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.

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.

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.

Impaired integrin ß3 delays endothelial cell regeneration and contributes to arteriovenous graft failure in mice.

OBJECTIVE: Neointima formation is associated with stenosis and subsequent thrombosis in arteriovenous grafts (AVGs). A role of integrin ß3 in the neointima formation of AVGs remains poorly understood. APPROACH AND RESULTS: In integrin ß3(-/-) mice, we found significantly accelerated occlusion of AVGs compared with the wild-type mice. This is caused by the development of neointima and lack of endothelial regeneration. The latter is a direct consequence of impaired functions of circulating angiogenic cells (CACs) and platelets in integrin ß3(-/-) mice. Evidence suggests the involvement of platelet regulating CAC homing to and differentiation at graft sites via transforming growth factor-ß1 and Notch signaling pathway. First, CACs deficient of integrin ß3 impaired adhesion activity toward exposed subendothelium. Second, platelets from integrin ß3(-/-) mice failed to sufficiently stimulate CACs to differentiate into mature endothelial cells. Finally, we found that transforming growth factor-ß1 level was increased in platelets from integrin ß3(-/-) mice and resulted in enhanced Notch1 activation in CACs in AVGs. These results demonstrate that integrin ß3 is critical for endothelial cell homing and differentiation. The increased transforming growth factor-ß1 and Notch1 signaling mediates integrin ß3(-/-)-induced AVG occlusion. This accelerated occlusion of AVGs was reversed in integrin ß3(-/-) mice transplanted with the bone marrow from wild-type mice. CONCLUSIONS: Our results suggest that boosting integrin ß3 function in the endothelial cells and platelets could prevent neointima and thrombosis in AVGs.

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.

Postmortem CT morphometry of great vessels with regard to the cause of death for investigating terminal circulatory status in forensic autopsy.

Postmortem CT (PM-CT) is useful to investigate the viscera in situ before opening the body cavities at autopsy. The present study involved a virtual morphometric analysis of thoracic and abdominal great vessels with regard to the cause of death as a possible index of terminal circulatory status in forensic autopsy cases, using PM-CT data of forensic autopsy cases within 3 days postmortem (n = 93). Perimeters and cross-sectional areas of the aorta and vena cava depended on the age and/or gender of subjects; however, when the vessel flattening index (vFI) was calculated as the ratio of the cross-sectional area (a) to the estimated circle area having the same perimeter (l), using the formula vFI = 4πa/l(2), the vFI showed distinct differences among the causes of death without significant postmortem time dependence. The index was low for each vessel in fatal bleeding, while the vFI of the abdominal aorta and inferior vena cava was low in hyperthermia (heatstroke), but higher in drowning, hypothermia (cold exposure) and sudden cardiac death. These CT findings provide quantitative data as supplementary indicators to reinforce autopsy findings for interpreting terminal circulatory status.

Heterotaxy syndrome with malrotation of the gut and interrupted vena cava does not preclude safe procurement of multivisceral graft.

We report the first successful procurement and transplantation of a multivisceral graft from a pediatric donor with polysplenic heterotaxy syndrome, including intestinal malrotation, midline liver with left-sided gallbladder and an interrupted inferior vena cava with azygous continuation. Procurement of the graft presented a surgical challenge in the presence of above anomalies. Modified approach to standard organ procurement and minor technical adaptation enabled successful transplantation. In an era of severe organ shortage of pediatric multivisceral grafts, a valuable organ offer should not lightly be declined for reasons of anatomic imperfections that might be overcome.

Optimizing 18F-FDG PET/CT imaging of vessel wall inflammation: the impact of 18F-FDG circulation time, injected dose, uptake parameters, and fasting blood glucose levels.

