UNLABELLED:Catheter angiography for early diagnosis of vascular complications in pediatric liver transplant yields excellent results but remains an extremely invasive examination for younger children, precluding its routine use. We assessed the efficacy of three-dimensional multislice computed tomographic angiography (3DCTA) as an alternative option in these patients. METHODS:Twenty children suspected of vascular complications on clinical grounds, laboratory findings, or Doppler ultrasound underwent 3DCTA between April 2000 and April 2003. Interventional procedures via conventional angiography were subsequently performed in 5 cases, thrombolytic therapy in 4, surgical in 1, and conservative treatment in 10. RESULTS:Two hepatic artery stenosis,1 hepatic artery thrombosis, 5 hepatic vein stenosis, 4 portal vein occlusion, 1 portal vein stenosis, and 7 non-vascular lesions were detected, all of which paralleled the findings of catheter angiography, Doppler ultrasound, and operations. The diagnostic accuracy for vascular complication was 90%. The sensitivity and specificity were 86.7% and 100%, respectively. The positive and negative predictive values were 100% and 71.4%, respectively. To date 19 patients are alive, with a median follow-up period of 24.8 months. In conclusion, 3DCTA is accurate and efficient in the identification of pathological vascular insults and offers essential information for major decision on further management of the vascular complications in pediatric recipients of liver transplant.

Living-related liver transplantation was developed in the context of deceased donor organ shortage, which is particularly acute for pediatric recipients. This retrospective study analyzes the surgical technique and complications in the first 100 pediatric liver transplantation using left segmental liver grafts from living donors, performed at Saint-Luc University Clinics between July 1993 and April 2002. Pre-operative evaluation in donors and recipients, analysis of the surgical technique, and postoperative complications were reviewed. After a median follow-up period of 2526 days, no donor mortality was encountered, with a minimal morbidity and no long-term sequelae. At one and five yr post-transplantation, the actuarial patient survival rates were 94% and 92%, the corresponding figures being 92% and 89% for graft survival. The incidences of portal vein and hepatic artery thromboses, and of biliary complications were 14%, 1%, and 27%, respectively. Living-related liver transplantation in children constitutes an efficient therapy for liver failure to face the increased demand for liver grafts. Donor morbidity was kept to acceptable incidence, and surgical technique in the recipient needs to be tailored to minimize postoperative complications.

Pediatric living donor liver transplantation (PLDLT) is a successful therapeutic option for children with chronic and acute liver disease. After early transplant results, many technical advancements were introduced in the field to reduce the rate of complications and improve survival. The aim of this study is to present the outcomes of 975 primary PLDLTs in 3 periods: initial practice (period 1, 29 patients, January 1995 to December 1999), second period (period 2, 331 patients, January 2000 to December 2009), and third period (period 3 [P3], 615 patients, January 2010 to September 2019). Among the technical refinements introduced in P3 are the use of hyperreduced left lateral segment grafts, abdominal wall prosthetic mesh closure, double hepatic artery anastomosis, and increased use of vascular grafts for portal vein reconstruction. The outcomes included significant reductions of hepatic artery thrombosis (HAT), early portal vein thrombosis (EPVT), and retransplantation, with better patient and graft survival in P3. Additional analyses showed that the factors independently associated with worse 90-day patient survival were HAT, EPVT, and increasing Pediatric End-Stage Liver Disease score. In conclusion, the introduction of technical refinements in P3, in addition to improvements in patient care, determined a reduction in EPVT, HAT, and retransplantation. Consequently, patient and graft survival rates increased in all time points studied.

PURPOSE:To analyze hepatic hemodynamic parameters detected by Doppler ultrasound (DU) of uncomplicated children with biliary atresia who underwent left lateral segment living donor liver transplantation (LLS-LDLT), explore its normal change trend over time and determine the normal reference interval. METHODS:We retrospectively involved the data from 227 biliary atresia patients (100 Males,127 Females). Hemodynamic parameters include peak systolic velocity (PSV), end-diastolic velocity (EDV), resistivity index (RI), and pulsation index (PI) of the hepatic artery (HA), portal vein velocity (PVV), portal vein flow (PVF) and hepatic vein velocity (HVV) during intra-operative and on the 1st, 3rd, 5th and 7th day after operation were collected. Repeated measures analysis of the variance and Friedman test were used to analyze the changing trend of hemodynamic parameters over time in the first week after the operation. RESULTS:PSV and EDV showed a similar changing tendency at one week after surgery, with an overall decrease-rise trend; RI and PI also changed similarly with an overall rise-decrease trend. The HVV and PVV at surgery were lower than at all time points after surgery. As for PVF, the value of POD5 was the highest and then decreased. Additionally, this study provided the normal reference interval of hemodynamic parameters for LLS-LDLT patients, which were PSV: 18.4-98.3 cm/s, EDV: 0-43.3 cm/s, RI: 0.41-1.0, PI: 0.51-2.0, PVV: 19.0-83.7 cm/s, HVV: 19.4-68.0 cm/s, and PVF:99.5-500.0 ml/min/100 g at intraoperation. Within the first postoperative week: PSV: 21.0-97.7 cm/s, EDV: 0-32.7 cm/s, RI: 0.47-1.0, PI: 0.62-2.0, PVV: 23.0-92.0 cm/s, HVV: 19.7-86.0 cm/s, and PVF: 100.0-513.0 ml/min/100 g. CONCLUSION:The hepatic hemodynamic of post-transplanted children detected by DU had specific changing trends and normal ranges, which provides valuable reference values for ultrasonologists and pediatric transplant clinicians.

The aim of the present investigation was to describe a new model of liver regeneration in growing rats with reduced portal flow. In addition, it was studied whether tacrolimus and insulin could have any pro-regenerative effect under such conditions. Ninety-five rats were divided into five groups: Group 1 (sham), abdominal incision without intervention; Group 2, 70% hepatectomy; Group 3, 70% hepatectomy + PV stenosis; Group 4, 70% hepatectomy + portal vein stenosis + insulin; and Group 5, 70% hepatectomy + portal vein stenosis + tacrolimus. The remnant liver lobes were harvested for analyses. The liver weight decreased in the PV stenosis group and it increased with the use of insulin and tacrolimus. The mitotic activity was higher in the hepatectomy, insulin and tacrolimus groups and this parameter was reduced by portal stenosis. Levels of interleukin 6 (IL-6) were higher in the hepatectomy group compared to the sham and PV stenosis groups. The expression of IL-6 and Ki67 was significantly increased in the insulin and tacrolimus groups compared to the portal stenosis group. A highly reproducible model was standardized to study liver regeneration with portal blood inflow reduction in weaning rats. It was demonstrated that insulin or tacrolimus administration may partially reverse the harmful effects of PV stenosis.

INTRODUCTION:Liver graft and patient survival in children have improved substantially over the years; nevertheless, graft-related complications persist as the most important risk factor for mortality and graft loss. Doppler ultrasound evaluation is routinely used after liver transplantation; however, there is no consensus defining normal values, timing or frequency of Doppler ultrasound postoperative evaluation. Identification of patients who require an intervention or change in postoperative management is therefore challenging. METHODS AND ANALYSIS:We will conduct a systematic review and meta-analysis to appraise and synthesise evidence describing Doppler ultrasound measurements and their association with graft complications in children who have received a liver transplant. We will search multiple databases: Ovid Medline, Embase, Wiley Cochrane Library, Web of Science-Science Citation Index Expanded, trial registry records and meeting abstracts using a combination of subject headings and keywords for liver transplantation, Doppler ultrasound and paediatric patients. All identified titles and abstracts of studies will be assessed for potential relevance. Selected studies will be retrieved and subjected to a second phase of screening, both selection phases will be done in duplicate by two independent reviewers, and discrepancies will be documented and resolved by a third reviewer. Data extraction will be done independently by two reviewers using a standardised data extraction form. Quality of evidence and risk of bias will be assessed, synthesised and pooled for meta-analysis if possible. We will perform a subgroup analysis if enough data are available. ETHICS AND DISSEMINATION:Strategies to disseminate our review include presenting in liver transplant review sessions, publishing in high-impact peer-reviewed medical journals, and presenting at national and international paediatric radiology and liver transplant meetings, conference presentations, events, courses and plain-language summaries. This knowledge will allow easier identification of patients with a higher risk of developing graft-related complications and could potentially improve patient and graft outcomes. We wish to disseminate our results to discover potential areas for future research and drive improved future practices and policies. Our target audience includes researchers, institutions, healthcare professionals, health system decision-makers, policy-makers and research funders community. TRIAL REGISTRATION NUMBER:CRD42019119986.

OBJECTIVE:To overcome the shortage of appropriate-sized whole liver grafts for children, technical variant liver transplantation has been practiced for decades. We perform a meta-analysis to compare the survival rates and incidence of surgical complications between pediatric whole liver transplantation and technical variant liver transplantation. METHODS:To identify relevant studies up to January 2014, we searched PubMed/Medline, Embase, and Cochrane library databases. The primary outcomes measured were patient and graft survival rates, and the secondary outcomes were the incidence of surgical complications. The outcomes were pooled using a fixed-effects model or random-effects model. RESULTS:The one-year, three-year, five-year patient survival rates and one-year, three-year graft survival rates were significantly higher in whole liver transplantation than technical variant liver transplantation (OR = 1.62, 1.90, 1.65, 1.78, and 1.62, respectively, p<0.05). There was no significant difference in five-year graft survival rate between the two groups (OR = 1.47, p = 0.10). The incidence of portal vein thrombosis and biliary complications were significantly lower in the whole liver transplantation group (OR = 0.45 and 0.42, both p<0.05). The incidence of hepatic artery thrombosis was comparable between the two groups (OR = 1.21, p = 0.61). CONCLUSIONS:Pediatric whole liver transplantation is associated with better outcomes than technical variant liver transplantation. Continuing efforts should be made to minimize surgical complications to improve the outcomes of technical variant liver transplantation.

Doppler ultrasonography is useful in monitoring intra-operative PV flow in LDLT. A retrospective cohort study included 550 pediatric recipients (<18 years) who underwent LDLT from October 2006 to August 2016 in our hospital. A total of 33 recipients (incidence 6%) were found to have insufficient intra-operative PV flow after PV reperfusion. The treatments included intra-operative stent placement (n=25), anticoagulation (n=3), thrombectomy and re-anastomosis (n=2), graft repositioning (n=1), collateral ligation (n=1), and replaced PV (n=1). The peak PV velocity, HAPSV, HARI, and HV velocity before and after the interventions were significantly improved 0(0,5.5) cm/s vs. 37.36±15.30 cm/s, 38.68±8.92 cm/s vs. 62.30±16.97 cm/s, 0.55±0.08 vs. 0.76±0.10, and 32.37±10.33 cm/s vs. 40.94±15.01 cm/s, respectively (P<.01). Insufficient PV flow and decreased HARI are two significant criteria indicating need for intra-operative PV management. Dramatic changes in the hepatic hemodynamics were detected after proper treatment. Immediate resolution of PV flow is feasible in pediatric LDLT.

