Pediatr Transplantation 2014: 18: 64–71
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Pediatric Transplantation DOI: 10.1111/petr.12204
Management of late-onset portal vein complications in pediatric living-donor liver transplantation Cho Y-P, Kim K-M, Ha T-Y, Ko G-Y, Hwang J-Y, Park H, Chung YS, Yoon T, Hwang S, Jun H, Kwon T-W, Lee S-G. Management of late-onset portal vein complications in pediatric living-donor liver transplantation.
Yong-Pil Cho1, Kyung-Mo Kim2, Tae-Yong Ha3, Gi-Young Ko4, Jae-Yeon Hwang4, Hojong Park1, Young Soo Chung1, Taein Yoon1, Shin Hwang3, Heungman Jun5, Tae-Won Kwon1 and Sung-Gyu Lee3
Abstract: 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.
Division of Vascular Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea, 2 Department of Pediatrics, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea, 3Division of Liver Transplantation, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea, 4 Department of Radiology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea, 5Department of Surgery, Daejeon Sun Hospital, Daejeon, Korea Key words: children – living donor liver transplantation – complications of liver transplantation – pediatric liver transplantation – portal hypertension Yong-Pil Cho, Division of Vascular Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Asanbyeongwon-gil 86, Songpa-gu, Seoul 138-736, Korea Tel.: +82 2 3010 5039 Fax: +82 2 474 9027 E-mail: [email protected]
Accepted for publication 7 November 2013
LT is an eﬀective treatment for a variety of irreversible liver diseases for which there is no other satisfactory therapy, as well as for cases in which late diagnosis precludes other therapeutic options (1–4). However, in pediatrics, relatively few donors are available in relation to the number of children waiting for LT. Therefore, several surgical techniques have been developed to overcome the shortage of available livers for these children, including transplantation of reducedAbbreviations: CT, computed tomographic; LDLT, livingdonor liver transplantation; LT, liver transplantation; PTA, percutaneous transluminal angioplasty; PV, portal vein; US, ultrasonography.
size livers, split livers, and livers from livingrelated organ donors (1–4). LDLT is now performed worldwide as an alternative to deceased LT for patients with end-stage liver disease. Adequate PV reconstruction allowing satisfactory portal ﬂow to the allograft is of vital importance during the immediate intra- and postoperative phase following LT (3–5). Particularly, in pediatric LT using reduced-size and living-related adult donors, the high incidence of narrow and sclerotic PV, recipient/graft size discrepancy and limitations of PV length can lead to early- and late-onset PV complications (4, 5). Two types of post-transplant PV complications may occur: Stenosis of the PV (either of the anas-
Late-onset PV complications
tomosis or of the vein) and complete obstruction or thrombosis of the PV (2). PV complications ordinarily require PTA or repeat surgery and can lead to retransplantation and/or recipient death. Although PTA, with or without stent, has markedly improved the ﬁrst treatment option for vascular complications after LT because of its minimal invasiveness, low rate of complications, high success rates, and good outcomes, the mesoRex shunt can be superior to PTA when the PV is completely occluded and cannot be salvaged by PTA (3–17). In this study, we evaluated retrospectively the results of PTA of late-onset (≥ three months after LT) PV complications after pediatric LDLT and assessed whether a mesoRex shunt is a viable option for treating recurrent or elastic restenosis of the PV after PTA in selected cases.
ﬂow in the PV; acceleration of the ﬂow rate in the post-stenotic PV to more than threefold that in the prestenotic PV, with narrowing of the PV diameter of Meso-Rex shunt PTA
BA, biliary atresia; FH, fulminant hepatitis; LL, left lobe; LLS, left lateral segment. *Months between LDLT and diagnosis of PV complication.
