaohua Bi
- Department of Neonatology, Anhui Provincial Children's Hospital, Anhui Medical University, Hefei, China
| | - Jian Zhang
- Department of Neonatology, Anhui Provincial Children's Hospital, Anhui Medical University, Hefei, China
| | - Ping Zha
- Department of Neonatology, Anhui Provincial Children's Hospital, Anhui Medical University, Hefei, China
| | - Liying Dai
- Department of Neonatology, Anhui Provincial Children's Hospital, Anhui Medical University, Hefei, China
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Nozawa A, Ozeki M, Yasue S, Endo S, Noguchi K, Kanayama T, Tomita H, Aoki Y, Ohnishi H. Characterization of kaposiform lymphangiomatosis tissue-derived cells. Pediatr Blood Cancer 2021; 68:e29086. [PMID: 33913609 DOI: 10.1002/pbc.29086] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 03/22/2021] [Accepted: 04/11/2021] [Indexed: 11/08/2022]
Abstract
BACKGROUND Kaposiform lymphangiomatosis (KLA) is a recently characterized systemic lymphatic anomaly. Activation of RAS/MAPK and PI3K/AKT/mTOR pathways may affect KLA pathogenesis, but the cellular basis of KLA is unclear. Abnormal-spindle endothelial cells that express lymphatic endothelial cell (LEC) markers are characteristic of KLA histopathology. This study evaluated patient-derived KLA cells to establish their morphological and biological characteristics. PROCEDURE We established cell lines from primary KLA tissues of two patients with KLA and examined their morphological and functional characteristics, messenger RNA and protein expression profiles, gene mutations, and responses to inhibitors of the RAS/MAPK and PI3K/AKT/mTOR pathways. RESULTS Both KLA cell lines showed spindle-shaped morphology, stained positive for podoplanin (PDPN), and exhibited impaired tube-formation properties. They expressed LEC marker PDPN and mesenchymal stem cell markers (CD90, CD105) in the absence of endothelial cell markers (CD34, CD31, VWF), per real-time polymerase chain reaction. Both mTOR inhibitor rapamycin and MEK inhibitor trametinib inhibited growth of the two cell lines. A NRAS p.Q61R variant was found in one of two independent KLA tissue samples, but not in the KLA cells (per targeted next-generation sequencing); and KLA cells with this variant had elevated AKT phosphorylation levels. ERK phosphorylation levels were undetectable in both KLA cell lines. CONCLUSIONS Inhibition of the RAS/MAPK and PI3K/AKT/mTOR pathways may represent potential therapeutic targets in KLA. These patient-derived KLA cell lines will be useful research tools to elucidate KLA etiology, and could pave the way for basic, translational, and preclinical studies of this disease.
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Affiliation(s)
- Akifumi Nozawa
- Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.,Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Michio Ozeki
- Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Shiho Yasue
- Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Saori Endo
- Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Kei Noguchi
- Department of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Tomohiro Kanayama
- Department of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Hiroyuki Tomita
- Department of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Yoko Aoki
- Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan
| | - Hidenori Ohnishi
- Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan
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Ostojic A, Mrzljak A, Mikulic D. Liver transplantation for benign liver tumors. World J Hepatol 2021; 13:1098-1106. [PMID: 34630877 PMCID: PMC8473500 DOI: 10.4254/wjh.v13.i9.1098] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 05/12/2021] [Accepted: 07/21/2021] [Indexed: 02/06/2023] Open
Abstract
Benign liver tumors are common lesions that are usually asymptomatic and are often found incidentally due to recent advances in imaging techniques and their widespread use. Although most of these tumors can be managed conservatively or treated by surgical resection, liver transplantation (LT) is the only treatment option in selected patients. LT is usually indicated in patients that present with life-threatening complications, when the lesions are diffuse in the hepatic parenchyma or when malignant transformation cannot be ruled out. However, due to the significant postoperative morbidity of the procedure, scarcity of available donor liver grafts, and the benign course of the disease, the indications for LT are still not standardized. Hepatic adenoma and adenomatosis, hepatic hemangioma, and hepatic epithelioid hemangioendothelioma are among the most common benign liver tumors treated by LT. This article reviews the role of LT in patients with benign liver tumors. The indications for LT and long-term outcomes of LT are presented.
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Affiliation(s)
- Ana Ostojic
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb 10000, Croatia
| | - Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb 10000, Croatia
| | - Danko Mikulic
- Department of Surgery, University Hospital Merkur, Zagreb 10000, Croatia.
