Pretransplant trends in α-fetoprotein levels as a predictor of recurrence after living donor liver transplantation for unresectable hepatoblastoma: A single-institution experience.

LT is a practical therapeutic alternative for unresectable hepatoblastoma; however, deciding when to perform LT is difficult. The aim of this study was to optimize the timing of LT for hepatoblastoma using pretransplant trends in AFP levels. Trends in pretransplant AFP levels and their influence on post-transplant outcomes were retrospectively evaluated. All patients who underwent living donor LT for hepatoblastoma in our institution since 2002 were included. Variables analyzed included history of prior tumor resection, pretransplant AFP responses to chemotherapy, metastatic disease at diagnosis, and post-transplant chemotherapy. Eight patients (seven boys and one girl; median age, 35 months; range, 15 months-12 years) were transplanted. The overall post-transplant recurrence-free survival rate was 62.5% (5/8) with a mean follow-up of 77 months. Patients with post-transplant recurrence showed a 0.573 log increase in AFP levels after the last chemotherapy session before LT. This was significantly higher than the 0.279 log decrease observed in patients without post-transplant recurrence (P = .024). Because the AFP response cannot be accurately predicted before each cycle of chemotherapy, it may be appropriate to perform LT when AFP levels do not decrease after the last cycle and before they are found to be elevated again.

Living donor liver transplantation from a heterozygous parent for classical maple syrup urine disease.

MSUD is a hereditary metabolic disorder that is characterized by impaired activity of the BCKADC. Liver transplantation has been approved as a treatment for some MSUD cases in which the control of BCAAs is insufficient. Although there have been several reports about DDLT for MSUD, few LDLT cases have been reported. Because either of parents who are heterozygote of this disease usually applies to be a candidate of donor in LDLT, the impairment of BCKADC activity of graft liver should be concerned. We performed LDLT for 10 month-old girl with a left lateral segment graft from her father. BCKADC activities of the patient and her parents were measured using lysates of lymphocytes isolated from peripheral blood specimen before the transplant. As a consequence, the activity of BCKADC of father was not inferior to a normal range. The patient tolerated the operation well. Postoperative course was uneventful and mixed milk was started at 8th POD. The serum BCAAs levels have remained within normal range. It should be necessary to follow the physical growth and mental development of the recipient in the future.

Single-center experience and long-term outcomes of duct-to-duct biliary reconstruction in infantile living donor liver transplantation.

The indications for duct-to-duct (DD) biliary reconstruction in living donor liver transplantation (LDLT) for small children are still controversial. In this study, the feasibility of DD biliary reconstruction versus Roux-en-Y (RY) biliary reconstruction was investigated in terms of long-term outcomes. Fifty-six children who consecutively underwent LDLT with a weight less than or equal to 10.0 kg were enrolled. Biliary reconstruction was performed in a DD fashion for 20 patients and in an RY fashion for 36 patients. During a minimum follow-up of 2 years, the incidence of biliary strictures was 5.0% in the DD group and 11.1% in the RY group. Cholangitis during the posttransplant period was observed in the RY group only. There were no deaths related to biliary problems. This study shows that DD reconstruction in LDLT for small children (weighing 10.0 kg or less) is a feasible option for biliary reconstruction.

Re-evaluation of the indications for liver transplantation in Wilson's disease based on the outcomes of patients referred to a transplant center.

The aim of this study was to re-evaluate the indications and timing of LT for WD. From 2000 to 2009, eight patients with WD who had been referred to our institution for LT were enrolled in this study. The mean patient age was 15.9 yr (range, 7-37 yr). Four patients could not receive LT, because there were no available donors. All four patients were treated with chelating agent medication. Three of them (two of two patients with fulminant WD and one of two with cirrhotic WD) who did not undergo LT are still alive and doing well with stable liver functional tests. Only one of the patients with cirrhotic WD who did not undergo LT died of hepatic failure. Even among the four patients who underwent LT, one with fulminant WD recovered from hepatic encephalopathy with apheresis therapy and chelating agent. He later required LT because of severe neutropenia from d-penicillamine. The other three patients who underwent LT recovered and have been doing well. Some of the patients with WD can recover and avoid LT with medical treatment. Even when WD has progressed liver cirrhosis and/or fulminant hepatic failure at the time of diagnosis, medical treatment should be tried before considering LT.