PURPOSE: (18)F-FDG PET is increasingly used for imaging of vessel wall inflammation. However, limited data are available on the impact of methodological variables, i.e. prescan fasting glucose, FDG circulation time and injected FDG dose, and of different FDG uptake parameters, in vascular FDG PET imaging. METHODS: Included in the study were 195 patients who underwent vascular FDG PET/CT of the aorta and the carotids. Arterial standardized uptake values (meanSUVmax), target-to-background ratios (meanTBRmax) and FDG blood-pool activity in the superior vena cava (SVC) and the jugular veins (JV) were quantified. Vascular FDG uptake values classified according to the tertiles of prescan fasting glucose levels, the FDG circulation time, and the injected FDG dose were compared using ANOVA. Multivariate regression analyses were performed to identify the potential impact of all variables described on the arterial and blood-pool FDG uptake. RESULTS: Tertile analyses revealed FDG circulation times of about 2.5 h and prescan glucose levels of less than 7.0 mmol/l, showing a favorable relationship between arterial and blood-pool FDG uptake. FDG circulation times showed negative associations with aortic meanSUVmax values as well as SVC and JV FDG blood-pool activity, but positive correlations with aortic and carotid meanTBRmax values. Prescan glucose levels were negatively associated with aortic and carotid meanTBRmax and carotid meanSUVmax values, but were positively correlated with SVC blood-pool uptake. The injected FDG dose failed to show any significant association with vascular FDG uptake. CONCLUSION: FDG circulation times and prescan blood glucose levels significantly affect FDG uptake in the aortic and carotid walls and may bias the results of image interpretation in patients undergoing vascular FDG PET/CT. The injected FDG dose was less critical. Therefore, circulation times of about 2.5 h and prescan glucose levels less than 7.0 mmol/l should be preferred in this setting.

Toll-like receptor 4 is involved in human and mouse vein graft remodeling, and local gene silencing reduces vein graft disease in hypercholesterolemic APOE*3Leiden mice.

OBJECTIVE: The goal of this study was to explore the role of Toll-like receptor 4 (TLR4) in vein graft remodeling and disease. METHODS AND RESULTS: First, expression of TLR4 was analyzed in freshly isolated human saphenous veins (huSV), in freshly isolated huSV ex vivo perfused in an extracorporeal circulation, or in huSV used as coronary vein grafts. Marked induction of focal TLR4 expression was observed in perfused fresh huSV. Moreover, TLR4 was abundantly present in lesions in fresh huSV or in intimal hyperplasia in coronary vein grafts. Second, mouse venous bypass grafting was performed. In grafts of hypercholesterolemic APOE*3Leiden mice, increased TLR4 mRNA and protein was detected over time by reverse transcription-polymerase chain reaction and immunohistochemistry. Furthermore, the local presence of the endogenous TLR4 ligands heat shock protein 60, high-mobility group box 1, tenascin-C, and biglycan in the grafts was demonstrated. TLR4 deficiency in C3H-Tlr4LPS-d (LPS indicates lipopolysaccharide) mice resulted in 48±12% less vein graft wall thickening (P=0.04) than in Balb/c controls. Moreover, local TLR4 gene silencing in hypercholesterolemic APOE*3Leiden mice using lentiviral short hairpin RNA against TLR4 administered perivascularly around vein grafts led to a 44±13% reduction of vessel wall thickening compared with controls (P=0.0059). CONCLUSIONS: These results indicate that TLR4 is involved in vein graft remodeling and can be used as a local therapeutic target against vein graft disease.

Pulmonary artery extension of uterine leiomyoma.

Intravenous leiomyomatosis is a rare tumor arising either from a uterine leiomyoma or from uterine vessel walls with extension into venous channels. Although intravenous leiomyomatosis is considered histologically "benign," intrusion to the cardiac chambers is almost malignant given its possibility for destruction of heart valves, extending into the pulmonary vasculature, and embolizing. We report a patient with an intravenous leiomyomatosis progressing through the left iliac vein, along the entire vena cava up to the right cardiac chambers and branches of pulmonary artery (PA), and review the literature on this subject.

[Prevention of spinal hypotension associated with cesarean section by aortocaval compression--left 15 degree table tilt vs. uterine displacement by hand].