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王 英, 戴 立, 王 丽, 张 健, 汪 松, 左 伟. [Clinical features of Kasabach-Merritt syndrome: an analysis of 16 neonates]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2021; 23:696-701. [PMID: 34266526 PMCID: PMC8292658 DOI: 10.7499/j.issn.1008-8830.2103146] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 04/29/2021] [Indexed: 06/13/2023]
Abstract
OBJECTIVE To study the clinical features, treatment, and prognosis of neonates with Kasabach-Merritt syndrome (KMS), and to provide a reference for optimizing the diagnosis and treatment of this disease. METHODS A retrospective analysis was performed for the clinical and follow-up data of 16 neonates with KMS who were admitted to the Anhui Children's Hospital, Anhui Medical University, from January 2016 to December 2020. RESULTS Of the 16 neonates, there were 13 boys (81%) and 3 girls (19%), with an age of 1 hour to 10 days on admission. Among these neonates, 13 (81%) had cutaneous hemangioma (2 in the head and face, 5 in the trunk, and 6 in the extremities) and 3 (19%) had liver hemangioma. The main clinical manifestations of bleeding tendency and scattered petechiae and ecchymosis were observed in 10 neonates (62%). All the 16 neonates had varying degrees of thrombocytopenia and coagulation disorders. They all received glucocorticoid treatment after admission and 7 (44%) of them had response, among whom 4 experienced recurrence. Among the neonates with no response to glucocorticoid treatment, 3 received sirolimus treatment, among whom 1 had the tumor volume reduced by 58.8% after 4 weeks of treatment, with platelet count and coagulation function returning to normal, while 2 had no significant reduction in tumor volume or significant increase in platelet count and achieved a tumor volume reduced by (43.7±0.4)% after 4 weeks of combined treatment with bleomycin arterial embolization, with platelet count and coagulation function returning to normal. After 4 weeks of bleomycin arterial embolization alone for 4 neonates, tumor volume was reduced by (52.0±3.4)%, and platelet count and coagulation function returned to normal. Blunt and sharp dissection was performed for 2 neonates. The tumor was removed completely during surgery in the 2 neonates, with no infection or recurrence after surgery, and platelet count and coagulation function returned to normal. The postoperative pathological examination showed Kaposiform hemangioendothelioma in 1 out of the 2 neonates. CONCLUSIONS KMS has characteristic clinical manifestations, histopathological features, and laboratory examination results. The KMS neonates who are not sensitive to glucocorticoids can achieve a good curative effect through arterial embolization and sirolimus treatment.
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Affiliation(s)
- 英豪 王
- 安徽医科大学附属省儿童医院新生儿科, 合肥安徽 230000Department of Neonatology, Anhui Children's Hospital, Anhui Medical University, Hefei 230000, China
| | - 立英 戴
- 安徽医科大学附属省儿童医院新生儿科, 合肥安徽 230000Department of Neonatology, Anhui Children's Hospital, Anhui Medical University, Hefei 230000, China
| | - 丽丽 王
- 安徽医科大学附属省儿童医院新生儿科, 合肥安徽 230000Department of Neonatology, Anhui Children's Hospital, Anhui Medical University, Hefei 230000, China
| | - 健 张
- 安徽医科大学附属省儿童医院新生儿科, 合肥安徽 230000Department of Neonatology, Anhui Children's Hospital, Anhui Medical University, Hefei 230000, China
| | - 松 汪
- 安徽医科大学附属省儿童医院影像中心, 合肥安徽 230000
| | - 伟 左
- 安徽医科大学附属省儿童医院新生儿外科, 合肥安徽 230000
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Intracranial kaposiform hemangioendothelioma presenting as epistaxis: a rare case report with review of literature. Childs Nerv Syst 2021; 37:2057-2062. [PMID: 32989498 DOI: 10.1007/s00381-020-04905-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 09/24/2020] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of intermediate malignancy with tendency for local invasion and recurrence. The tumor almost exclusively occurs in children, especially in infants. Intracranial KHE are extremely rare with only two cases reported in the literature. REPORT We report the clinical and pathological features of this rare tumor arising from basitemporal region in a 21-month child. Our case did not present with Kasabach-Merritt phenomenon. Histopathological examination confirmed the diagnosis of KHE. CONCLUSION KHE should be considered in the differential diagnosis of intracranial extra-axial neoplasm in children, and histopathological examination plays an important role in distinguishing KHE from its morphologic mimics. It is essential to diagnose KHE due to its locally aggressive nature.
