Portal vein (PV) reconstruction is 1 of the key components for success in pediatric liver transplantation (LT).1 In patients with biliary atresia (BA), the native PV becomes sclerotic and hypoplastic due to inflammation of the hepatoduodenal ligament and recurrent cholangitis.2 The narrowing PV trunk should be evaluated to determine its usability before implantation at the time of LT. If it has become sclerotic with wall thickening, it should be removed; otherwise, subsequent thrombosis can easily occur.1 Several technical modifications in PV reconstruction have been reported, including vein graft (VG) interposition and longitudinal venoplasty.2-4 We have preferred VG interposition for PV reconstruction during living donor LT (LDLT) as it allows for sufficient portal flow to be obtained and we previously reported excellent short-term outcomes of this technique.5
The aims of this retrospective study were to review our accumulated experience of PV reconstruction in LDLT for children with BA and to analyze the outcomes of PV reconstruction with VG interposition.
MATERIALS AND METHODS
From November 2005 to December 2017, a total of 204 consecutive pediatric patients with BA (<18 y of age) underwent LDLT at the National Center for Child Health and Development in Tokyo, Japan. Among these, 116 patients aged 1 or younger (56.9%) were enrolled in this study. The method of graft selection in our hospital and the surgical procedure have been described in detail elsewhere.6-8 The immunosuppressive protocol consisted of tacrolimus and low-dose steroids for patients aged 1 or younger, regardless of the ABO-compatibility between the donor and the recipient. Informed consent was obtained from all donors and recipients before enrollment, and their anonymity was preserved. The study was approved by the Ethics Committee of the National Center for Child Health and Development and was conducted in accordance with the Declaration of Helsinki (2008).
The surgical procedure of PV reconstruction has been reported in detail in previous studies.1,2,5 Briefly, we dissected the collateral vessels of the portal venous system, including the left gastric vein, splenorenal shunt, and retroperitoneal shunt to obtain sufficient front flow into the graft. Anastomosis was performed by interrupted or continuous sutures with 6-0 or 7-0 absorbable polydioxanone monofilament. We selected the type of anastomosis based on the discrepancy in the diameters of the graft and the native PV, the distance between them, and the extent and severity of the sclerosis of the native PV (Figure 1). If the native PV was not severely sclerotic with good wall extensibility and we obtained sufficient front flow, we selected direct anastomosis using the native PV trunk (type 1) or a branch patch between the left and right PV branches (type 2). If the whole length of the native PV up to the superior mesenteric vein and splenic vein junction became severely sclerotic, we preferred to perform VG interposition (type 3); however, if a VG of appropriate size and length could not be obtained, we selected longitudinal venoplasty using a patch graft on the anterior side of the site of anastomosis (type 4). Although type 4 PV reconstruction was applied to 3 cases in the same study period, and 1 of them experienced PV stenosis (PVS), this type was excluded from the analysis in this study due to the small number of cases.
The Evaluation of the Patency of the Reconstructed PV and Further Management for PV Complications
We routinely monitored PV flow by Doppler ultrasonography (US) twice daily after LDLT until postoperative day 7, then once daily until postoperative day 14, and afterward at least once weekly depending on the patient’s condition until the patient was discharged. Anticoagulant agents such as heparin or warfarin were not routinely used, except for cases involving patients with intraoperative PV thrombosis (PVT). Thereafter, the PV flow and the patency of the reconstructed veins were assessed during regular outpatient follow-up by Doppler US. When PV complications (PVCs) were suspected because of symptoms such as gastrointestinal bleeding or findings from Doppler US and/or computed tomography, percutaneous transhepatic portography was performed to confirm the presence of anastomotic PVS, complete PV occlusion with no blood flow, or partial PVT with a detectable blood flow.9 When PVS was diagnosed, balloon dilatation was performed, and when PVT was diagnosed, a PV catheter was placed near the PVT followed by the infusion of urokinase via the tube. When venoplasty by means of percutaneous transhepatic portography was not successful or had to be repeated, the correction of the PV flow was attempted surgically or by stent insertion.3
Data Collection and Definitions
We collected clinical data from electronic medical records and surgical data from operation records. The recipients’ postoperative complications were graded according to the Clavien-Dindo classification system.10 A hypoplastic PV was defined by a diameter of <4 mm on preoperative Doppler US.5 The period of patency of the reconstructed PV was defined as the duration from LDLT to the time of the diagnosis of PVCs by portography.
Continuous variables were summarized as the mean and SD and were compared using the Mann–Whitney U test. Categorical variables were summarized as frequencies and percentages and were compared using the χ2 test. Survival curves were estimated using the Kaplan–Meier method and compared using the log-rank test. Risk factors for PVCs after LDLT were identified using the log-rank test for a univariate analysis and the Cox proportional hazard model for a multivariate analysis to estimate the hazard ratio and its 95% confidence interval. Receiver operating characteristic curves were plotted, and areas under the curve were calculated to determine the optimal cutoff value for the pediatric end-stage liver disease score in the analysis of risk factors for PVCs. P = 0.05 were used for variable selection and were considered to indicate statistical significance. All statistical analyses were performed using the SPSS software program (version 21; IBM, Chicago, IL).