Good evolution Good evolution Good evolution Good evolution Good evolution
Late-onset PV complications
the occluded main PV, and they underwent meso-Rex shunt. The mean percent stenosis of the PV anastomosis in the four PV stenosis patients was 70% (range 50–90%). The mean PV diameters in these patients before and after PTA were 2.0 mm (range 1.5–2.3 mm) and 4.7 mm (range 4.0–5.2 mm), respectively, and the mean pressure gradients were 8.75 mmHg (range 1– 17 mmHg) and 1.75 mmHg (range 1–2 mmHg), respectively. One of these four patients, with initial PV stenosis of 90%, underwent stent placement because of residual stenosis of 70% after balloon dilation (Patient 2 in Table 1), and simultaneous embolization of severe portosystemic shunts was performed in one patient (Patient 4 in Table 1). During the follow-up period, Doppler US showed adequate PV inﬂow in the four patients in whom technical and clinical success had been achieved without procedurerelated complications, and follow-up CT scan showed that the collateral ﬂow to the varices had decreased in two of these patients. Meso-Rex shunt
Meso-Rex shunt was performed in the two children with failed PTA. The ﬁrst case, a ninemonth-old boy (Patient 1 in Table 1), received LDLT using the left lobe from his mother. In this patient, a vein graft from deceased donor was interposed between the graft PV and the recipient’s portal system for PV anastomosis because of insuﬃcient length and the diﬀerence in size between the graft and recipient PVs. Eleven months after transplantation, complete obstruction of the main PV was detected by Doppler US and CT scan. Although stable graft function was maintained (normal serum liver enzymes and bilirubin levels) and there were no clinical symptoms, the occluded main PV was approached by direct percutaneous transhepatic puncture, guided by US under general anesthesia for PTA because of a newly detected esophageal varix and splenomegaly, but the guide wire was unable to pass the occluded segment, and eventually, an attempt by transhepatic angiography to alleviate the PV obstruction failed. The subsequent evolution of the child was initially uneventful, with stable graft function and no symptoms of advanced portal hypertension. However, 61 months after transplantation, Doppler US and CT scan revealed aggravated esophageal/paraesophageal varix and progressive splenomegaly, with preserved intrahepatic left PV. A meso-Rex shunt was performed using a fresh vein allograft from deceased donor between the graft extrahepatic left PV and the recipient conﬂuence of the
superior mesenteric and splenic veins. An intraoperative splenic venogram of the hilar area showed extrahepatic collaterals communicating with paraesophageal varices. The varices were embolized using 10 coils and three NBCA, and a ﬁnal venogram revealed disappearance of the collaterals with patent PV inﬂow via the mesoRex shunt. Postoperative recovery was rapid and uneventful, with liver function tests within the normal range and normal portal ﬂow by Doppler US. The second case, an 11-month-old boy (Patient 5 in Table 1), received LDLT using the left lateral segment from his mother. In this patient, an end-to-end anastomosis was performed without a vein graft between the graft PV and the recipient’s portal system. However, immediately after transplantation, PTA with stent placement was performed because of the diﬀerence in size and insuﬃcient PV ﬂow, and stable graft function was maintained (normal serum liver enzymes and bilirubin levels) without clinical symptoms. Twenty-six months after transplantation, in-stent stenosis with total thrombosis and huge portosystemic shunts were detected by endoscopy, Doppler US, and CT scan. PV approach by direct percutaneous transhepatic puncture guided by US under general anesthesia failed to cannulate the totally thrombosed PV stent. Thirty-seven months after transplantation, deterioration of liver function tests was noted and a laparotomy was performed. At that time, an intra-operative portogram via a branch of the superior mesenteric vein showed an occluded stent in the main PV, with huge coronary varices as well as reversed ﬂow to the splenic vein, along with opaciﬁed intrahepatic portal branches through indistinct collateral pathways (Fig. 1). Surgical thrombectomy of the extrahepatic left PV was performed following localized stent mesh resection, and a meso-Rex shunt was constructed using a fresh vein allograft from deceased donor between the graft extrahepatic left PV and the recipient superior mesenteric vein (Fig. 2). An intra-operative venogram after the meso-Rex shunt showed preserved PV ﬂow but huge remaining collaterals. The splenic and coronary veins were embolized with four coils (Fig. 3). Postoperative recovery was rapid and uneventful, with liver function tests within the normal range, and normal portal ﬂow in Doppler US and multidetector helical CT scan. Outcomes
Of the six late-onset PV complications, technically and clinically successful PTA was achieved 67
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Fig. 1. Prior to the meso-Rex shunt, the intra-operative portogram via a branch of the superior mesenteric vein shows the occluded stent placed in the main PV (arrow), with coronary varices (arrowheads) as well as reversed ﬂow to the splenic vein (SP). Note the opaciﬁed intrahepatic portal branches (*) through indistinct collateral pathways.
