Koichi Mizuta

Small-for-size grafts in living-related liver transplantation

BACKGROUND The problems associated with small-for-size grafts in living-related liver transplantation are not fully understood. STUDY DESIGN A consecutive series of 79 patients underwent 80 living-related liver transplantation procedures, including one retransplant, at the University of Tokyo from January 1996 to January 2000. They were divided into two groups by graft size: graft weight/recipient standard liver volume ratios of 40% or less (n = 24), and more than 40% (n = 56). Preoperative status, mortality, morbidity, duration of hospital stay, and postoperative graft function were examined and compared between the groups. RESULTS The rate of patients who were restricted to the intensive care unit preoperatively was comparable between the groups (33% versus 21%, p = 0.27). The mean standard liver volume ratios were 37% in the small graft group and 84% in the large group. Survival rates were 80% (5 of 24) for the small graft group, which was significantly lower than that for the large group (96%, 54 of 56, p = 0.02). The rate of acute rejection was comparable between the groups (33% versus 43%, p = 0.47). Vascular complication was observed in 17% of the small graft group patients and 23% of the large group (p = 0.77). No difference was observed in the frequency of bile leakage or bile duct stenosis (25% versus 21%, p=0.77). Hyper-bilirubinemia and elongation of prothrombin time persisted longer in the small graft group than in the large group (p < 0.0001 for both). CONCLUSIONS Our surgical results may suggest that a graft weight ratio of 40% or less provides a lower chance of survival after living-related liver transplantation.

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. (Liver Transpl 2005;11:1608–1610.)

Efficacy and safety of immunization for pre- and post- liver transplant children.

Background. Infection is a serious complication after liver transplantation. Immunization is one means of controlling infections. The objective of this study was to investigate the efficacy and safety of simultaneous administration of several vaccines before transplantation and the efficacy and safety of administration under immunosuppressive conditions after transplantation. Methods. Fifty-eight patients who underwent living-related liver transplantation between April 1994 and March 2000 were included in this study. Simultaneous administration of a maximum of six vaccines was performed in a short period of time before transplantation. We also readministered vaccines to 15 patients with waning antibody titers after transplantation from June 1999. We investigated whether patients could seroconvert for measles, rubella, mumps, and varicella after immunization and how long antibody titers could be retained by measuring them several times throughout the period before and after transplantation. We also examined side effects caused by immunization. Results. The rates of seroconversion against measles, rubella, mumps, and varicella after the pretransplantation vaccination were 82%, 100%, 90%, and 95%, respectively. The rates of reseroconversion against measles, rubella, mumps, and varicella after the posttransplantation revaccination were 85%, 100%, 100%, and 71%, respectively. Although antibody titers against these viruses generally waned with time, no patient exhibited any serious illness or side effects. Conclusion. Although 12 of 58 patients (21%) had an infection, pretransplantation immunization was effective to prevent serious illness, especially for the 6 months after transplantation. Posttransplantation live-vaccine administration under immunosuppressive conditions is effective and safe.

Stool Color Card Screening for Early Detection of Biliary Atresia and Long-Term Native Liver Survival: A 19-Year Cohort Study in Japan

OBJECTIVE To evaluate the sensitivity and specificity of a stool color card used for a mass screening of biliary atresia conducted over 19 years. In addition, the age at Kasai procedure and the long-term probabilities of native liver survival were investigated. STUDY DESIGN From 1994 to 2011, the stool color card was distributed to all pregnant women in Tochigi Prefecture, Japan. Before or during the postnatal 1-month health checkup, the mothers returned the completed stool color card to the attending pediatrician or obstetrician. All suspected cases of biliary atresia were referred for further examination. Diagnosis was confirmed by laparotomy or operative cholangiography for high-risk cases before the Kasai procedure. Patients with biliary atresia were followed from the date of their Kasai procedure until liver transplantation, death, or October 31, 2013, whichever comes sooner. RESULTS A total of 313,230 live born infants were screened; 34 patients with biliary atresia were diagnosed. The sensitivity and specificity of stool color card screening at the 1-month check-up was 76.5% (95% CI 62.2-90.7) and 99.9% (95% CI 99.9-100.0), respectively. Mean age at the time of Kasai procedure was 59.7 days. According to Kaplan-Meier analysis, the native liver survival probability at 5, 10, and 15 years was 87.6%, 76.9%, and 48.5%, respectively. CONCLUSIONS The sensitivity and specificity of the stool color card have been demonstrated by our 19-year cohort study. We found that the timing of Kasai procedure and long-term native liver survival probabilities were improved, suggesting the beneficial effect of stool color card screening.

