Takuya Kimura

FTY720 reduces T-cell recruitment into murine intestinal allograft and prevents activation of graft-infiltrating cells.

Background. Effective immunosuppression is a critical determinant of graft survival in small-bowel transplantation (SBTx). The present study was designed to determine the potency of FTY720, a newly synthesized immunosuppressant, in rat SBTx and examine the phenotype of graft-infiltrating cells to evaluate its effect on intestinal allografts. Materials and Methods. A segment of intestine of Dark Agouti rats was transplanted heterotopically into Lewis rats. The recipients were treated with or without oral FTY720 at a dose of 1 mg/kg per day. Six days after surgery, peripheral blood lymphocytes and lymphocytes from the mesenteric lymph nodes, Peyer’s patches, intraepithelial site, and lamina propria of the intestinal allograft were isolated. After the number of lymphocytes in each site was counted, the lymphocyte subpopulations in the intestinal allograft were evaluated by means of a FACScan flow cytometer using several monoclonal antibodies. Results. FTY720 treatment significantly prolonged recipient survival and strongly inhibited rejection histologically in comparison with control rats. FTY720 immunosuppression resulted in a marked reduction of lymphocyte number in the graft epithelium and lamina propria and the proportion of CD8+ and CD25+ cells. FTY720 also significantly decreased T-cell receptors and increased B cells in the graft Peyer’s patches. Conclusion. FTY720 promoted long-term SBTx recipient survival and maintained the architecture of intestinal allografts. FTY720 immunosuppression may be associated with a reduction of T-cell recruitment subsequent to the redistribution of lymphocyte subpopulations to control the proliferation and activation of graft-infiltrating cells in intestinal allografts.

Biliary reconstruction in pediatric live donor liver transplantation: Duct-to-duct or Roux-en-Y hepaticojejunostomy

BACKGROUND Duct-to-duct biliary reconstruction (DD) is currently a standard procedure in adult live donor liver transplantation (LDLT). Its pediatric feasibility, however, has rarely been reported. The goal of this study is to assess the incidence and treatment of biliary complication after pediatric LDLT with DD or Roux-en-Y hepaticojejunostomy (RY). METHOD Sixty children received LDLT between November 2005 and June 2008, and their database was reviewed. RESULTS Biliary reconstruction was achieved with DD in 14 patients and with RY in 46 patients with mean follow-up period of 26.0 and 22.3 months, respectively. The incidence of biliary leakage in the DD and RY groups was 7.1% and 8.7%, respectively, and that of stricture was 28.6% and 10.9%, respectively; but the differences were not statistically significant. Biliary stricture in the DD group tended to require revision surgery with RY and longer treatment with percutaneous transhepatic cholangiodrainage compared with that in the RY group. CONCLUSION Theoretical advantages of DD over RY were not confirmed in this study. Duct-to-duct biliary reconstruction tended to encounter more biliary complications, especially stricture, with more difficulty in treating it than RY. Roux-en-Y hepaticojejunostomy seems preferable to DD in the setting of pediatric LDLT, but DD must be considered when making new Roux-en-Y limb seems impossible or troublesome owing to abdominal dense adhesion or short bowel syndrome.

Does pancreatico-biliary maljunction play a role in spontaneous perforation of the bile duct in children?

Abstract Spontaneous perforation of the bile duct (SPBD) is a rare disease in children. Pancreatico-biliary maljunction (PBM) has been postulated to contribute to its etiology. We have treated three children with SPBD over 30 years, two of whom had PBM. There was one boy and two girls aged 10 months to 2 years with symptoms of abdominal distension, vomiting, abdominal pain, jaundice, and acholic stools. The diagnosis of SPBD was made by paracentesis showing biliary ascites, and primary biliary and intra-abdominal drainage was performed in all cases. The site of perforation was at the connection of the common bile duct (CBD) with the cystic duct in all cases. In two cases reflux of contrast into the pancreatic duct was noted, the common channel was long (17 and 12 mm, respectively), and the bile amylase level in the CBD was abnormally high (50,000 and 67,000 IU/l, respectively). In the third patient there was no reflux of contrast into the pancreatic duct and the bile amylase and trypsin levels in the CBD and gallbladder were not measurable. Thus, SPBD in children may not be due solely to PBM, but may involve multiple mechanisms.

