Toshiharu Matsuura

Auxiliary partial orthotopic living donor liver transplantation with a small‐for‐size graft for congenital absence of the portal vein

Congenital absence of the portal vein (CAPV) with an extrahepatic portosystemic shunt is a rare malformation; the completely absent type, Abernethy malformation type I, is especially rare. Liver transplantation for CAPV type I has been recently recognized as the only curative operation, but few reports have been published so far; meanwhile, auxiliary partial orthotopic liver transplantation (APOLT) has been proposed to be a very effective option, especially for pediatric patients. Here we present an 18‐year‐old adult patient with CAPV, asplenia, and an iliac shunt vessel who was managed successfully with APOLT using a small‐for‐size graft. To the best of our knowledge, this is the first adult patient who has experienced success with APOLT for CAPV. This is a feasible procedure: it not only fulfills the metabolic demands of the liver for adult patients but also potentially cures CAPV. Liver Transpl 16:1437–1439, 2010.

In vivo hepatogenic capacity and therapeutic potential of stem cells from human exfoliated deciduous teeth in liver fibrosis in mice.

IntroductionLiver transplantation is a gold standard treatment for intractable liver diseases. Because of the shortage of donor organs, alternative therapies have been required. Due to their potential to differentiate into a variety of mature cells, stem cells are considered feasible cell sources for liver regeneration. Stem cells from human exfoliated deciduous teeth (SHED) exhibit hepatogenic capability in vitro. In this study, we investigated their in vivo capabilities of homing and hepatocyte differentiation and therapeutic efficacy for liver disorders in carbon tetrachloride (CCl4)-induced liver fibrosis model mice.MethodsWe transplanted SHED into CCl4-induced liver fibrosis model mice through the spleen, and analyzed the in vivo homing and therapeutic effects by optical, biochemical, histological, immunological and molecular biological assays. We then sorted human leukocyte antigen-ABC (HLA-ABC)-positive cells from primary CCl4-damaged recipient livers, and analyzed their fusogenicity and hepatic characteristics by flow cytometric, genomic DNA, hepatocyte-specific gene assays. Furthermore, we examined the treatment effects of HLA-positive cells to a hepatic dysfunction by a secondary transplantation into CCl4-treated mice.ResultsTransplanted SHED homed to recipient livers, and expressed HLA-ABC, human hepatocyte specific antigen hepatocyte paraffin 1 and human albumin. SHED transplantation markedly recovered liver dysfunction and led to anti-fibrotic and anti-inflammatory effects in the recipient livers. SHED-derived HLA-ABC-positive cells that were sorted from the primary recipient liver tissues with CCl4 damage did not fuse with the host mouse liver cells. Sorted HLA-positive cells not only expressed human hepatocyte-specific genes including albumin, cytochrome P450 1A1, fumarylacetoacetase, tyrosine aminotransferase, uridine 5′-diphospho-glucuronosyltransferase, transferrin and transthyretin, but also secreted human albumin, urea and blood urea nitrogen. Furthermore, SHED-derived HLA-ABC-positive cells were secondary transplanted into CCl4-treated mice. The donor cells homed into secondary recipient livers, and expressed hepatocyte paraffin 1 and human albumin, as well as HLA-ABC. The secondary transplantation recovered a liver dysfunction in secondary recipients.ConclusionsThis study indicates that transplanted SHED improve hepatic dysfunction and directly transform into hepatocytes without cell fusion in CCl4-treated mice, suggesting that SHED may provide a feasible cell source for liver regeneration.

Relevance of HLA compatibility in living donor liver transplantation: the double‐edged sword associated with the patient outcome

HLA compatibility in living donor liver transplantation (LDLT) seems relevant to the acceptability of graft livers because LDLT recipients often share most or some part of HLAs with the respective donors. This study retrospectively investigated whether HLA compatibility affected the outcome of LDLT. Three hundred ninety LDLTs were performed in this hospital, and 346 pairs of HLAs (HLA‐A, B, DR) were retrieved from the medical record between October 1996 and March 2011. The dates of the deaths were censored when a recipient apparently died of or was retransplanted by other causes than graft failure because of host‐versus‐graft (HVG) response to purely analyze the outcomes of LDLT in view of HVG response. The relationship between HLA compatibility and graft‐versus‐host disease (GVHD) was also analyzed. No recipients with recipient‐against‐donor HLA mismatch (R→D MM) 0 experienced graft failure by HVG response. On the other hand, three of five recipients with “R→D MM 0” together with “donor‐against‐recipient MM 3” died of fatal GVHD. HLA compatibility in LDLT not only affected the long‐term acceptance of graft livers but also the risk of fatal GVHD.

