RESUMEN
RATIONALE: Intimal sarcoma of inferior vena cava (IVC) is a rare soft tissue sarcoma with no typical symptoms and specific imaging features in the early stage, and there is a lack of standardized treatment and methods. PATIENT CONCERNS: A 54-year-old female patient presented to Fenghua District People's Hospital with a post-active cough and hemoptysis and was subsequently referred to our hospital. DIAGNOSES: The patient was pathologically diagnosed as intimal sarcoma of IVC complicating multiple intrapulmonary metastases. Chest CT revealed left lung malignant tumor with multiple intrapulmonary metastases; while enhanced upper abdominal CT showed cancer embolus of IVC with extension to right atrium and bilateral renal veins. Besides, hematoxylin and eosin staining suggested intimal sarcoma of veins. Immunohistochemical staining showed positivity for PD-L1, Ki-67, CD31, Desmin and ERG. INTERVENTIONS: The patient initially received GT chemotherapy (gemcitabine injectionâ +â docetaxel). Then, immunotherapy (tislelizumab) was added based on the results of genetic testing (TP53 gene mutation). OUTCOMES: The disease was stabilized after receiving the treatment. LESSONS: Given the lack of characteristic clinical manifestations in patients with intimal sarcoma of IVC, imaging examination combined with immunohistochemical index were helpful for diagnosis of intimal sarcoma of IVC. Furthermore, the combination of tislelizumab and GT chemotherapy was feasible in such patients with positive PD-L1 expression and TP53 mutation.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Sarcoma , Vena Cava Inferior , Humanos , Femenino , Persona de Mediana Edad , Vena Cava Inferior/patología , Sarcoma/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias Vasculares/tratamiento farmacológico , Neoplasias Vasculares/patología , Neoplasias Vasculares/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Gemcitabina , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Desoxicitidina/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/patologíaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Anciano , Humanos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/diagnóstico , Síndrome , Neoplasias Vasculares/complicaciones , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/tratamiento farmacológico , Vasoconstricción/efectos de los fármacosRESUMEN
OBJECTIVES: To investigate independent factors for the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of diffuse malignant peritoneal mesothelioma (DMPM). METHODS: The clinical database of 110 DMPM patients treated with CRS + HIPEC at our hospital was retrospectively analyzed. Independent prognostic factors were screened using univariate and multivariate analyses and the safety of the perioperative period was evaluated based on adverse events. RESULTS: Among the 110 patients with DMPM, 34 (30.9%) had a peritoneal cancer index (PCI) < 20 and 76 (69.1%) had PCI ≥20; 59 (53.6%) patients achieved completeness of cytoreduction (CC) 0/1 and 51 (46.4%) cases achieved CC 2/3. At the median follow-up of 43.3 (95%CI: 37.3-49.4) months, 48 (43.6%) patients were still alive and 62 (56.4%) patients died. The median overall survival was 32.6 months. Serious adverse events (SAEs) occurred in 41 patients (37.3%) and the perioperative mortality rate was 2.7%. Univariate analysis identified nine prognostic factors: Karnofsky performance status score, perioperative tumor markers, PCI, red blood cell infusion, pathological type, vascular tumor emboli, lymphatic metastasis, Ki-67 index, and perioperative SAEs (all p < 0.05). Multivariate analysis identified four independent prognostic factors: pathological type (p = 0.007), vascular tumor emboli (p = 0.044), Ki-67 index (p = 0.044), and SAEs (p = 0.004). CONCLUSIONS: CRS + HIPEC for DMPM treatment resulted in prolonged survival with acceptable safety. Tumor pathology and SAEs are key factors for successful CRS + HIPEC.
Asunto(s)
Hipertermia Inducida , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneales , Neoplasias Vasculares , China , Procedimientos Quirúrgicos de Citorreducción/métodos , Humanos , Hipertermia Inducida/métodos , Quimioterapia Intraperitoneal Hipertérmica , Antígeno Ki-67 , Mesotelioma/tratamiento farmacológico , Mesotelioma/cirugía , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/cirugía , Estudios Retrospectivos , Neoplasias Vasculares/tratamiento farmacológicoRESUMEN
Intravascular large B-cell lymphoma is a rare disease of the large B cells characterized by selective growth in the lumina of small vessels in systemic organs. Since first reported in 1959, the difficulty of obtaining sufficient tumor cells from biopsy specimens has hampered the elucidation of its underlying biology. Recent progress using xenograft models and plasma cell-free DNA has uncovered genetic features that are similar to those of activated B-cell type diffuse large B-cell lymphoma, including MYD88 and CD79B mutations and frequent alterations in immune check point-related genes such as PD-L1 and PD-L2. Given the improvement in clinical outcomes and a higher risk of secondary central nervous system (CNS) involvement in the rituximab era, a phase 2 trial of R-CHOP combined with high-dose methotrexate and intrathecal chemotherapy as a CNS-oriented therapy has been conducted. This trial, the PRIMEUR-IVL study, has displayed good progression-free survival and a low cumulative incidence of secondary CNS involvement. Long-term follow-up within this trial is still ongoing. Further understanding of the pathophysiology of the disease and improvements in clinical outcomes are still needed.
