Co-occurrence of nonanastomotic biliary stricture and acute cellular rejection in liver transplant.

BACKGROUND: Nonanastomotic biliary stricture is generally considered the most troublesome biliary complication after liver transplant. Nonanastomotic biliary stricture owing to immunologic cholangiopathy (such as acute cellular rejection) has not been reported. We describe 2 patients with the co-occurrence of nonanastomotic biliary stricture and acute cellular rejection after pediatric live-donor liver transplant. CASE 1: A 13-month-old male infant with liver cirrhosis underwent an ABO-identical live-donor liver transplant using a left lateral segment graft. Eighty days after the live-donor liver transplant, ever with liver dysfunction and dilatation of the intrahepatic bile duct occurred. Percutaneous transhepatic biliary drainage and a liver biopsy were performed. The histopathologic evaluation indicated the presence of acute cellular rejection. After percutaneous transhepatic biliary drainage and steroid pulse treatment, the patient showed good clinical outcome. CASE 2: A 21-month-old female infant with biliary atresia underwent an ABO-identical live-donor liver transplant using a left lateral segment graft. Twenty-six days after the live-donor liver transplant, percutaneous transhepatic biliary drainage for B3 and a liver biopsy were performed, owing to fever, with liver dysfunction, and dilatation of the intrahepatic bile duct. Histopathologic evaluation indicated the presence of acute cellular rejection. After percutaneous transhepatic biliary drainage and steroid pulse treatment, the patient showed good clinical outcome. CONCLUSIONS: It is important for patients with nonanastomotic biliary stricture to undergo early liver biopsy because the nonanastomotic biliary stricture may be coincident with, or caused by, acute cellular rejection.

Hepatocellular telomere length in biliary atresia measured by Q-FISH.

BACKGROUND: Liver transplantation for biliary atresia is indicated whenever a Kasai portoenterostomy is considered unfeasible. However, the timing of liver transplantation in biliary atresia has not been precisely defined. Excessive shortening of hepatocellular telomeres may occur in patients with biliary atresia, and therefore, telomere length could be a predictor of hepatocellular reserve capacity. METHODS: Hepatic tissues were obtained from 20 patients with biliary atresia who underwent LT and 10 age-matched autopsied individuals (mean age, 1.7 and 1.2 years, respectively). Telomere lengths were measured by Southern blotting and quantitative fluorescence in situ hybridization using the normalized telomere-centromere ratio. The correlation between the normalized telomere-centromere ratio for the hepatocytes in biliary atresia and the pediatric end-stage liver disease score was analyzed. RESULTS: The median terminal restriction fragment length of the hepatic tissues in biliary atresia was not significantly different from that of the control (p = 0.425), whereas the median normalized telomere-centromere ratio of hepatocytes in biliary atresia was significantly smaller than that of the control (p < 0.001). Regression analysis demonstrated a negative correlation of the normalized telomere-centromere ratio with the pediatric end-stage liver disease score in biliary atresia (p < 0.001). CONCLUSIONS: Telomere length analysis using quantitative fluorescence in situ hybridization could be an objective indicator of hepatocellular reserve capacity in patients with biliary atresia, and excessive telomere shortening supports the early implementation of liver transplantation.

The role of operative intervention in management of congenital extrahepatic portosystemic shunt.

BACKGROUND AND AIMS: Congenital extrahepatic portosystemic shunt (CEPS) is a rare venous malformation in which mesenteric venous blood drains directly into the systemic circulation. It is still a matter of debate whether conservative or operative strategies should be used to treat symptomatic CEPS. The aim of this study was to evaluate the role of operative intervention in the management of CEPS. METHODS: Between June 2004 and August 2010, 6 consecutive patients with symptomatic CEPS were treated in our department. There were 3 male and 3 female patients, with a median age of 3.5 years (range, 1-8). Their demographic, clinical, and laboratory data were analyzed. All patients were scheduled to undergo shunt ligation or liver transplantation (LT). RESULTS: Living donor LT was carried out in 4 patients, and shunt ligation in 2. After a median follow-up of 25 months, all the patients are alive currently with marked relief of symptoms. CONCLUSION: Shunt ligation or LT for symptomatic CEPS is potentially curative.

Endovascular interventions for hepatic artery complications immediately after pediatric liver transplantation.

