Leiomiosarcoma de vena cava metastásico con larga supervivencia: opciones terapéuticas / No disponible

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Critical Review of Large Animal Models for Central Deep Venous Thrombosis.

OBJECTIVE: To review the existing literature on large animal models of central venous thrombosis (CVT) and to evaluate its relevance in regard to the development and testing of dedicated therapeutics applicable to humans. METHODS: A systematic literature search was conducted in PubMed and Embase. Articles describing an in vivo experimental protocol of CVT in large animals, involving the iliac vein and/or the vena cava and/or the brachiocephalic vein, were included. The primary aim of the study, animal characteristics, experimental protocol, and thrombus evaluation were recorded. RESULTS: Thirty-eight papers describing more than 30 different protocols were included. Animals used were pigs (53%), dogs (21%), monkeys (24%), and cattle (3%). The median number of animals per study was 12. Animal sex, strain, and weight were missing in 18 studies (47%), seven studies (18%), and eight studies (21%), respectively. CVT was always induced by venous stasis: solely (55%), or in addition to hypercoagulability (37%) or endothelial damage (10%). The size of the vessel used for thrombus creation was measured in four studies (10%). Unexpected animal death occurred in nine studies (24%), ranging from 3% to 37% of the animals. Twenty-two studies (58%) in the acute phase and 31 studies in the chronic phase (82%) evaluated the presence or absence of the thrombus created, and its occlusive characteristic was reported, respectively, in five and 17 studies. Histological examination was performed in 24 studies (63%) with comparison to human thrombus in one study. CONCLUSION: This review showed advantages and weaknesses of the existing large animal models of CVT. Future models should insist on more rigour and consistency in reporting animal characteristics, as well as evaluating and comparing the thrombus created to human thrombus.

Massive deep venous thrombosis in a patient addicted to cocaine / Trombosis venosa profunda masiva en un paciente adicto a la cocaína

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Activated Endothelial TGFß1 Signaling Promotes Venous Thrombus Nonresolution in Mice Via Endothelin-1: Potential Role for Chronic Thromboembolic Pulmonary Hypertension.

RATIONALE: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by defective thrombus resolution, pulmonary artery obstruction, and vasculopathy. TGFß (transforming growth factor-ß) signaling mutations have been implicated in pulmonary arterial hypertension, whereas the role of TGFß in the pathophysiology of CTEPH is unknown. OBJECTIVE: To determine whether defective TGFß signaling in endothelial cells contributes to thrombus nonresolution and fibrosis. METHODS AND RESULTS: Venous thrombosis was induced by inferior vena cava ligation in mice with genetic deletion of TGFß1 in platelets (Plt.TGFß-KO) or TGFß type II receptors in endothelial cells (End.TGFßRII-KO). Pulmonary endarterectomy specimens from CTEPH patients were analyzed using immunohistochemistry. Primary human and mouse endothelial cells were studied using confocal microscopy, quantitative polymerase chain reaction, and Western blot. Absence of TGFß1 in platelets did not alter platelet number or function but was associated with faster venous thrombus resolution, whereas endothelial TGFßRII deletion resulted in larger, more fibrotic and higher vascularized venous thrombi. Increased circulating active TGFß1 levels, endothelial TGFßRI/ALK1 (activin receptor-like kinase), and TGFßRI/ALK5 expression were detected in End.TGFßRII-KO mice, and activated TGFß signaling was present in vessel-rich areas of CTEPH specimens. CTEPH-endothelial cells and murine endothelial cells lacking TGFßRII simultaneously expressed endothelial and mesenchymal markers and transcription factors regulating endothelial-to-mesenchymal transition, similar to TGFß1-stimulated endothelial cells. Mechanistically, increased endothelin-1 levels were detected in TGFßRII-KO endothelial cells, murine venous thrombi, or endarterectomy specimens and plasma of CTEPH patients, and endothelin-1 overexpression was prevented by inhibition of ALK5, and to a lesser extent of ALK1. ALK5 inhibition and endothelin receptor antagonization inhibited mesenchymal lineage conversion in TGFß1-exposed human and murine endothelial cells and improved venous thrombus resolution and pulmonary vaso-occlusions in End.TGFßRII-KO mice. CONCLUSIONS: Endothelial TGFß1 signaling via type I receptors and endothelin-1 contribute to mesenchymal lineage transition and thrombofibrosis, which were prevented by blocking endothelin receptors. Our findings may have relevant implications for the prevention and management of CTEPH.