in four (66.7%) with PV stenosis and in the other two children, in whom there had been failure to cannulate the occluded main PV, successful application of the meso-Rex shunt restored PV ﬂow. During the mean follow-up period of 1.9 yr (range 0.3–4.6 yr), periodic Doppler US and multidetector helical CT scan showed adequate PV ﬂow in all six children with normal liver function tests, and there was no procedure- or operation-related morbidity and mortality. Discussion
Adequate PV inﬂow is mandatory for rapid regeneration of transplanted liver during the immediate intra- and postoperative phase, partic-
ularly in pediatric LT recipients with reducedsize and living-related adult donors (1–5). Lateonset PV complications, such as PV stenosis (either of the anastomosis or of the vein) or complete obstruction or thrombosis of the PV, are mainly associated with clinical signs of portal hypertension, limitations of quality of life, recurrent thrombosis, growth retardation, neurocognitive impairment, and symptomatic portal biliopathy in pediatric LT recipients (10–12, 18– 20). Although recent improvements in surgical techniques have contributed to decreased vascular complications after LT, PV complications are still a signiﬁcant cause of postoperative graft failure and morbidity, occurring in 1–2% of adult deceased LT and in 3–19% of pediatric or LDLT; early-onset complications are generally caused by technical problems and late-onset complications by ﬁbrous hyperplasia of the new intima followed by ﬁbrous and organic thrombus (1–4, 7–9). Biliary atresia is the most common indication for pediatric LT (4). In our study, there was a trend toward an increased rate of PV complications when the primary cause of end-stage liver disease was biliary atresia (12.2% vs. 2.9%, p = 0.21), although the eﬀect was not statistically signiﬁcant because of the small number of patients. A high rate of PV complications in biliary atresia could be explained by several synergistic eﬀects: The rapidly progressing sclerosis and ﬁbrosis could damage the PV; previous Kasai procedures could produce PV sclerosis; repeated attacks of cholangitis could lead to inﬂammatory changes of the PV and possibly to PV ﬁbrotic changes; and the particularly intense portal hypertension could lead to a sclerotic rearrangement of the PV wall with a reduction in the diameter of the vessel (4). Although most patients with late-onset PV complications are asymptomatic and they are usually detected during routine periodic Doppler US or CT, clinical
Fig. 2. (Left) A fresh venous allograft from a deceased donor anastomosed end-to-side to the ventral portion of the extrahepatic left PV (white arrows) using non-absorbable monoﬁlament interrupted sutures. (Right) The venous conduit was then positioned behind the pylorus, across the mesocolon, and in front of the pancreas to reach the mesenteric veins to which it was anastomosed end-to-side (white arrow).
Late-onset PV complications
Fig. 3. (Left) Intra-operative portogram following the creation of a meso-Rex shunt (open arrows) from the superior mesenteric vein to the extrahepatic left PV following localized stent mesh resection, showing brisk ﬂow to the intrahepatic PV. Note remaining ﬂow through the coronary varices (black arrowheads) and reversed ﬂow to the splenic vein (SP). (Right) Intraoperative portogram following embolization (black arrowheads) of the varices and the splenic vein showing brisk ﬂow via the meso-Rex shunt with signiﬁcantly decreased ﬂow via the varices and the splenic vein.