Hepatic artery complications after living donor liver transplantation (LDLT) can directly affect both graft and recipient outcomes. For this reason, early diagnosis and treatment are essential. In the past, relaparotomy was generally employed to treat them. Following recent advances in interventional radiology, favorable outcomes have been reported with endovascular treatment. However, there is ongoing discussion regarding the best and safe time for definitive endovascular interventions. We herein report a retrospective analysis for six children with early hepatic artery complication after pediatric LDLT who underwent endovascular treatment as primary therapy at our institution. We evaluate the usefulness of endovascular treatment for hepatic artery complication and its optimal timing. The mean patient age was 11.9 months and mean body weight at LDLT was 6.7 kg. The mean duration between the transplantation and first endovascular treatment was 5.3 days. Five of the six patients were technically successful treated by only endovascular treatment. Of these five patients, two developed biliary complications. Endovascular procedures were performed 10 times in six patients without any complications and nine of the 10 procedures were successful. By selecting optimal devices, our findings suggest that endovascular treatment can be feasible and safe in the earliest time period after pediatric LDLT.

Pediatric living donor liver transplantation using liver allograft with hemangioma.

BACKGROUND: Although liver transplantation using liver allograft with hemangiomas has been previously reported, little is known about the fate of hemangiomas in the transplanted liver. We herein describe a case of pediatric living donor liver transplantation (LDLT) using living donor liver allograft with a hemangioma which is considered to the first reported case performing in vivo hemangioma resection. CASE REPORT: A 27-year-old female was evaluated as a donor for her 2-year-old son with cholestatic cirrhosis due to biliary atresia. Preoperative ultrasonography and computed tomography revealed a 20-mm hemangioma located at lateral side of segment 3. During LDLT, an in vivo partial hepatic resection of the hemangioma of segment 3 was performed without the Pringle maneuver using intraoperative ultrasonography to keep the main portal triad of segment 3 before the donor liver resection, and the left lateral segment graft without the hemangioma, which underwent an intraoperative pathologic diagnosis, was transplanted into the recipient. The donor's postoperative course was uneventful and the recipient course was not observed subsequent liver necrosis, bleeding or bile leakage from the resection site. CONCLUSIONS: Liver allografts with hemangiomas can be accepted as potential liver allografts, and such hemangiomas should undergo be performed in vivo resection during LDLT irrespective of tumor size.

Bowel perforation after pediatric living donor liver transplantation.

PURPOSE: Bowel perforation after liver transplantation (LT) is a rare, but highly lethal complication with a poor prognosis. Here, we report the outcome of cases of bowel perforation after pediatric LT in our department. PATIENTS AND METHODS: The study subjects were 148 patients who underwent pediatric living donor liver transplantation. The 114 with biliary atresia (BA) were divided into two groups: those with associated bowel perforation (Group A) and those without (Group B). RESULTS: Four patients in all (2.5%) suffered bowel perforation. Their original disease was BA and emergency surgery was performed in all cases, with a mortality rate of 50.0%. Comparison of Groups A and B revealed significant differences in the patient age, body weight, duration of surgery, cold ischemic time, and blood loss volume. The survival rates in Groups A and B were 50.0 and 99.1%, respectively (p < 0.01). Duration of surgery was an independent risk factor (p = 0.05). CONCLUSION: Bowel perforation after LT is a potentially fatal complication. LT is a procedure that requires care and precision, and the possibility of bowel perforation should always be borne in mind during post-operative management, when the duration of surgery has been long.

Double-balloon enteroscopy for bilioenteric anastomotic stricture after pediatric living donor liver transplantation.

Bilioenteric anastomotic stricture after liver transplantation is still frequent and early detection and treatment is important. We established the management using double-balloon enteroscopy (DBE) and evaluated the intractability for bilioenteric anastomotic stricture after pediatric living donor liver transplantation (LDLT). We underwent DBE at Jichi Medical University from May 2003 to July 2009 for 25 patients who developed bilioenteric anastomotic stricture after pediatric LDLT. The patients were divided into two types according to the degree of dilatation of the anastomotic sites before and after interventional radiology (IVR) using DBE. Type I is an anastomotic site macroscopically dilated to five times or more, and Type II is an anastomotic site dilated to less than five times. The rate of DBE reaching the bilioenteric anastomotic sites was 68.0% (17/25), and the success rate of IVR was 88.2% (15/17). There were three cases of Type I and 12 cases of Type II. Type II had a significantly longer cold ischemic time and higher recurrence rate than Type I (P = 0.005 and P = 0.006). In conclusion, DBE is a less invasive and safe treatment method that is capable of reaching the bilioenteric anastomotic site after pediatric LDLT and enables IVR to be performed on strictures, and its treatment outcomes are improving. Type II and long cold ischemic time are risk factors for intractable bilioenteric anastomotic stricture.