Complete response of renal cell carcinoma vena cava tumor thrombus to neoadjuvant immunotherapy.

BACKGROUND: Clinically localized renal cell carcinoma is treated primarily with surgery followed by observation or adjuvant sunitinib in selected high-risk patients. The checkpoint inhibitor immunotherapeutic agents nivolumab and ipilimumab have recently shown a survival benefit in the first-line metastatic setting. To date, there have been no reports on the response of localized renal cancer to modern immunotherapy. We report a remarkable response of an advanced tumor thrombus to combined immunotherapy which facilitated curative-intent resection of the non-responding primary renal tumor. We characterized the tumor microenvironment within the responding and non-responding tumors. CASE PRESENTATION: A 54-year-old female was diagnosed with a locally advanced clear cell renal cell carcinoma with a level IV tumor thrombus of the vena cava. She was initially deemed unfit for surgical resection due to poor performance status. She underwent neoadjuvant immunotherapy with nivolumab and ipilimumab with a complete response of the vena cava and renal vein tumor thrombus, but had stable disease within her renal mass. She underwent complete surgical resection with negative margins and remains disease-free longer than 1 year after her diagnosis with no further systemic therapy. Notably, pathologic analysis showed a complete response within the vena cava and renal vein, but substantial viable cancer remained in the kidney. Multichannel immunofluorescence was performed and showed marked infiltration of immune cells including CD8+ T cells and Batf3+ dendritic cells in the thrombus, while the residual renal tumor showed a non-T cell-inflamed phenotype. CONCLUSIONS: Preoperative immunotherapy with nivolumab and ipilimumab for locally advanced clear cell renal cancer resulted in a complete response of an extensive vena cava tumor thrombus, which enabled curative-intent resection of a non-responding primary tumor. If validated in larger cohorts, preoperative immunotherapy for locally advanced renal cell carcinoma may ultimately impact surgical planning and long-term prognosis.

Transabdominal Intrapericardial Approach in Liver Transplantation for Unresectable Primary Hepatic Functioning Paraganglioma With Invasion Into Hepatic Veins and Suprahepatic Vena Cava: A Surgical and Anesthesia Management Challenge.

Primary hepatic functional paraganglioma is a rare form of extra-adrenal catecholamine-secreting tumor. Definitive treatment of functioning paraganglioma is challenging because of the critical location of the tumor frequently in close proximity to vital structures and risk of excessive catecholamine release during operative manipulation. We report the multidisciplinary management approach for a case of unresectable primary hepatic functional paraganglioma with invasion into the hepatic veins and suprahepatic vena cava. To our knowledge, this is the first report showing that orthotopic liver transplantation is curative for patients with unresectable primary hepatic paraganglioma. For locally advanced unresectable hepatic paraganglioma that involves the intrapericardial vena cava, a meticulous pre- and intraoperative medical management and transabdominal intrapericardial vascular control of the suprahepatic vena cava during orthotopic liver transplantation allows for complete extirpation of the tumor and achieves optimal outcome.

The Mouse Aortocaval Fistula Model with Intraluminal Drug Delivery.

The arteriovenous fistula (AVF) is the most common type of vascular access currently used for hemodialysis, but long-term outcomes remain poor in many patients; understanding the basic mechanisms of venous remodeling within the fistula environment is critical to improve our understanding of AVF maturation. In this chapter, we describe a method to create a murine aortocaval fistula that allows intraluminal drug delivery. This model reliably recapitulates human AVF maturation and therefore is a good consideration to study venous remodeling.

Histopathological abnormalities in the central arteries and veins of Fontan subjects.

OBJECTIVE: Fontan circulations have obligatory venous hypertension, depressed cardiac output and abnormal arterial elastance. Ventriculovascular coupling is known to be abnormal, but the underlying mechanisms are poorly defined. We aim to describe the histopathological features of vascular remodelling encountered in the central arteries and veins in the Fontan circulation as a possible underlying pathological representation of abnormal ventriculovascular coupling. METHODS: Postmortemvasculature (inferior vena cava (IVC), superior vena cava (SVC), pulmonary artery (PA), pulmonary vein (PV) and aorta) of 13 patients with a Fontan circulation (mean age 29.9 years, range 9.0-59.8 years) and 2 biventricular controls (ages 17.9 and 30.2 years) was examined. RESULTS: IVC and SVC: Eccentric and variable intimal fibromuscular proliferation occurred in 11 Fontan subjects. There was variable loss of medial smooth muscle bundles with reciprocal replacement with dense collagenous tissue.PA: Similar intimal fibromuscular proliferation was seen; however, these intimal changes were accompanied by medial thinning rather than expansion, medial myxoid degeneration and elastic alteration.PV: The PVs demonstrated intimal fibroproliferation and disorganisation of the muscular media.Aorta: The aortic lamina intima was thickened, with associated fibromuscular proliferation and elasticisation. There was also moderate lymphocytic inflammation in the aortic wall. CONCLUSIONS: Vascular architectural remodelling is common in Fontan patients. The central veins demonstrate profound changes of eccentric intimal expansion and smooth muscle replacement with collagen. The pulmonary demonstrated abnormal intimal proliferation, and aortic remodelling was characterised by intima lamina thickening and a moderate degree of aortic wall inflammation.