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Rikhotso RE, Alharbi AA. Management of Refractory Mandibular Kaposiform Hemangioendothelioma with Sirolimus: A Case Report and Review of the Literature. J Oral Maxillofac Surg 2021; 79:2086.e1-2086.e8. [PMID: 34153244 DOI: 10.1016/j.joms.2021.05.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 05/11/2021] [Accepted: 05/11/2021] [Indexed: 10/21/2022]
Abstract
Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm of intermediate malignancy that generally occurs in infancy and early childhood. Typically, the lesion arises from superficial or deep soft tissues of the extremities, trunk and retroperitoneum. The paucity of reported cases of head and neck KHEs is evidence of the rarity of the disease in this region. We report on the presentation and treatment of KHE in an 11-month-old boy who presented with a mandibular lesion. We include a brief discussion about the differential diagnosis of KHE. Management involved preoperative interventional radiology, surgical excision and chemotherapeutic treatment with Sirolimus. The lesion resolved without evidence of relapse 12 months later.
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Affiliation(s)
- Risimati Ephraim Rikhotso
- Department Head, Department of Maxillofacial and Oral Surgery, Wits School of Oral Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
| | - Abdulaziz Abdullah Alharbi
- Consultant, Department of Maxillofacial and Oral Surgery, Faculty of Dentistry, Taif University, Alhawiah, Saudi Arabia
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Shan Y, Tian R, Gao H, Zhang L, Li J, Xie C, Liang Y, Chen Y, Wang J, Xu M, Gu S. Sirolimus for the treatment of kaposiform hemangioendothelioma: In a trough level-dependent way. J Dermatol 2021; 48:1201-1209. [PMID: 33932303 DOI: 10.1111/1346-8138.15905] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 03/15/2021] [Accepted: 03/30/2021] [Indexed: 12/22/2022]
Abstract
With the accumulation of clinical practice, sirolimus is now widely viewed as an effective agent in kaposiform hemangioendothelioma (KHE) treatment using a dose based on experience. Therefore, this retrospective research aimed to provide evidence-based suggestions on the most appropriate dose and trough level of sirolimus. All unresectable KHE cases diagnosed at our center from January 2016 to December 2019 were included. Sirolimus monotherapy was initiated when there was no sign of Kasabach-Merritt phenomenon (KMP) at a dose of 0.8 mg/m2 twice a day in order to keep the trough level at 5-20 ng/mL. Patients' clinical information, tumor volume change, trough level fluctuation, and complication occurrence were all recorded. Efficacy represented by tumor shrinkage speed and safety manifested by complication grades were compared between different trough level groups (5-10 vs. 10-15 vs. >15 ng/mL). Twenty-one patients (10 girls and 11 boys) were enrolled. There were eight patients in the 5-10 ng/mL group, seven in the 10-15 ng/mL group, and six in the more than 15 ng/mL group. Trough level over 10 ng/mL manifested better efficacy in tumor shrinkage (t-test, p = 0.011) while a level over 15 ng/mL had no further benefit in efficacy (t-test, p = 0.65). In addition, tumors at a central location reacted better to sirolimus (t-test, p = 0.022). No significant differences were observed in complication occurrence among different concentrations, although boys seemed to be at higher risk of more severe complications (>grade II, χ2 -test, p = 0.009, odds ratio = 4.52, range = 1.20-17.24). It proved to be most efficacious in the management of KHE at a trough level between 10 and 15 ng/mL. Such concentration was safe and well tolerated.