Incidence and risk factors for new-onset diabetes in living-donor liver transplant recipients.

With the increased number of long-term survivors after liver transplantation, new-onset diabetes after transplantation (NODAT) is becoming more significant in patient follow-up. However, the incidence of new-onset diabetes after living-donor liver transplantation (LDLT) has not been well elucidated. The aim of this study was to evaluate the incidence and risk factors for NODAT in adult LDLT recipients at a single center in Japan. A retrospective study was performed on 161 adult patients without diabetes who had been followed up for ≥three months after LDLT. NODAT was defined according to the 2003 American Diabetes Association/World Health Organization guidelines. The recipient-, donor-, operation-, and immunosuppression-associated risk factors for NODAT were assessed. Overall, the incidence of NODAT was 13.7% (22/161) with a mean follow-up of 49.8 months. In a multivariate analysis, the identified risk factors for NODAT were donor liver-to-spleen (L-S) ratio (hazard ratio [HR] = 0.022, 95% confidence interval [CI] = 0.001-0.500, p = 0.017), and steroid pulse therapy for acute rejection (HR = 3.320, 95% CI = 1.365-8.075, p = 0.008). In conclusion, donor L-S ratio and steroid pulse therapy for acute rejection were independent predictors for NODAT in LDLT recipients. These findings can help in screening for NODAT and applying early interventions.

Peritransplant gastrointestinal symptoms in familial amyloidotic polyneuropathy.

OBJECTIVES: Gastrointestinal dysfunction is a common complication in familial amyloidotic polyneuropathy, and gastrointestinal symptoms are associated with a patient's nutritional status. The object of this study was to evaluate changes in peritransplant gastrointestinal symptoms and the nutritional status of familial amyloidotic polyneuropathy patients using the modified body mass index following a living-donor liver transplant. MATERIALS AND METHODS: In a retrospective analysis, we compared 17 Japanese familial amyloidotic polyneuropathy patients who underwent living-donor liver transplant in Kumamoto University Hospital between 2000 and 2009 with a control group of 28 patients with chronic liver disease. We analyzed the peritransplant gastrointestinal symptoms, nutritional status, duration of central venous catheterization, and postoperative hospital stay. The Mann-Whitney U test and Fisher exact test were used to analyze relations between the familial amyloidotic polyneuropathy group and control group, and the Wilcoxon signed-rank test, to analyze the relation of perioperative modified body mass index, with a value for P < .05 considered statistically significant. RESULTS: The duration of central venous catheterization and postoperative hospital stay were significantly longer in the familial amyloidotic polyneuropathy group than they were in the control group. There was no significant difference between modified body mass index preoperatively and 1 year after living-donor liver transplant. Although gastrointestinal symptoms were typically mild before living-donor liver transplant, the familial amyloidotic polyneuropathy group experienced a temporary deterioration in gastrointestinal symptoms after receiving the living-donor liver transplant but recovered after approximately 2 months. CONCLUSIONS: Although familial amyloidotic polyneuropathy patients experienced temporary exacerbations of gastrointestinal symptoms, their nutritional status was not affected during the peritransplant period, and they generally recovered within 2 months.

Sclerosing encapsulating peritonitis after living donor liver transplantation: a case successfully treated with tamoxifen: report of a case.

Sclerosing encapsulating peritonitis (SEP) is a rare cause of bowel obstruction. It is difficult to diagnose and the prognosis is poor. This report describes a case of SEP after living donor liver transplantation that was successfully treated with tamoxifen. A 56-year-old male, that had received a liver transplant for hepatitis C virus-related hepatocellular carcinoma 5 years earlier, was admitted with continuous abdominal pain and nausea. He had increased C-reactive protein levels and white blood cell count, and underwent laparotomy 5 days after hospitalization. The surgical findings showed ascites and SEP of the small bowel. An attempt to peel off the adhesions was stopped because there was a strong risk of intestinal tract damage. Tamoxifen treatment was initiated for SEP after surgery. The patient's symptoms gradually improved and he was able to resume feeding. He had been symptom-free for over 3 years at the last follow-up.

Liver transplant from an ABO-incompatible and hepatitis C antibody-positive but an HCV-RNA negative living donor in a familial amyloid polyneuropathy patient.