Women undergoing elective cesarean delivery were randomly assigned to receive a spinal anesthesia in either the semi-lateral (group SL) position or the supine position with uterine displacement (group UD). After spinal injection, group SL patients were turned to a 15 degrees left lateral supine position, and group UD patients had uterine displacement by hand. Ephedrine 4 mg i.v. was administered in case of nausea/vomiting and/or hypotension, defined as a systolic blood pressure below 100 mmHg. Arm systolic arterial pressure and leg systolic arterial pressure were similar in both groups, but the lowest leg systolic arterial pressure until delivery was significantly lower in the UD group (P < 0.05). Mean ephedrine requirement was significantly less in the SL group (P < 0.05). Apgar scores did not differ, but umbilical artery pH values were significantly higher in patients of the group SL (P < 0.01).

Incidence of and risk factors for iliocaval venous obstruction in patients with active or healed venous leg ulcers.

BACKGROUND: Iliocaval venous obstruction (ICVO) can be a significant contributor to venous hypertension in patients with advanced disease. The incidence of ICVO in patients with CEAP clinical class 5 and 6 disease has not been reported. In this study, we reviewed a series of patients with healed or active venous leg ulcers to determine the incidence of ICVO and the risk factors related to its occurrence. METHODS: Patients with CEAP clinical class 5 and 6 venous insufficiency underwent evaluation with duplex ultrasound scan to identify the presence of venous reflux in the deep and superficial systems and either computed tomography (CT) or magnetic resonance (MR) venography to identify ICVO. The venograms were evaluated by two separate examiners to calculate the percentage of obstruction in the iliocaval outflow tract. Demographics and risk factors related to venous disease were collected and examined for their association with severe ICVO. RESULTS: A total of 78 CEAP clinical class 5 and 6 patients evaluated with either a CT or MR venogram were retrospectively reviewed. The average patient age was 59.3 years and 53.4% were men. The ulcer affected the left lower extremity in 46% of cases and 50% of patients reported a medical history of deep vein thrombosis (DVT). Overall, 37% of imaging studies demonstrated ICVO of at least 50% and 23% had obstruction of >80%. Risk factors that were found to be independently associated with a significantly higher incidence of >80% ICVO included female gender (P = .023), a medical history of DVT (P = .035), and reflux in the deep venous system (P = .035). No limb with superficial venous reflux (SVR) alone was found to have ICVO >80%. CONCLUSIONS: ICVO is a frequent and underappreciated contributor to venous hypertension in patients with venous leg ulcers. Women and patients with a history of DVT or duplex scan-diagnosed deep venous reflux (DVR) have a higher incidence of outflow obstruction and should be routinely studied with CT or MR venography to allow correction in this high-risk group of patients.

Great vessel/cardiac extension and tumor embolism in pleuropulmonary blastoma: a report from the International Pleuropulmonary Blastoma Registry.

BACKGROUND: Types II and III pleuropulmonary blastoma (PPB) are aggressive sarcomas of lung and pleura in young children. Similar to cavoatrial extension of Wilms tumor, PPB may extend into thoracic great vessels and the heart and may involve both venous and arterial circulations and right and left cardiac chambers. Serious embolic complications occur. PROCEDURE: Review International PPB Registry databases and literature (1) for PPB cases with vascular/cardiac extension and (2) for neoadjuvant chemotherapy results in vascular extension cases. RESULTS: Among 179 Registry-confirmed and approximately 200 literature Type II and III PPB cases, 11 examples (approximately 3%) of great vessel/cardiac extension were identified; 1 case is presented in detail. Nine cases involved the left circulation, one the right and one both. Various radiographic techniques including echography, computed tomography and gated magnetic resonance imaging identified vascular tumor. Seven children had arterial embolic events: cerebrovascular accidents (six, including one femoral artery occlusion) and acute aortic occlusion (1). Six of these seven died from complications that may be attributed to vascular involvement. In three of four children with vascular involvement, neoadjuvant chemotherapy lessened the involvement; in one the effect could not be assessed. None of these four had embolic events. Effect on survival could not be assessed due to small numbers. CONCLUSIONS: Involvement of thoracic great vessels and the heart is a serious complication of PPB, with fatal embolic complications possible. Radiographic evaluation of the central circulation should be performed in children with suspected or diagnosed PPB to identify this complication.