Asunto(s)
Linfoma de Células B Grandes Difuso , Neoplasias Vasculares , Antimetabolitos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/genética , Puntos de Control del Ciclo Celular/genética , Neoplasias del Sistema Nervioso Central/prevención & control , Ensayos Clínicos Fase II como Asunto , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Predicción , Xenoinjertos , Humanos , Inyecciones Espinales , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Trasplante de Neoplasias , Prednisona/uso terapéutico , Proteína 2 Ligando de Muerte Celular Programada 1/genética , Supervivencia sin Progresión , Rituximab/uso terapéutico , Neoplasias Vasculares/diagnóstico por imagen , Neoplasias Vasculares/tratamiento farmacológico , Neoplasias Vasculares/genética , Neoplasias Vasculares/patología , Vincristina/uso terapéuticoAsunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso/cirugía , Neoplasias Vasculares/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Consolidación , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Persona de Mediana Edad , Rituximab/uso terapéutico , Trasplante Autólogo , Resultado del Tratamiento , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/tratamiento farmacológico , Neoplasias Vasculares/patologíaRESUMEN
INTRODUCTION: Infantile hemangioma (IH) is a common vascular tumor in children. It is reported that IHs are associated with immunochemical markers such as vascular endothelial growth factor (VEGF)-A, glucose transporter isoform 1 (GLUT1), and insulin-like growth factor-2 (IGF-2). MATERIAL AND METHODS: This cross-sectional study focused on pediatric patients with IH. A total of 46 patients (mean age 14.2±21.9 months) with IH and 45 healthy controls (mean age 21.8±15.08 months) were enrolled. Demographic data, clinical findings, and laboratory parameters were recorded. Blood samples were collected. Serum GLUT1, IGF-2, VEGF-A, fibroblast growth factor 1 (FGF1), and angiopoietin 2 levels were assessed by enzyme-linked immunosorbent assay. RESULTS: Serum GLUT1, IGF-2, and VEGF-A levels were significantly higher in patients with IH than in healthy controls (8.80±4.07pg/mL vs. 5.66±4.34pg/mL, 281.10±84.12pg/mL vs. 234.19±75.38pg/mL, 1196.99±389.34pg/mL vs. 996.99±349.16pg/mL, respectively, p=0.026, p=0.030, and p=0.036). Serum GLUT1, IGF-2, and VEGF-A levels in patients with complicated hemangioma were significantly higher than in healthy controls (9.69±3.94pg/mL vs. 5.66±4.34pg/mL, 289.94±83.18pg/mL vs. 234.19±75.38pg/mL, 1276.22±388.24pg/mL vs. 996.99±349.16pg/mL, respectively, p=0.017, p=0.022, and p=0.011). Serum GLUT1, IGF-2, and VEGF-A levels in patients with hemangioma receiving propranolol treatment were significantly higher than in healthy controls. Serum FGF1 levels were higher in patients with IH, complicated hemangioma, and hemangioma receiving propranolol treatment than in healthy controls but the difference was not statistically significantly. CONCLUSION: Serum GLUT1, IGF-2, and VEGF-A levels were positively correlated with disease severity in patients with hemangioma, for example, in complicated hemangioma and hemangioma requiring propranolol treatment. However, further research on larger and different age subgroups is warranted to assess these markers.