signs of portal hypertension and elevated liver functions can be seen in symptomatic patients, and sometimes, a low platelet count is observed (3, 19). Delayed diagnosis and treatment of PV complications may lead not only to graft failure and life-threatening variceal bleeding, but also to hepatopulmonary syndrome or pulmonary hypertension, which make retransplant diﬃcult or impossible (19). Once PV complications occur, prompt diagnosis and treatment is crucial to avoid complete obstruction or subsequent graft failure (3). Doppler US and CT are the most reliable and sensitive diagnostic tests for early diagnosis of PV complications (3, 7–9, 19). Recent procedures for periodic Doppler US and multidetector helical CT have led to early diagnosis of late-onset PV complications prior to the development of clinical symptoms or complete PV obstruction, allowing us to avoid regrafting and patient loss (3, 19). Therapeutic strategies for PV complications after LT involve PTA, with or without stent, and surgical revision (4–9). Although surgical revision of the PV complications may be deﬁnitive, such intervention can be extremely diﬃcult technically (7). Recently, PTA has become widely accepted as a safe and eﬃcient therapeutic modality and, in many cases, the initial treatment option for vascular complications after LT (6–9). It is minimally invasive and essential for both deﬁnitive diagnosis and eﬀective treatment of PV complications (2, 3, 6–9). However, the management of recurrent PV complications is another problem with PTA (7–9, 19). In some cases of late-onset PV complications, the elasticity of the stricture may be as an important
determinant characteristic that leads to recurrence and needs for PTA with stent placement or surgical revision, not manageable with PTA with balloon dilation alone. Although successful PTA with stent placement for recurrent PV complications has been reported in LT recipients, stent placement has usually been used restrictively to treat recurrent or elastic restenosis after PTA with balloon dilation, because the procedure has several potential complications, such as PV thrombosis and in-stent or stent edge restenosis (7–9, 19). Additionally, in pediatric LT recipients, surgical treatment can be a better alternative to PTA with stent placement for recurrent PV complications because children are expected to grow, and the stent is ﬁxed in size (2, 8, 19). Surgical possibilities are surgical revision and thrombectomy of the anastomosis, meso-Rex shunt, other shunt operations, and retransplantation. When intrahepatic PVs are permeable without acute liver necrosis or liver ﬁbrosis, despite extrahepatic PV thrombosis, a meso-Rex shunt that redirects portal ﬂow to the liver physiologically may be the indicated therapy (1, 2). Although extension of the thrombosis to the intrahepatic branches sometimes precludes the use of this technique, it is surgically feasible in most pediatric transplant recipients even when the intrahepatic PV is poorly visible or not seen at all in postoperative periodic imaging studies (1, 2, 4, 10). Restoration of the portal ﬂow by this technique implies a cure of the portal hypertension and prevention of extrahepatic complications (1, 2). In our study, there were six late-onset PV complications (6/75, 8.0%) among the 75 pediatric LDLT recipients, and the initial therapeutic approach was PTA. 69
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Technical and clinical success was achieved in four of the six patients (66.7%) who showed late-onset PV stenosis and received PTA with balloon dilation (three children) and stent placement (one child). A meso-Rex shunt was performed in the two children with failed PTA: Complete obstruction of the main PV and restenosis with total thrombosis after PTA with stent placement. In pediatric patients with late-onset PV complications after LDLT, a meso-Rex shunt is performed preferably with interposition of the patient’s own internal jugular vein as vascular autograft, because this material is associated with best outcomes (1). In our study, a meso-Rex shunt was performed using a fresh venous allograft from a deceased donor in the two children with failed PTA. We did not use the patient’s own internal jugular vein, because of the inadequate length in that setting. There was no procedure- or operation-related morbidity or mortality in any of the six patients. In the treatment of late-onset PV complications with clinical signs of portal hypertension, decreased portal ﬂow due to severe portosystemic shunt may contribute to recurrent PV thrombosis, and restoration of the portal ﬂow with simultaneous embolization or surgical ligation of portosystemic shunts may be important for achieving patency of the PV (7). In our study, severe portosystemic shunts were embolized simultaneously during one of the PTA and both mesoRex shunt operations, and the ﬁnal portograms showed disappearance of the collaterals with patent PV ﬂow. In conclusion, PTA, with or without stents, is a safe and eﬀective procedure for treating late-onset PV stenosis after pediatric LDLT, without signiﬁcant morbidity or mortality. However, in growing pediatric recipients with recurrent or elastic restenosis of the PV after PTA or chronic PV thrombosis, a meso-Rex shunt, which redirects portal ﬂow to the liver, can be a superior alternative to PTA with stent placement.
Authors’ contributions Design: Yong-Pil Cho, Kyung-Mo Kim, and Sung-Gyu Lee. Analysis and interpretation of data: Yong-Pil Cho, Kyung-Mo Kim, Gi-Young Ko, Jae-Yeon Hwang, Hojong Park, Young Soo Chung, Taein Yoon, and Heungman Jun. Drafting the paper: Yong-Pil Cho, Tae-Yong Ha, and Gi-Young Ko. Data collection: Yong-Pil Cho, Kyung-Mo Kim, Gi-Young Ko, Shin Hwang, and Sung-Gyu Lee. Writing: Yong-Pil Cho, Kyung-Mo Kim, Tae-Yong Ha, and Gi-Young Ko. Review: Yong-Pil Cho, Kyung-Mo Kim, Tae-Yong Ha, Gi-Young Ko, and Sung-Gyu Lee. All the authors approved of the submitted and ﬁnal versions.
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