Familial amyloid polyneuropathy is a rare, progressively disabling, and ultimately fatal inherited disease. Liver transplant is currently the only available treatment proven to halt the progression of familial amyloid polyneuropathy. We report a 31-year-old woman with familial amyloid polyneuropathy who received a living-donor liver transplant from her husband who was hepatitis C virus antibody-positive but HCV-RNA negative and ABO incompatible. Six years after the transplant, both donor and recipient have normal liver biochemistry results; no hepatitis C viral load has been detectable in the recipient. This is the first report of a living ABO-incompatible liver transplant from an anti-hepatitis C virus antibody-positive but an HCV-RNA negative donor. This experience suggests that the use of an anti-hepatitis C virus antibody-positive hepatic graft is possible in select circumstances.

Current state of domino transplantation in Japan in terms of surgical procedures and de novo amyloid neuropathy.

The status of domino liver transplantation (DLT) in Japan was evaluated. DLT and familial amyloidotic polyneuropathy (FAP) recipients who underwent living donor liver transplantation (LDLT) at Kumamoto University were reviewed with attention to surgical procedures. Thirty-nine DLTs were performed in Japan until 2010, and survival rates at 1 and 3 years were 82% and 63.6%, respectively. Six of 21 DLT recipients who survived for more than 3 years developed amyloid depositions within organs, and de novo amyloid neuropathy was reported in three patients. DLT from FAP recipients in Kumamoto was safely performed with preservation of the retrohepatic inferior vena cava in FAP recipients. All 20 FAP recipients who were DLT donors are alive with the exception of one who died of the original FAP 9 years after LDLT. The outcomes of DLT and FAP recipients in Kumamoto were satisfactory.

A thoracoabdominal approach in revision of the hepatic hilum after left lobe living donor liver transplantation.

We present an approach to safely expose the hepatic hilum for revision procedures after left lobe living donor liver transplantation. A 14-year-old adolescent girl who had undergone left lobe living donor liver transplantation experienced repeated episodes of cholangitis. Because treatment with interventional techniques failed, surgical revision was indicated. The right thoracoabdominal approach was selected to minimize dissection. Intraoperative findings showed adhesive kinking of the Roux-Y limb just distal to the bilioenteric anastomosis, and a side-to-side jejunojejunostomy was performed. The thoracoabdominal approach leads to easy and excellent reoperative exposure of the hilar site of a left lobe liver graft.

Heterochronous bilateral adrenal neuroblastoma: stage 4S in early infancy following resection of stage I lesion in the neonatal period.

A girl presented with a right adrenal mass, and multiple hepatic lesions and subcutaneous nodules 3 months after complete resection of left adrenal neuroblastoma in the neonatal period. She was treated with six cycles of chemotherapy and is well after 13 months' follow-up. This is the first case report of heterochronous bilateral adrenal stage 4S NB.

Factors predicting persistent thrombocytopenia after living donor liver transplantation in pediatric patients.

Thrombocytopenia is common after LT for pediatric end-stage liver diseases. Seventy-six pediatric patients (≤15 yr old) who underwent LDLT were evaluated for the incidence and predictive factors of post-transplant thrombocytopenia (PLT <100, 000/mm(3) ). The prevalence of thrombocytopenia at two wk and at 12 months post-transplant was 22/76 (28.9%) and 11/62 (17.7%), respectively. Thrombocytopenia at two wk after LDLT was significantly associated with age at transplant, preoperative PLT, GRWR, acute rejection, and CMV infection in univariate analysis. Moreover, preoperative PLT, GRWR, and acute rejection had a strong correlation in multivariate analysis. Thrombocytopenia at 12 months after LDLT was associated only with preoperative PLT. We also demonstrated that vascular complications caused thrombocytopenia and that successful treatment recovered the PLT. These results showed that, in addition to considering the preoperative PLT, post-operative monitoring of platelets is very helpful for the early detection of adverse events related to the graft liver in pediatric liver transplant patients.

Development of hepatic angiomyolipoma accompanied with focal nodular hyperplasia long after treatment of pelvic rhabdomyosarcoma.

Survivors of childhood cancer have a higher risk of developing a secondary neoplasm in their lifetime. The increased risk of a second malignant neoplasm is related to treatment of the primary tumor and genetic predisposition. We describe a 19-year-old man with 2 hepatic masses, one of which was diagnosed as a hepatic angiomyolipoma and the other as focal nodular hyperplasia 14 years after the treatment of stage IV pelvic rhabdomyosarcoma. The combination of these tumors has not previously been reported in the literature.