Asunto(s)
Angiopoyetina 2/sangre , Factor 1 de Crecimiento de Fibroblastos/sangre , Transportador de Glucosa de Tipo 1/sangre , Hemangioma/tratamiento farmacológico , Factor II del Crecimiento Similar a la Insulina/análisis , Propranolol/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/sangre , Neoplasias Vasculares/tratamiento farmacológico , Angiopoyetina 2/uso terapéutico , Biomarcadores/sangre , Niño , Preescolar , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Factor 1 de Crecimiento de Fibroblastos/uso terapéutico , Hemangioma/sangre , Hemangioma/patología , Humanos , Lactante , Masculino , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Neoplasias Vasculares/sangre , Neoplasias Vasculares/patologíaRESUMEN
BACKGROUND AND OBJECTIVES: Caval leiomyosarcomas (cLMS) are rare soft tissue sarcomas historically associated with high recurrence rates and poor prognosis. While radical resection remains the mainstay of therapy for cLMS, new systemic therapies have presented opportunities for multimodality treatment. We examined the clinical outcomes of patients with cLMS treated with modern, multimodality approaches, and compared their outcomes to those of patients with noncaval retroperitoneal LMS (ncLMS). METHODS: A retrospective, single-institution review identified all patients diagnosed with primary retroperitoneal LMS from 2012 to 2018. Radiographic and pathologic review distinguished patients with cLMS and ncLMS. Standard clinicopathologic variables and response to chemotherapy (when applicable) were analyzed. Primary endpoints were overall (OS) and progression-free survival (PFS). RESULTS: Eleven patients with cLMS were identified. Median tumor size was 7.5 cm (IQR, 5.0-14.3 cm); all patients had Stage II/III disease. Seven patients received neoadjuvant chemotherapy. Nine cLMS patients underwent R0/R1 resection; two did not complete resection. Six patients received adjuvant systemic therapy. Twenty patients with ncLMS were treated during the same period. No statistical intergroup differences were noted in tumor size, pathologic grade, stage, or resection margin status. Patients with ncLMS were less likely to receive neoadjuvant (10% vs. 64%) and adjuvant chemotherapy (30% vs. 55%). Two-year OS (81% vs. 78%; p = NS) and PFS (55% vs. 46%; p = NS) were comparable between cLMS and ncLMS patients. CONCLUSIONS: Multimodality treatment with systemic therapy and aggressive surgical resection may achieve equivalent survival outcomes for patients with cLMS versus similar ncLMS. We recommend that all patients with cLMS be evaluated for multidisciplinary treatment. Genomic and proteomic expression profiling may identify novel or targetable mutations.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leiomiosarcoma/tratamiento farmacológico , Leiomiosarcoma/cirugía , Neoplasias Retroperitoneales/tratamiento farmacológico , Neoplasias Retroperitoneales/cirugía , Neoplasias Vasculares/tratamiento farmacológico , Neoplasias Vasculares/cirugía , Vena Cava Inferior/patología , Anticuerpos Monoclonales/administración & dosificación , Estudios de Cohortes , Dacarbazina/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Leiomiosarcoma/genética , Leiomiosarcoma/patología , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias Retroperitoneales/genética , Neoplasias Retroperitoneales/patología , Estudios Retrospectivos , Neoplasias Vasculares/genética , Neoplasias Vasculares/patología , Vena Cava Inferior/cirugíaRESUMEN
PURPOSE OF REVIEW: Superficial vascular anomalies are a heterogeneous group of malformative and tumoral lesions, developed from various types of abnormal lymphatic and/or blood vessels. They are mostly benign but their clinical evolution can lead to dramatic cosmetic concern, functional impairment and even life-threatening conditions. Until recently, treatments relied on invasive procedures such as embotherapy/sclerotherapy and/or surgery. Recent molecular findings pave the way of new medical therapies. RECENT FINDINGS: Two main signaling pathways PI3K-AKT-mTOR and RAS-MAPK-ERK are now identified to encounter for the causative pathogenic genetic variants of most vascular anomalies. Involved genes are also responsible for several common neoplasms for which targeted therapies are already available or under development. Repurposing treatment strategy is considered for vascular anomalies treatment with promising results. SUMMARY: The mTOR inhibitor sirolimus is the most used targeted therapy so far but new molecules are tested currently.