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Affiliation(s)
- Yuhua Shan
- Department of Pediatric Surgery, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Ruicheng Tian
- Department of Pediatric Surgery, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Honxiang Gao
- Department of Pediatric Surgery, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Lei Zhang
- Department of Pediatric Surgery, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jingjing Li
- Department of Pediatric Surgery, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Chenjie Xie
- Department of Pediatric Surgery, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yu Liang
- Department of Pediatric Surgery, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yiwei Chen
- Department of Pediatric Surgery, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jing Wang
- Department of Pediatric Surgery, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Min Xu
- Department of Pediatric Surgery, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Song Gu
- Department of Pediatric Surgery, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
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Yao W, Li K, Wang Z, Wang J, Ji Y, Zhou L, Huang H, Gao X, Huang Z, Gu S, Yang H, Zheng S. Comparison of efficacy and safety of corticosteroid and vincristine in treating kaposiform hemangioendothelioma and tufted angioma: A multicenter prospective randomized controlled clinical trial. J Dermatol 2021; 48:576-584. [PMID: 33608936 DOI: 10.1111/1346-8138.15767] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 01/04/2021] [Indexed: 02/05/2023]
Abstract
Kaposiform haemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors that can cause life-threatening Kasabach-Merritt phenomenon. No evidence-based treatment strategies have yet been established, and its management is still a challenge. The purpose of this multicenter prospective randomized controlled study was to evaluate and compare the efficacy of corticosteroid and vincristine (VCR) in the treatment of KHE and TA. All patients with KHE/TA who met the diagnostic criteria were consecutively recruited. The patients were randomized into a methylprednisolone (MP) group and a VCR group. The primary outcome was the single main parameter effective rate and overall effective rate of corticosteroid and VCR over 1 month after treatment. The single main parameters included platelets, fibrinogen, tumor size, texture, and appearance. From May 2016 to April 2018, a total of 59 patients completed the clinical trial, including 29 in the MP group and 30 in the VCR group. The results showed that VCR was superior to corticosteroid in the improvement of platelet (80.0% vs 44.0%, P = 0.019) and tumor texture (68.9% vs 30.8%, P = 0.007). Although the efficacy of VCR on fibrinogen (23.3% vs 20.7%, P = 1.000), tumor size (23.3% vs 13.8%, P = 0.273), and appearance (65.5% vs 46.2%, P = 0.120) was higher than that of corticosteroid, there was no significant difference (P > 0.05). Meanwhile, the overall effective rate of VCR was higher than that of corticosteroid (56.7% vs 31.0%), but the difference was also not statistically significant (P = 0.067). In conclusion, the therapeutic effect of VCR was significantly better than that of corticosteroid with regard to treating thrombocytopenia and tumor texture. We recommend that VCR could be an option for first-line treatment in KHE/TA patients.
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Affiliation(s)
- Wei Yao
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China
| | - Kai Li
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China
| | - Zuopeng Wang
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China
| | - Jinhu Wang
- Department of Pediatric Surgery, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yi Ji
- Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Lin Zhou
- Department of Pediatric Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Haijin Huang
- Department of Pediatric Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Xiaoyun Gao
- Department of Pediatric Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Zhijian Huang
- Department of Burns and Plastic Surgery, Children's Hospital of Soochow University, Suzhou, China
| | - Song Gu
- Department of General Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Heying Yang
- Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shan Zheng
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China
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Yao W, Li KL, Qin ZP, Li K, Zheng JW, Fan XD, Ma L, Zhou DK, Liu XJ, Wei L, Li L, Tai MZ, Wang JH, Ji Y, Zhou L, Huang HJ, Gao XY, Huang ZJ, Gu S, Yang HY. Standards of care for Kasabach-Merritt phenomenon in China. World J Pediatr 2021; 17:123-130. [PMID: 32851561 DOI: 10.1007/s12519-020-00379-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 06/10/2020] [Indexed: 02/05/2023]
Abstract
Kasabach-Merritt phenomenon (KMP) is a rare disease that is characterized by severe thrombocytopenia and consumptive coagulation dysfunction caused by kaposiform hemangioendothelioma or tufted hemangioma. This condition primarily occurs in infants and young children, usually with acute onset and rapid progression. This review article introduced standardized recommendations for the pathogenesis, clinical manifestation, diagnostic methods and treatment process of KMP in China, which can be used as a reference for clinical practice.
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Affiliation(s)
- Wei Yao
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, 201102, China
| | - Ke-Lei Li
- Special Department of Vascular Anomalies, Tumor Hospital of Linyi City, Linyi, 276001, China
| | - Zhong-Ping Qin
- Special Department of Vascular Anomalies, Tumor Hospital of Linyi City, Linyi, 276001, China.