Vascular complications continue to have a devastating effect on liver transplantation recipients, even though their nature, incidence, and outcome might have actually changed with increasing experience and proficiency in high-volume centers. The aim of this study was to analyze the trends observed in vascular complications with changing protocols in adult and pediatric living donor liver transplantation over 10 years in 2 time frames in terms of nature, incidence, and outcome. It is a retrospective analysis of 391 (group 1, January 2006 to December 2010) and 741 (group 2, January 2011 to October 2013) patients. With a minimum follow-up of 2 years, incidence of hepatic artery thrombosis (HAT) in adults has reduced significantly from 2.2% in group 1 to 0.5% in group 2 (P = 0.02). In group 2, nonsignificantly, more adult patients (75% with HAT) could be salvaged compared with only 25% patients in group 1 (P = 0.12). However, HAT in children had 100% mortality. Incidence of portal vein thrombosis (PVT) in complicated transplants in 2 eras remained the same (P = 0.2) and so has its mortality. The thrombosis rate of the neo-middle hepatic vein was significantly reduced in group 2 (P = 0.01). The incidence of HAT, particularly in adults, has decreased significantly though PVT has continued to puzzle surgeons in complicated transplants. In high-volume centers, increasing proficiency, technical modifications, early diagnosis, and multimodality of treatment is the key to decrease overall morbidity and mortality due to vascular complications. Liver Transplantation 23 457-464 2017 AASLD.

The effect of occlusive portal vein thrombosis (PVT) on the mortality of pediatric liver transplant candidates and recipients is poorly defined. Using standard multivariate techniques, we studied the relationship between PVT and waiting-list and posttransplant survival rates with data from the Scientific Registry of Transplant Recipients (September 2001 to December 2007). In all, 5087 liver transplant candidates and 3630 liver transplant recipients were evaluated during the period. PVT was found in 1.4% of the liver transplant candidates (n = 70) and in 3.7% of the liver transplant recipients (n = 136). PVT was not associated with increased wait-list mortality [hazard ratio (HR) = 1.1, 95% confidence interval (CI) = 0.5-2.4, P = 0.77]. Conversely, PVT patients had a significantly lower unadjusted survival rate in the posttransplant period (P = 0.01). PVT was independently associated with increased posttransplant mortality in multivariate models (30-day survival: HR = 2.9, 95% CI = 1.6-5.3, P = 0.001; overall survival: HR = 1.7, 95% CI = 1.1-2.4, P = 0.01). The presence of PVT in pediatric liver candidates was not associated with increased wait-list mortality but was clearly associated with posttransplant mortality, especially in the immediate postoperative period.

Vascular complications are a major cause of patient and graft loss after LTs. The aim of this study was to evaluate the effect of a multimodal perioperative strategy aimed at reducing the incidence of vascular complications. A total of 126 first isolated LTs-performed between November 2008 and December 2015-were retrospectively analyzed. A minimum follow-up period of 24 months was analyzable for 124/126 patients (98.4%). The aggressive preemptive strategy consisted of identifying and immediately managing any problem and any abnormality in the vascular flow, in any of the hepatic vessels, and at any time after the liver graft revascularization. As a result, with a median follow-up of 57 months (3-112 months), not a single graft has been lost from vascular or biliary problems. The actuarial 8-year graft survival is 96.5%. These results have shown that a combination of technical attention, medical prevention, an early diagnosis, and rapid interventions reduced the negative impact of vascular problems on the outcome of both grafts and patients.

After decades of dramatic surgical innovations in pediatric living donor liver transplantation (LDLT), LDLT for biliary atresia (BA) still poses various challenges. This study reviewed our experience with LDLT for children with post-Kasai BA and evaluated outcomes and prognostic factors. From 2005 to 2016, 168 post-Kasai BA LDLT patients were enrolled and divided into 3 groups by age. Patient characteristics and perioperative data were compared. Predictors of morbidity and mortality following LDLT were analyzed in 93 infants. Outcome was relatively worse in infants than older children, with overall survival at 1 and 5 years of 94.5% and 93.2%, respectively, and graft survival at 1 and 5 years of 91.1% each. Incidence of vascular complications was not significantly higher in infants. High Pediatric End-Stage Liver Disease (PELD) score (odds ratio [OR], 3.72; 95% confidence interval [CI], 1.30-10.67; P = 0.02) and portal vein (PV) hypoplasia (OR, 3.23; 95% CI, 1.10-9.52; P = 0.03) were independent risk factors for morbidity. Low weight-for-age z score (hazard ratio, 5.76; 95% CI, 1.05-31.47; P = 0.03) was identified as a significant risk factor for mortality after LDLT, but not age or absolute body weight (BW). Infants with BW deficit had a significantly smaller PV diameter (P = 0.005), greater blood loss (P = 0.001), and higher incidence of postoperative bacteremia (P = 0.01). In conclusion, high PELD score and PV hypoplasia were independent risk factors for morbidity, and BW deficit was associated with poor survival in infants with post-Kasai BA after LDLT. However, LDLT in these infants at the earliest possible time after referral is a feasible option with excellent patient survival in an experienced center. Liver Transplantation 23 1199-1209 2017 AASLD.

BACKGROUND AND PURPOSE:It is controversial whether small size recipient is associated with adverse outcome in liver transplantation. This study aims to evaluate the outcomes of pediatric liver transplantation according to body weight of recipients. METHODS:Liver transplant recipients (age <18years, from 1993 to 2011) were studied retrospectively. They were categorized according to the body size at the time of transplantation (A: <6kg; B: between 6kg to 10kg; C: >10kg). RESULTS:A total of 113 patients (83 LDLTs and 30 DDLTs) were studied. Thirteen (11.5%) belonged to group A, 56 (49.6%) belonged to group B, and 44 (38.9%) belonged to group C. The best graft and patient survivals were found in group A (Figs. 1 and 2), and none of the patients required re-laparotomy for general surgical complications, while 32 patients (32%) in groups B and C did. Regarding transplant-related complications, although group A patients had the highest incidence of biliary tract complications (38.5%, n=5), the incidence of vascular complications (hepatic artery: 7%, portal vein: 0%, hepatic vein: 0%) in this group was the lowest among the three groups. CONCLUSION:Outcomes of small-sized recipients are not inferior. Less technical-related vascular complications, which may lead to early graft loss, were observed. This could be patient-related (less advanced cirrhosis) or surgeon-related (additional attention paid).

BACKGROUND:Accurate diagnosis of portal vein (PV) stenosis by real-time and color Doppler US (CD-US) after segmental liver transplantation in children can decrease morbidity by avoiding unnecessary biopsy, PV hypertension, thrombosis and loss of the graft. OBJECTIVE:To evaluate CD-US parameters for the prediction of PV stenosis after segmental liver transplantation in children. MATERIALS AND METHODS:We retrospectively reviewed 61 CD-US examinations measuring the diameter at the PV anastomosis, velocities at the anastomosis (PV1) and in the segment proximal to the anastomosis (PV2), and the PV1/PV2 velocity ratio. The study group comprised patients with stenosis confirmed by angiography and the control group comprised patients with a good clinical outcome. RESULTS:PV stenosis was seen in 12 CD-US examinations. The mean PV diameter was smaller in the study group (2.6 mm versus 5.7 mm) and a PV diameter of <3.5 mm was highly predictive of stenosis (sensitivity 100%, specificity 91.8%). CONCLUSION:A PV diameter of <3.5 mm is a highly predictive CD-US parameter for the detection of hemodynamically significant stenosis on angiography.

PURPOSE:After undergoing the Kasai procedure for biliary atresia (BA), most patients develop severe splenomegaly that tends to be improved by liver transplantation. However, fluctuations in splenic volume long after transplantation remain to be elucidated. PATIENTS AND METHODS:Seventy-one consecutive patients who had undergone pediatric living donor liver transplantation (LDLT) for BA were followed up in our outpatient clinic for 5 years. They were classified into 3 groups according to their clinical outcomes: a good course group (GC, n = 41) who were maintained on only 1 or without an immunosuppressant, a liver dysfunction group (LD, n = 18) who were maintained on 2 or 3 types of immunosuppressants, and a vascular complication group (VC, n = 11). Splenic and hepatic volumes were calculated by computed tomography in 464 examinations and the values compared before and after the treatment, especially in the VC group. RESULTS:Splenic volume decreased exponentially in the GC group, with splenic volume to standard spleen volume ratio (SD) being 1.59 (0.33) 5 years after liver transplantation. Splenic volume to standard spleen volume ratios were greater in the VC and LD groups than in the GC group. Patients in the VC group with portal vein stenosis developed liver atrophy and splenomegaly, whereas those with hepatic vein stenosis developed hepatomegaly and splenomegaly. Interventional radiation therapy tended to improve the associated symptoms. CONCLUSIONS:Fluctuations in splenic volume long after pediatric LDLT for BA may reflect various clinical conditions. Evaluation of both splenic and hepatic volumes can facilitate understanding clinical conditions following pediatric LDLT.

Despite continued advancements in perioperative care for pediatric liver transplant (LT), graft-threatening vascular occlusion events including hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) remain a source of significant morbidity and mortality. Perioperative anticoagulation is commonly used for the prevention of HAT and PVT, but evidence-based guidelines are lacking. The goals of this survey were to determine the frequency of use of an anticoagulation protocol and to describe variation in anticoagulation practices among pediatric LT centers. The study consisted of an online survey distributed to members of SPLIT. The survey focused on institutional anticoagulation practices employed to reduce the incidence of graft and life-threatening vascular occlusion events. Responses were received from 31 of 39 SPLIT centers. All respondents report using anticoagulation after pediatric LT, and approximately 90% have institutional anticoagulation protocols. Subgroup analysis of high volume pediatric LT centers revealed similar variability in anticoagulation patterns. All participating SPLIT centers reported the use of post-transplant anticoagulation and nearly all use a protocol. However, there is marked variability in the type and dose of anticoagulation as well as the timing of initiation and duration of therapy across centers.

  This paper has the objective to evaluate retrospectively the long-term results of transhepatic treatment of PV stenoses after pediatric LT. During an eight-yr period, 15 children with PV stenoses underwent PTA with balloon dilation or stent placement in case of PTA failure after LT. Patients' body weights ranged from 9.3 to 46kg (mean, 15.5kg). PV patency was evaluated in the balloon dilation and in the stent placement groups. Technical and clinical successes were achieved in all cases with no complication. Eleven patients (11/15; 73.3%) were successfully treated by single balloon dilation. Four patients (4/15; 26.7%) needed stent placement. One patient was submitted to stent placement during the same procedure because of PTA failure. The other three developed clinical signs of portal hypertension because of PV restenoses two, eight, and twenty-eight months after the first PTA. They had to be submitted to a new procedure with stent placement. The follow-up time ranged from 3 to 8.1 yr (mean, 6.3 yr). In conclusion, transhepatic treatment of PV stenoses after pediatric LT with balloon dilation or stent placement demonstrated to be a safe and effective treatment that results in long-term patency.

Portal vein stenosis (PVS) after living donor liver transplantation (LDLT) is a serious complication that can lead to graft failure. Few studies of the diagnosis and treatment of late-onset (> or = 3 months after liver transplantation) PVS have been reported. One hundred thirty-three pediatric (median age 7.6 years, range 1.3-26.8 years) LDLT recipients were studied. The patients were followed by Doppler ultrasound (every 3 months) and multidetector helical computed tomography (once a year). Twelve patients were diagnosed with late-onset PVS 0.5-6.9 years after LDLT. All cases were successfully treated with balloon dilatation. Five cases required multiple treatments. Early diagnosis of late-onset PVS and interventional radiology therapy treatment may prevent graft loss.

