Hepatobiliary scintigraphy for the assessment of biliary stricture after pediatric living donor liver transplantation for hepaticojejunostomy reconstruction: the value of the excretion rate at 60 min

HBS is performed to determine the presence of biliary stricture after liver transplantation. We focused on the Ex-60 after an intravenous injection of tracer during HBS. The aim of this study was to review the cutoff values for the diagnosis of biliary stricture by HBS after pediatric LDLT. We analyzed 114 HBS studies using (99m) Tc-PMT in 80 cases after pediatric LDLT. HBS was performed three months after LDLT on a routine basis and/or was performed when ultrasonography and blood test findings indicated biliary stricture. A ROC curve analysis was performed to identify the cutoff value for the correlation between Ex-60 and biliary stricture. The Ex-60 (mean ± s.d.) in the cases diagnosed as having biliary stricture and in normal subjects were 49.1 ± 20.2% vs. 78.0 ± 9.7% (p < 0.01), respectively. As a result of an ROC curve analysis of the Ex-60, the recommended cutoff value to diagnose biliary stricture was set at 69.2% (sensitivity 87.0%, specificity 81.8%). In cases where the Ex-60 by (99m) Tc-PMT HBS is <69.2%, it is recommended that further treatment for biliary stricture should be provided.     

Biliary strictures in pediatric liver transplant recipients – Early diagnosis and treatment results in excellent graft outcomes

Anderson CD, Turmelle YP, Darcy M, Shepherd RW, Weymann A, Nadler M, Guelker S, Chapman WC, Lowell JA. Biliary strictures in pediatric liver transplant recipients – Early diagnosis and treatment results in excellent graft outcomes.
Pediatr Transplantation 2010: 14:358–363. © 2009 John Wiley & Sons A/S. Abstract: Biliary complications in pediatric LT are important causes of morbidity and graft loss. We examined our recent pediatric LT experience to determine the outcome of post‐LT biliary complications and their relationship to graft type. All initially isolated LTs performed at our institution between January 1, 2000 and August 20, 2007 were reviewed. Recipient data, donor type, graft survival, and biliary complications data were examined. Of 66 LTs, 32 patients received whole organ grafts, and 34 received partial grafts; 11 split, seven reduced size, and 16 live donors. Seventy‐seven percent of patients had biliary reconstruction using a RYH. Overall, 17 (26%) developed biliary complications, and 15 were diagnosed within six months post‐LT. Live donor and split allografts had more biliary complications than reduced size or whole allografts (50% and 36% vs. 0% and 16%, respectively). Seventy‐one percent responded to percutaneous or endoscopic treatment. Five failed initial non‐operative management and required reoperation (one retransplantation). These data suggest that biliary strictures occur most frequently in live donor and split allografts and that non‐operative therapy is highly successful. Partial grafts are essential in pediatric LT, and a high clinical suspicion for biliary complications combined with aggressive and early diagnosis and therapy rarely results in graft loss.     

Simultaneous surgical and interventional radiological approach to treat complicated biliary strictures after pediatric liver transplantation

Post-transplantation biliary strictures occur in 5-15% of the pediatric liver transplant patients and are conventionally managed by interventional radiological techniques. Failure of this treatment leads to reoperation and sometimes to retransplantation. Herein, we describe a surgical approach and interventional radiologic approach to manage biliary strictures that failed the conventional radiologic treatment, in order to avoid retransplantation. Included in the study were eight children who underwent liver transplantation at our center or referred to our institution for evaluation of the biliary strictures that failed radiological treatment. Biliary strictures were confirmed by a narrowing of the biliary anastomosis on the percutaneous transhepatic cholangiogram. At surgery, a guide wire was introduced into the distal bile system through the use of an enterotomy in Roux limb. Over the guide wire, the stricture was ballooned and the diameter of the biliary tree was determined. A pigtail catheter was introduced on the biliary tree across the abdominal wall, the liver, the stricture and the anastomosis into the enterotomy. A final cholangiogram confirmed the positioning of the catheter. Mean follow-up was 39.8 +/- 20.8 months. All patients had their strictures successfully treated and survived the procedure. Three patients were readmitted to the hospital with fever. It was necessary to revise the hepaticojejunostomy in three patients because of cholangitis and/or recurrence of biliary stricture. Of the eight patients of this study, two required retransplantation and one died. We conclude that an aggressive combined surgical and radiologic approach can avoid retransplantation in patients with complicated post-transplant biliary strictures.     