Successful prolonged rituximab treatment for post-transplant lymphoproliferative disorder following living donor liver transplantation in a child

Abstract: PTLD is a serious complication of immunosuppression in solid organ transplant recipients. The incidence of PTLD is significantly higher in pediatric recipients than in adult because children are often EBV‐seronegative and they may develop primary EBV infection after transplantation. We herein describe a case of GI‐PTLD who achieved a complete remission by prolonged rituximab, a chimeric monoclonal antibody against CD20, mono‐therapy. A one‐yr‐old female underwent a LDLT for liver failure after having previously undergone the Kasai procedure for biliary atresia. At sixty days following the transplantation, GI‐PTLD developed. Withdrawal of immunosuppression and a surgical resection were thus performed. A histopathological examination of tumor revealed atypical medium to large cell lymphoid proliferation with strong CD20 immunopositivity indicating their B‐cell origin. Polymorphic PTLD was diagnosed. Rituximab was administered at a dose of 375 mg/m2 once a week, and the monotherapy resulted in a complete remission after 34 administrations. Based on this case, rituximab appears to be beneficial as a first‐line therapy for PTLD.

Excellent long-term outcome of hepaticojejunostomy for biliary atresia with a hilar cyst

BACKGROUND Biliary atresia (BA) with hilar cyst is an uncommon variant, which constitutes less than 10% of all types of BA, and the operative procedure for this type of BA remains controversial. METHODS We have had 200 cases with BA from 1963 to 2008 in our institute and our branch hospitals, in which 12 cases (6%) were BA with a hilar cyst. The clinical records of all cases were evaluated retrospectively. RESULTS Twelve BA patients with a hilar cyst included 2 boys and 10 girls. The diagnosis of BA was confirmed by intraoperative cholangiography (cloudy or treelike pattern). In all 12 cases, a hepaticojejunostomy was performed at a median age of 71.6 days (range, 24-136 days). The follow-up periods were 1.2 to 23.2 years. The current mean total bilirubin level was 0.8 mg/dL (range, 0.2-3.5 mg/dL), and the mean direct bilirubin level was 0.2 mg/dL (range, 0.0 to 0.8 mg/dL). Methylprednisolone or oral prednisolone was administered in 8 cases after operation, and 10 of 12 cases achieved a jaundice free state. The postoperative complications were cholangitis (n = 10), gastroesophageal varices (n = 7), splenomegaly (n = 3), ileus (n = 1), and pulmonary hypertension (n = 1). The overall survival rate with a native liver was 10 (83.3%) of 12 cases, of which 9 cases were jaundice-free and only 1 case showed recurrent jaundice. The other 2 cases underwent living-donor liver transplantation at age of 2 and 20 years, respectively, and they are currently doing well. CONCLUSIONS Most cases of BA with a hilar cyst achieved excellent clinical outcome after a hepaticojejunostomy.

Outcome of modified portal vein anastomosis for recipients with portal vein thrombosis or stenosis before living donor liver transplantation

BACKGROUND Portal vein thrombosis (PVT) or stenosis (PVS) often requires challenging techniques for reconstruction in living donor liver transplantation (LDLT). MATERIALS AND METHODS A total of 57 LDLTs were performed between October 1996 and December 2010. There were 16 cases (28%) with PVT/PVS that underwent modified portal vein anastomosis (m-PVa). The m-PVa techniques were classified into 3 groups: patch graft (Type-1), interposition graft (Type-2), and using huge shunt vessels (Type-3). The reconstruction patterns were evaluated with regard to age, graft vessels, PV flow, and complication rate. RESULTS The m-PVas were Type-1 in 10 cases, Type-2 in 3 cases, and Type-3 in 3 cases. The vessel graft in Type-1 was the inferior mesenteric vein (IMV) in 8 and the jugular vein in 2 cases, whereas the vessel graft in Type-2 was IMV in 2 and the saphenous vein in 1 case; in Type-3, the vessel grafts were renoportal, gonadal-portal, and coronary-portal anastomoses, respectively. The postoperative PV flow was sufficient in all types and slightly higher in Type-3. The postoperative complications occurred in 20% of the patients who underwent Type-1, in 33% who underwent Type-2, and in 0% who underwent Type-3. CONCLUSION The m-PVa was effective to overcome the surgical difficulty during transplantation. Pretransplant planning for the selection of the type of reconstruction is important for recipients with PVT/PVS.