Asunto(s)
Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/uso terapéutico , Animales , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Terapia Molecular Dirigida , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias Vasculares/congénito , Neoplasias Vasculares/tratamiento farmacológico , Neoplasias Vasculares/metabolismo , Proteínas ras/metabolismoRESUMEN
BACKGROUND: Metastatic germ cell cancer of the testis is characterized by favorable prognosis since effective treatment methods are available even in cases of extensive disease. Retroperitoneal masses frequently encroach major blood vessels requiring a vascular intervention usually performed in association with the post-chemotherapy retroperitoneal lymph node dissection (RPLND). Reported clinical case describes a successful pre-treatment endovascular surgery for abdominal aortic rupture allowing for full-dose systemic chemotherapy administration, and subsequent radical surgical intervention at primary tumor site as well as metastatic retroperitoneal lymph node dissection including the reconstruction of inferior caval vein. CASE PRESENTATION: Patient presented with left-sided testicular tumor and voluminous retroperitoneal mass with vascular involvement. Soon after the patient had been admitted for the first cycle of cisplatin-based chemotherapy, computed tomographic angiography (CTA) revealed a dorsal aortic wall rupture with active extravasation and irregular pseudoaneurysmatic dilatation of the aorta below the leak area. Retroperitoneal intratumoral hemorrhage associated with the bilateral iliac venous thrombosis required an endovascular repair procedure of infrarenal abdominal aorta. CONCLUSIONS: Following the successful endovascular aortic repair 3 cycles of BEP (bleomycin, etoposide, cisplatin) regimen were administered with subsequent delayed left radical orchiectomy and RPLND associated with vena cava inferior (VCI) resection. Reconstruction of VCI was originally not deemed necessary as collateral blood flow appeared sufficient, however, intraoperative complications resulted in the need for unilateral VCI reconstruction, using the interposed bypass between right common iliac vein and infrarenal segment of VCI. Histopathologic examination of the attained specimen detected no vital cancer structures. The patient remains disease-free 18 months after the RPLND.
Asunto(s)
Rotura de la Aorta/cirugía , Procedimientos Endovasculares/métodos , Hemorragia/cirugía , Neoplasias de Células Germinales y Embrionarias , Neoplasias Retroperitoneales , Neoplasias Testiculares , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/patología , Aorta Abdominal/cirugía , Rotura de la Aorta/diagnóstico por imagen , Rotura de la Aorta/etiología , Rotura de la Aorta/patología , Bleomicina/administración & dosificación , Cisplatino/administración & dosificación , Angiografía por Tomografía Computarizada , Etopósido/administración & dosificación , Hemorragia/diagnóstico por imagen , Hemorragia/etiología , Humanos , Vena Ilíaca , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/diagnóstico por imagen , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/secundario , Neoplasias de Células Germinales y Embrionarias/cirugía , Orquiectomía , Neoplasias Retroperitoneales/diagnóstico por imagen , Neoplasias Retroperitoneales/tratamiento farmacológico , Neoplasias Retroperitoneales/secundario , Neoplasias Retroperitoneales/cirugía , Neoplasias Testiculares/diagnóstico por imagen , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/patología , Neoplasias Testiculares/cirugía , Neoplasias Vasculares/diagnóstico por imagen , Neoplasias Vasculares/tratamiento farmacológico , Neoplasias Vasculares/secundario , Neoplasias Vasculares/cirugía , Vena Cava Inferior/cirugía , Trombosis de la Vena/cirugíaRESUMEN
BACKGROUND: Hemangiondothelioma is a rare vascular tumor that can occur in the bone. Temporal bone involvement has been reported extremely rare in the literature. CASE: Radiological examination of a one-year-old girl who was admitted due to facial paralysis revealed vascular tumor of the temporal bone and Galen vein aneurysm. Pathological examination showed retiform hemangioendothelioma. She was treated with propranolol, prednisolone, vincristine, and endovascular embolization followed by oral sirolimus. With sirolimus treatment, a partial response was obtained first, then the tumor remained stable and sirolimus treatment was discontinued. No progression was observed in the disease after discontinuation of treatment. CONCLUSION: In this article, a case of hemangioendothelioma originating from the temporal bone is discussed in the light of other case reports in the literature.
Asunto(s)
Hemangioendotelioma , Neoplasias Vasculares , Femenino , Hemangioendotelioma/diagnóstico , Hemangioendotelioma/tratamiento farmacológico , Humanos , Lactante , Sirolimus , Hueso Temporal , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/tratamiento farmacológico , VincristinaRESUMEN
We present a case of primary pulmonary arterial sarcoma (PPAS) treated with endostatin (endostar) injection and radiotherapy discuss the diagnosis, clinical manifestations, and pathology of PPAS. The patient complained of cough with sputum, fever, and chest pain with hemoptysis. Numerous nodules were observed in the computed tomography (CT) scan. The patient was diagnosed with pulmonary embolism (PE) by computed tomography pulmonary angiography (CTPA). The pathology and immunohistochemistry results indicated soft tissue sarcomas, indicative of angiosarcoma. The nodules shrunk after 5 courses of endostatin and one course of radiotherapy, as determined in the CT scan. Primary pulmonary arterial sarcoma is clinically rare with nonspecific symptoms. Hence, it can be easily misdiagnosed as PE, and biopsy must be performed for confirmation. Current treatment methods, including surgery, are limited. Therefore, administration of endostatin injection combined with other therapies may be an alternative treatment methods.
