Objective: To evaluate the long-term impact of liver transplantation on ocular manifestations of familial amyloid polyneuropathy (FAP) in Japanese patients.Methods: Medical records were retrospectively reviewed in a long-term follow-up study. Of 52 patients with FAP amyloidogenic transthyretin Val30Met, 22 patients underwent liver transplantation. We assessed ocular manifestations, including amyloid deposition at the pupillary border, pupillary border with irregularity, vitreous opacities, and glaucoma, in patients who underwent liver transplantation. In addition, we compared the clinical characteristics of vitreous opacities-the most common ocular manifestation of FAP-in patients who underwent liver transplantation and those who did not to determine the effect of transplantation on the progression of ocular amyloidosis.Results: Mean time after FAP onset was 10 years and after liver transplantation was 7 years in patients who underwent liver transplantation. All ocular manifestations increased with time after transplantation. Eight patients (36%) developed vitreous opacities and 4 patients (18%) developed glaucoma during follow-up. Mean time from FAP onset to vitreous opacities onset was significantly shorter in patients with early-onset disease who underwent liver transplantation than in those who did not. Conclusions:Patients with FAP who undergo liver transplantation continue to have a long-term risk of severe ocular manifestations, especially vitreous opacities and glaucoma, which can restrict their daily lives, even after liver transplantation.

FAP may shift to systemic WT TTR amyloid formation after LT, which seems to be similar to the process in SSA. The truncation of TTR in amyloid deposits may depend on some genetic or environmental factors other than undergoing LT.

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.

Hepaticojejunostomy is a standard biliary reconstruction method for infantile living donor liver transplantation (LDLT), but choledochocholedochostomy for infants is not generally accepted yet. Ten pediatric recipients weighing no more than 10 kg underwent duct-to-duct choledochocholedochostomy (DD) for biliary reconstruction for LDLT. Patients were followed up for a median period of 26.8 months (range: 4.0-79.0 months). The incidence of posttransplant biliary complications for DD was compared with that for Roux-en-Y hepaticojejunostomy (RY). No DD patients and 1 RY patient (5%) developed biliary leakage (P Ͼ 0.05), and biliary stricture occurred in 1 DD patient (10%) and none of the RY patients (P Ͼ 0.05); none of the DD patients and 5 RY patients (25%) suffered from uncomplicated cholangitis after LDLT (P Ͼ 0.05), and 1 DD patient (10%) and 2 RY patients (10%) died of causes unrelated to biliary complications. In conclusion, both hepaticojejunostomy and choledochocholedochostomy resulted in satisfactory outcome in terms of biliary complications, including leakage and stricture, for recipients weighing no more than 10 kg. Liver Transpl 14: [1761][1762][1763][1764][1765] 2008 Liver transplantation is an established curative therapy for children with end-stage chronic liver disease or acute liver failure. Outcomes following liver transplantation for children have significantly improved over the past 2 decades because of advances in surgical procedures, preservation technology, immunosuppressants, and perioperative management. 1 However, despite refinements in surgical techniques for living donor liver transplantation (LDLT), biliary complications are still associated with significant morbidity and mortality. 2 Duct-to-duct choledochocholedochostomy (DD) and Roux-en-Y hepaticojejunostomy (RY) are now generally accepted procedures for biliary reconstruction in adult-to-adult LDLT. 3,4 However, RY has remained the standard method for pediatric LDLT because of the dominance of biliary atresia and technical difficulties related to the size and fragility of recipients' bile ducts. Only a few reports can be found in the literature on pediatric LDLT using DD, 5,6 and to the best of our knowledge, there have been no studies focused on DD for infantile LDLT. This is therefore the first report to investigate the viability of DD in LDLT for infants weighing no more than 10 kg. PATIENTS AND METHODS PatientsBetween February 2001 and January 2008, 57 pediatric patients (less than 15 years old) underwent 60 LDLTs at Kumamoto University Hospital. Thirty-four of these pediatric recipients (59.6%) weighed no more

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.