| | - Kai Li
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, 201102, China
| | - Jia-Wei Zheng
- Department of Oral and Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Xin-Dong Fan
- Department of Intervention Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Lin Ma
- Department of Dermatology, Beijing Children's Hospital Affiliated to Capital Medical University, Beijing, 100045, China
| | - De-Kai Zhou
- Department of Infantile Hemangioma, Gastrointestinal and Neonatal Surgery, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
| | - Xue-Jian Liu
- Department of Oncology, People's Hospital of Linyi Economic Development Zone, Linyi, 276023, China
| | - Li Wei
- Department of Dermatology, Beijing Children's Hospital Affiliated to Capital Medical University, Beijing, 100045, China
| | - Li Li
- Department of Dermatology, Beijing Children's Hospital Affiliated to Capital Medical University, Beijing, 100045, China
| | - Mao-Zhong Tai
- Special Department of Vascular Anomalies, Tumor Hospital of Linyi City, Linyi, 276001, China
| | - Jin-Hu Wang
- Department of Pediatric Surgery, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yi Ji
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chendu, 610041, China
| | - Lin Zhou
- Department of Pediatric Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumchi, 830001, China
| | - Hai-Jin Huang
- Department of Pediatric Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China
| | - Xiao-Yun Gao
- Department of Pediatric Surgery, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Zhi-Jian Huang
- Department of Pediatric Surgery, Children's Hospital of Soochow University, Suzhou, 215025, China
| | - Song Gu
- Department of Pediatric Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - He-Ying Yang
- Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
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42
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Maruyama S, Koda M, Matono T, Isomoto H. Association of tumor size and internal echo pattern with coagulopathy associated with hepatic hemangioma. Mol Clin Oncol 2021; 14:83. [PMID: 33758664 PMCID: PMC7947948 DOI: 10.3892/mco.2021.2245] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 02/05/2021] [Indexed: 01/18/2023] Open
Abstract
Little is known concerning causal factors associated with the size and echogenicity of hepatic hemangiomas. The aim of the present study was to investigate the associations between tumor size and echo pattern and coagulation factors, and to elucidate the growth pattern of hemangiomas. In 214 consecutive patients with hepatic hemangiomas, ultrasonography was performed to determine total tumor number, size, echogenicity and location, and serum laboratory tests for liver function and coagulation factors were carried out. The ultrasonographic appearance of hemangiomas was homogeneous in 75.7% of cases and mixed in 24.3% of cases. A mixed echo pattern was seen in 1 out of 145 masses (0.7%) with a diameter <20 mm, in 30 out of 48 (62.5%) with a diameter of 20-40 mm, and in all of the 21 (100%) with a diameter >40 mm. Platelet counts (P<0.0001) and fibrinogen levels (P<0.01) were lower in patients with larger and mixed tumors. Levels of thrombin-antithrombin III complex (TAT), D-dimer, and fibrin and fibrinogen degradation products (FDP) were significantly elevated along with an increase in tumor size (all P<0.0001), and the number of patients with the abnormal values of TAT, D-dimer, and FDP was significantly higher in the mixed group than in the homogeneous group (all P<0.0001). Fibrinogen (P<0.01), platelet count (P<0.001), portal vein diameter (P<0.0001), splenic index (P<0.01), and levels of TAT, D-dimer and FDP (all P<0.0001) were significantly associated with tumor size. Multivariate analysis revealed TAT, D-dimer and FDP as independent predictors of tumor size. The internal echo pattern became mixed as size increased. The size and echogenicity of hemangiomas were closely associated with coagulation factors. Therefore, it was speculated that differences in size and echogenicity were caused by intratumoral thrombosis and subsequent hemorrhage.
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Affiliation(s)
- Shigeo Maruyama
- Department of Internal Medicine, Maruyama Medical Clinic, Hamada, Shimane 697-0034, Japan
| | - Masahiko Koda
- Department of Internal Medicine, Hino Hospital, Hino, Tottori 689-4504, Japan
| | - Tomomitsu Matono
- Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8504, Japan
| | - Hajime Isomoto
- Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8504, Japan
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43
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Brill R, Uller W, Huf V, Müller-Wille R, Schmid I, Pohl A, Häberle B, Perkowski S, Funke K, Till AM, Lauten M, Neumann J, Güttel C, Heid E, Ziermann F, Schmid A, Hüsemann D, Meyer L, Sporns PB, Schinner R, Schmidt VF, Ricke J, Rössler J, Kapp FG, Wohlgemuth WA, Wildgruber M. Additive value of transarterial embolization to systemic sirolimus treatment in kaposiform hemangioendothelioma. Int J Cancer 2020; 148:2345-2351. [PMID: 33231291 DOI: 10.1002/ijc.33406] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 10/16/2020] [Accepted: 11/09/2020] [Indexed: 01/19/2023]
Abstract
Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor in children, which can be accompanied by life-threatening thrombocytopenia, referred to as Kasabach-Merritt phenomenon (KMP). The mTOR inhibitor sirolimus is emerging as targeted therapy in KHE. As the sirolimus effect on KHE occurs only after several weeks, we aimed to evaluate whether additional transarterial embolization is of benefit for children with KHE and KMP. Seventeen patients with KHE and KMP acquired from 11 hospitals in Germany were retrospectively divided into two cohorts. Children being treated with adjunct transarterial embolization and systemic sirolimus, and those being treated with sirolimus without additional embolization. Bleeding grade as defined by WHO was determined for all patients. Response of the primary tumor at 6 and 12 months assessed by magnetic resonance imaging (MRI), time to response of KMP defined as thrombocyte increase >150 × 103 /μL, as well as rebound rates of both after cessation of sirolimus were compared. N = 8 patients had undergone additive embolization to systemic sirolimus therapy, sirolimus in this group was started after a mean of 6.5 ± 3 days following embolization. N = 9 patients were identified who had received sirolimus without additional embolization. Adjunct embolization induced a more rapid resolution of KMP within a median of 7 days vs 3 months; however, tumor response as well as rebound rates were similar between both groups. Additive embolization may be of value for a more rapid rescue of consumptive coagulopathy in children with KHE and KMP compared to systemic sirolimus only.