Table 1 summarizes the details of the patients enrolled in this study. The mean age at LDLT was 7.8 ± 2.0 months (range: 4–12 mo), and the mean body weight (BW) was 6.5 ± 1.1 kg (range: 3.7–9.2 kg). Fourteen patients (12.1%) were treated in the intensive care unit, and 31 patients (26.7%) received multiple abdominal surgeries before LDLT. Fifty-five patients (47.4%) revealed a hypoplastic PV, and 28 patients (24.1%) revealed retrograde PV flow. With the exception of 1 patient who received a graft from their grandmother, all patients received grafts from their parents (father, n = 39; mother, n = 76). The mean age of the donor was 33.4 ± 5.4 years (range: 20–47 y). Twenty-six donor and the recipient pairs (22.4%) showed ABO incompatibility. The graft types included left lateral segment (LLS) grafts (n = 64; 55.2%) and reduced LLS grafts (n = 52; 44.8%). The mean graft-to-recipient body weight ratio (GRWR) was 3.3 ± 0.7 (range 1.3–5.6). The median follow-up period was 4.7 years (range: 37 days to 11.6 y).
Details of PV Reconstruction
Intraoperative PVT, which necessitated reanastomosis, was encountered at the time of primary PV anastomosis in 17 cases (14.7%). We finally performed the following types of PV reconstruction: type 1 (n = 36; 36.2%), type 2 (n = 47; 46.6%), and type 3 (n = 33; 17.5%). In type 3 PV reconstruction, the left ovarian vein (n = 16) and inferior mesenteric vein (n = 13) were retrieved from the donors and used as VGs, while the left renal vein (n = 3), left jugular vein (n = 2), and the left external iliac vein (n = 1) were retrieved from the recipients and used as VGs. The graft umbilical vein was used as a VG in 1 case. Three cases required 2 VGs for PV reconstruction. In 8 of 17 cases in which intraoperative PVT was experienced, a PV catheter was inserted through the tributary of the portal venous system for a week with a continuous infusion of heparin and urokinase. The remaining cases in which type 3 PV reconstruction was performed received systemic heparinization for a week, followed by the oral administration of warfarin for 3 months after LDLT.
Incidence of PVCs and Their Outcomes
PVCs occurred in 10 cases (7.2%). The types of PV reconstruction performed in these cases were as follows: type 1 (n = 2), type 2 (n = 3), and type 3 (n = 5). PVS and PVT occurred in 10 cases and 3 cases, respectively. Three cases suffered from PVS and PVT simultaneously or intertemporally. Three cases were surgically treated for PVCs, and while 1 case (case 1) was successfully treated, the other 2 subsequently died (case 3) or required retransplantation (re-Tx) (case 5) due to graft failure related to PVCs. Two cases (cases 7 and 9) underwent stent insertion for short-term recurrence after the initial treatment. In addition to case 5, 2 more cases (cases 4 and 7) who showed insufficient PV flow despite the good patency of the reconstructed PV required re-Tx due to graft failure, which was mainly related to refractory rejection.
Table 2 shows the details of the cases with PVCs. Patients with early PVCs frequently required reanastomosis or stent insertion, and some cases consequently died or required re-Tx.
The Outcomes of Recipients With and Without a VG
Table 3 summarizes the pretransplant characteristics and surgical details of recipients who underwent PV reconstruction with a VG (VG group, consisting of type 3 PV reconstruction) and without a VG (non-VG group, consisting of type 1 and type 2 PV reconstruction). Regarding the findings of PV before LDLT, the patients in the VG group had a significantly smaller PV trunk and a significantly higher proportion of retrograde PV flow in comparison to the non-VG group. In the VG group, the operation time was significantly longer, and the estimated blood loss was greater in comparison to the non-VG group. More than half of the patients in the VG group received a reduced LLS graft; this rate was higher than that in the non-VG group. Table 4 shows the posttransplant outcomes. The incidence of severe postoperative complications, defined by more than 3b grade according to the Clavien-Dindo classification system, and that of PVCs were higher in the VG-group, although they were not significantly different between the 2 groups. The proportion of recipients who required re-Tx was significantly higher in the VG-group (P = 0.022); however, the mortality rates of the 2 groups did not differ to a statistically significant extent.
The patient survival rates in the VG and non-VG groups were 97.0% and 96.4% at 1 year and 93.9% and 96.4% at 5 years, respectively. On the contrary, the graft survival rates in the VG and non-VG groups were 87.9% and 96.4% at 1 year and 87.9% and 96.4% at 5 years, respectively. The patient survival rates of the 2 groups did not differ to a statistically significant extent (P = 0.581); however, the graft survival rate of the VG group tended to be lower (P = 0.089). The PVC-free survival rates in the VG and non-VG groups were 87.9% and 93.8% at 1 year and 84.6% and 93.8% at 5 years, respectively. The PVC-free survival rate in the VG group was lower than that in the non-VG group, although it was not significantly different between the 2 groups (P = 0.121; Figure 2).