Intrahepatic cholangiojejunostomy for complex biliary stenosis after pediatric living‐donor liver transplantation

The treatment of biliary stenosis after pediatric LDLT is challenging. We describe an innovative technique of peripheral IHCJ for the treatment of patients with complex biliary stenosis after pediatric LDLT in whom percutaneous treatment failed. During surgery, the percutaneous biliary drainage is removed and a flexible metal stylet is introduced trough the tract. Subsequently, the most superficial aspect of the biliary tree is recognized by palpation of the stylet's round tip in the liver surface. The liver parenchyma is then transected until the bile duct is reached. A side‐to‐side anastomosis to the previous Roux‐en‐Y limb is performed over a silicone stent. Among 328 pediatric liver transplants performed between 1988 and 2015, 26 patients developed biliary stenosis. From nine patients requiring surgery, three patients who had received left lateral grafts from living‐related donors due to biliary atresia were successfully treated with IHCJ. After a mean of 45.6 months, all patients are alive with normal liver morphological and function tests. The presented technique was a feasible and safe surgical option to treat selected pediatric recipients with complex biliary stenosis in whom percutaneous procedures or rehepaticojejunostomy were not possible, allowing complete resolution of cholestasis and thus avoiding liver retransplantation.     

Risk factors for early and late biliary complications in pediatric liver transplantation

BC are a common source of morbidity after pediatric LT. Knowledge about risk factors may help to reduce their incidence. Retrospective analysis of BC in 116 pediatric patients (123 LT) (single institution, 05/1990–12/2011, medium follow‐up 7.9 yr). One‐, five‐, and 10‐yr survival was 91.1%, no patient died of BC. Prevalence and risk factors for anastomotic and intrahepatic BC were examined. There were 29 BC in 123 LT (23.6%), with three main categories: 10 (8.1%) primary anastomotic strictures, eight (6.5%) anastomotic leaks, and three (2.4%) intrahepatic strictures. Significant risk factors for anastomotic leaks were total operation time (increase 1.26‐fold) and early HAT (<30 days post‐LT; increase 5.87‐fold). Risk factor for primary anastomotic stricture was duct‐to‐duct choledochal anastomosis (increase 5.96‐fold when compared to biliary‐enteric anastomosis). Risk factors for intrahepatic strictures were donor age >48 yr (increase 1.09‐fold) and MELD score >30 (increase 1.2‐fold). To avoid morbidity from anastomotic BC in pediatric LT, the preferred biliary anastomosis appears to be biliary‐enteric. Operation time should be kept to a minimum, and HAT must by all means be prevented. Children with a high MELD score or receiving livers from older donors are at increased risk for intrahepatic strictures.     

Outcomes after discontinuation of routine use of transanastomotic biliary stents in pediatric liver transplantation at a single site

Routine use of transanastomotic biliary stents (RTBS) for biliary reconstruction in liver transplantation (LT) is controversial, with conflicting outcomes in adult randomized trials. Pediatric literature contains limited data. This study is a retrospective review of 99 patients who underwent first LT (2005–2014). In 2011, RTBS was discontinued at our center. This study describes biliary complications following LT with and without RTBS. 56 (56%) patients had RTBS. Median age at LT was 1.9 yr (IQR 0.7, 8.6); 55% were female. Most common indication for LT was biliary atresia (36%). Most common biliary reconstruction was Roux‐en‐Y choledochojejunostomy (75% with RTBS, 58% without RTBS, p = 0.09). Biliary complications (strictures, bile leaks, surgical revision) occurred in 23% without significant difference between groups (20% with RTBS, 28% without RTBS, p = 0.33). Patients with RTBS had routine cholangiography via the tube at 6–8 wk; thus, significantly more patients with RTBS had cholangiograms (91% vs. 19%, p < 0.0001). There was no difference in the number of patients who required therapeutic intervention via endoscopic or percutaneous transhepatic cholangiography (11% with RTBS, 19% no RTBS, p = 0.26). Routine use of RTBS for biliary reconstruction in pediatric LT may not be necessary, and possibly associated with need for costlier, invasive imaging without improvement in outcomes.     