Liver transplantation for an infant with neonatal intrahepatic cholestasis caused by citrin deficiency using heterozygote living donor

Shigeta T, Kasahara M, Kimura T, Fukuda A, Sasaki K, Arai K, Nakagawa A, Nakagawa S, Kobayashi K, Soneda S, Kitagawa H. Liver transplantation for an infant with neonatal intrahepatic cholestasis caused by citrin deficiency using heterozygote living donor.
Pediatr Transplantation 2010: 14:E86–E88.

Successful percutaneous transluminal angioplasty for hepatic artery stenosis in an infant undergoing living-related liver transplantation

Abstract: A 1‐yr‐old girl underwent a living‐related liver transplant, with reconstruction of hepatic artery of 2 mm in diameter under microscopy. She developed intestinal perforation requiring closure on day 4 post‐transplant and suffered from hepatic artery stenosis (HAS) on post‐transplant day 9. Conservative therapies, such as intravenous or transluminal administration of anti‐coagulants, vasodilators or fluids, were unsuccessful and caused remarkable general edema and multiple arrhythmias as a result of increased preload. On day 15 post‐transplant, because flow velocity was remarkably reduced (as shown by Doppler ultrasound) the patient underwent percutaneous transluminal angioplasty (PTA) using a kit for coronary angioplasty. The balloon catheter was inflated [first: 1.5 mm diameter, 4 atmospheric pressure (a.p.) for 30 seconds (s); second: 2.0 mm diameter, 4 a.p. for 30 s; third: 2.5 mm diameter, 10 a.p. for 30 s]. The stenosis was successfully dilated without any complication. The patient has been doing well with normal liver functions for 4 months after PTA. From this experience, PTA can be performed for HAS after liver transplantation, even in an infantile case, with a careful technique and a special device.

Living-related liver transplantation for biliary atresia associated with polysplenia syndrome

Abstract: This report describes a 1‐yr‐old boy with biliary atresia (BA) and polysplenia syndrome (PS) who underwent successful living‐related liver transplantation (LTx). At the time of initial hepatic portoenterostomy, he was noticed to have a preduodenal portal vein (PV), non‐rotation of the intestine, and polysplenia. Because he did not achieve good bile excretion, he underwent a living‐related LTx (using a left lateral segment from his mother) at the age of 14 months. Evaluation of the vascular anatomy was made by angiography, magnetic resonance imaging (MRI), computerized tomography (CT), and Doppler ultrasound. The PV was stenotic from the confluence of the superior mesenteric vein (SMV) and splenic vein (SpV) to the hepatic hilum. The retrohepatic inferior vena cava (IVC) was deficient cranially to the renal vein and was connected to the azygous vein. The supra‐hepatic IVC was detected below the diaphragm and was connected to three hepatic veins. The common hepatic artery (HA) originated from the superior mesenteric artery. At LTx, the PV was dissected to the level of confluence of the SMV and the SpV, from which the venous graft was interposed using the donors ovarian vein. Three hepatic veins were plastied into one orifice, which was anastomosed to the grafts hepatic vein under the diaphragm. The graft vascularity and function has been good for 1 yr after LTx. In the present case, sufficient pre‐LTx evaluation of vascular anomalies seemed to help performance of the successful LTx.

Effects of isolated small bowel transplantation on liver dysfunction caused by intestinal failure and long-term total parenteral nutrition