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Affiliation(s)
- Richard Brill
- Klinik und Poliklinik für Radiologie, Universitätsklinikum Halle, Halle/Saale, Germany
| | - Wibke Uller
- Institut für Röntgendiagnostik, Universitätsklinik Regensburg, Regensburg, Germany
| | - Veronika Huf
- Institut für Röntgendiagnostik, Universitätsklinik Regensburg, Regensburg, Germany
| | - René Müller-Wille
- Institut für diagnostische und interventionelle Radiologie, Universitätsmedizin Göttingen, Göttingen, Germany
| | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, Klinikum der Universität München, Munich, Germany
| | - Alexandra Pohl
- Kinderchirurgische Klinik und Poliklinik im Dr. von Haunerschen Kinderspital, Klinikum der Universität München, Munich, Germany
| | - Beate Häberle
- Kinderchirurgische Klinik und Poliklinik im Dr. von Haunerschen Kinderspital, Klinikum der Universität München, Munich, Germany
| | - Sybille Perkowski
- Abteilung für Kinderchirurgie, Universitätsklinikum Münster, Münster, Germany
| | - Katrin Funke
- Abteilung für Kinderchirurgie, Universitätsklinikum Münster, Münster, Germany
| | - Anne-Marie Till
- Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany
| | - Melchior Lauten
- Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany
| | - Jacob Neumann
- Klinik für Kinder- und Jugendmedizin, Helios Kliniken Schwerin, Schwerin, Germany
| | - Christian Güttel
- Klinik für Kinder- und Jugendmedizin, Helios Kliniken Schwerin, Schwerin, Germany
| | - Esther Heid
- Klinik für Kinder und Jugendmedizin, Klinikum rechts der Isar, TU München, Munich, Germany
| | - Franziska Ziermann
- Klinik für Kinder und Jugendmedizin, Klinikum rechts der Isar, TU München, Munich, Germany
| | - Axel Schmid
- Radiologisches Institut Universitätsklinikum Erlangen, Erlangen, Germany
| | - Dieter Hüsemann
- Klinik für Kinder- und Jugendmedizin, Werner Forßmann Krankenhaus, Eberswalde, Germany
| | - Lutz Meyer
- Abteilung Kinderchirurgie-Zentrum für Vasculäre Malformationen Eberswalde (ZVM), Klinik für Kinder- und Jugendmedizin, Werner Forßmann Krankenhaus, Eberswalde, Germany
| | - Peter B Sporns
- Diagnostische und Interventionelle Neuroradiologie, Universitätsspital Basel, Basel, Switzerland
| | - Regina Schinner
- Klinik und Poliklinik für Radiologie, Klinikum der Universität München, Munich, Germany
| | - Vanessa F Schmidt
- Klinik und Poliklinik für Radiologie, Klinikum der Universität München, Munich, Germany
| | - Jens Ricke
- Klinik und Poliklinik für Radiologie, Klinikum der Universität München, Munich, Germany
| | - Jochen Rössler
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Friedrich G Kapp
- Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Walter A Wohlgemuth
- Klinik und Poliklinik für Radiologie, Universitätsklinikum Halle, Halle/Saale, Germany
| | - Moritz Wildgruber
- Klinik und Poliklinik für Radiologie, Klinikum der Universität München, Munich, Germany
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44
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Famularo G. Kasabach-Merritt Syndrome. Am J Med 2020; 133:e747. [PMID: 33248667 DOI: 10.1016/j.amjmed.2020.02.032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Revised: 02/20/2020] [Accepted: 02/21/2020] [Indexed: 10/22/2022]