Duct-to-duct biliary reconstruction in pediatric living donor liver transplantation

The results of duct-to-duct biliary reconstruction in six pediatric patients who received a living donor liver transplant aged from 2 months to 11 yr old are reported. The graft was either entire or a part of the left lateral segments. The orifice of the bile duct of the graft was anastomosed to the recipients' hepatic duct in an end-to-end fashion by interrupted suture using 6-0 absorbable material. A transanastomotic external stent tube (4 Fr) was passed through the stump of the recipients' cystic duct. Mean time for reconstruction was 24 min. All the recipients survived the operation and reinitiated oral intake on postoperative day 3. There were no early biliary complications. One 5-yr-old boy suffered from an anastomotic stenosis 9 months after transplantation. He underwent re-anastomosis by Roux-en Y (R-Y) procedure and recovered uneventfully. Duct-to-duct anastomosis in pediatric living donor liver transplantation has benefits while the complication rate is comparable to R-Y reconstruction.     

Choledochoduodenostomy in pediatric liver transplantation

Campsen J, Zimmerman MA, Narkewicz MR, Sokol RJ, Mandell MS, Kam I, Dovel D, Karrer FM. Choledochoduodenostomy in pediatric liver transplantation. Pediatr Transplantation 2011: 15: 237–239. © 2011 John Wiley & Sons A/S. Abstract: Reconstruction of the bile ducts during pediatric liver transplantation is generally performed by a Roux‐en‐Y CDJ because direct duct‐to‐duct anastomosis CC is often not possible. Anastomosis of the donor liver bile duct to the duodenum CDD provides another option. We provide preliminary evidence that CDD is an alternative technique for biliary reconstruction when CC is not possible in pediatric liver transplant recipients that have a hostile abdomen or to preserve bowel length. Methods: From 2007 to 2008, a total of 19 pediatric cadaveric liver transplants were performed at our center. Four of the 19 had a bile duct reconstruction by CDD. Results: CDD reconstruction was used in patients who received a liver transplant for a diagnosis of PSC, congenital hepatic fibrosis, biliary atresia, and Alagille syndrome. The ages of the patients were 17 and 10 yr and 10 and 17 months. Three grafts were whole cadaveric livers, and one was a reduced left lobe. CDD was used to revise a prior anastomosis in one patient who had a previous Roux‐en‐Y that was unusable during the retransplant, and another to repair a stricture in a second patient with a CC. We also performed a CDD in a patient with a hostile abdomen from previous surgery, and another patient to avoid short gut syndrome that a Roux‐en‐Y may have created. All patients are alive with functioning grafts with a follow‐up of at least one yr. None of the patients developed clinically significant biliary complications (leak, stricture, cholangitis). Conclusion: Our preliminary experience suggests that CDD is an option for biliary reconstruction in pediatric transplant patients with hostile abdomens or to preserve bowel length.     

New‐onset diabetes mellitus after pediatric liver transplantation

In the first five yr after liver transplant, approximately one in 10 pediatric recipients will develop NODAT. Factors associated with higher risk for NODAT have been difficult to identify due to lack of uniformity in reporting and data collection. Limited studies have reported higher risk in those who are at an older age at transplant, those with high‐risk ethnic backgrounds, and in those with particular underlying conditions, such as CF and primary sclerosing cholangitis. Immunosuppressive medications, including tacrolimus, cyclosporine A, GC, and sirolimus, have been implicated as contributing to NODAT, to varying degrees. Identifying those at highest risk, appropriately screening, and diagnosing NODAT is critical to initiating timely treatment and avoiding potential complications. In the pediatric population, treatment is limited primarily to insulin, with some consideration for metformin. Children with NODAT should be monitored carefully for complications of DM, including microalbuminuria, hypertension, hyperlipidemia, and retinopathy.     