Coefficient factor for graft weight estimation from preoperative computed tomography volumetry in living donor liver transplantation.

In the clinical setting of living donor liver transplantation (LDLT), it is common to find a discrepancy between the graft volume estimated by preoperative computed tomography volumetry and the actual graft weight (AGW) measured on the back-table. In this study, we attempt to find the coefficient factor that correlates the estimated graft volume to the AGW. Whole livers explanted in 25 LDLT recipients (17 cirrhotic and 8 morphologically normal with familial amyloid polyneuropathy) were evaluated to compare cirrhotic livers and noncirrhotic normal livers. In addition, right lobe grafts (n = 39) and left lobe grafts (n = 35) used in LDLTs were also evaluated to further determine the correlation between estimated graft volume and AGW. The correlation coefficient between estimated liver volume and actual liver weight was 1.01 in whole cirrhotic livers, whereas it was 0.85 in whole livers with familial amyloid polyneuropathy. In the partial liver grafts, it was 0.84 in right lobe grafts and 0.85 in left lobe grafts. In conclusion, we suggest that a correlation coefficient of 0.85 should be applied for the accurate calculation of the graft weight from the volume estimated by preoperative computed tomography in LDLT.

The Skt gene, required for anorectal development, is a candidate for a molecular marker of the cloacal plate.

BACKGROUND AND AIMS: It has been reported that a dorsal cloacal plate defect is associated with anorectal malformations (ARMs); however, there has been very little information reported about the developmental mechanisms involved with cloacal plate formation. Danforth's short tail (Sd) mutant mice show ARMs. In our previous study, the co-presence of Skt ( Gt ) mutation, in which Skt gene is disrupted by the gene-trap vector (p-U8), increased the incidence of ARMs in Sd mutant to 100%. Our aims in this study are determining the Skt expression around the cloaca during the anorectal development and demonstrating the role of Skt gene in ARMs. METHODS: Embryos, normal controls [+Skt ( Gt )/+Skt ( Gt )] and ARMs models [Sd Skt ( Gt )/+Skt ( Gt )], from embryonic day (E) 9.5 to E12.5, were evaluated with X-gal staining. RESULTS: In control embryos, Skt expression was detected both in the endoderm and ectoderm of the cloacal plate from E9.5 onward. At E12.5, Skt expression was also detected in the mesenchyme neighboring the dorsal cloacal plates. In [Sd Skt ( Gt )/+Skt ( Gt )] mutant embryos, the cloacal plates failed to extend proximodistally and, consequently, the dorsal part of cloacal plate was defective at E11.5. Skt expressing cells were detected in the shortened cloacal plate and in the thickened mesenchyme dorsal to it. CONCLUSIONS: We showed the spatial and temporal expression of Skt gene in the cloacal plate formation. This gene could be a marker for the cloacal plate during the anorectal development. Furthermore, Skt was considered to be associated with the embryogenesis of ARMs.

Aortopexy for tracheomalacia with dextrocardia, pulmonary artery sling, and congenital tracheal stenosis.

We report a rare case of coexisting pulmonary artery sling, congenital tracheal stenosis, and dextrocardia caused by right lung hypoplasia. Successful treatment of severe postoperative tracheomalacia was achieved by aortopexy, aiming displacement of the aortic arch across orthogonally in front of the trachea due to dextrocardia. The aim of this surgery was different from the usual aortopexy for tracheomalacia, which lifts the tracheal wall with the aorta. The three-dimensional evaluation considering the patient's associated malformations led to a successful result.

How to handle a huge portosystemic shunt in adult living donor liver transplantation with a small-for-size graft: report of a case.

Little attention has been paid to a ligation of the spontaneous portosystemic shunt in adult living donor liver transplantation (LDLT). A 33-year-old Japanese man with cryptogenic liver cirrhosis accompanied by a huge splenorenal shunt underwent LDLT. Acute cellular rejection produced "to and fro" portal venous flow on postoperative day (POD) 10. Steroid bolus therapy reversed the rejection, but the recovery of the portal venous flow was incomplete and the recipient subsequently started to have episodes of encephalopathy. Angiography showed portal hypoperfusion and portal flow steal via a huge splenorenal shunt. The patient underwent a shunt occlusion on POD 58. Portography showed marked improvement of the portal hypoperfusion. The encephalopathy thereafter dramatically reversed and the patient was discharged with no complications related to shunt ligation on POD 110. This case suggested that a ligation of a huge portosystemic shunt should therefore be considered at the time of transplantation, even when a relatively small graft is implanted.