Effect of matrix metalloproteinase-9 knockout on vein graft remodelling in mice.

Long-term success in vein grafting for bypassing arteries blocked by atherosclerosis is limited by migration and proliferation of smooth muscle cells to form a neointima. Matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9, are implicated in neointimal formation by freeing smooth muscle cells from the cell-matrix contacts that normally restrict migration. We investigated the role of MMP-9 in vein grafts directly, using knockout mice. Vein grafts in MMP-9(-/-) and wild-type mice had similar luminal and graft areas at 1, 4 and 8 weeks after engraftment, increasing with time. There was a relationship between the perimeter of the external elastic lamina and graft thickness (indicating graft remodelling) in MMP-9(-/-) mice at 1 week after surgery not apparent in control mice until later (r(2) = 0.933 for MMP-9(-/-) mice, r(2) = 0.040 for wild-type mice). Grafts in MMP-9(-/-) mice had 6-fold more pro- and active MMP-2 (p = 0.013, p = 0.026) than grafts in wild-type mice. Grafts from MMP-9(-/-) mice also had more collagen (p = 0.046 at 8 weeks), without any difference in cell number. Thus, while a lack of MMP-9 did not alter vein graft wall area or cellularity, grafts from MMP-9(-/-)mice accumulated more collagen and had earlier linear expansive remodelling, possibly due to an early compensatory increase in MMP-2.

In vivo suppression of vein graft disease by nonviral, electroporation-mediated, gene transfer of tissue inhibitor of metalloproteinase-1 linked to the amino terminal fragment of urokinase (TIMP-1.ATF), a cell-surface directed matrix metalloproteinase inhibitor.

BACKGROUND: Smooth muscle cell (SMC) migration and proliferation are important in the development of intimal hyperplasia, the major cause of vein graft failure. Proteases of the plasminogen activator (PA) system and of the matrix metalloproteinase (MMP) system are pivotal in extracellular matrix degradation and, by that, SMC migration. Previously, we demonstrated that inhibition of both protease systems simultaneously with viral gene delivery of the hybrid protein TIMP-1.ATF, consisting of the tissue inhibitor of metalloproteinase-1 (TIMP-1) and the receptor-binding amino terminal fragment (ATF) of urokinase, reduces SMC migration and neointima formation in an in vitro restenosis model using human saphenous vein cultures more efficiently than both protease systems separately. Because use of viral gene delivery is difficult in clinical application, this study used nonviral delivery of TIMP-1.ATF plasmid to reduce vein graft disease in a murine bypass model. Nonviral gene transfer by electroporation was used to avert major disadvantages of viral gene delivery, such as immune responses and short-term expression. METHODS: Plasmids encoding ATF, TIMP-1, TIMP-1.ATF, or luciferase, as a control, were injected and electroporated in both calf muscles of hypercholesterolemic apolipoprotein E3-Leiden (APOE*3Leiden) mice (n = 8). One day after electroporation, a venous interposition of a donor mouse was placed into the carotid artery of a recipient mouse. In this model, vein graft thickening develops with features of accelerated atherosclerosis. Vein grafts were harvested 4 weeks after electroporation and surgery, and histologic analysis of the vessel wall was performed. RESULTS: Electroporation-mediated overexpression of the plasmid vectors resulted in a prolonged expression of the transgenes and resulted in a significant reduction of vein graft thickening (ATF: 36% +/- 9%, TIMP-1: 49% +/- 5%, TIMP-1.ATF: 58% +/- 5%; P < .025). Although all constructs reduced vein graft thickening compared with the controls, the luminal area was best preserved in the TIMP-1.ATF-treated mice. CONCLUSION: Intramuscular electroporation of TIMP-1.ATF inhibits vein graft thickening in vein grafts in carotid arteries of hypercholesterolemic mice. Binding of TIMP-1.ATF hybrid protein to the u-PA receptor at the cell surface enhances the inhibitory effect of TIMP-1 on vein graft remodeling in vitro as well as in vivo and may be an effective strategy to prevent vein graft disease.

[The caudate hepatic lobe syndrome. Peculiarities of clinical course, surgical tactics].