Abstract: It has not been fully determined whether isolated small bowel transplantation (ISBTx) can reverse liver dysfunction caused by intestinal failure requiring long‐term total parenteral nutrition (TPN). A boy with congenital microvillus inclusion disease presented with vomiting and severe diarrhea since the first day of life and had been managed by TPN since then. He suffered from catheter‐related sepsis several times. At 14 yr of age he developed progressive hepatosplenomegaly with thrombocytopenia and coagulopathy. He underwent ISBTx with an ileal graft from his blood‐identical grandmother at the age of 16 yr. Oral feeding was started on the 14th day after ISBTx and gradually increased. TPN was completely withdrawn after 5 months. Liver was palpated 5 cm below the costal margin before ISBTx, while it became non‐palpable 5 months after ISBTx. Serum liver enzyme levels and prothrombin time normalized in the 5 months following ISBTx. Liver biopsy showed marked steatosis, slight cholestasis, and mild bridging fibrosis before ISBTx. Although histological examination of liver biopsy revealed complete disappearance of steatosis 7 and 11 months after ISBTx, liver fibrosis remained unchanged. This clinical experience has shown that although steatosis and cholestasis are reversible after successful ISBTx and withdrawal of TPN, liver fibrosis may remain unchanged.

Sialyl-Tn antigen as a useful predictor of poor prognosis in patients with advanced stomach cancer

Sialyl-Tn antigen (STn) expression was studied immunohistochemically in 211 primary advanced gastric carcinomas. The overall rate of positive STn staining was 17% (35/211), and positive STn staining was found not to be correlated with tumor size, depth of invasion, lymph node metastasis, liver metastasis, or peritoneal metastasis. However, patients with tumors that were immunoreactive for STn demonstrated significantly lower survival (P<0.05). Multivariate analysis revealed that STn staining was an independent prognostic factor. From these findings we conclude that careful followup and intense postoperative therapy are required for patients with advanced gastric cancer who have positive immunoreactivity for STn.

Laparoscopic correction of congenital portosystemic shunt in children.

Congenital portosystemic shunt is a rare clinical entity that may progress to jaundice, severe encephalopathy, and pulmonary hypertension and require surgical correction or coil embolization. We present a novel approach to the management of children with congenital portosystemic shunt by means of a minimally invasive surgical technique. Congenital portosystemic shunts were identified between the superior mesenteric vein and inferior vena cava in case 1 and between the splenic vein and left renal vein in case 2. Both of them were successfully ligated by laparoscopic approach, and catheters were subsequently replaced to monitor portal venous pressure. The patients tolerated the procedure well, and short-term results were excellent. Laparoscopic ligation of congenital portosystemic shunt is technically feasible and less invasive to the management of patients with congenital portosystemic shunts, preventing late onset, life-threatening complications.

Zoom endoscopic evaluation of rejection in living-related small bowel transplantation

Background. This study evaluated zoom endoscopic findings according to four components in comparison with the histologic findings of acute cellular rejection (ACR) in a living-related small bowel transplantation (SBTx) patient. Methods. A 16-year-old boy with microvillus inclusion disease underwent SBTx with a 150-cm-long ileal graft from a blood-identical living-related donor. The endoscope was inserted into the distal stoma of the graft, and the mucosal architecture was observed under zoom. The observed findings were expressed by the following four components and graded as 0 to 2: H, homogeneity of mucosal change, minimal (H-0), patchy (H-1), diffuse (H-2); V, appearance of villi, stringlike (V-0), tonguelike (V-1), domelike (V-2); W, widening of crypt area, narrow (W-0), slightly widened within a width of one villus (W-1), markedly widened beyond a width of one villus (W-2); E, erythema in crypt area: no redness (E-0), sporadic erythema (E-1), diffuse erythema (E-2). Results. Histologic ACR was grade 0 in 27, grade 1 in 6, grade 2 in 3, and grade 3 in 0 occasions during 11 months after SBTx. In grade 0, 1, and 2 histology, H-0/H-1/H-2 was 85.2%/14.8%/0%, 33.3%/66.7%/0%, and 0%/100%/0%, respectively, with a significant difference among the groups by grade (P <0.05). V-0/V-1/V-2 was 48.1%/51.9%/0%, 0%/100%/0%, and 0%/66.7%/33.3% (P <0.05), W-0/W-1/W-2 was 85.2%/14.8%/0%, 0%/100%/0%, and 0%/66.7%/33.3% (P <0.05), and E-0/E-1/E-2 was 100%/0%/0%, 66.7%/33.3%/0%, and 0%/100%/0% (P <0.05), respectively. Conclusion. Zoom endoscopic findings, graded on four components, may reflect the histologic severity of ACR and minimize the performance of biopsies in SBTx.