The existing knowledge on anatomy of segmental branches of left portal vein (LPV) is limited. This study aims to describe the surgical anatomy and variations of LPV and its segmental branching pattern. Forty fresh cadaveric liver dissections were performed. The dissection of LPV was carried out from its emergence at the level of the portal vein bifurcation to its segmental branches penetrating the left hemiliver. LPV characteristics, the number, and situation of its segmental branches were recorded. LPV comprises two portions: a 28 ± 6.7 mm-long transverse portion (TPLPV) and a 34.9 ± 4.4 mm-long umbilical portion (UPLPV). Mean number of LPV branches to segments I, II, III, and IV was 2 ± 1 (1-6), 2 ± 1 (1-4), 2 ± 1 (1-5), and 8 ± 2 (4-14), respectively. A single large vein supplied segment II in 90% of the cases. Segment III constantly had one vein arising from the left horn of UPLPV with mean diameter of 5.9 ± 1.6 mm. Most of the veins to segment IV took origin from the right horn of UPLPV with a mean number of 5 ± 2 (2-8). Segmental veins arising from UPLPV and TPLPV and supplying segment IV were present in 90 and 45% of the cases respectively. Segmental veins arising from LPV are often multiple and variable in position. Detailed knowledge of these veins is mandatory in order successfully perform anatomical liver resections or monosegment graft harvest for pediatric liver transplantation. Clin. Anat. 31: 1122-1128, 2017. © 2017 Wiley Periodicals, Inc.

BACKGROUND:Portal vein (PV) complications in pediatric living donor liver transplantation (LDLT) are often asymptomatic in the early stages after transplantation and can be serious enough to lead to graft failure. There have been few reports on risk factors for PV complications in LDLT. The aim of this study is to investigate the influence of hepatic inflow upon PV complications and to predict patients at risk for these complications. MATERIAL/METHOD:From 1997 to 2008, 46 pediatric patients underwent LDLT at our center. Portal venous and hepatic arterial flows and PV diameter were analyzed. RESULTS:PV complications were identified in seven patients (15.2%) and occurred at a younger age and lower weight. As a result of appropriate treatment, none of the patients suffered graft failure. Analysis of the 46 patients and 27 patients under two yr of age identified smaller PV diameter in recipient and larger discrepancy of PV diameter as risk factors. Portal venous flow tended to be low, in contrast to hepatic arterial flow, which tended to be high. CONCLUSION:PV size strongly influences PV complications. Other factors such as younger age, low portal venous flow, and high hepatic arterial flow may be risk factors for PV complications.

There are few long-term outcome reports for interventional radiology (IVR) treatments for vascular and biliary complications following pediatric living donor liver transplantation (LDLT). Herein, we presented our institution's experience and investigated the efficacy and issues of long-term outcome with IVR treatments. Between May 2001 and September 2016, 279 pediatric LDLTs were performed. The median age at LDLT was 1.4 years old, and the median observation period was 8.2 years. All the biliary reconstructions at LDLT were hepaticojejunostomy. The IVR treatments were selected as endovascular, radiological, or endoscopic interventions. Post-transplant hepatic vein, portal vein, hepatic artery, and biliary complications were present in 7.9%, 14.0%, 5.4%, and 18.3%, respectively. IVR treatment was the first treatment option in 81.8%, 94.9%, 46.7%, and 94.1%, respectively. The recurrence and cure rates following IVR treatment were 42.1%, 21.1%, 44.4%, and 34.0% and 84.2%, 97.4%, 100%, and 88.0%, respectively. The graft survival rates in patients with and without post-transplant vascular and biliary complications were 94.4% and 90.6%, respectively (P = 0.522). The IVR treatments for vascular and biliary complications following pediatric LDLT are the first choice option. Although the recurrence following IVR treatment is a major problem and it is necessary to carefully perform long-term follow-up, IVR treatments have good treatment outcomes.

OBJECTIVE:To identify changes in demographics, outcomes, and risk factors for patient and graft loss in patients with biliary atresia undergoing liver transplantation since Pediatric End-Stage Liver Disease implementation (2002). STUDY DESIGN:Demographics and outcomes were compared between patients enrolled in the Society of Pediatric Liver Transplantation registry before (n = 547) and after (n = 1477) 2002. Kruskal-and χ Wallis tests identified significant differences between eras. Risk factors for patient and graft loss after 2002 were determined by Cox regression model analysis of time to event data. RESULTS:Significant patient differences after 2002 support increasing disease severity including more status 1 patients and those with a derived Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease score of greater than 30 awaiting transplant. Both patient and graft survival improved after 2002 from 90% to 97% and 81% to 90%, respectively (primary transplant; P < .0001). Significant differences in complications within 30 days included reduced relisting for transplant, rejection, culture-positive infection, repeat operation, hepatic artery thrombosis, portal vein thrombosis, and death/transplant before discharge. Multivariable analysis identified deceased technical variant vs whole graft and retransplantation predictive for patient death, hazard ratios of 4.041 and 8.308, respectively. Deceased technical variant vs whole graft (hazard ratio, 1.963) and donor age 0-5 months vs 1-17 years (hazard ratio, 5.525) were risk factors for graft loss. CONCLUSIONS:The overall outcomes of patients receiving liver transplantation for patients with biliary atresia have improved since 2002 despite evidence of increased disease severity at the time of transplant. Risk factors impacting post-transplant morbidity and mortality in patients with biliary atresia are now mainly surgical including donor variables.

PURPOSE:To evaluate the long-term efficacy of stent placement versus balloon angioplasty for portal vein (PV) stenosis in pediatric liver transplant (LT) recipients. MATERIALS AND METHODS:Fifty patients (<18 years old; median, 14 months) who underwent percutaneous transhepatic balloon angioplasty (n = 12), transhepatic stent placement (n = 18), or intraoperative transmesenteric stent placement (n = 20) between 1994 and 2015 were retrospectively analyzed. The median intervals from LT to percutaneous transhepatic angioplasty, stent, and intraoperative stent were 145 days (range, 27-2072), 98 days (range, 5-2289), and 0 days (range, 0-14), respectively. The primary study endpoint was the primary patency of each group. Secondary study endpoints included procedural complications, functional stent stenosis, and stent fractures. RESULTS:The median clinical follow-up periods were 81 months (range, 13-179), 118 months (range, 65-181), and 112 months (range, 47-168) in each group, respectively. In the angioplasty group, the 1-, 5-, and 10-year primary patency rates were all 75% ± 13%. The corresponding rates were all 100% in the percutaneous transhepatic stent group and 90% ± 7%, 90% ± 7%, and 85% ± 8%, respectively, in the intraoperative transmesenteric stent group (P = .103). Major procedural complications occurred in 4 patients, including 1 case with PV tear after percutaneous transhepatic post-stent angioplasty, and 3 cases with acute PV thrombosis after intraoperative transmesenteric stent. Functional stent stenosis and stent fractures occurred in 1 and 2 patients, respectively. CONCLUSIONS:No statistically significant difference was observed between the 3 groups in terms of the long-term primary patency rates. Therefore, angioplasty should be considered first to treat PV stenosis in pediatric LT recipients.

Portal vein complications after liver transplantation (LT) are serious complications that can lead to graft liver failure. Although the treatment of interventional radiology (IVR) by means of balloon dilatation for portal vein stenosis (PVS) after LT is an effective method, the high rate of recurrent PVS is an agonizing problem. Anticoagulant therapy for PVS is an important factor for preventing short-term recurrence following IVR, but no established regimen has been reported for the prevention of recurrent PVS following IVR. In our population of 197 pediatric patients who underwent living donor liver transplantation (LDLT), 22 patients (22/197, 11.2%) suffered PVS. In the 9 earliest patients, unfractionated heparin was the only anticoagulant therapy given following IVR. In the 13 more recent patients, 3-agent anticoagulant therapy using low-molecular-weight heparin, warfarin, and aspirin was employed. In the initial group of 9 patients, 5 patients (55.6%) suffered recurrent PVS and required repeat balloon dilatation. Among the 13 more recent patients, none experienced recurrent PVS (P = 0.002). In conclusion, our 3-agent anticoagulant therapy following IVR for PVS in pediatric LDLT can be an effective therapeutic strategy for preventing recurrent PVS.

BACKGROUND:SPLIT was founded in 1995 in order to collect comprehensive prospective data on pediatric liver transplantation, including waiting list data, transplant, and early and late outcomes. Since 2011, data collection of the current registry has been refined to focus on prospective data and outcomes only after transplant to serve as a foundation for the future development of targeted clinical studies. OBJECTIVE:To report the outcomes of the SPLIT registry from 2011 to 2018. METHODS:This is a multicenter, cross-sectional analysis characterizing patients transplanted and enrolled in the SPLIT registry between 2011 and 2018. All patients, <18 years of age, received a first liver-only, a combined liver-kidney, or a combined liver-pancreas transplant during this study period. RESULTS:A total of 1911 recipients from 39 participating centers in North America were registered. Indications included biliary atresia (38.5%), metabolic disease (19.1%), tumors (11.7%), and fulminant liver failure (11.5%). Greater than 50% of recipients were transplanted as either Status 1A/1B or with a MELD/PELD exception score. Incompatible transplants were performed in 4.1%. Kaplan-Meier estimates of 1-year patient and graft survival were 97.3% and 96.6%. First 30 days of surgical complications included reoperation (31.7%), hepatic artery thrombosis (6.3%), and portal vein thrombosis (3.2%). In the first 90 days, biliary tract complications were reported in 13.6%. Acute cellular rejection during first year was 34.7%. At 1 and 2 years of follow-up, 39.2% and 50.6% had normal liver tests on monotherapy (tacrolimus or sirolimus). Further surgical, survival, allograft function, and complications are detailed.

BACKGROUND:Endovascular intervention with stent placement to treat portal vein (PV) and hepatic vein (HV) stenosis after pediatric liver transplantation (LT) is still controversial in small children owing to the potential risk of functional stenosis after growth. The aim of this study is to evaluate the safety and efficacy of stent placement in this population. METHODS:Between 2004 and 2016, 6 children (all <3 years) received HV (n = 2) and PV (n = 4) stents placement among 46 pediatric LT patients at our institution. The clinical outcome and patency rate were followed. Morphologic changes of stents were assessed from plain films by a new index: the stent diameter ratio (SDR). RESULTS:The median age of the patients at LT was 8.9 months. The patency rate was 100% without functional stenosis during a median follow-up period of 65.5 months. The "stent growth" phenomenon was demonstrated by SDR with significant resolution of hourglass deformity 2 years after stent placement (p for trend <.001). CONCLUSION:Vascular stent placement is a safe and effective method for the management of PV and HV stenosis following pediatric LT because these stents will enlarge as children grow. TYPE OF STUDY:Case Series with no Comparison Group LEVEL OF EVIDENCE: Level IV.

Cirrhosis in adults is associated with modifications of systemic and liver hemodynamics, whereas little is known about the pediatric population. The aim of this work was to investigate whether alterations of hepatic and systemic hemodynamics were correlated with cirrhosis severity in children. The impact of hemodynamic findings on surgical management in pediatric living donor liver transplantation (LT) was evaluated. Liver and systemic hemodynamics were studied prospectively in 52 children (median age, 1 year; 33 with biliary atresia [BA]). The hemodynamics of native liver were studied preoperatively by Doppler ultrasound and intraoperatively using invasive flowmetry. Portosystemic gradient was invasively measured. Systemic hemodynamics were studied preoperatively by Doppler transthoracic echocardiography and intraoperatively by using transpulmonary thermodilution. Hemodynamic parameters were correlated with Pediatric End-Stage Liver Disease (PELD) score and the histological degree of fibrosis (collagen proportionate area [CPA]). Cirrhosis was associated with a 60% reduction of pretransplant total liver flow (n = 46; median, 36 mL/minute/100 g of liver) compared with noncirrhotic livers (n = 6; median, 86 mL/minute/100 g; P = 0.002). Total blood flow into the native liver was negatively correlated with PELD (P < 0.001) and liver CPA (P = 0.005). Median portosystemic gradient was 14.5 mm Hg in children with cirrhosis and positively correlated with PELD (P < 0.001). Portal vein (PV) hypoplasia was observed mainly in children with BA (P = 0.02). Systemic hemodynamics were not altered in our children with cirrhosis. Twenty-one children met the intraoperative criteria for PV reconstruction using a portoplasty technique during the LT procedure and had a smaller PV diameter at pretransplant Doppler ultrasound (median = 3.4 mm; P < 0.001). Cirrhosis in children appears also as a hemodynamic disease of the liver, correlated with cirrhosis severity. Surgical technique for PV reconstruction during LT was adapted accordingly. Liver Transplantation 23 1440-1450 2017 AASLD.