Duct-to-duct biliary reconstruction in selected cases in pediatric living-donor left-lobe liver transplantation

Abstract:  The feasibility of D-D biliary reconstruction in pediatric LDLT using left-lobe graft has been discussed in few reports. The use of a trans-anastomotic biliary tube seemed to be the favorable method to avoid the complications according to these reports. We had performed left-lobe LDLT for seven pediatric cases and D-D was done originally. Three cases were converted to R-Y hepaticojejunostomy due to radical resection of hepatoduodenal ligament (n = 1) and severe kinking of D-D (n = 2). Four cases received D-D using 6-0 PDS interrupted sutures without external stent tube. One D-D case died of intra-cerebral hemorrhage 10 days after operation with a functioning graft. There was one biliary leakage in a D-D patient who required PTCD stent for 4 months without any sequale. From our limited experience, D-D biliary reconstruction without external stent tube in left-lobe LDLT is feasible in certain pediatric cases having normal extra-hepatic bile ducts. In smaller recipient with larger graft, the use of a trans-anastomotic biliary tube can prevent anastomotic kinking although we suggest R-Y biliary reconstruction is better for this condition.     

Percutaneous interventional management of biliary complications after pediatric liver transplantation: A 16‐year single‐institution experience

The aim of the study was to investigate the BiCx after the pediatric OLT and to assess the efficacy of the fluoroscopic‐guided PBI in the patients with BiCx as compared to the SR. A total of 340 OLTs were performed in 302 patients over the last 16 years. The inclusion criteria were the presence of BS or BL as a complication after OLT. The management of the BiCx was studied. Graft revision, graft loss, and survival were evaluated following PBI and SR. BiCx occurred in 17.1% (58/339) of the transplants; 6.2% (21/339) of transplants demonstrated BL and 12.7% (43/339) of the transplants had BS. Overall graft survival rates at 1 and 3 years in OLT with BL treated with PBI were 75.0% and 68.8% as compared with 75% and 66.7% in OLT treated with SR (P>.05). Overall graft survival rates at 1 and 3 years in OLT with BS treated with PBI were 70.6% and 54.5% as compared with 71.4% and 50% in OLT with SR or ERCP, respectively (P>.05). Based on the results, we conclude that PBI is as effective as SR in patients with the BL and BS after OLT.     

Percutaneous removal of biliary stones post‐liver transplant in a pediatric patient: Case report and review of the literature

This case report describes an 8‐year‐old girl who underwent a segmental LT for a primary diagnosis of citrullinemia at the age of 12 months. She presented with cholangitis secondary to stenosis of the biliary‐enteric anastomosis. MRI revealed dilatation of intrahepatic bile ducts associated with multiple stones. An endoscopic approach failed to decompress the bile ducts and remove the stones. A percutaneous approach was then undertaken. After placement of a temporary external biliary drain for 12 days, a 26 French sheath was placed to access the bile ducts. Using a 14Fr flexible cystoscope, 80%‐90% of the biliary stones were removed. This was followed by antegrade balloon dilatation of the biliary‐enteric anastomosis. Two months later, the procedure was repeated, resulting in complete clearance of the biliary stones. An internal‐external biliary drain was maintained in placed for 10 months. The patient has been asymptomatic, with no evidence of stone recurrence for 13 months after drain removal. Percutaneous biliary stone removal is commonly performed in adults with non‐transplanted livers, especially in complex cases, and has also been shown to be successful in the pediatric population. However, it is rarely reported in transplanted livers in adults, and to the best of our knowledge, no pediatric cases have been reported. This case illustrates that this technique can be successfully utilized in pediatric LT patients.     