Recently, we found that resident myogenic stem satellite cells upregulate a multi-functional secreted protein, semaphorin 3A (Sema3A), exclusively at the early-differentiation phase in response to muscle injury; however, its physiological significance is still unknown. Here we show that Sema3A impacts slow-twitch fiber generation through a signaling pathway, cell-membrane receptor (neuropilin2-plexinA3) → myogenin-myocyte enhancer factor 2D → slow myosin heavy chain. This novel axis was found by small interfering RNA-transfection experiments in myoblast cultures, which also revealed an additional element that Sema3A-neuropilin1/plexinA1, A2 may enhance slow-fiber formation by activating signals that inhibit fast-myosin expression. Importantly, satellite cell-specific Sema3A conditional-knockout adult mice (Pax7CreER -Sema3A ° activated by tamoxifen-i.p. injection) provided direct in vivo evidence for the Sema3A-driven program, by showing that slow-fiber generation and muscle endurance were diminished after repair from cardiotoxin-injury of gastrocnemius muscle. Overall, the findings highlight an active role for satellite cell-secreted Sema3A ligand as a key "commitment factor" for the slow-fiber population during muscle regeneration. Results extend our understanding of the myogenic stem-cell strategy that regulates fiber-type differentiation and is responsible for skeletal muscle contractility, energy metabolism, fatigue resistance, and its susceptibility to aging and disease. Stem Cells 2017;35:1815-1834.

Neutrophils are considered responsible for the pathophysiological changes resulting from hepatic ischemia-reperfusion (I/R) injury, which is a complication of trauma, shock, liver resection, and transplantation. Recently, evidence is accumulating that formyl-peptide receptor (FPR) signaling constitutes an important danger signal that guides neutrophils to sites of inflammation. This study aimed to investigate dynamic neutrophil recruitment using two-photon laser-scanning microscopy (TPLSM) in response to FPR1 blockade during hepatic I/R. LysM-eGFP mice were subjected to partial warm hepatic I/R. They were pretreated with an FPR1 antagonist, cyclosporine H (CsH), or formyl peptide, fMLF. Liver was imaged after hepatic laser irradiation or I/R using the TPLSM technique. CsH treatment alleviated hepatic I/R injury, as evidenced by decreased serum transaminase levels, reduced hepatocyte necrosis/apoptosis, and diminished inflammatory cytokine, chemokine, and oxidative stress. In contrast, systemic administration of fMLF showed few effects. Time-lapse TPLSM showed that FPR1 blockade inhibited the accumulation of neutrophils in the necrotic area induced by laser irradiation in vivo. In the CsH-treated I/R group, the number and crawling velocity of neutrophils in the nonperfused area were lower than those in the control group. Meanwhile, FPR1 blockade did not affect monocyte/macrophage recruitment. Hepatic I/R promoted the retention of neutrophils and their active behavior in the spleen, whereas CsH treatment prevented their changes. Intravital TPLSM revealed that formyl-peptide-FPR1 signaling is responsible for regulating neutrophil chemotaxis to allow migration into the necrotic area in hepatic I/R. Our findings suggest effective approaches for elucidating the mechanisms of immune cell responses in hepatic I/R.

LLS reduction has been frequently used in infants weighing <7 kg. Twenty recipients weighing <7 kg at the time of LDLT, median age 11.0 months and body weight 5.6 kg, were treated with an RLLS (n = 12) or LLS (n = 8) graft. Absolute indication of size reduction was that the estimated GRWR was >4.0%. Even if the preoperative GRWR was <4.0%, the RLLS graft was considered to ensure a size match. A flatfish-type LLS was preferred to a blowfish-type to make an RLLS graft for such a small infantile population. The RLLS recipients had significantly more flatfish-type grafts, while the LLS recipients had more blowfish-type grafts. Primary full-layer wound closure could be performed successfully in all LLS recipients, while in the RLLS group, two patients were forced to have partial skin closure. There were no graft losses related to graft compression. Reducing an LLS is a useful procedure to promote the comfortable accommodation of the graft in an infant weighing <7 kg. Flatfish-type LLS allowed more flexibility to make the suitable volume.