The aim of this report is to assess the rate of portal vein complications (PVCs), the success rate of treatment for PVCs and the prognosis of patients with PVCs for pediatric living donor liver transplantation (LDLT). Pre- and postoperative records of 521 pediatric LDLTs, using left-side grafts were retrospectively reviewed. The overall rate of PVC was 9%, with early PVC occurring in nine patients (1.7%) with a mortality rate of 67% and late PVC in 38 patients (7.3%). Fifteen of these patients with late PVC showed complete portal vein occlusion despite various treatments, and in six of them the graft was lost. Histological examination revealed fibrosis in portal areas in 13 patients, around the central veins associated with cholestasis in the parenchyma in 10, and hepatocyte ballooning in 12. Correction of portal vein flow or retransplantation is necessary for the rescue of patients with early PVCs. Graft loss in the long term may be high with the occurrence of liver failure or portal hypertension related causes, such as hepatopulmonary syndrome and gastrointestinal bleeding in patients with late PVCs. For the rescue of these patients, especially for patients with body weight < 6 kg, regular monitoring of portal vein flow is essential.

BACKGROUND AND OBJECTIVE:Portal vein (PV) complications are the most frequent vascular complications in pediatric liver transplant (LT). We hypothesized that pre-LT liver hemodynamic parameters and PV reconstruction technique could predict the risk of PV complications post-LT. METHODS:Three hundred seventy-three children had a primary LT. A detailed ultrasound study of the pre-LT native liver hemodynamics was available in 198 cases, with details of PV anastomosis available for 197 of these: end-to-end anastomosis (n = 146, 74%), interposition vein graft technique (n = 28, 14%), or portoplasty (latero-lateral anastomosis of vein graft and recipient PV) (n = 23, 12%). RESULTS:Overall 5-year patient survival rate was 90%. Among the 198 patients with pre-LT hemodynamic data, 79 (40%) had PV hypoplasia (diameter ≤4 mm), 64 (32%) had a pathological portal flow (nonhepatopetal flow), and 47 (24%) had an arterial resistance index (ARI) ≥1. Abnormal hemodynamics were mostly observed in biliary atresia (BA). Among these 3 parameters, only ARI ≥1 was significantly correlated with a higher rate of PV complications post-LT (P = 0.041). PV complication-free survival at 5 years were 91% for end-to-end anastomosis, 91% for portoplasty, and 62% for interposition vein graft technique (P = 0.002). At multivariate analysis, the use of an interposition vein graft was the only factor to be significantly associated with a higher rate of PV complications post-LT (P = 0.003). CONCLUSIONS:PV hypoplasia with liver hemodynamic disturbances was mainly observed in BA. Hepatic ARI ≥1 might be a good predictor of PV complications post-LT. Latero-lateral portoplasty seemed to provide the best results when end-to-end anastomosis is not feasible.

Portal vein thrombosis (PVT) occurs in ≤12% of pediatric recipients of liver transplantation (LT). Known complications of PVT include portal hypertension, allograft loss, and mortality. The management of PVT is varied. A single-center, case-control study of pediatric LT recipients with portal vein (PV) changes after LT was performed. Cases were categorized as early PVT (if PVT was detected within 30 days of transplantation) or late PVT (if PVT was detected more than 30 days after transplantation or if early PVT persisted beyond 30 days). Two non-PVT control patients were matched on the basis of the recipient weight, transplant indication, and allograft type to each patient with PVT. Thirty-two of the 415 LT recipients (7.7%) received 37 allografts and developed PVT. In comparison with control patients, a higher proportion of patients with PVT had PVT present before LT (13.3% versus 0%, P = 0.01). Patients with early PVT usually returned to the operating room, and 9 of 15 patients (60%) had PV flow restored. Patients with late PVT had lower white blood cell (4.9 [1000/μL] versus 6.8 [1000/μL], P < 0.01) and platelet counts (140 [1000/μL] versus 259 [1000/μL], P < 0.01), an elevated international normalized ratio (1.2 versus 1.0, P < 0.001), and more gastrointestinal bleeding (25% versus 8.3%, P = 0.03) compared to controls. Patients with PVT were also less frequently at the expected grade level (52% versus 88%, P < 0.001). The patient survival rates were 84%, 78%, and 78% and 91%, 84%, and 79% for cases and controls at 1, 5, and 10 years, respectively. The allograft survival rates were 90%, 80%, and 80% for cases and 94%, 89%, and 87% for controls at 1, 5, and 10 years, respectively. In conclusion, patients with early and late PVT had preserved allograft function, and there was no impact on mortality. Patients diagnosed with early PVT often underwent operative interventions with successful restoration of flow. Patients diagnosed with late PVT experienced variceal bleeding, and some required portosystemic shunting procedures. Academic delays were also more common. In late PVT, the clinical presentation dictates care because the optimal management algorithm has not yet been determined. Multi-institutional studies are needed to confirm these findings and improve patient outcomes.

PURPOSE:To evaluate technical and clinical success and report long-term outcomes of portal vein (PV) recanalization in pediatric orthotopic liver transplant (OLT) patients with chronic PV occlusion. MATERIALS AND METHODS:This is a retrospective review of 15 OLT patients (5 males) with chronic PV occlusion who underwent PV recanalization (33 procedures) between October 2011 and February 2018. Median age was 4.5 years (range, 1-16 years); median weight was 16.6 kg (range, 11.5-57.3 kg). Median time interval from OLT to first intervention was 3.25 years (range, 0.6-15.7 years). Clinical presentations included hypersplenism (n = 12), gastrointestinal bleeding (n = 9), and ascites (n = 3). One patient had incidental diagnosis of PV occlusion. Primary, primary-assisted, and secondary patency at 3, 6, 12, and 24 months were evaluated. RESULTS:Technically successful PV recanalization and reduction of PV pressure gradient to ≤ 5 mm Hg was performed in 13/15 patients (87%). Ten of 15 (67%) patients had successful recanalization with the first attempt. Clinical success, defined as improvement in signs and symptoms of portal hypertension, was achieved in 12/13 (92%) patients. Five of 33 (15%) major complications (Society of Interventional Radiology class C), including perisplenic hematoma (n = 2), hemoperitoneum (n = 2), and hepatic artery pseudo aneurysm (n = 1), were managed with pain medication and blood product replacement. Median follow-up was 22 months (range, 1-77 months). Median primary patency was 5 months. Primary patency at 3, 6, 12, and 24 months was 53.8%, 46.2%, 38.5%, and 30.8%, respectively. Primary-assisted patency was 84.6%, 76.9%, 53.8%, and 46.2%, respectively. Secondary patency was 92.3%, 84.6%, 53.8%, and 46.2%, respectively. CONCLUSIONS:PV recanalization is a safe and effective minimally invasive option in the management of chronic PV occlusion after pediatric OLT.

PURPOSE:Portal vein complications (PVC) after pediatric living donor liver transplantation (LDLT) have rarely been reported. We evaluated the long-term incidence and of the risk factors for PVC after pediatric LDLT. METHODS:From April 1997 to November 2008, 96 pediatric patients underwent LDLT using left lateral segments or left lobes. We investigated recipient factors, donor factors, and operative factors through medical records. The portal vein sizes in 96 recipients ranged from 2.7 mm to 13.0 mm (median=5.0 mm). Portal vein reconstruction was usually performed with the graft portal vein anastomosed to the bifurcation of the recipient right and left portal veins, the so-called "branch patch". RESULTS:PVC occurred in 11 patients (11.5%) including early PVC (n=3), late PVC (n=8). The disease-free survivals at 1, 5, and 10 years after LDLT were 94.7%, 88.7%, and 86.0%. Upon univariate analysis, a portal vein size<5 mm graft-to-recipient weight ratio (GRWR)>or=4%, transfusion volume>or=270 mL were significant risk factors for PVC. Body weight<8 kg and previous operative history tendes to be adverse for PVC. Upon multivariate analysis by Cox regression, portal vein size<5 mm was a highly significant factor for PVC after pediatric LDLT (hazard ratio=5.627, P=.027). CONCLUSION:The disease-free survival at 10 years after LDLT was 86.0%. If the recipient's portal vein size<5 mm received a large-for-size graft (GRWR>or=4%), it is important to observe by regular Doppler ultrasonography follow-up to detect PVC.

Relatively few pediatric donors are available in relation to the number of children waiting for a liver transplant. This limited number of pediatric donor livers leads to the use of adult livers, usually requiring more complex portal vein (PV) anastomoses. These anastomoses are complicated by differences in PV caliber between donors and recipients, as well as by limitations of PV length, which may be inadequate to reach the recipient spleno-mesenteric junction. Three types of post-transplant complications result from these complexities: 1) anomalies of the portal flow; 2) stenosis of the PV anastomosis; and 3) PV thrombosis. Abnormal portal flow may rarely need a specific intervention, but persistent stenosis or appearance of signs of portal hypertension need to be corrected. Balloon dilatation and placement of a stent are usually successful to repair stenosis. Portal vein thromboses are in general diagnosed in the immediate post-operative period and frequently lead to re-transplantation; however, thrombolytic therapy should be attempted in children without major signs of liver necrosis. When intra-hepatic portal vein(s) are permeable, despite extrahepatic PV thrombosis, a Meso-Rex shunt may be the indicated therapy.

BACKGROUND:To enhance the technical feasibility of portal vein (PV) interposition grafting for pediatric PV hypoplasia, we performed a computational simulation to establish a customized surgical technique allowing a secure anastomosis of an iliac vein graft to a severely hypoplastic PV stump. METHODS:Based on the literature and on our own experience with reconstruction of PV hypoplasia, we devised three types of recipient PV stump preparations and three types of interposition vein grafts, yielding five technically feasible combinations. RESULTS:The computational simulation model for PV reconstruction using an interposition vein graft revealed the most feasible combination to be a sequential inverted-T incision to the confluence of the superior mesenteric vein and splenic vein with a longitudinal slit in the transverse vein graft end, the technical feasibility was validated by an artificial suture model. This reconstruction was clinically applied to treat a 7.2-kg 10-month-old female patient with biliary atresia and a severely hypoplastic PV. The PV reconstruction was successful; the patient recovered uneventfully. CONCLUSIONS:We have presented a simplified surgical technique for PV interposition that is applicable to pediatric PV hypoplasia, which also appears to be a feasible option for pediatric liver transplantation.