Indication of liver transplantation for jaundice-free biliary atresia with portal hypertension.

BACKGROUND: At the present time, indications of liver transplantation (LT) for jaundice-free biliary atresia (BA) patients include intractable cholangitis, portal hypertension and pulmonary vascular disorders. However, the timing of LT remains unclear. In the current study, we describe the therapeutic strategies for jaundice-free BA patients. MATERIAL/METHODS: 129 BA patients were undergone LDLT between May, 2001 and April, 2010 in the Department of Transplant Surgery, Jichi Medical University, Japan. RESULTS: The indications of LDLT for jaundice-free BA patients was 30 patients (30/129, 23%), and included portal hypertension (16 patients, 53%). Among the 16 patients with portal hypertension, there were 7 patients (7/16, 23%) in which uncontrollable gastrointestinal bleeding was an indication of LDLT. There were 5 patients (5/7; 71%) in which bleeding sites were not identified, and 3 patients (3/7; 43%) in which supportive treatments against collateral vessels were performed as a previous treatment. CONCLUSIONS: Even in jaundice-free BA patients, after supportive treatments for portal hypertension are performed, it is necessary to assess the esophageal and gastrointestinal varices regularly and to also prepare for LT simultaneously because there is a probability of the complication of uncontrollable gastrointestinal bleeding.

Strategy to prevent recurrent portal vein stenosis following interventional radiology in pediatric liver transplantation.

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.

Diagnosis and treatment of pediatric patients with late-onset portal vein stenosis after living donor liver transplantation.

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.

Paralysis in the left phrenic nerve after living-donor liver transplantation for biliary atresia with situs inversus.

A 7-month-old boy with biliary atresia accompanied by situs inversus and absent inferior vena cava (IVC) underwent living-donor liver transplantation (LDLT). Because a constriction in the recipient hepatic vein (HV) was detected during the preparation of the HV in LDLT, a dissection in the cranial direction and a total clamp of the suprahepatic IVC was performed, and the suprahepatic IVC and the graft HV were anastomosed end-to-end. Postoperatively, atelectasis in the left upper lobe and ventilator failure accompanied by an elevation of the left hemidiaphragm were observed and mechanical ventilation was repetitively required. Paralysis in the left phrenic nerve was diagnosed by chest radiograph and ultrasonography. In our patient, conservative treatment was administrated, because weaning him from mechanical ventilation was possible a few days after intubation and the ventilator function was expected to be improved with growth. The disease course was good, and he was discharged from the hospital at 78 days after LDLT. Complications of paralysis in the phrenic nerve after cadaveric liver transplantation have been reported to be high. Although using a conventional technique during the reconstruction of the HV may injure the phrenic nerve directly, use of the piggyback technique with preservation of the IVC is rare. Even if LDLT was undertaken, a dissection of the HV or a total clamp of the suprahepatic IVC as a conventional technique can directly injure the phrenic nerve. Therefore, a dissection of the HV or a total clamp of the suprahepatic IVC at the reconstruction of the HV in LDLT should be carefully performed, and the possibility of paralysis in the phrenic nerve should be considered in patients with a relapse of respiratory symptoms and an elevation of the hemidiaphragm after LDLT.

Successful pediatric living donor liver transplantation from carrier to carrier of hereditary butyrylcholinesterase variant.

Hypocholinesterasemia is often observed clinically, especially in various liver diseases. Not well known, however, is the fact that some patients have a hereditary BChE variant. Little has been reported on liver transplants associated with this hereditary BChE variant. Furthermore, no cases have been reported of a LDLT involving hereditary BChE variant that had been diagnosed preoperatively. A 23-month-old girl who had had a failed Kasai operation for biliary atresia underwent a liver transplant using as a graft her father's lateral segment. Preoperatively, she had been diagnosed with hypocholinesterasemia. As the donor, her father had undergone a preoperative examination, during which he was found to also have hypocholinesterasemia. DNA sequencing revealed that both had the hereditary BChE variant. The unique mutation caused a frame-shift mutation. Variant K was also detected. The patient was discharged 143 days after the operation and has had no problems with immunosuppression since. In conclusion, we report that the hereditary BChE variant is not a contraindication for either transplantation or living liver donation.