Biliary strictures and hepatic artery flow abnormalities in split liver transplants

O'Loughlin EV, Stormon MO, Shun A, Verran D, Jermyn V, Wong C, Lord D. Biliary strictures and hepatic artery flow abnormalities in split liver transplants.
Pediatr Transplantation 2010: 14: 121–125. © 2009 John Wiley & Sons A/S.
Abstract:  The aim of this study was to examine the role of HA flow abnormalities in the development of biliary strictures following split liver transplants. Data was obtained from a prospective data base of all patients undergoing split liver transplants from 2000–2008 with a follow up time of at least six months. Forty-six transplants were performed in 44 patients. Fourteen of 46 developed strictures of whom four were intrahepatic and 10 anastomotic. Nine of 14 with strictures had either hepatic artery thromobosis (HAT, four) or abnormalities of HA flow identified by routine Doppler ultrasound (5) compared with two of 32 without strictures (p < 0.02, (one temporary loss of flow and one HA aneurysm). There were no differences between the stricture and non stricture group with regard to age or weight at transplant, donor age, cold and warm ischemia times or intraoperative portal vein flow though there was a significant decrease in intraoperative HA flow in the stricture group. In conclusion, both HAT and hepatic artery flow abnormalities are associated with biliary strictures in the majority of split liver transplants. However, unrecognised abnormalities in HA flow and or other factors are likely to contribute.     

Roux‐en‐Y enterolith leading to obstruction and ischemic necrosis after pediatric orthotopic liver transplantation

Biliary complications are a common cause of morbidity after liver transplantation, with biliary stone formation being a known occurrence generally upstream of a stricture. A 12‐year‐old boy, who underwent an orthotopic liver transplantation at 11 months of age for biliary atresia, presented acutely with fever and abdominal pain. Cross‐sectional imaging revealed Roux‐en‐Y limb dilatation and thickening. He was explored and was found to have an ischemic Roux limb secondary to an obstructing enterolith. A segmental bowel resection and revision of his hepaticojejunostomy was performed. While rare, biliary enteroliths may present as either a bowel obstruction or cholangitis and should be considered in the differential diagnosis of a patient following biliary reconstruction. Additionally, anatomic etiologies should be considered and potentially surgically corrected.     

Graft fibrosis in patients with biliary atresia after pediatric living-related liver transplantation

Although an LDLT can successfully treat biliary atresia (BA), some patients develop liver fibrosis or inflammation. To study the incidence and risk factors associated with these complications, we performed serial protocol biopsies. Twenty-four patients with BA who received a pediatric LDLT underwent protocol biopsies. All patients received standard tacrolimus-based immunosuppression and steroids. The last available biopsies were assessed. The mean age at the time of transplant was 4.8yr and the follow-up period ranged from 1.2 to 12.3yr. The GRWR ranged from 0.8% to 4.5%. The mean time from transplantation to the latest biopsy was 4.7yr. No complications occurred with the biopsy protocol. The last available biopsies for 13 (54%) and 4 (17%) patients indicated grade 1 and grade 2 portal fibrosis, respectively, and 14 patients (54%) had inflammation. No ductopenia was detected. A younger age at LDLT was significantly correlated with graft fibrosis (p=0.036). These results indicate that biopsy-proven fibrosis can be detected in patients with BA after LDLT, even in the context of normal liver function blood tests. Therefore, a serial biopsy is a safe and effective follow-up procedure for pediatric LDLT.     

An institutional experience of pre‐emptive liver transplantation for pediatric primary hyperoxaluria type 1