Revisited impact of recipient age on the outcome of living donor liver transplantation for biliary atresia in the recent "transplantation era" in Japan.

To re-evaluate the impact of recipient age on the outcome of LDLT for BA in an era in which LDLT is the established treatment for BA in Japan. Thirty-one patients with BA who underwent LDLT were divided into four groups regarding the age at LDLT: infants <1 yr old (group A; n = 14); young children 1 to 6 yr old (group B; n = 8); school children 6 to 15 yr old (group B; n = 5); and adults > or =15 yr old (group D; n = 4). Pre-, peri-, and postoperative factors were compared among the four groups. There was no significant difference in number of the previous laparotomy among the groups. Cholestasis was the dominant indication in group A. PELD score in group B was lower than that in the other groups, and blood loss in group B was significantly less than in groups A and D. Ratio of the graft weight to the recipient's body weight (GRWR) in group A was significantly higher than in other groups. Duration of operation in group D was lower than in groups A and B, but there was no significant difference in the length of postoperative hospital stay and graft survival. Although the case volume was not big, the age of the recipient did not have any significant impact on the outcome of LDLT in our series.

Management of undifferentiated sarcoma of the liver including living donor liver transplantation as a backup procedure.

We present the cases of 3 children with huge undifferentiated sarcoma of the liver who were treated with surgical excision including liver transplantation as an option and adjuvant chemotherapy. All 3 patients were males aged 10, 13, and 15 years old. The size of the tumor was 10, 15, and 20 cm in diameter, respectively. The youngest patient is disease free and doing well 43 months after resection. The 13-year-old patient presented with tumor rupture and underwent operation. The primary tumor and the ruptured tissue fragments were removed and he was given postoperative chemotherapy. The patient is disease free and doing well 52 months after surgery. The oldest patient had an unresectable tumor in the hilar region. Preoperative chemotherapy was given but later discontinued owing to severe side effects. He underwent living donor liver transplantation followed by postoperative chemotherapy. The patient had recurrent tumor 24 months after transplantation that was excised at reoperation. He is doing well and is disease free 18 months after the second procedure. Complete removal of the tumor including total hepatectomy and transplantation when indicated and suitable pre- and/or postoperative chemotherapy is an effective treatment for children with undifferentiated sarcoma of the liver.

Induction of molecular chaperones in carbon tetrachloride-treated rat liver: implications in protection against liver damage.

Carbon tetrachloride (CCl4) induces liver damage, apparently through the formation of free-radical metabolites. Molecular chaperones such as heat shock protein (Hsp) of 70 kDa have been found to protect cells from various stresses. We previously found that cytosolic chaperone pairs of the Hsp70 family and their DnaJ homolog cochaperones prevent nitric oxide-mediated apoptosis and heat-induced cell death. Expression of cytosolic chaperones, including Hsp70; heat shock cognate (Hsc) 70; and DnaJ homologs dj1 (DjB1/Hsp40/hdj-1), dj2 (DjA1/HSDJ/hdj-2), dj3 (DjA2), and dj4 (DjA4), in the liver of CCl4-treated rats was analyzed. Messenger ribonucleic acids for all these chaperones were markedly induced 3-12 hours after CCl4 treatment with a maximum at 6 hours. Hsp70 and dj1 proteins were markedly induced at 6-24 hours with a maximum at 12 hours, whereas dj2 and dj4 were moderately induced at around 12 hours. Hsc70 was weakly induced after treatment, and dj3 was little induced. To better understand the significance of the induction of chaperones, the effect of preinduction of chaperones on CCl4-induced liver damage was analyzed. When chaperones were preinduced in the liver by heat treatment, increase in serum alanine aminotransferase activity after CCl4 treatment was significantly attenuated. Hsp90, another major cytosolic chaperone, also was induced by heat treatment. On the other hand, Mn- and Cu/Zn-superoxide dismutase were not induced by heat treatment or by CCl4 treatment. These results suggest that cytosolic chaperones of Hsp70 and DnaJ families or Hsp90 (or both) are induced in CCl4-treated rat liver to protect the hepatocytes from the damage being inflicted.