A case of successful enteroscopic balloon dilation for late anastomotic stricture of choledochojejunostomy after living donor liver transplantation.

Biliary complications remain a major concern after living donor liver transplantation. We describe a pediatric case who underwent a successful endoscopic balloon dilatation of biliary-enteric stricture following living donor liver transplantation using a newly developed method of enteroscopy. The 7-year-old boy with late biliary stricture of choledochojejunostomy was admitted 6 years after transplantation. Since percutaneous transhepatic cholangiography was technically difficult in this case, endoscopic retrograde cholangiography was performed using a double-balloon enteroscope under general anesthesia. The enteroscope was advanced retrograde through the duodenum, jejunum, and the leg of Roux-Y by the double-balloon method, and anastomotic stricture of choledochojejunostomy was clearly confirmed by endoscopic retrograde cholangiography and endoscopic direct vision. Balloon dilatation was performed and the anastomosis was expanded. Restenosis was not noted as of 2 years after the treatment. In conclusion, endoscopic balloon dilation of biliary-enteric anastomotic stricture using a new enteroscopic method can be regarded as an alternative choice to percutaneous transhepatic management and surgical re-anatomists.

Obstructive jaundice as a presentation of ganglioneuroblastoma.

Obstructive jaundice is a rare symptom in the neuroblastic tumor. Seven cases of obstructive jaundice caused by neuroblastoma have been reported, and only three of these patients had the symptom at the onset of the disease. The authors report a case of ganglioneuroblastoma presenting with obstructive jaundice as a rare initial feature. After the histologic diagnosis with open biopsy, chemotherapy consisting of cisplatin, pirarubicin hydrochloride/doxorubicin, cyclophosphamide, and vincristine was given. The treatment resulted in reduction in the tumor size and relief of the obstructive jaundice. Complete resection of the tumor was possible after five courses of chemotherapy.

A case of laryngeal atresia (congenital high airway obstruction syndrome) with chromosome 5p deletion syndrome rescued by ex utero intrapartum treatment.

The authors report a case of laryngeal atresia (congenital high airway obstruction syndrome [CHAOS]) that was diagnosed prenatally. The patient underwent successfully tracheostomy by ex utero intrapartum treatment (EXIT). The fetal ultrasonography and magnetic resonance imaging MRI showed a typical CHAOS pattern with expanded hyperechogenic lungs, inverted diaphragms, and a dilated trachea. Recently, 3 cases of prenatally diagnosed CHAOS were reported to be treated successfully by EXIT. The clinical manifestation and course of this case was not similar to these 3 cases. The 3 previous patients did not fare as well during gestation and were delivered earlier than that in our case. In our case, fetal hydrops was seen at 23 gestational weeks, but it gradually subsided and disappeared at 30 gestational weeks. The fetus was stable and well. After delivery at 39 weeks, the baby received respiratory assistance by ventilator assistance. After 3 days, she could breath well on her own. The patient also had chromosome 5p deletion syndrome and perineal groove. More experience in treating CHAOS cases with EXIT to fully estimate its clinical course and prognosis is needed.

Effect of pediatric living-donor liver transplantation on splenomegaly.

BACKGROUND: The effect of pediatric partial liver transplantation on hypersplenism has not yet been clarified. METHODS: Fifty-five consecutive pediatric patients who underwent living-donor liver transplantation were analyzed. The volume of the spleen was measured by computed tomography, and the spleen volume-to-standard spleen volume ratio (R) was calculated in each patient. The platelet counts were examined preoperatively and at 1, 6, 12, 18, 24, 36, and 48 months after the operation. The rate of the decline in this ratio during 1 year was calculated, and correlations with clinical factors were examined. RESULTS: The ratio decreased gradually after the operation in all of the patients except for three with an eventful postoperative course. The rate of the reduction in R within 1 year after the operation was well correlated with preoperative R (R(O); P<0.0001), which led to an equation for R at n months after the operation: R(n) =(0.31-0.21R(O) )Ln(3.3n+1)+R(O). The platelet counts increased rapidly in the patients with the uneventful postoperative course. CONCLUSIONS: The normalization of spleen size can be expected with an uneventful living-donor liver transplantation. The spleen volume decreased more rapidly in patients with a larger spleen.