Risk Factors for PVCs After LDLT
Table 5 shows the results of the univariate and multivariate analysis to determine the risk factors for PVCs (n = 10) after LDLT. Early transplant era and retrograde PV flow were significant risk factors. A multivariate analysis with the candidate variables (P < 0.05 in the univariate analysis) revealed that early transplant era (hazard ratio, 5.58; 95% confidence interval, 1.39-37.07; P = 0.014) was the only independent risk factor for PVCs after LDLT.
Although the incidence of PVCs in the cases undergoing PV reconstruction with a VG was high (15.2%), this study showed an acceptable incidence of PVCs and the long-term patency of reconstructed PVs with an excellent patient survival in pediatric LDLT.
With recent advances in technical refinements of surgical procedures and perioperative management in pediatric LT, LT has been more frequently indicated for small children. When considering LT for smaller children with BA, the vasculature in the portal venous system, including the development of collateral vessels, should be carefully evaluated before performing LT. The potential collaterals should be interrupted to the maximum possible extent to obtain sufficient PV flow during the operation.1 If the PV trunk does not become fully distended due to sclerotic change of the wall, despite complete collateral interruption, the sclerotic part of the wall should be removed and technical modification of PV reconstruction may be considered. These techniques are broadly classified into 2 technical modifications, VG interposition and longitudinal venoplasty with vein patch.2-4 We prefer to select VG interposition rather than longitudinal venoplasty because we consider the complete removal of the sclerotic part of the PV wall to be important for preventing intraoperative PVT and subsequent PVCs. Therefore, longitudinal venoplasty was applied only when a VG of appropriate size and length could not be obtained for VG interposition at our center. However, several studies have suggested that longitudinal venoplasty with a vein patch is associated with better outcomes,4 or a higher rate of PVT after VG interposition.11 Our study population only included a small number of cases in which longitudinal venoplasty was performed; thus, we could not compare these 2 technical modifications in PV reconstruction. This was 1 of the limitations of the present study.
Some studies have reported that the use of VG is a risk factor for PVCs.11-13 However, it is pertinent to note that development of thrombosis partially depends on the type of VG. Buell et al reported that the use of cryo-preserved venous conduits was associated with a higher incidence of PVS in comparison to native vessel conduits (50% versus 16%),12 and Kyoden et al concluded that the use of jump or interposition cryo-preserved VGs was a risk factor for PVCs.13 Thus, it is the use of fresh VGs obtained from the recipient’s or living donor’s native vessels seems important for preventing PVCs after LDLT. In contrast, intraoperative or immediate posttransplant PVT formation during LDLT is closely associated with the occurrence of PVCs, which might be caused by insufficient PV flow due to incomplete collateral interruption. Another cause of PVT formation might be inappropriate decisionmaking in relation to the technique of PV reconstruction, especially the errant use of a sclerotic PV or a native PV with wall thickening. Although it is clear that we must pay attention to the technical aspects of anastomosis with VGs, we believe that the most essential factor in preventing PVCs after LDLT is to obtain sufficient PV flow, either by intensive collateral interruption or appropriate decisionmaking in relation to the need for PV reconstruction.1 Furthermore, retrograde PV flow was identified as 1 of the significant risk factors for PVCs after LDLT in the univariate analysis, which can support the importance to obtain sufficient PV flow, as noted earlier.
This study is associated with several limitations. First, it was a single-center study, which may have led to a selection biases, including biases in relation to race, indications for surgery, and surgical procedures. Second, this study was retrospective in nature, and the decision to select PV reconstruction depended on the subjective impression of the individual surgeons. In addition, because the study period was relatively long and the number of LTs performed at our institute each year has been growing, the learning curve may have affected the results of this study decision-making and the surgical procedures in PV reconstruction. In fact, 8 PVCs (16.0%) occurred in cases undergoing LDLT before December 2012 (n = 50), while only 2 cases (3.0%) developed PVCs after January 2013 (n = 66), and the multivariate analysis revealed that early transplant era was the only independent risk factor for PVCs after LDLT. Conversely, high pediatric end-stage liver disease score, hypoplastic PV, retrograde PV flow, the use of interposition VG, and intraoperative PVT formation were not identified as significant risk factors of PVCs. Those results may indicate that our current decisionmaking to use interposition VG and its surgical procedures could be properly done for the clinical background of patients, who are considered to be more vulnerable to PVCs. Finally, the incidence of PVCs may have been underestimated due to the low sensitivity of screening Doppler US, especially in the long term.
In conclusion, VG interposition for PV reconstruction in LDLT appears to be a feasible alternative option with acceptable outcomes for patients with BA in this current study. The achievement of sufficient PV flow is essential for preventing PVCs after LT. However, other recent studies showed good results of longitudinal venoplasty, and further studies are be needed to elucidate the best procedure for PV reconstruction of the hypoplastic PV in pediatric LT.
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