Fatal abdominal injuries in a bicycle-pedestrian collision - Reconstruction using multibody simulation.

Fatal bicycle-pedestrian collisions do not occur frequently and thus are rarely reported in literature. Pedestrians in bicycle-pedestrian accidents often sustain severe craniocerebral injuries caused by a collision induced fall with head impact on the road surface. We describe a case where a pedestrian crossing a road was hit by a bicycle. Hematomas of the left lower leg and of the left flank/abdomen were found to be caused by the primary impact. However, the fatal injuries were found to be contralateral with a rupture of the right renal pedicle, a rupture of the right lobe of the liver and a tear of the vena cava. Neither the bicycle impact nor a fall onto the road surface could cause these injuries. Multibody simulation (PC Crash 9.2) revealed entanglement between the bicyclist and the pedestrian followed by a contact interaction between the pedestrian laying on the road surface and the falling bicyclist. In forensic case work post-crash contact interactions between the bicyclist and the pedestrian should be considered as a potential source of severe injuries.

Novel microspheres reduce the formation of deep venous thrombosis and repair the vascular wall in a rat model.

: L-Arginine (L-arg), widely known as a substrate for endogenous nitric oxide synthesis, can improve endothelial function associated with the vasculature, inhibit platelet aggregation, and alter the activity of vascular smooth muscle cells. P-selectin is a membrane component of the platelet alpha-granule and the endothelial cell-specific Wiebel-Palade body that plays a central role in mediating interactions between platelets and both leukocytes and the endothelium. The experiment was designed to evaluate the effect of novel microspheres with L-arg targeting P-selectin on the formation of deep vein thrombosis and repair of vascular wall in a rat model. Thrombosis of the inferior vena cava was induced by applying a piece of filter paper (5 mm × 10 mm) saturated with 10% FeCl3 solution for 5 min. Targeted microspheres with L-arg, targeted microspheres with water, and saline were injected into the tail veins of the rats after 30 min of applying the filter paper saturated with 10% FeCl3 solution. The dry weight and length of the thrombus isolated from the inferior vena cava were significantly decreased in the group with L-arg in microsphere after 24 h. No significant differences in prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen among the groups were indicated. Images revealed that apoptosis in the vascular wall was less in the group injected with targeted microspheres with L-arg than in the other two groups at 1 and 8 d postsurgery. Meanwhile, cell proliferation was considerably excessive in the group injected with L-arg wrapped in targeted microspheres. Therefore, these novel microspheres could decrease the formation of thrombus in the early stages and in the subsequent periods of thrombosis. The microspheres can also enhance the vitality of impaired endothelial cells and reduce cell apoptosis.

Leiomiosarcoma de vena cava: A propósito de un caso / Leiomyosarcoma of the vena cava: a case report

Los sarcomas de grandes vasos son tumores raros, siendo el de cava uno de los más frecuentes. Presentamos un caso de una mujer de 50 años con un leiomiosarcoma de vena cava infrahepatica con afectación de la vena renal derecha. Se efectuó una resección en bloque incluyendo la vena cava desde la vena renal derecha con el riñón derecho hasta casi la bifurcación. Se realizó una reconstrucción con una prótesis de PTFE anillada. El resultado del estudio anatomopatológico fue de leiomiosarcoma de vena cava inferior. Este tipo de tumores precisan de un manejo multidisciplinar debido a su rareza y complejidad

Large vessel sarcomas are very rare, one of the most common is originated from the cava. We present a 50 year-old woman with a leiomyosarcoma of the infrahepatic vena cava encompassed the right renal vein. Excision of the tumor was performed in block, from the right renal vein to the bifurcation of the vena cava. A vascular reconstruction was performed with ringed PTFE prosthesis. The anatomopathological study revealed a leiomyosarcoma of the inferior vena cava. This tumors require a multidisciplinary approach due to they are very rare and complex

Contraindications and image-defined risk factors in laparoscopic resection of abdominal neuroblastoma.