Asunto(s)
Endostatinas/administración & dosificación , Arteria Pulmonar , Proteínas Recombinantes/administración & dosificación , Sarcoma/tratamiento farmacológico , Sarcoma/radioterapia , Neoplasias Vasculares/tratamiento farmacológico , Neoplasias Vasculares/radioterapia , Adulto , Terapia Combinada , Diagnóstico Diferencial , Errores Diagnósticos/prevención & control , Humanos , Inyecciones Intraarteriales , Masculino , Embolia Pulmonar , Sarcoma/diagnóstico , Sarcoma/patología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/patologíaRESUMEN
A case of primary pulmonary arterial sarcoma (PPAS) treated with Endostar injection and radiotherapy and discuss the diagnosis, clinical characteristics, and pathology of PPAS. The patient complained of cough, sputum, fever, and chest pain with hemoptysis. Numerous nodules were seen in the computed tomography scan. The patient was diagnosed as pulmonary embolism (PE) by computed tomography pulmonary angiography. The pathology and immunohistochemistry results indicated soft tissue sarcomas, indicative of angiosarcoma. The nodules shrunk after 5 courses of endostatin and one course of radiotherapy, as seen by CT scan. Therefore, PPAS is clinically rare with nonspecific symptoms. Hence, it can be easily misdiagnosed as PE, biopsy for confirmation. Current treatment is limited and includes surgery. Hence, endostatin injection combined with other therapy may be an alternative treatment.
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Endostatinas/administración & dosificación , Hemangiosarcoma/tratamiento farmacológico , Hemangiosarcoma/radioterapia , Arteria Pulmonar , Proteínas Recombinantes/administración & dosificación , Neoplasias Vasculares/tratamiento farmacológico , Neoplasias Vasculares/radioterapia , Adulto , Terapia Combinada , Angiografía por Tomografía Computarizada , Diagnóstico Diferencial , Hemangiosarcoma/diagnóstico por imagen , Humanos , Inyecciones Intraarteriales , Masculino , Arteria Pulmonar/diagnóstico por imagen , Embolia Pulmonar , Resultado del Tratamiento , Neoplasias Vasculares/diagnóstico por imagenRESUMEN
This is an extremely rare reported case of intravascular large B-cell lymphoma (IVLBCL) presenting with acute hemorrhages and numerous microbleeds. An 80-year-old man presented with consciousness disturbances after convulsion. Computed tomography revealed multiple hemorrhages, and susceptibility-weighted imaging (SWI) demonstrated numerous microbleeds. Brain biopsy showed CD20-positive cells in small vessels; accordingly, IVLBCL was diagnosed. IVLBCL should be considered as a differential diagnosis in multiple cerebral hemorrhages and microbleeds.