Clinical and diagnostic peculiarities of the tumor affection of caudate hepatic lobe, which, by the sum of criteria, are divided on four stages of the caudate lobe syndrome, were discussed. The authors had proposed an optimal preoperative preparation and adequate surgical tactics, depending on the present stage.

CCR2-mediated antiinflammatory effects of endothelial tetrahydrobiopterin inhibit vascular injury-induced accelerated atherosclerosis.

BACKGROUND: Vascular injury results in loss of endothelial nitric oxide (NO), production of reactive oxygen species (ROS), and the initiation of an inflammatory response. Both NO and ROS modulate inflammation through redox-sensitive pathways. Tetrahydrobiopterin (BH4) is an essential cofactor for endothelial nitric oxide synthase (eNOS) that regulates enzymatic synthesis of either nitric oxide or ROS. We hypothesized that endothelial BH4 is an important regulator of inflammation and vascular remodeling. METHODS AND RESULTS: Endothelium-targeted overexpression of GTP cyclohydrolase 1 (GCH), the rate limiting enzyme in BH4 synthesis, increased levels of tetrahydrobiopterin (BH4), reduced endothelial superoxide, improved eNOS coupling, and reduced vein graft atherosclerosis in transgenic GCH/ApoE-KO mice compared to ApoE-KO controls. Immunohistochemistry using anti-MAC-3 and MAC-1 antibody staining revealed a marked reduction in vein graft macrophage content, as did RT-PCR expression of macrophage marker CD68 mRNA levels in GCH/ApoE-KO mice. When we investigated the potential mediators of this reduction, we discovered that mRNA and protein levels of MCP-1 (CCL2) but not RANTES (CCL5) were significantly reduced in GCH/ApoE-KO aortic tissue. Consistent with this finding we found a decrease in CCR2-mediated, but not CCR5-mediated, chemotaxis in vascular tissue and plasma samples from GCH/ApoE-KO animals. CONCLUSIONS: Increased endothelial BH4 reduces vein graft neointimal hyperplasia and atherosclerosis through a reduction in vascular inflammation. These findings highlight the importance of MCP-1/CCR2 signaling in the response to vascular injury and identify novel pathways linking endothelial BH4 to inflammation and vascular remodeling.

Orthotopic, but reversed implantation of the liver allograft in situs inversus totalis-a simple new approach to a difficult problem.

Situs inversus totalis is a rare congenital anomaly in which the heart and abdominal organs are oriented in a mirror image of normal. It provides a unique challenge as there is no established technique for liver transplantation in these patients. Employing two major alterations from our standard technique, a liver was transplanted in the left subphrenic space of a patient with situs inversus totalis. First, the liver was flipped 180 degrees from right to left (facing backward). Second, a reversed cavaplasty (anterior, not posterior, donor suprahepatic caval incision) was performed. Otherwise, it was standard, with end-to-end anastomoses of the portal vein, hepatic artery and bile duct. Three years after the entirely uneventful transplant, the recipient continues to enjoy the benefits of a normally functioning liver. The described technique prevented torsion, kinking and tension on the anastomosed structures by allowing the liver to sit naturally in an anatomical position in the left hepatic fossa. As it required no special measurements or maneuvers, the technique was easy to execute and required no donor liver size restrictions. This novel technique, with a reversed cavaplasty and a 180 degrees right-to-left flip of the liver into a left-sided hepatic fossa, may be ideal for situs inversus totalis.

Massive venous air embolism in the semi-sitting position during surgery for a cervical spinal cord tumor: anatomic and surgical pitfalls.

Although venous air embolism (VAE) in neurological surgery is mainly associated with posterior fossa procedures, this complication may also occur, with comparable severity, in the posterior cervical spine approach in patients who are semi-sitting. We report a patient with a massive VAE that occurred in the semi-sitting position during a posterior approach to an extended cervical-thoracic level (C3-T2) intramedullary tumor, which interrupted the surgical procedure. We discuss the possible causes of air embolism, the anatomic and pathogenetic mechanisms, treatment and preventive measures.