Portal vein (PV) size matching between recipient and liver graft is important in preventing anastomotic stenosis in living donor liver transplantation (LDLT). In right liver grafts, the diameter of graft PV is usually >10 mm. Thus, PV size matching does not become critical in adult recipients. If the recipient PV is very large, funneling fence can be attached to graft PV. However, if the diameter of graft PV is <8 mm, it can induce anastomotic stenosis. We experienced a few cases of PV anastomotic stenosis due to small-sized graft PV in >5000 LDLT cases, but graft PV widening was not performed because graft PV is considered as being a no-touch area. In thinking out of the box, we performed wedged-patch venoplasty to exceptionally narrow graft PV. A 4 year-old female patient underwent second LDLT due to progressive deterioration of graft function after 3 years. At first LDLT operation for biliary stresia, an iliac vein conduit was interposed for PV reconstruction. At second LDLT operation, the diameter of interposed PV was 10 mm, but the left liver graft PV was only 6 mm-sized. Uniquely, the left PV was waist only at first-order PV. To resolve this PV waist, a longitudinal incision was made to release the waist. A cold-preserved fresh iliac vein patch was inserted to widen the PV orifice. The patch size was adjusted to match the size of the recipient PV. The patient recovered uneventfully. This wedged-patch venoplasty technique can be applied to small-sized graft PV, to cope with PV size mismatching in LDLT.

The purpose of this study was to evaluate retrospectively the results of PTA for late-onset PV complications after pediatric LDLT and to assess whether a meso-Rex shunt is a viable option for treating restenosis of the PV after PTA in selected cases. Seventy-five children who underwent adult-to-child LDLT were included in this study, and there were six late-onset PV complications (8.0%). The initial therapeutic approach was PTA, with or without stent: PTA with balloon dilation for three children, PTA with stent placement for one child, and failure to cannulate the occluded PV for two children. A meso-Rex shunt was performed in the two children after failed PTA: One suffered complete obstruction of the main PV, and the other, restenosis with total thrombosis after PTA with stent. The PTA was a technical and clinical success in four with PV stenosis of the six patients (66.7%), and successful application of a meso-Rex shunt in the other two children resulted in restoration of PV flow. In conclusion, PTA is a safe and effective procedure for treating late-onset PV stenosis after pediatric LDLT. However, in growing pediatric recipients with restenosis of the PV after PTA or chronic PV thrombosis, a meso-Rex shunt may be a better choice for late-onset PV complications.

PURPOSE:To evaluate retrospectively the long-term outcomes of percutaneous transhepatic balloon angioplasty performed for portal vein stenosis (PVS) after pediatric living donor liver transplantation (LDLT). MATERIALS AND METHODS:Between October 1997 and December 2013, of 527 pediatric patients (age < 18 y) who underwent LDLT in a single institution, 43 patients (19 boys, 24 girls; mean age, 4.1 y ± 4.1) were confirmed to have PVS at direct portography with or without manometry and underwent percutaneous interventions, including balloon angioplasty with or without stent placement. Technical success, clinical success, laboratory findings, manometry findings, patency rates, and major complications were evaluated. Follow-up periods after initial balloon angioplasty ranged from 5-169 months (mean, 119 mo). RESULTS:Technical success was achieved in 65 of 66 sessions (98.5%) and in 42 of 43 patients (97.7%), and clinical success was achieved in 37 of 43 patients (86.0%). Platelet counts improved significantly. Of 32 patients undergoing manometry, 19 showed significant improvement of pressure gradient across the stenosis after percutaneous transhepatic balloon angioplasty. At 1, 3, 5, and 10 years after balloon angioplasty, the rates of primary patency were 83%, 78%, 76%, and 70%, and the rates of primary-assisted patency were 100%, 100%, 100%, and 96%. Two major complications subsequent to balloon angioplasty were noted: severe asthma attack and portal vein thrombosis. CONCLUSIONS:Percutaneous transhepatic balloon angioplasty is a safe and effective treatment with long-term patency for PVS after pediatric LDLT.

BACKGROUND:Stenosis of the portal vein (PV) is a rare complication after liver transplantation (LT) in pediatric patients, and it adversely affects outcomes. We reviewed the safety and efficacy of percutaneous transhepatic balloon angioplasty (PTBA) as a treatment for post-LT late-onset PV stenosis (PVS). METHODS:Three hundred eighteen patients between the ages of 0 and 21 years received an LT from 2001 to 2016 at this tertiary center. Twenty-one children were evaluated for PVS using percutaneous portal venography. RESULTS:Of the 21, 19 patients (7 female, 12 male) with a median age of 12 years (7-15 years) were diagnosed with PVS and received PTBA. Two patients were excluded: one did not have PVS, and one received shunt surgery. Median time between LT and PTBA was 83 months (interquartile range, 49-138). For patients in whom pressure could be accurately measured (n = 9), mean PV pressure gradient was 6.3 mm Hg (SD, 5.0) preprocedure and 0.9 mm Hg (SD, 1.2) postprocedure. Mean percentage improvement in gradient across the stenotic region was 86.2% (SD, 15.9%; P < 0.01). At 12-month postprocedure, there was a mean improvement (pre-PTBA vs post-PTBA means) in bilirubin by 28.2% (0.6 mg/dL vs 0.4 mg/dL, P = 0.07), aspartate aminotransferase by 31.2% (116.3 IU/L vs 28.1 IU/L, P = 0.04), alanine aminotransferase by 40.7% (140.3 IU/L vs 28.6 IU/L, P = 0.07), γ-glutamyltransferase by 29.0% (337.2 IU/L vs 38.0 IU/L, P = 0.06) and platelets by 62.1% (128.3 vs 191.1 × 10/L, P = 0.03). The PV patency was successfully maintained in 18 of 19 patients for a median of 16 months (interquartile range, 5-35). One patient received a successful repeat procedure for restenosis at 6 weeks. CONCLUSION:Angioplasty for PVS after pediatric LT is a safe and effective treatment with good patency and improved clinical outcomes. Longer follow-up studies are required.

BACKGROUND:Portal vein thrombosis (PVT) is one of the main vascular complications after liver transplantation (LT), especially in pediatric patients with biliary atresia (BA). This study aimed to assess the preoperative hepatic hemodynamics in pediatric patients with BA using Doppler ultrasound and determine whether ultrasonographic parameters may predict early PVT after LT. METHODS:One hundred and twenty-eight pediatric patients with BA younger than 3 years of age underwent Doppler ultrasound within seven days before LT, between October 2006 and June 2013. The preoperative hepatic hemodynamic parameters were then compared between patients with early PVT (within 1 month following LT) and those without PVT. Receiver operating characteristic analysis was performed to determine the optimal cutoff value for predicting early PVT. RESULTS:Of the 128 transplant recipients, 41 (32.03%) had a hypoplastic portal vein (PV), 52 (40.63%) had hepatofugal PV flow and 40 (31.25%) had a high hepatic artery resistance index (HARI) of ≥1. Nine cases (7.03%) experienced early PVT. A PV diameter ≤4 mm (sensitivity 88.89%, specificity 72.27%), and a hepatofugal PV flow (sensitivity 77.78%, specificity 62.18%) with a high HARI ≥1 (sensitivity 77.78%, specificity 72.27%) were hepatic hemodynamic risk factors for early PVT. CONCLUSIONS:Hepatic hemodynamic disturbances in pediatric recipients with BA were more common. Small PV diameter (≤4 mm) and hepatofugal PV flow combined with high HARI (≥1) are strong warning signs of early PVT after LT in pediatric patients with BA. Intense monitoring of vascular patency and prophylactic thrombolytic therapy should be considered in pediatric patients undergoing LT for BA.

INTRODUCTION:Portal vein thrombosis (PVT) and portal vein stenosis (PVS) are rare complications after liver transplantation that can lead to graft failure and patient death. MATERIAL AND METHODS:The aim of this study was to evaluate the effect of interventional treatment for PVT and PVS occlusion after liver transplantation. Follow-up data of 7 patients who underwent stent replacement for PVT and/or PVS were analyzed. The clinical success, complications, and portal vein patency were analyzed. RESULTS:Clinical success was obtained in 6 of the 7 patients. No portal hypertension-related symptoms reoccurred in the 6 patients during the follow-up. CONCLUSIONS:Interventional radiologic treatment produced a high success rate and a favorable long-term outcome.

PV reconstruction is an important aspect of LDLT, with post-transplant outcomes depending on PV reconstruction methods. However, it is unclear whether the preferential selection of these techniques is dependent on preoperative recipient characteristics. This retrospective study assessed whether preoperative recipient factors differed in pediatric patients who did and did not receive VGs for PV reconstruction. Of 113 pediatric patients who underwent LDLT from January 2010 to July 2015, 31 (27%) underwent PV reconstruction with VGs and the other 82 (73%) without VGs. The presence of collateral vessels (P<.0001) and ascites (P=.02); PV size (P<.001), thrombosis (P=.01) and the direction of flow (P=.01), Child-Pugh class A vs B/C liver function (P=.01), Alb concentration (P=.02), primary diagnosis: BA vs non-BA (P=.03), and previous abdominal surgery (P<.005) differed significantly in patients who did and did not receive VGs for PV reconstruction. PV complications, patient survival, and graft survival did not differ significantly in patients with and without VGs at 1-year follow-up. VGs should be harvested for recipients with pretransplant hypoplastic PV, intense collaterals, hepatofugal flow, poor liver status, or previous abdominal surgery.

PURPOSE:Pediatric living donor liver transplantation (LDLT) in low weight recipients remains one of the most complex surgical procedures, with portal vein (PV) complications occurring in up to 19% of cases. When decreased PV flow is diagnosed intra- or perioperatively, intraoperative stent placement is a good substitute for surgical adjustment. Still, at the present moment, little is known about the technical feasibility, safety, efficacy, and long-term outcome of intraoperative stenting in LDLT. METHODS:Between 2006 and 2017, seven pediatric recipients underwent PV stent placement during the transplant or in the immediate post-operative setting. Preoperative, operative, and post-operative parameters were documented retrospectively. RESULTS:In total, nine stents were placed in seven patients. Procedures were technically successful in all patients. During the mean imaging follow-up period of 1313 days, none of the patients showed PV abnormality and PV stent remained patent throughout the post-transplant course. There were no deaths or graft loses during the follow-up period. CONCLUSIONS:Intraoperative stenting through the inferior mesenteric vein approach offers both a high feasibility and satisfactory results, with the potential for excellent long-term primary patency despite continued growth in children.

OBJECTIVE:To analyze the incidence and risk factors of portal vein stenosis (PVS) in pediatric liver transplantation (LT). METHODS:This retrospective analysis of 396 cases of pediatric LT (patients aged ≤ 14 years old) was conducted at the Liver Transplantation Center of Beijing Friendship Hospital (China) from June 2013 to December 2017. We collected relevant data and calculated the incidence. We analyzed a total of 23 risk factors for PVS children during the perioperative period. RESULTS:The incidence of PVS in pediatric LT was 6.6%. The following were identified as risk factors for PVS in pediatric LT: Preoperative portal hypertension was complicated, weight (≤7 kg), recipients of portal vein diameter ≤4 mm, GRWR (≥3.5%), the use of cold preservation vein grafts, anastomosis in the region of superior mesenteric vein and splenic vein and reverse blood flow in the portal vein shown in preoperative ultrasound examination. Recipients of portal vein diameter ≤4 mm and the use cold preservation grafts were independent risks factors for PVS in pediatric LT. CONCLUSION:For recipients with the risk factors identified in this study, we strongly recommend a strict follow-up and the provision of suitable interventions when indicated.