PURPOSE: Minimally invasive surgery (MIS) has become widely accepted as a technique for abdominal neuroblastoma resection. However, the indications for MIS are still controversial. The aim of this study was to evaluate image-defined risk factors (IDRFs), complications, and oncologic outcomes in patients with abdominal neuroblastomas treated with MIS. METHODS: Between August 1998 and February 2016, MIS was planned for 20 children with abdominal neuroblastomas. Clinical data were retrospectively reviewed and compared between the IDRF-negative and IDRF-positive patients. RESULTS: On the basis of the latest IDRF guidelines, five patients were classified as IDRF-positive and four of them had operative complications; namely, partial infarction of the ipsilateral kidney or open conversion. Concerning the two patients who needed open conversion, the primary reason for open conversion was difficulty in dissection of the tumor from the vena cava. Preoperative images of these cases showed either deformation or subtotal encasement of the vena cava. Relapse occurred in three high-risk patients and in none of the low/intermediate-risk patients. No complication occurred in the IDRF-negative cases. CONCLUSIONS: IDRF-negative might be a good indication for MIS for abdominal neuroblastoma. However, deformation or subtotal encasement of the vena cava should be considered as IDRF-positive for MIS.

Unusual caudal vena cava thrombosis in a cow, secondary to Trueperella (Arcanobacterium) pyogenes infection / Rara trombose da veia cava caudal em bovino, secundária à infecção por Trueperella (Arcanobacterium) pyogenes

The caudal vena cava thrombosis, or pulmonary thromboembolism, in cattle is correlated with lactic acidosis, caused by diets rich in grains and highly fermentable, associated or not to septic situations, used in feedlots of beef or high-producing dairy cattle. This paper reports an unusual caudal vena cava thrombosis in a cow, secondary to Trueperella (Arcanobacterium) pyogenes infection, resulting in reduced milk production, anorexia, pale mucous membranes, ruminal atony, sternal decubitus and autoauscultation position. The heart was enlarged at necropsy, presence of clots distributed along the thoracic cavity, adherence between lung and pleura, abscesses, emphysema, petechiae, suffusions and ecchymosis in lungs, thickening of the caudal vena cava wall, hepatomegaly with chronic passive congestion ("nutmeg" aspect), and rumenitis. In lab, the actinomycete Trueperella (Arcanobacterium) pyogenes was isolated from liver and lung samples, probably resulting through dissemination of the bacteria of the rumen content, what reaffirms the opportunistic behavior of this actinomycete.(AU)

A síndrome da veia cava caudal ou tromboembolismo pulmonar bovino está relacionada à acidose láctica causada por dietas ricas em grãos e altamente fermentáveis, associados ou não a quadros sépticos, usadas em confinamentos de bovinos de corte ou para vacas leiteiras de alta produção. O presente artigo reporta caso raro de trombose da veia cava caudal em uma vaca, secundária a infecção por Trueperella (Arcanobacterium) pyogenes, apresentando reduzida produção de leite, anorexia, palidez de mucosas, atonia ruminal, decúbito esternal e posição de autoauscultação. À necrópsia observou-se coração aumentado de tamanho, coágulos distribuídos por toda cavidade torácica, aderência entre os pulmões e pleura, abscessos, enfisema, petéquias, sufusões, equimoses nos pulmões, espessamento da parede da veia cava caudal com trombo, hepatomegalia com congestão passiva crônica (aspecto de "noz moscada"), e ruminite. Em laboratório isolou-se o actinomiceto Trueperella (Arcanobacterium) pyogenes a partir de amostras de fígado e pulmão, provavelmente resultando da disseminação da bactéria proveniente do conteúdo ruminal, e reafirma o comportamento oportunista deste actinomiceto.(AU)

Valor pronóstico de la medición del diámetro y colapso inspiratorio de la vena cava inferior en la insuficiencia cardiaca aguda / Prognostic value of measuring the diameter and inspiratory collapse of the inferior vena cava in acute heart failure