Primary hyperoxaluria type 1 (PH1) is an inherited metabolic disease that culminates in ESRF. Pre‐emptive liver transplantation (pLTx) treats the metabolic defect and avoids the need for kidney transplantation (KTx). An institutional experience of pediatric PH1 LTx is reported and compared to the literature. Between 2004 and 2015, eight children underwent pLTx for PH1. Three underwent pLTx with a median GFR of 40 (30–46) mL/min/1.73 m² and five underwent sequential combined liver‐kidney transplantation (cLKTx); all were on RRT at the time of cLKTx. In one case of pLTx, KTx was required eight and a half yr later. pLTx was performed in older (median 8 vs. 2 yr) and larger children (median 27 vs. 7.75 kg) that had a milder PH1 phenotype. In pediatric PH1, pLTx, ideally, should be performed before renal and extrarenal systemic oxalosis complications have occurred, and pLTx can be used “early” or “late.” Early is when renal function is preserved with the aim to avoid renal replacement. However, in late (GFR < 30 mL/min/1.73 m²), the aim is to stabilize renal function and delay the need for KTx. Ultimately, transplant strategy depends on PH1 phenotype, disease stage, child size, and organ availability.     

Predicting chance of liver transplantation for pediatric wait‐list candidates

Information about wait‐list time has been reported as one of the single most frequently asked questions by individuals awaiting a transplant but data regarding wait‐list time have not been processed in a useful way for pediatric candidates. To predict chance of receiving a DDLT, we identified 6471 pediatric (<18 years), non status‐1A, liver‐only transplant candidates between 2006 and 2017 from the SRTR. Cox regression with shared frailty for DSA level effect was used to model the association of blood type, weight, allocation PELD and MELD, and DSA with chance of DDLT. Jackknife technique was used for validation. Median (interquartile range) wait‐list time was 100 (34‐309) days. Non‐O Blood type, higher PELD/MELD score at listing, and DSA were associated with increased chance of DDLT, while age 1‐5 years and 10‐18 years was associated with lower chance of DDLT (P < 0.001 for all variables). Our model accurately predicted chance of transplant (C‐statistic = 0.68) and was able to predict DDLT at specific follow‐up times (eg, 3 months). This model can serve as the basis for an online tool that would provide useful information for pediatric wait‐list candidates.     

The role of liver transplantation for hepatic adenomatosis in the pediatric population: Case report and review of the literature

Wellen JR, Anderson CD, Doyle M, Shenoy S, Nadler M, Turmelle Y, Shepherd R, Chapman WC, Lowell JA. The role of liver transplantation for hepatic adenomatosis in the pediatric population: Case report and review of the literature.
Pediatr Transplantation 2010: 14: E16–E19. © 2009 John Wiley & Sons A/S. Abstract: Hepatic adenomas are benign lesions often found in young women during childbearing age. These tumors are often solitary but can also be multiple in which case this is referred to as hepatic adenomatosis (HA). HA is defined as having greater than or equal to ten adenomas within an otherwise normal liver. We present a case of a teenager with HA who underwent an orthotopic liver transplant for complications of her HA. To date there are only four reports of teenagers, without an underlying glycogen storage disease, who have undergone a liver transplant for HA. Liver transplantation within the pediatric population is an acceptable treatment for HA that are deemed unresectable.     

The technical pitfalls of duct-to-duct biliary reconstruction in pediatric living-donor left-lobe liver transplantation: the impact of stent placement

Abstract:  The feasibility of D-D biliary reconstruction in pediatric LDLT using a left-lobe graft is still controversial. The medical records of 19 pediatric patients (age: four months to 16 yr) were reviewed. The biliary reconstruction was performed in an end-to-end fashion using absorbable sutures. An external biliary tube was placed into the bile duct through the anastomotic site (n = 10) and not through the anastomotic site (n = 4). An external tube was not used in five patients. The median follow-up was 4.7 yr. Nine patients had 11 biliary complications (leakage, n = 2; stricture, n = 7; stricture with leakage, n = 2). Due to biliary complications, conversion to an R-Y was required in five patients, and four patients required radiological or endoscopic management. The patients younger than one yr of age required conversion to R-Y within one wk after LDLT. The analysis of factors related to biliary complications revealed that the use of a trans-anastomotic biliary tube was the only significant factor to avoid biliary complications. In conclusion, D-D biliary reconstruction in LDLT using a left-lobe graft is feasible in selected cases, though it remains challenging. The use of a trans-anastomotic biliary tube is important to avoid biliary complications.