BACKGROUND The aim of this study was to investigate the outcomes and stent implantation timing of portal vein stenosis intervention after pediatric liver transplantation (pLT). MATERIAL AND METHODS The clinical data of 30 children with post-liver transplantation portal vein stenosis/occlusion (PVS/O) between Jan 2008 and Jun 2015 were retrospectively analyzed. The successfully re-opened cases used balloon angioplasty or stent implantation. SPSS13.0 software was used for statistical analysis and paired t test of the pressure gradient at both ends of the stenosis, diameter and flow rate within the stenosis, platelet count, and albumin in the PVS children before and after balloon angioplasty, with p<0.05 considered as statistically significant. Among the 30 patients, 6 received a stent implant in their first treatment, 22 received balloon angioplasty in their first treatment, and in 2 the re-opening could not be achieved. RESULTS The diameter of the stenotic segment, portal vein velocity, pressure gradient at both ends of the stenosis, and platelet count in these children with portal vein stenosis/occlusion (PVS/O) showed statistically significant differences when comparing values before and after intervention (p<0.05), but albumin showed no statistically significant difference (p>0.05). CONCLUSIONS Intervention therapy for portal vein stenosis after pediatric liver transplantation (pLT-PVS) is a safe and effective treatment, and patients with portal vein torsion, intimal tearing, or long portal vein segment occlusion should undergo stent implantation.

BACKGROUND AND OBJECTIVE:Liver transplantation (LT) is the gold-standard treatment for end-stage liver disease; however, late-onset complications such as fatty liver can occur in the absence of metabolic comorbidities. We report a unique case of post-transplant hepatic steatosis developing in only a part of the liver graft. CASE REPORT:A 1-year-old boy underwent ABO-incompatible living donor liver transplantation (LDLT) with a left lateral liver graft donated from his mother for biliary atresia. The biliary tract was reconstructed by hepaticojejunostomy using the previous Roux-en-Y limb. Liver function tests increased by up to 2-fold of the upper normal limit after the second year. He developed segmental steatosis in a part of the liver graft 2 years after LDLT. Venous blood drained into the area of the liver graft from veins in the Roux-en-Y limb of the jejunum. Pathologic findings from a liver biopsy showed fatty depositions without steatohepatitis, acute rejection, or tumors. Portal vein stricture (PVS) subsequently became apparent, which was complicated by the symptoms of portal hypertension, such as gastrointestinal varices. We treated PVS with 2 sessions of percutaneous transhepatic portal vein angioplasty (PTPA), after which the segmental steatosis disappeared. We hypothesize that PVS caused local hemodynamic anomalies, leading to fatty deposition in a part of the liver graft. CONCLUSION:We experienced a case of post-LT with segmental steatosis that was successfully treated by portal vein flow modification with PTPA. Steatosis of the graft might indicate a vascular abnormality, and further examinations should be performed after LT.

Secure reconstruction of the right hepatic vein (RHV) is essential for the successful implantation of a right liver graft during living donor liver transplantation (LDLT). To develop reliable surgical techniques for RHV reconstruction, we performed 3 concurrent studies: a simulation study using a fluid dynamics experimental model and a computational simulation model; an observational study analyzing the hemodynamic changes during radiological interventions for RHV stenosis; and a prospective clinical study establishing hemodynamics-compliant surgical techniques. The simplified fluid dynamics experimental model revealed that actually measured outflow volumes were very similar to theoretical values derived from a fluid dynamics formula. The computational simulation model showed that outflow decreases were nearly linearly correlated with the degree of stenosis when it exceeded 50%. The clinical observational study revealed that mild (≤50%), moderate (50%-75%), and severe RHV stenoses (≥75%) had mean pressure gradients of 2.5 ± 1.0, 6.6 ± 2.3, and 9.6 ± 2.8 mm Hg, respectively. The prospective clinical study was performed for patients who underwent RHV reconstruction with RHV angle blunting and inferior vena cava enlargement (n = 274); a historical control group of patients who underwent reconstruction by other methods (n = 225) was also used. RHV stenting within 2 weeks and 1 year was necessary for 1 patient (0.4%) and 5 patients (1.8%) in the study group, respectively, and for 9 patients (4.0%) and 21 patients (9.1%) in the control group, respectively (P < 0.01). The mean cephalocaudal length of patulous RHV anastomoses was greater in the study group versus the control group (P < 0.001). In conclusion, our modified RHV reconstruction technique significantly reduces the risk of RHV stenosis. We thus suggest the routine or selective use of this technique as a part of graft standardization for LDLT using a right liver graft.

AIM:An arteriovenous fistulae (AVF) is the preferred vascular access for maintenance haemodialysis patients. Its dysfunction is often due to venous stenosis, which is mainly caused by neointimal hyperplasia. Additionally, haemodynamic forces, especially wall shear stress (WSS), as a mechanical stimuli to venous wall have a significant role in neointimal hyperplasia. The purpose of this study was to evaluate the association between WSS and neointimal hyperplasia. METHODS:An 'end-to-side' AVF was created between the right femoral artery and vein of canines. Canines were killed at 7 and 28 days post-surgery. The velocity and WSS in the three-dimensional computational model of AVF were simulated using computational fluid dynamics (CFDs). The four typical sites of the vein evaluated in this study, chosen according to the haemodynamic analysis, included the arteriovenous anastomosis (A-V), the juxta-anastomotic segment (J-V), the juxta-ligation segment (L-V) and the proximal vein (P-V). The specimens were haematoxylin-eosin stained and the intima-media thickening was then measured. RESULTS:Neointimal hyperplasia was more obvious in the inner wall of the J-V and L-V (low-and-disturbed WSS) sites compared with the P-V and A-V sites, and the outer wall of the L-V and J-V segments (high or laminar WSS) (P < 0.01). CONCLUSION:In this study, we described the haemodynamic condition in the AVF and found that neointimal hyperplasia predisposed to occur in the inner wall of venous segment near the anastomosis. We also found that not only the neointimal hyperplasia has a strong inverse correlation with WSS levels, but also is related to flow patterns.

INTRODUCTION::Autogenous arteriovenous fistula is the preferred vascular access for hemodialysis, but it has high rates of non-maturation and early failure due to vascular stenosis. Convincing evidence supports a key role of local hemodynamics in vascular remodeling, suggesting that unsteady and disturbed flow conditions may be related to stenosis formation in arteriovenous fistula. The purpose of our study was to explore the feasibility of coupling contrast-free magnetic resonance imaging and computational fluid dynamics in longitudinal studies to identify the role of local hemodynamic changes over time in inducing vessel wall remodeling in arteriovenous fistula. METHODS::We acquired contrast-free magnetic resonance imaging of arm vasculature at 1 week and 6 weeks after arteriovenous fistula creation in a 72-year-old patient. We then generated three-dimensional models and evaluated lumen cross-sectional area of arteriovenous fistula limbs. We performed high-resolution computational fluid dynamics to evaluate changes in local hemodynamics over time. RESULTS::Our contrast-free magnetic resonance imaging protocol provided good quality images in a short scan duration. We observed a homogeneous dilatation in the proximal artery, while there was a more pronounced lumen dilatation in the venous outflow as compared to a limited dilatation in the juxta-anastomotic vein. Furthermore, we observed a slight stabilization of the flow pattern over time, suggesting that vascular outward remodeling accommodates the flow to a more helicoidally phenotype. CONCLUSION::Coupling contrast-free magnetic resonance imaging and high-resolution computational fluid dynamics represents a promising approach to shed more light in the mechanisms of vascular remodeling and can be used for prospective clinical investigations aimed at identifying critical hemodynamic factors contributing to arteriovenous fistula failure.

BACKGROUND:Carotid angioplasty and stenting (CAS) is emerging as an alternative treatment for carotid stenosis, but neointimal hyperplasia (NIH) remains a drawback of this treatment strategy. This study aimed to evaluate the effect of variations of carotid bifurcation geometry on local hemodynamics and NIH. METHODS AND RESULTS:Hemodynamic and geometric effects on NIH were compared between 2 groups, by performing computational fluid dynamics (CFD) simulations both on synthetic models and patient-specific models. In the idealized models, multiple regression analysis revealed a significant negative relationship between internal carotid artery (ICA) angle and the local hemodynamics. In the patient-derived models, which were reconstructed from digital subtraction angiography (DSA) of 25 patients with bilateral CAS, a low time-average wall shear stress (TAWSS) and a high oscillatory shear index (OSI) were often found at the location of NIH. Larger difference values of the OSI percentage area (10.56±20.798% vs. -5.87±18.259%, P=0.048) and ECA/CCA diameter ratio (5.64±12.751% vs. -3.59±8.697%, P=0.047) were detected in the NIH-asymmetric group than in the NIH-symmetric group. CONCLUSIONS:Changes in carotid bifurcation geometry can make apparent differences in hemodynamic distribution and lead to bilateral NIH asymmetry. It may therefore be reasonable to consider certain geometric variations as potential local risk factors for NIH.

The relationship between carotid blood flow and carotid intraplaque haemorrhage (IPH) is not fully understood. This study was to investigate the relationship between local haemodynamics and carotid plaques with IPH associated with severe artery stenosis. Fifty-nine patients with carotid atherosclerosis were enrolled in this study and underwent magnetic resonance imaging (MRI) measurement. IPH and non-IPH compositions were differentiated based on plaque sequences. Haemodynamic simulations were performed by using computational fluid dynamics (CFD). All the carotids were categorised into IPH and non-IPH groups. In each group, the artery stenosis was divided into mild (<50%), moderate (50-70%) and severe (>70%) subgroups. Maximum wall shear stress (mWSS) was calculated and comparisons made between IPH and non-IPH groups using independent t-test. Furthermore, the relationship between mWSS and IPH volume was examined using Pearson's correlation. The mWSS result calculated from the IPH group was significantly higher than that of the non-IPH group; at mild stenosis (P = 0.001) and moderate stenosis (P = 0.002) respectively. However, there was no significant difference in cases of severe stenosis (P = 0.42). Furthermore, the results showed a positive correlation between mWSS and IPH volume (r = 0.763, P < 0.001) in the cases of stenosis of less than 70%. mWSS was found to be significantly associated with IPH for carotids with stenosis of less than 70%. This highlights that mWSS is a potential quantitative parameter for the risk diagnosis of the carotid atherosclerosis.

In cases of severe carotid artery stenosis (CAS), carotid endarterectomy (CEA) is performed to recover lumen patency and alleviate stroke risk. Under current guidelines, the decision to surgically intervene relies primarily on the percent loss of native arterial lumen diameter within the stenotic region (i.e. the degree of stenosis). An underlying premise is that the degree of stenosis modulates flow-induced wall shear stress elevations at the lesion site, and thus indicates plaque rupture potential and stroke risk. Here, we conduct a retrospective study on pre-CEA computed tomography angiography (CTA) images from 50 patients with severe internal CAS (>60% stenosis) to better understand the influence of plaque and local vessel geometry on local hemodynamics, with geometrical descriptors that extend beyond the degree of stenosis. We first processed CTA images to define a set of multipoint geometric metrics characterizing the stenosed region, and next performed computational fluid dynamics simulations to quantify local wall shear stress and associated hemodynamic metrics. Correlation and regression analyses were used to relate obtained geometric and hemodynamic metrics, with inclusion of patient sub-classification based on the degree of stenosis. Our results suggest that in the context of severe CAS, prediction of shear stress-based metrics can be enhanced by consideration of readily available, multipoint geometric metrics in addition to the degree of stenosis.