Asunto(s)
Hemorragia Cerebral/etiología , Hematoma/etiología , Linfoma de Células B/complicaciones , Neoplasias Vasculares/complicaciones , Anciano de 80 o más Años , Antígenos CD20/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores de Tumor/análisis , Biopsia , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/patología , Ciclofosfamida/administración & dosificación , Imagen de Difusión por Resonancia Magnética , Doxorrubicina/administración & dosificación , Hematoma/diagnóstico por imagen , Hematoma/patología , Humanos , Inmunohistoquímica , Linfoma de Células B/diagnóstico por imagen , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/patología , Masculino , Prednisona/administración & dosificación , Rituximab/administración & dosificación , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Neoplasias Vasculares/diagnóstico por imagen , Neoplasias Vasculares/tratamiento farmacológico , Neoplasias Vasculares/patología , Vincristina/administración & dosificaciónAsunto(s)
Leiomiomatosis/patología , Neoplasias Vasculares/patología , Administración Oral , Adulto , Femenino , Humanos , Leiomiomatosis/diagnóstico , Leiomiomatosis/tratamiento farmacológico , Progestinas/administración & dosificación , Hemorragia Uterina/etiología , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/tratamiento farmacológicoRESUMEN
BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease for which there is no available standard treatment. We aimed to ascertain the safety and activity of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) with high-dose methotrexate and intrathecal chemotherapy as CNS-oriented therapy for patients with previously untreated IVLBCL. METHODS: PRIMEUR-IVL is a multicentre, single-arm, phase 2 trial at 22 hospitals in Japan. Eligible patients had untreated histologically confirmed IVLBCL, were aged 20-79 years, had an Eastern Cooperative Group performance status of 0-3, and had no apparent CNS involvement at diagnosis. Patients received three cycles of R-CHOP (rituximab 375 mg/m2 intravenously on day 1 [except cycle one, which was on day 8]; cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2·0 mg] intravenously on day 1 of cycle one and day 2 of cycles two and three; and prednisolone 100 mg/day orally on days 1-5 of cycle one and days 2-6 of cycles two and three) followed by two cycles of rituximab with high-dose methotrexate (3·5 g/m2 intravenously on day 2 of cycles four and five) every 2 weeks and three additional cycles of R-CHOP. Intrathecal chemotherapy (methotrexate 15 mg, cytarabine 40 mg, and prednisolone 10 mg) was administered four times during the R-CHOP phase. The primary endpoint was 2-year progression-free survival. Efficacy analyses were done in all enrolled patients; safety analyses were done in all enrolled and treated patients. The trial is registered in the UMIN Clinical Trials Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165); the trial is ongoing for long-term follow-up. FINDINGS: Between June 16, 2011, and July 21, 2016, 38 patients were enrolled, of whom 37 were eligible; one patient was excluded because of a history of testicular lymphoma. Median follow-up was 3·9 years (IQR 2·5-5·5). 2-year progression-free survival was 76% (95% CI 58-87). The most frequent adverse events of grade 3-4 were neutropenia and leucocytopenia, which were reported in all 38 (100%) patients. Serious adverse events were hypokalaemia, febrile neutropenia with hypotension, hypertension, and intracerebral haemorrhage (reported in one [3%] patient each). No treatment-related deaths occurred during protocol treatment. INTERPRETATION: R-CHOP combined with rituximab and high-dose methotrexate plus intrathecal chemotherapy is a safe and active treatment for patients with IVLBCL without apparent CNS involvement at diagnosis, and this regimen warrants future investigation. FUNDING: The Japan Agency for Medical Research and Development, the Center for Supporting Hematology-Oncology Trials, and the National Cancer Center.
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Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Metotrexato/administración & dosificación , Neoplasias Vasculares/tratamiento farmacológico , Adulto , Anciano , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Estudios Prospectivos , Rituximab/administración & dosificación , Vincristina/administración & dosificación , Adulto JovenAsunto(s)
Linfoma de Células B Grandes Difuso/diagnóstico , Isquemia de la Médula Espinal/diagnóstico , Médula Espinal/diagnóstico por imagen , Neoplasias Vasculares/diagnóstico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Hipoestesia/diagnóstico , Hipoestesia/etiología , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Paraparesia/diagnóstico , Paraparesia/etiología , Médula Espinal/irrigación sanguínea , Isquemia de la Médula Espinal/etiología , Isquemia de la Médula Espinal/fisiopatología , Neoplasias Vasculares/complicaciones , Neoplasias Vasculares/tratamiento farmacológicoRESUMEN
OBJECTIVE: The management of vascular anomalies is complex and requires a multidisciplinary team with a combination of medical, surgical, and intervention treatments. Medical treatment is limited and has conflicting results. Off-label use of mammalian target of rapamycin inhibitors shows promising results. The objective of this study was to systematically evaluate the literature published about the efficacy and safety of sirolimus in the treatment of vascular anomalies. METHODS: A systematic review of the published literature was conducted using the PubMed database and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: There were 73 articles included: 2 randomized controlled studies, 2 nonrandomized prospective studies, and 69 retrospective case reports and case series. In total, 373 patients were included. Sirolimus was administered topically to 56 patients and orally to 317 patients. Sirolimus was highly effective in the treatment of vascular tumors associated with Kasabach-Merritt phenomenon (95.5% of the patients clinically improved and 93% had normalization of coagulopathy), venous malformations (size reduction was observed in 88.9% of patients), and lymphatic malformations (clinical improvement in 94.9% of patients). Topical sirolimus results were conflicting. Arteriovenous malformations were not improved by sirolimus. CONCLUSIONS: Low-level evidence suggests that sirolimus can improve the prognosis of vascular anomalies, most notably vascular tumors associated with life-threatening coagulopathy and venous and lymphatic malformations. Further research is needed to establish the benefits of sirolimus in the management of vascular anomalies.