Morphological and physiological changes of interstitial cells of Cajal after small bowel transplantation in rats

Intestinal dysmotility has been reported to be associated with a decreased number of interstitial cells of Cajal (ICCs). However, the chronological changes in ICCs after small bowel transplantation (SBT) have not yet been elucidated. In this study, we aimed to evaluate the chronological change of ICCs after SBT. Orthotopic syngeneic SBT was performed in rats. Graft specimens were obtained at postreperfusion, and on 1, 3, 7, 14, and 30 postoperative day (POD). Thereafter, immunohistochemical staining was performed and the spontaneous contractions measured. During the initial period after SBT, the temporal impairment of ICCs was found. In an immunohistochemical study, c‐Kit‐positive cells appeared to decrease on POD 0, 1, and 3. Thereafter, the number of cells increased gradually up to POD 7. In contrast, the recovery of the spontaneous contractile amplitude took more time. The frequency of the electrical signal was preserved at almost exactly the same levels throughout this experimental period. Although the network of ICCs was found to be temporarily impaired after SBT in an immunohistochemical examination, this change was reversible. Moreover, the recovery of the function of the intestinal motility associated with ICCs was delayed after the early postoperative period.

Intracranial hemorrhage associated with vitamin K-deficiency bleeding in patients with biliary atresia: focus on long-term outcomes.

Background and Aim: The prophylactic oral administration of vitamin K to newborns has markedly reduced the incidence of vitamin K deficiency (VKD); however, intracranial hemorrhage (ICH) is still one of the complications found in biliary atresia (BA) patients and is associated with VKD bleeding. Therefore, we aimed to investigate the incidence and long-term outcome of ICH in patients with BA who previously received prophylactic vitamin K during the neonatal period. Methods: Eighty-eight consecutive infants with BA were treated and followed up at Kyushu University Hospital from 1979 to 2009. The clinical records and imaging study results were retrospectively reviewed in the infants with BA who presented with ICH. Results: ICH occurred in 7.95% of patients with BA. The onset of ICH occurred at 47 to 76 days after birth, before the patients underwent surgery for BA (9–37 days after the onset of ICH). Coagulopathy was found upon admission in all of the cases with available data and improved after intravenous administration of vitamin K. A craniotomy was required in 2 cases before the surgery for BA. During the 22 to 278 months of follow-up, some neurologic sequelae persisted in 5 of 7 cases. Follow-up head computed tomography scans showed a low-density area in the left hemisphere in 5 cases. Conclusions: Although vitamin K prophylaxis had been given during the neonatal period, ICH-associated VKD bleeding was still found in 7.95% of patients with BA. Persistent neurologic sequelae were found in 5 of 7 cases, with low-density area in the left hemisphere.

Umbilical crease incision for duodenal atresia achieves excellent cosmetic results

BackgroundThe surgical procedure for treating congenital duodenal atresia has normally been performed by an upper abdominal transverse incision. Recently, duodenoduodenostomy has been attempted using an umbilical crease incision to improve the cosmetic results.MethodsEighteen cases of duodenal obstruction, including 15 atresia, 2 stenosis, and 1 atresia and stenosis, were treated from June 2001 to August 2009, in which 8 cases were performed via the umbilical crease incision and 10 cases via the conventional transverse incision. The clinical records of all cases were evaluated retrospectively.ResultsAll cases underwent radical operation safely. There were no differences in the operating time between the two kinds of incision. Two cases of umbilical crease incision showed minor complications. All the cases operated via the umbilical crease incision achieved a scarless abdomen within a few months after the operation.ConclusionsThe outcome of duodenal atresia is satisfactory with excellent cosmesis after a duodenoduodenostomy performed via the umbilical crease incision.

In vivo and ex vivo methods of growing a liver bud through tissue connection

Cell-based therapy has been proposed as an alternative to orthotopic liver transplantation. The novel transplantation of an in vitro-generated liver bud might have therapeutic potential. In vivo and ex vivo methods for growing a liver bud are essential for paving the way for the clinical translation of liver bud transplantation. We herein report a novel transplantation method for liver buds that are grown in vivo involving orthotopic transplantation on the transected parenchyma of the liver, which showed long engraftment and marked growth in comparison to heterotopic transplantation. Furthermore, this study demonstrates a method for rapidly fabricating scalable liver-like tissue by fusing hundreds of liver bud-like spheroids using a 3D bioprinter. Its system to fix the shape of the 3D tissue with the needle-array system enabled the fabrication of elaborate geometry and the immediate execution of culture circulation after 3D printing—thereby avoiding an ischemic environment ex vivo. The ex vivo-fabricated human liver-like tissue exhibited self-tissue organization ex vivo and engraftment on the liver of nude rats. These achievements conclusively show both in vivo and ex vivo methods for growing in vitro-generated liver buds. These methods provide a new approach for in vitro-generated liver organoids transplantation.