PURPOSE:The paper focuses on the numerical and experimental evaluation of the fluid flow inside chosen fragments of blood vessels. In the first stage of the study, the experimental tests were conducted using a research test stand, designed to be used in this evaluation. The study evaluated the blood flow through a silicone vessel with an implanted coronary stent. METHODS:The PIV method was used in order to visualize the flow vectors inside a silicone vessel. Deformed vessel geometry implemented for computational fluid dynamics purposes was obtained owing to a non-linear simulation of the stent expansion (angioplasty process) in a silicone vessel. Additionally, a vessel model with a statistical 55% area stenosis and an irregular real vessel with an atherosclerotic plaque were also subjected to analysis from the hemodynamic flow point of view. A vessel with a statistical stenosis was also used to simulate the angioplasty process, which resulted in obtaining a flow domain for the vessel with an atherosclerotic plaque after the stent implantation. RESULTS:For each case, distributions of parameters such as OSI or TAWSS were also analyzed and discussed. The areas of low TAWSS values appear close to the stent struts. CONCLUSIONS:Stents with increased diameters, compared to the normal vessel diameter, create a higher risk of occurrence of the areas with low WSS values. Excessive stent deformation can cause inflammation by injuring the vessel and can initiate the restenosis and thrombotic phenomena through the increased vessel diameter.

Biomechanical forces may play a key role in saphenous vein graft (SVG) disease after coronary artery bypass graft (CABG) surgery. Computed tomography angiography (CTA) of 430 post-CABG patients were evaluated and 15 patients were identified with both stenosed and healthy SVGs for paired analysis. The stenosis was virtually removed, and detailed 3D models were reconstructed to perform patient-specific computational fluid dynamic (CFD) simulations. Models were processed to compute anatomic parameters, and hemodynamic parameters such as local and vessel-averaged wall shear stress (WSS), normalized WSS (WSS), low shear area (LSA), oscillatory shear index (OSI), and flow rate. WSS was significantly lower in pre-diseased SVG segments compared to corresponding control segments without disease (1.22 vs. 1.73, p = 0.012) and the area under the ROC curve was 0.71. No differences were observed in vessel-averaged anatomic or hemodynamic parameters between pre-stenosed and control whole SVGs. There are currently no clinically available tools to predict SVG failure post-CABG. CFD modeling has the potential to identify high-risk CABG patients who may benefit from more aggressive medical therapy and closer surveillance. Graphical Abstract.

Stenosis due to neointimal hyperplasia (NIH) is among the major causes of peripheral graft failure. Its link to abnormal hemodynamics in the graft is complex, and isolated use of hemodynamic markers is insufficient to fully capture its progression. Here, a computational model of NIH growth is presented, establishing a link between computational fluid dynamics simulations of flow in the lumen and a biochemical model representing NIH growth mechanisms inside the vessel wall. For all three patients analyzed, NIH at proximal and distal anastomoses was simulated by the model, with values of stenosis comparable to the computed tomography scans.

Background and Purpose- There is debate over an optimal systolic blood pressure (SBP) in secondary stroke prevention of patients with symptomatic intracranial atherosclerotic stenosis (sICAS). We investigated whether translesional pressure gradient across sICAS would alter the relationship between SBP and risk of recurrent stroke in such patients. Methods- We recruited patients with sICAS (50%-99% stenosis) confirmed in computed tomography angiography. We simulated blood flow across sICAS with computed tomography angiography-based computational fluid dynamics models. Translesional pressure ratio (PR=Pressure/Pressure) was calculated in each case. Pressure ratio (PR) ≤ median was defined as low PR, indicating larger translesional pressure gradient across sICAS. All patients received optimal medical treatment. We investigated the interaction of translesional PR and mean SBP during follow-up (SBP) in determining the risk of the primary outcome, recurrent ischemic stroke in the same territory within 1 year. Results- Among 157 patients with sICAS, the median PR was 0.93. Multivariate Cox regression revealed significant PR-SBP interaction on the primary outcome (=0.008): in patients with normal PR, risk of primary outcome significantly decreased with lower SBP (hazard ratio for 10 mm Hg decrement =0.46; =0.018); however, in those with low PR, SBP≤130 mm Hg was associated with significantly increased risk of primary outcome, compared with 130

BACKGROUND:Fractional flow reserve is an accurate method for diagnosing stenosis. The difficulty in using this procedure lies in placing the guidewire precisely at the blood vessel centerline. Owing to the long distance between the insertion point and the stenosis, a guidewire inclination can occur. Therefore, the main objective of this study is to investigate how the measured pressure in a blood vessel varies with the guidewire position. METHODS:A three-dimensional model of blood flow is developed and numerically simulated. Two positions and two inclination angles from the blood vessel centerline and three throat diameters are investigated. The predicted results are validated using the available experimental data. The predicted results and actual measurements are observed to agree well with each other. RESULTS:The pressure drop coefficient (CDP) increases because of guidewire insertion. When the guidewire is placed at inclined positions in moderate stenosis, the values of CDP are 66 and 68, depending on the inclination angle; the errors in CDP are 69% and 76%, respectively. At a high flow rate, the errors are reduced to 67% and 70%, respectively. The error in the CDP ranges from 42% to 61% when the guidewire is placed parallel to the centerline. For severe stenosis, the CDP is nearly the same at all positions and varies between 240 and 250; without a guidewire, the CDP is 163. CONCLUSIONS:The findings confirmed that practitioners should be aware of the guidewire position during the operation. The displacement of the guidewire should be estimated, and the corresponding error must be considered.

The ongoing advances in the field of cardiovascular modelling during the past years have allowed for the creation of accurate three-dimensional models of the major coronary arteries. The aforementioned 3D models can accurately mimic the human coronary vasculature if they are combined with sophisticated computational fluid dynamics algorithms and shed light to non-trivial issues that concern the clinicians. One of these issues is to define whether a coronary lesion is more dangerous to present with ischemia if it is at a proximal or a distal part of the vessel. In this work, we aim to investigate the aforementioned issue by reconstructing in 3D a coronary arterial model from a healthy subject using Computed Tomography Coronary Angiography images and by editing it to create eight diseased arterial models that contain one or two lesions of different severities. After carrying out the appropriate blood flow simulations using the finite element method, we observed that the distal lesions are more dangerous than the proximal ones in terms of hemodynamic significance. Moreover, the distal severe stenosis (i.e. 70% diameter reduction) present with the highest peak Wall Shear Stress (WSS) values in comparison to the proximal ones.

BACKGROUND:The objective of this study was to evaluate the hemodynamic characteristics of multiple sequential coronary artery bypass grafting using a computational fluid dynamics study. METHODS:First anastomosis was configured into parallel and diamond anastomoses, and the second anastomosis was set as end-side anastomosis. The anastomosis incision lengths were fixed at 2 mm. Various combinations of the degree of first and second stenoses were studied. The diameter of both the native and graft vessels was set at 2 mm. The inlet boundary condition was set by a sample of the transient time flow measurement, which was measured intraoperatively. RESULTS:Both swirl and stagnation were observed at the outlets of the stenosis and the anastomosis sites. When the severity of the second stenosis was larger than that of the first, the flow at the outlet of the second stenosis was more unstable. Higher wall shear stress and larger oscillatory shear index regions were observed when the severe stenosis was bypassed by the first anastomosis, especially with diamond anastomoses. Less energy loss and higher energy efficiency were present when the vessel with more severe stenosis was bypassed as the second anastomosis. Energy loss was lower and energy efficiency was higher with parallel anastomosis than diamond anastomosis when the severity of the two stenoses was the same. CONCLUSIONS:It is ideal to bypass the less severe stenosis vessel first with a parallel anastomosis method when employing multiple sequential bypass grafting. This improves hemodynamic stability and energy efficiency, according to a computational fluid dynamics model.

The juxta-anastomotic stenosis of an arteriovenous fistula (AVF) is a significant clinical problem in hemodialysis patients with no effective treatment. Previous studies of AV anastomotic angles on hemodynamics and vascular wall injury were based on computational fluid dynamics (CFD) simulations using standardized AVF geometry, not the real-world patient images. The present study is the first CFD study to use angiographic images with patient-specific outcome information, i.e., the exact location of the AVF stenotic lesion. We conducted the CFD analysis utilizing patient-specific AVF geometric models to investigate hemodynamic parameters at different locations of an AVF, and the association between hemodynamic parameters and the anastomotic angle, particularly at the stenotic location. We analyzed 27 patients who used radio-cephalic AVF for hemodialysis and received an angiographic examination for juxta-anastomotic stenosis. The three-dimensional geometrical model of each patient's AVF was built using the angiographic images, in which the shape and the anastomotic angle of the AVF were depicted. CFD simulations of AVF hemodynamics were conducted to obtain blood flow parameters at different locations of an AVF. We found that at the location of the stenotic lesion, the AV angle was significantly correlated with access flow disturbance ( = 0.739; < 0.001) and flow velocity ( = 0.563; = 0.002). Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that the AV angle determines the lesion's flow disturbance with a high area under the curve value of 0.878. The ROC analysis also identified a cut-off value of the AV angle as 46.5°, above or below which the access flow disturbance was significantly different. By applying CFD analysis to real-world patient images, the present study provides evidence that an anastomotic angle wider than 46.5° might lead to disturbed flow generation, demonstrating a reference angle to adopt during the anastomosis surgery.

The advances in cardiovascular modelling over the past two decades have given the opportunity to create accurate three dimensional models of the coronary vasculature which, combined with advanced computational fluid dynamics algorithms can shed light to intriguing matters that concern clinicians. One of these issues is the presence of a stenosis near bifurcations in one of the major coronary vessels. In this work, we try to shed light on the aforementioned matter by creating a healthy arterial bifurcation reconstructed using the fusion of Optical Coherence Tomography and X-Ray angiography images. The healthy model was edited by adding an artificial stenosis of 50% diameter reduction into three different locations after the bifurcation, thus creating three diseased models. After performing the appropriate blood flow simulations, we observed that the location of the stenosis affects the Wall Shear Stress (WSS) distribution but it does not affect the functional significance of the stenosis itself.

BACKGROUND:Pulsatile tinnitus (PT) is a debilitating condition that can be caused by a vascular abnormality, such as an arterial or venous lesion. Although treatment of PT-related venous lesions has been shown to successfully cure patients of the associated 'tormenting' rhythmical sound, much controversy still exists regarding their role in the etiology of PT. METHODS:A patient presented with a history of worsening, unilateral PT. A partial venous sinus obstruction related to the large arachnoid granulation was detected on the right side, and subsequently stented at the right transverse sinus. High-fidelity computational fluid dynamics (CFD) was performed on a 3D model digitally segmented from the pre-stent venogram, with assumed pulsatile flow rates. A post-stent CFD model was also constructed from this. Data-driven sonification was performed on the CFD velocity data, blinded to the patient's self-reported sounds. RESULTS:The patient reported that the PT was completely resolved after stenting, and has had no recurrence of the symptoms after more than 2 years. CFD simulation revealed highly disturbed, turbulent-like flow at the sigmoid sinus close to auditory structures, producing a sonified audio signal that reproduced the subjective sonance of the patient's PT. No turbulence or sounds were evident at the stenosis, or anywhere in the post-stent model. CONCLUSIONS:For the first time, turbulence generated distal to a venous stenosis is shown to be a cause of PT. High-fidelity CFD may be useful for identifying patients with such 'torrents' of flow, to help guide treatment decision-making.