Objetivos. Valorar la utilidad de la medición del diámetro y colapso de la vena cava inferior (VCI) en la insuficiencia cardiaca aguda (ICA), su relación con el pronóstico y con biomarcadores séricos de congestión. Pacientes y métodos. Estudio prospectivo observacional que incluyó 85 pacientes con ICA, clasificándolos en 4 grupos según el diámetro de la VCI (≤ o >20mm) y su colapso inspiratorio (< o ≥50%) al ingreso. Las variables de valoración fueron la mortalidad por IC y el evento combinado de mortalidad y reingreso por IC a los 180días. Resultados. El 24,7% de los pacientes presentó una VCI no dilatada y colapso ≥50% (grupo 1); el 20% VCI no dilatada y colapso <50% (grupo 2); el 5,9% VCI dilatada y colapso ≥50% (grupo 3); el 49,4% VCI dilatada y colapso <50% (grupo 4). La ausencia de colapso inspiratorio, pero no la dilatación de la VCI, se relacionó con concentraciones más elevadas de urea (p=0,007), creatinina (p=0,004), ácido úrico (p=0,008), NT-proBNP (p=0,009) y CA125 (p=0,005). La supervivencia libre de evento combinado a los 180días fue inferior en aquellos pacientes sin colapso de la VCI. Conclusiones. La dilatación y la ausencia de colapso inspiratorio de la VCI es frecuente en el contexto de la ICA. La ausencia de colapso inspiratorio de la VCI durante la fase de descompensación identifica un subgrupo de pacientes con peor pronóstico a los 6 meses (AU)

Objectives. To assess the utility of measuring the diameter and collapse of the inferior vena cava (IVC) in acute heart failure (AHF), its relationship with the prognosis and serum biomarkers of congestion. Patients and methods. An observational prospective study was conducted that included 85 patients with AHF, classifying them into 4 groups according to IVC diameter (≤ or >20mm) and inspiratory collapse (< or ≥50%) at admission. The endpoints were mortality due to HF and the combined event of mortality and readmission for HF at 180 days. Results. Some 24.7% of the patients had an undilated IVC and ≥50% collapse (group 1); 20% had an undilated IVC and <50% collapse (group 2), 5.9% had a dilated IVC and ≥50% collapse (group 3); and 49.4% had a dilated IVC and <50% collapse (group 4). The lack of inspiratory collapse but not IVC dilation was related to higher concentrations of urea (P=.007), creatinine (P=.004), uric acid (P=.008), NT-proBNP (P=.009) and CA125 (P=.005). Survival free of the combined event at 180 days was lower in those patients with no IVC collapse. Conclusions. Dilation and the absence of the inspiratory collapse of the IVC are common in the context of AHF. The lack of inspiratory collapse of the IVC during the decompensation phase identifies a subgroup of patients with poorer prognosis at 6 months (AU)

Systematic Review of Surgical Management of Nonmetastatic Renal Cell Carcinoma with Vena Caval Thrombus.

CONTEXT: Overall, 4-10% of patients with renal cell carcinoma (RCC) present with venous tumour thrombus. It is uncertain which surgical technique is best for these patients. Appraisal of outcomes with differing techniques would guide practice. OBJECTIVE: To systematically review relevant literature comparing the outcomes of different surgical therapies and approaches in treating vena caval thrombus (VCT) from nonmetastatic RCC. EVIDENCE ACQUISITION: Relevant databases (Medline, Embase, and the Cochrane Library) were searched to identify relevant comparative studies. Risk of bias and confounding assessments were performed. A narrative synthesis of the evidence was presented. EVIDENCE SYNTHESIS: The literature search identified 824 articles. Fourteen studies reporting on 2262 patients were included. No distinct surgical method was superior for the excision of VCT, although the method appeared to be dependent on tumour thrombus level. Minimal access techniques appeared to have better perioperative and recovery outcomes than traditional median sternotomy, but the impact on oncologic outcomes is unknown. Preoperative renal artery embolisation did not offer any oncologic benefits and instead resulted in significantly worse perioperative and recovery outcomes, including possibly higher perioperative mortality. The comparison of cardiopulmonary bypass versus no cardiopulmonary bypass showed no differences in oncologic outcomes. Overall, there were high risks of bias and confounding. CONCLUSIONS: The evidence base, although derived from retrospective case series and complemented by expert opinion, suggests that patients with nonmetastatic RCC and VCT and acceptable performance status should be considered for surgical intervention. Despite a robust review, the findings were associated with uncertainty due to the poor quality of primary studies available. The most efficacious surgical technique remains unclear. PATIENT SUMMARY: We examined the literature on the benefits of surgery to remove kidney cancers that have spread to neighbouring veins. The results suggest such surgery, although challenging and associated with high risk of complications, appears to be feasible and effective and should be contemplated for suitable patients if possible; however, many uncertainties remain due to the poor quality of the data.