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Liu Y, Wu X, Ye L, Xu H. Successful treatment of a patient with Kasabach-Merritt syndrome and multiple giant hepatic hemangiomas. J Int Med Res 2020; 48:300060519898358. [PMID: 31948308 PMCID: PMC7113715 DOI: 10.1177/0300060519898358] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Kasabach–Merritt syndrome (KMS) is a rare complication of hemangioma. KMS mostly occurs in the pediatric population with typical clinical manifestations, including thrombocytopenia, consumptive coagulation, and purpura. However, the pathogenesis of KMS is still unclear and the KMS therapy is controversial. We report here a case of KMS and multiple, giant, hepatic hemangiomas in a 34-year-old female patient who was successfully treated in our hospital. Glucocorticoid along with supportive treatments was administrated immediately to reverse fatal disseminated intravascular coagulation and acute hemolysis. After the acute phase, glucocorticoid was tapered slowly and sirolimus was added to treat the hemangiomas. In conclusion, the risk factors of gestation, interventional treatment, and autoimmune disturbance might contribute to the pathogenesis of KMS. Additionally, treatment with glucocorticoid and sirolimus is effective in KMS and multiple giant hepatic hemangiomas.
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Affiliation(s)
- Yaqun Liu
- Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, the Second Military Medical University, Shanghai, P.R. China
| | - Xin Wu
- Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, the Second Military Medical University, Shanghai, P.R. China
| | - Lingying Ye
- Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, the Second Military Medical University, Shanghai, P.R. China
| | - Huji Xu
- Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, the Second Military Medical University, Shanghai, P.R. China.,Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, P.R. China.,Peking-Tsinghua Center for Life Sciences, Tsinghua University, Beijing, P.R. China
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46
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Ji Y, Chen S, Xia C, Zhou J, Jiang X, Xu X, Yang K, Zhang X, Kong F, Lu G, Zhang Y. Chronic lymphedema in patients with kaposiform hemangioendothelioma: incidence, clinical features, risk factors and management. Orphanet J Rare Dis 2020; 15:313. [PMID: 33160383 PMCID: PMC7648422 DOI: 10.1186/s13023-020-01595-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 10/26/2020] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVES There are no cohort studies of chronic lymphedema in patients with kaposiform hemangioendothelioma (KHE). We sought to characterize the incidence, clinical features, risk factors and management of chronic lymphedema in patients with KHE. METHODS We conducted a multicenter retrospective analysis of patients who had a minimum of 3 years of follow-up after the onset of KHE and/or Kasabach-Merritt phenomenon (KMP). Clinical features were reviewed to determine the possible cause of chronic lymphedema. The degree of lymphedema, risk factors and management strategies were analyzed. RESULTS Among the 118 patients, chronic lymphedema was confirmed by lymphoscintigraphy 1 year after the onset of KHE and/or KMP in 13 patients. In 8 patients with lymphedema, extremity swelling was evident in the presence of KHE and/or KMP. In all patients with lymphedema, a unilateral extremity was affected, along with ipsilateral KHE. Most (84.6%) patients reported moderate lymphedema. Lymphedema was more common in patients with larger (≥ 10 cm) and mixed lesions involving the extremities (P < 0.01). A history of KMP and sirolimus treatment were not predictors of lymphedema (P > 0.05). Overall, 76.9% of patients received sirolimus treatment after referral, including 53.8% who presented extremity swelling before referral. Seven (53.8%) patients received compression therapy. Five (38.5%) patients reported lymphedema-associated decreased range of motion at the last follow-up. CONCLUSIONS Chronic lymphedema is a common sequela of KHE and can occur independently of KMP and sirolimus treatment. Patients with large and mixed KHE involving extremities should be closely monitored for this disabling complication.