Asunto(s)
Fármacos Cardiovasculares/administración & dosificación , Sirolimus/administración & dosificación , Malformaciones Vasculares/tratamiento farmacológico , Neoplasias Vasculares/tratamiento farmacológico , Administración Oral , Administración Tópica , Fármacos Cardiovasculares/efectos adversos , Femenino , Humanos , Masculino , Uso Fuera de lo Indicado , Sirolimus/efectos adversos , Resultado del Tratamiento , Malformaciones Vasculares/diagnóstico por imagen , Malformaciones Vasculares/fisiopatología , Neoplasias Vasculares/diagnóstico por imagen , Neoplasias Vasculares/fisiopatologíaRESUMEN
Vascular anomalies (VAs) may be associated with significant morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of sirolimus (rapamycin) in the treatment of children and young adults with complicated VAs. A retrospective chart was created that included 19 patients treated with sirolimus for complicated VAs. Concurrently, a search of the PubMed database for VA cases treated with sirolimus was conducted. Descriptive analysis was performed and the efficiency rate of sirolimus was calculated. This retrospective study included 19 patients, 17 of whom were treated with oral sirolimus and 2 with topical sirolimus. Clinical improvement occurred in 15 patients (79%). One patient experienced near-complete resolution. Only 2 patients showed poor response and discontinued treatment. The literature review analysed 150 cases of VA treated with sirolimus. Sirolimus was efficient in 85% of cases, including 5 cases of complete resolution. Sirolimus appears to be an effective and safe treatment for children and young adults with complicated VAs.
Asunto(s)
Antineoplásicos/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Sirolimus/administración & dosificación , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Malformaciones Vasculares/tratamiento farmacológico , Neoplasias Vasculares/tratamiento farmacológico , Administración Cutánea , Administración Oral , Adolescente , Factores de Edad , Antineoplásicos/efectos adversos , Niño , Preescolar , Femenino , Humanos , Lactante , Israel , Masculino , Inhibidores de Proteínas Quinasas/efectos adversos , Inducción de Remisión , Estudios Retrospectivos , Transducción de Señal , Sirolimus/efectos adversos , Serina-Treonina Quinasas TOR/metabolismo , Factores de Tiempo , Resultado del Tratamiento , Malformaciones Vasculares/diagnóstico , Malformaciones Vasculares/enzimología , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/enzimología , Adulto JovenRESUMEN
Combretastatin A4-phosphate (CA4P) is an anti-vascular agent which selectively shuts down blood supply in tumours, resulting in extensive tumour necrosis. The aim of this study was to assess in vivo, non-invasive ultrasound techniques for the early evaluation of tumour perfusion following CA4P treatment of spontaneous tumours. Eight dogs that bore spontaneous tumours were enrolled and were subsequently treated with a single dose of intravenous CA4P. Perfusion of tumours was evaluated by power Doppler ultrasound (PDUS) pre-treatment (0 h), during the injection (10 min, 20 min, 30 min) and after CA4P infusion (24 and 72 h). Vascularity index (VI) of the tumour tissue was quantitatively analysed and accuracy was verified by correlation analysis with the results of immunohistochemical evaluation of microvessel density (MVD). Central and peripheral perfusion was evaluated by contrast-enhanced ultrasound (CEUS) pre-treatment and at 72 h post-treatment. Post-treatment, PDUS demonstrated a significant decrease in VI within 10 min of CA4P infusion. CEUS parameters demonstrated a significant decrease in blood velocity and volume in the central aspect of the tumour. Histology revealed a 4.4-fold reduction (p < 0.001, 95% CI [2.2,9.4]) in MVD and a 4.1-fold increase (p = 0.003, 95% CI [1.4,11.8]) in necrotic tumour tissue. A strong correlation between PDUS results and immunohistochemical results was found (Pearson R2 = 0.957, p < 0.001). Furthermore, the findings of PDUS were supported by the objective results of the CEUS analyses. These data suggest a role for ultrasound in real-time, non-invasive monitoring of tumour vascular response as an early indicator of CA4P treatment efficacy.