Elevated blood concentrations of calcineurin inhibitors during diarrheal episode in pediatric liver transplant recipients: Involvement of the suppression of intestinal cytochrome P450 3A and P-glycoprotein

Abstract:  We encountered two cases of pediatric living‐related liver transplant recipients who showed increases in blood concentration of cyclosporine or tacrolimus, a dual substrate for cytochrome P450 (CYP) 3A and P‐glycoprotein (P‐gp), during a diarrheal episode. To investigate the effect of intestinal inflammation on the metabolic and efflux pump activities, we conducted the experiments using the lipopolysaccharide (LPS)‐induced intestinal damage model.

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 (≥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.

Rendezvous penetration method using double-balloon endoscopy for complete anastomosis obstruction of hepaticojejunostomy after pediatric living donor liver transplantation

A 12-year-old boy underwent a living donor liver transplantation at another facility in March 2006 after undergoing a failed Kasai operation. The left lobe from his mother was used for the graft with a single-orifice bile duct 4 mm in diameter. The biliary reconstruction was performed via a Roux-en-Y hepaticojejunostomy with an interrupted 6-0 absorbable monofilament suture material without a biliary stent. The patient was treated with tacrolimusand methylprednisolone-based immunosuppression. The postoperative course was uneventful, except for an episode of postoperative diabetes requiring a subcutaneous insulin injection. In September 2006, he was referred to our department because of intrahepatic bile duct dilatation. Image findings and laboratory data revealed biliary stricture with liver dysfunction. A percutaneous transhepatic cholangiodrainage (PTCD) was performed, with placement of a 7-French PTCD tube. Complete obstruction of the anastomosis was observed on cholangiography 2 weeks later. The PTCD tube was changed from a 7-French tube to a 9-French tube in order to observe the anastomosis with a 2.8-mm-diameter cholangioscope (CHF-CB30S, Olympus, Tokyo, Japan). This proved ineffective, however, as the guide wire could not be passed through the anastomosis. Because in our experience double-balloon endoscopy (DBE) can reveal the outline of a complete obstruction of hepaticojejunostomy, we were compelled to apply the rendezvous penetration method using DBE. RENDEZVOUS PENETRATION METHOD USING DBE

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.

Evolution of Mirizzi syndrome with biliobiliary fistula

The mechanisms of fistula formation were analyzed in eight patients with Mirizzi syndrome with biliobiliary fistula. The fistula was type 1 in three patients and type 2 in five, according to the Corlette-Bismuth classification. The apparent mechanisms of fistula formation include inflammation of the gallbladder, its subsequent fusion to the bile duct, and increase in the internal pressure due to either contraction of the gallbladder or multiple stones. However, no predisposing conditions other than a longstanding history of cholelithiasis have been suggested. Differences in the type of fistula are considered to be due to the mode of fusion of the gallbladder to the bile duct, and the size of the perforation, which is apparently determined by the area in contact with the stone.

Living Donor Liver Transplantation for Neonates Using Segment 2 Monosubsegment Graft

The prognosis of liver transplantation for neonates with fulminant hepatic failure (FHF) continues to be extremely poor, especially in patients whose body weight is less than 3 kg. To address this problem, we have developed a safe living donor liver transplantation (LDLT) modality for neonates. We performed LDLTs with segment 2 monosubsegment (S2) grafts for three neonatal FHF. The recipient age and body weight at LDLT were 13–27 days, 2.59–2.84 kg, respectively. S2 or reduced S2 grafts (93–98 g) obtained from their fathers were implanted using temporary portacaval shunt. The recipient portal vein was reconstructed at a more distal site, such as the umbilical portion, to have the graft liver move freely during hepatic artery (HA) reconstruction. The recipient operation time and bleeding were 11 h 58 min–15 h 27 min and 200–395 mL, respectively. The graft‐to‐recipient weight ratio was 3.3–3.8% and primary abdominal wall closure was possible in all cases. Although hepatic artery thrombosis occurred in one case, all cases survived with normal growth. Emergency LDLT with S2 grafts weighing less than 100 g can save neonates with FHF whose body weight is less than 3 kg. This LDLT modality using S2 grafts could become a new option for neonates and very small infants requiring LT.