BACKGROUND:This study aimed to adopt computational fluid dynamics to simulate the blood flow dynamics in inferior vena cava stenosis based on time-dependent patient-specific models of Budd-Chiari syndrome as well as a normal model. It could offer valuable references for a retrospective insight into the underlying mechanisms of Budd-Chiari syndrome pathogenesis as well as more accurate evaluation of postoperative efficacy. METHODS:Three-dimensional inferior vena cava models of Budd-Chiari syndrome patient-specific (preoperative and postoperative) and normal morphology model were reconstructed as per magnetic resonance images using Simpleware. Moreover, computational fluid dynamics of time-resolved inferior vena cava blood flow were simulated using actual patient-specific measurements to reflect time-dependent flow rates. FINDINGS:The assessment of the preoperative model revealed the dramatic variations of hemodynamic parameters of the stenotic inferior vena cava. Moreover, the comparison of the preoperative and postoperative models with the normal model as benchmark showed that postoperative hemodynamic parameters were markedly ameliorated via stenting, with the attenuation of overall velocity and wall shear stress, and the increase of pressure. However, the comparative analysis of the patient-specific simulations revealed that some postoperative hemodynamic profiles still bore some resemblance to the preoperative ones, indicating potential risks of restenosis. INTERPRETATION:Computational fluid dynamics simulation of time-resolved blood flow could reveal the tight correlation between the hemodynamic characteristics and the pathological mechanisms of inferior vena cava stenosis. Furthermore, such time-resolved hemodynamic profiles could provide a quantitative approach to diagnosis, operative regimen and postoperative evaluation of Budd-Chiari syndrome with inferior vena cava stenosis.

The clinical diagnosis of aorta coarctation (CoA) constitutes a challenge, which is usually tackled by applying the peak systolic pressure gradient (PSPG) method. Recent advances in computational fluid dynamics (CFD) have suggested that multi-detector computed tomography angiography (MDCTA)-based CFD can serve as a non-invasive PSPG measurement. The aim of this study was to validate a new CFD method that does not require any medical examination data other than MDCTA images for the diagnosis of CoA. Our study included 65 pediatric patients (38 with CoA, and 27 without CoA). All patients underwent cardiac catheterization to confirm if they were suffering from CoA or any other congenital heart disease (CHD). A series of boundary conditions were specified and the simulated results were combined to obtain a stenosis pressure-flow curve. Subsequently, we built a prediction model and evaluated its predictive performance by considering the AUC of the ROC by 5-fold cross-validation. The proposed MDCTA-based CFD method exhibited a good predictive performance in both the training and test sets (average AUC: 0.948 vs. 0.958; average accuracies: 0.881 vs. 0.877). It also had a higher predictive accuracy compared with the non-invasive criteria presented in the European Society of Cardiology (ESC) guidelines (average accuracies: 0.877 vs. 0.539). The new non-invasive CFD-based method presented in this work is a promising approach for the accurate diagnosis of CoA, and will likely benefit clinical decision-making.

In post-operative scenarios of arterial graft surgeries to bypass coronary artery stenosis, fluid dynamics plays a crucial role. Problems such as intimal hyperplasia have been related to fluid dynamics and wall shear stresses near the graft junction. This study focused on the question of the use of Newtonian and non-Newtonian models to represent blood in this type of problem in order to capture important flow features, as well as an analysis of the performance of geometry from the view of Constructive Theory. The objective of this study was to investigate the effects rheology on the steady-state flow and on the performance of a system consisting of an idealized version of a partially obstructed coronary artery and bypass graft. The Constructal Design Method was employed with two degrees of freedom: the ratio between bypass and artery diameters and the junction angle at the bypass inlet. The flow problem was solved numerically using the Finite Volume Method with blood modeled employing the Carreau equation for viscosity. The Computational Fluid Dynamics model associated with the Sparse Grid method generated eighteen response surfaces, each representing a severe stenosis degree of 75% for specific combinations of rheological parameters, dimensionless viscosity ratio, Carreau number and flow index at two distinct Reynolds numbers of 150 and 250. There was a considerable dependence of the pressure drop on rheological parameters. For the two Reynolds numbers studied, the Newtonian case presented the lowest value of the dimensionless pressure drop, suggesting that the choice of applying Newtonian blood may underestimate the value of pressure drop in the system by about 12.4% (Re =150) and 7.8% (Re = 250). Even so, results demonstrated that non-Newtonian rheological parameters did not influence either the shape of the response surfaces or the optimum bypass geometry, which consisted of a diameter ratio of 1 and junction angle of 30°. However, the viscosity ratio and the flow index had the greatest impact on pressure drop, recirculation zones and wall shear stress. Rheological parameters also affected the recirculation zones downstream of stenosis, where intimal hyperplasia is more prevalent. Newtonian and most non-Newtonian results had similar wall shear stresses, except for the non-Newtonian case with high viscosity ratio. In the view of Constructal Design, the geometry of best performance was independent of the rheological model. However, rheology played an important role on pressure drop and flow dynamics, allowing the prediction of recirculation zones that were not captured by a Newtonian model.

In recent years, the role of computational fluid dynamics for Budd-Chiari syndrome evaluation has become the focus of certain studies. The purpose of the present study was to evaluate the role of computational fluid dynamics in Budd-Chiari syndrome with obstruction of the inferior vena cava (IVC). Magnetic resonance venous angiography was used to obtain original IVC and hepatic venous blood flow images from patients with Budd-Chiari syndrome. The computational fluid dynamics method was used to establish a three-dimensional model and simulate the blood flow velocity, wall shear stress and wall pressure. The results revealed that the hemodynamic parameters of Budd-Chiari syndrome were successfully simulated by computational fluid dynamics. The hemodynamic parameters of the IVC stenosis varied with the cardiac cycle. Vascular flow velocity (pre-operative, 1.64±0.10 m/sec; post-operative, 0.34±0.14 m/sec; t=34.97, P<0.001) and wall shear stress (pre-operative, 25.69±2.85 Pa; post-operative, 3.51±1.70 Pa; t=29.86, P<0.001) at the area of stenosis decreased after interventional therapy and the wall pressure increased (pre-operative, -119.33±251.50 Pa; post-operative, 1,128.42±207.70 Pa; t=17.10, P<0.001). In conclusion, the computational fluid dynamics method was able to effectively simulate the hemodynamic parameters of Budd-Chiari syndrome with obstruction of the IVC and may provide an effective quantitative method for the evaluation of vascular function post-treatment.

OBJECTIVE:To investigate the effect of different types of transverse sinus stenosis on blood flow patterns in the ipsilateral superior curve of the sigmoid sinus. METHODS:According to the morphology of transverse and sigmoid sinus sections in pulsatile tinnitus patients, ten idealized models with different degrees and positions of transverse sinus stenosis were constructed. Computational fluid dynamics simulations were performed to compare the hemodynamic characteristics among these models. Follow-up images of previous cases were included, which preliminarily confirmed the hypothesis that bone plate erosion of the sigmoid sinus sulcus is related to blood flow impingement. RESULTS:Blood flow impingement on the superior curve of the sigmoid sinus wall intensified with increasing degree of stenosis and decreased with increasing distance between the stenosis and the sigmoid sinus. The impact zone was generally confined to the anterior and lateral walls of the superior curve of the sigmoid sinus. When the stenosis was located far from the middle of the transverse sinus, the blood flow impingement on the sigmoid sinus wall was very weak. CONCLUSIONS:When stenosis is located far from the sigmoid sinus, the causes of tinnitus should be comprehensively considered instead of assuming that stenosis is the main cause. Bone plate erosion of the sigmoid sinus sulcus was promoted by blood flow impingement. KEY POINTS:• Ten idealized models with different degrees and positions of stenosis were constructed. • The causes of pulsatile tinnitus should be comprehensively considered. • Sigmoid sinus plate dehiscence was promoted by blood flow impingement.

Haemodynamics was widely believed to correlate with anastomosis restenosis. Utilizing the haemodynamic parameters as indicator functions, distal anastomosis was redesigned by some researchers so as to improve the long-term graft patency rate. However, there were few studies upon the proximal anastomosis. Therefore, in this study, flow characteristics and distributions of the haemodynamic parameters in proximal anastomosis under physiological flow condition have been investigated numerically for three different grafting angles: namely, 45 degrees forward facing, 45 degrees backward facing, and 90 degrees anastomotic joints. The simulation results showed a flow separation region along the graft inner wall immediately after the heel at peak flow phase and it decreased in size with the grafting angle shifting from 45 degrees forward facing to 45 degrees backward facing. At the same time, a pair of vortex was found in the cross-sectional planes of the 45 degrees backward facing and 90 degrees grafts. In addition, stagnation point was found along the graft outer wall with small shifting during the physiological cycle. High spatial and temporal wall shear stresses gradients (WSSG) were observed around the anastomotic joint. Low time-averaged wall shear stress (WSS) with elevated oscillation shear index (OSI) was found near the middle of anastomosis at the aorta wall and along the graft inner wall respectively, while high time-averaged WSS with low OSI was found at the heel, the toe, and the region downstream of the toe. These regions correlated to early lesion growth. Elevated time-averaged WSSG was found at the same region, where the elevated low-density lipoprotein (LDL) permeability was observed as reported in the literature. The existence of nearly fixed stagnating location, flow separation, vortex, high time-averaged WSS with low OSI, low time-averaged WSS with elevated OSI, and high time-averaged WSSG may lead to graft stenosis. Moreover, the simulation results obtained were consistent with those of experimental measurements. Based on the validated simulation results, the 45 degrees backward-facing graft was found to have the lowest variation range of time-averaged WSS and the lowest segmental average of WSSG among the three models investigated. The 45 degrees backward-facing graft is thus recommended for the bypass operation with expected higher patency rate.

PURPOSE:To identify post-liver transplant CT findings which predict graft failure within 1 year. MATERIALS AND METHODS:We evaluated the CT scans of 202 adult liver transplants performed in our institution who underwent CT within 3 months after transplantation. We recorded CT findings of liver perfusion defect (LPD), parenchymal homogeneity, and the diameters and attenuations of the hepatic vessels. Findings were correlated to 1-year graft failure, and interobserver variability was assessed. RESULTS:Forty-one (20.3%) of the 202 liver grafts failed within 1 year. Graft failure was highly associated with LPD (n = 18/25, or 67%, versus 15/98, or 15%, p < 0.001), parenchymal hypoattenuation (n = 20/41, or 48.8% versus 17/161, or 10.6%, p < 0.001), and smaller diameter of portal veins (right portal vein [RPV], 10.7 ± 2.7 mm versus 14.7 ± 2.2 mm, and left portal vein [LPV], 9.8 ± 3.0 mm versus 12.4 ± 2.2 mm, p < 0.001, respectively). Of these findings, LPD (hazard ratio [HR], 5.43, p < 0.001) and small portal vein diameters (HR, RPV, 3.33, p < 0.001, and LPV, 3.13, p < 0.05) independently predicted graft failure. All the measurements showed fair to moderate interobserver agreement (0.233~0.597). CONCLUSION:For patients who have CT scan within the first 3 months of liver transplantation, findings of LPD and small portal vein diameters predict 1-year graft failure. KEY POINTS:•Failed grafts are highly associated with liver perfusion defect, hypoattenuation, and small portal vein. •Right portal vein < 11.5 mm and left portal vein < 10.0 mm were associated with poor graft outcome. •Liver perfusion defect and small portal vein diameter independently predicted graft failure.

We present a case of a patient who underwent portal vein (PV) stenting for PV stenosis after a living-donor liver transplantation. A pretreatment 3D cine phase-contrast (4D-flow) MRI showed decreased, though hepatopetal, blood flow in the PV. After stenting, 4D-flow MRI confirmed an improvement in PV flow, with a more homogeneous flow distribution to each hepatic segment. 4D-flow MRI are valuable for understanding the hemodynamics of this area, planning for treatments, and evaluating the outcome of the interventions.