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Affiliation(s)
- Yi Ji
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, 610041, China.
| | - Siyuan Chen
- Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University, #37# Guo-Xue-Xiang, Chengdu, 610041, China.
| | - Chuncao Xia
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, 610041, China
| | - Jiangyuan Zhou
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, 610041, China
| | - Xian Jiang
- Department of Dermatology, West China Hospital of Sichuan University, Chengdu, 610041, China
| | - Xuewen Xu
- Department of Burn and Plastic Surgery, West China Hospital of Sichuan University, Chengdu, 610041, China
| | - Kaiying Yang
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, 610041, China
| | - Xuepeng Zhang
- Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University, #37# Guo-Xue-Xiang, Chengdu, 610041, China
| | - Feiteng Kong
- Department of Pediatric Surgery, Sichuan Women and Children's Hospital, Chengdu, 610045, China
| | - Guoyan Lu
- Pediatric Intensive Care Unit, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
| | - Yongbo Zhang
- Department of Pediatric Surgery, Chengdu Women and Children's Central Hospital, Chengdu, 610031, China
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47
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Abstract
Vascular anomalies, comprised of vascular tumors and malformations, are frequently associated with coagulopathy. Recognition of and familiarity with these vascular anomaly-associated hematologic abnormalities prior to surgery or interventional procedures is essential for pre-operative pre-operative planning. Complicated coagulopathies present within the framework of either Kasabach-Merritt phenomenon (KMP) or localized intravascular coagulopathy (LIC), and their management benefits from the expertise of a hematologist for optimal intra- and peri‑operative care. Furthermore, with the recent broadening of understanding of vascular anomalies and the addition of new classification sub-groups, distinctions of these two classic coagulopathy phenotypes have been recognized. This review summarizes the main features of these coagulopathies, described according to their vascular anomaly type, highlighting clinical aspects relevant to surgical management.
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Affiliation(s)
- Kiersten W Ricci
- Hemangioma and Vascular Malformation Center, Division of Hematology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, MLC 7015, Cincinnati 45229, OH, United States.
| | - Leonardo R Brandão
- The Hospital for Sick Children, Division of Haematology-Oncology, Toronto, Ontario, Canada
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48
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Chandrakantan A, Bryant BE, Hensch L, Adler AC. Anesthetic considerations for patients with the Kasabach-Merritt phenomenon. Paediatr Anaesth 2020; 30:1155-1156. [PMID: 32777122 DOI: 10.1111/pan.13992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 07/29/2020] [Accepted: 08/05/2020] [Indexed: 11/28/2022]
Affiliation(s)
- Arvind Chandrakantan
- Department of Anesthesiology, Perioperative and Pain Medicine, Texas Children's Hospital, Houston, Texas.,Baylor College of Medicine, Houston, Texas
| | | | - Lisa Hensch
- Baylor College of Medicine, Houston, Texas.,Department of Pathology & Immunology, Texas Children's Hospital, Houston, Texas
| | - Adam C Adler
- Department of Anesthesiology, Perioperative and Pain Medicine, Texas Children's Hospital, Houston, Texas.,Baylor College of Medicine, Houston, Texas
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49
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Yang Y, Guo Z, Wang Z, Luo L, Chen Y. Successful management of a pregnant woman with Kasabach-Merritt syndrome and preeclampsia: A case report. Medicine (Baltimore) 2020; 99:e21198. [PMID: 32664166 PMCID: PMC7360294 DOI: 10.1097/md.0000000000021198] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION Kasabach-Merritt Syndrome (KMS) is an extremely rare disease in adults, which lead to consumptive coagulopathy characterized by severe hypofibrinogenemia and thrombocytopenia. PATIENT CONCERNS:: a 25-year-old Chinese pregnant women complicated by preeclampsia and KMS presented with refractory postpartum hemorrhage and incision bleeding after cesarean section. DIAGNOSIS The diagnosis of KMS was made based on clinical manifestation of Kaposiform Hemangioendothelioma, severe hypofibrinogenemia and thrombocytopenia. INTERVENTIONS After a poor response to massive blood products transfusion for 1 week, corticosteroid treatment was initiated for 3 days. OUTCOMES The patient reached a normal platelet count and a mild anemia within 4 weeks. Two months later, all laboratory values had returned to normal, and the incision was healing well. CONCLUSION Pregnancy complicated by preeclampsia and surgery may have contributions for the development of Kasabach-Merritt syndrome. Corticosteroid is indicated in the episode of acute Kasabach-Merritt syndrome after the failure of massive blood transfusion.
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Affiliation(s)
- Yi Yang
- Center of Reproductive Medicine and Center of Prenatal Diagnosis
| | | | - Zhenpeng Wang
- Department of Gynecologic Oncologic, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Lili Luo
- Center of Reproductive Medicine and Center of Prenatal Diagnosis
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50
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Tangled Up in Red Cells: A Large Liver Mass with Intravascular Hemolysis. Dig Dis Sci 2020; 65:1960-1963. [PMID: 32394332 DOI: 10.1007/s10620-020-06311-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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