Hironori Kudo

Long-term outcome of children with biliary atresia who were not transplanted after the Kasai operation: >20-year experience at a children's hospital.

Objective: Sequential strategies combining the Kasai operation as a first-line treatment and liver transplantation as a second-line option, if necessary, have been accepted for patients with biliary atresia (BA). To understand the role of the Kasai operation in the treatment of BA, it is necessary to analyze the long-term outcome of the operation alone and to evaluate the present status of survivors retaining their native livers. Materials and Methods: A retrospective chart review was carried out for a group of 80 patients who had undergone the Kasai operation between 1970 and 1986 at the Kanagawa Childrens Medical Center. Results: The 5-, 10-, and 20-year survival rates of patients with their native livers were 63%, 54%, and 44%, respectively. The survival rates varied significantly depending on the type of BA, age at initial Kasai operation, era of surgery, and surgical method. By age 20, nearly half of the adult survivors had already developed liver cirrhosis and its sequelae. Episodes of cholangitis and gastrointestinal bleeding occurred after 20 years of age in 37% and 17% of the adult patients, respectively, and 20% of the adult patients died of liver failure or underwent living-related partial liver transplantation in their 20s. Five female patients gave birth to a total of 9 children, and 1 male patient fathered a child. Conclusions: Although increasing numbers of patients with BA survive 20 years or more after the Kasai operation, meticulous lifelong postoperative care should be continued for the survivors because of the possibility of hepatic deterioration.

OX40 and IL‐7 play synergistic roles in the homeostatic proliferation of effector memory CD4+ T cells

T‐cell homeostasis preserves the numbers, the diversity and functional competence of different T‐cell subsets that are required for adaptive immunity. Naïve CD4+ T (TN) cells are maintained in the periphery via the common γ‐chain family cytokine IL‐7 and weak antigenic signals. However, it is not clear how memory CD4+ T‐cell subsets are maintained in the periphery and which factors are responsible for the maintenance. To examine the homeostatic mechanisms, CFSE‐labeled CD4+CD44highCD62Llow effector memory T (TEM) cells were transferred into sublethally‐irradiated syngeneic C57BL/6 mice, and the systemic cell proliferative responses, which can be divided distinctively into fast and slow proliferations, were assessed by CFSE dye dilution. We found that the fast homeostatic proliferation of TEM cells was strictly regulated by both antigen and OX40 costimulatory signals and that the slow proliferation was dependent on IL‐7. The simultaneous blockade of both OX40 and IL‐7 signaling completely inhibited the both fast and slow proliferation. The antigen‐ and OX40‐dependent fast proliferation preferentially expanded IL‐17‐producing helper T cells (Th17 cells). Thus, OX40 and IL‐7 play synergistic, but distinct roles in the homeostatic proliferation of CD4+ TEM cells.

Postnatal management of prenatally diagnosed biliary cystic malformation

PURPOSEnRecent advances in ultrasonography have increased prenatal diagnosis of biliary atresia (BA) and choledochal cyst (CC). These conditions are not easy to distinguish before or just after birth. This study investigated diagnostic and therapeutic problems in prenatal diagnosis of BA and CC.nnnMETHODSnWe retrospectively studied clinical characteristics and progression of hepatobiliary cysts in 10 patients (4 cases of BA, 6 cases of CC) from the time of diagnosis. Chronological changes in cyst size and gallbladder morphology were assessed and measured sequentially by ultrasonography.nnnRESULTSnThree cases of BA were type I cyst and 1 case was type III-d. All cases of CC were type Ia. Cyst size decreased between birth and surgery in BA but increased in CC. The gallbladder appeared atrophic in BA. There was no significant difference in gestational age or cyst size at prenatal diagnosis, changes in cyst size between birth and surgery, and degree of liver fibrosis.nnnCONCLUSIONSnBA should be suspected if cyst size decreases before and after birth and the gallbladder atrophies after birth. Cholangiography is the only reliable method to differentiate BA from CC. Neonatal surgery is indicated for CC with icterus and liver dysfunction.

Liver transplantation following the Kasai procedure in treatment of biliary atresia: a single institution analysis

PurposeThis study aimed to assess outcomes of liver transplantation (LTx) in patients with biliary atresia (BA).MethodsThe Kasai procedure was performed for 358 patients at Tohoku University Hospital between January 1955 and December 2013; 64 (17.9xa0%) required LTx. These 64 patients were divided into 4 groups according to their age at the time of transplantation: Group 1, aged <2xa0years (nxa0=xa027); Group 2, aged 2–9xa0years (nxa0=xa016); Group 3, aged 10–19xa0years (nxa0=xa011); and Group 4, aged ≥20xa0years (nxa0=xa010). Clinical parameters were evaluated retrospectively.ResultsBoth living-donor (nxa0=xa057) and deceased-donor (nxa0=xa07) LTx were performed. Indications were irreversible jaundice (nxa0=xa053), intractable cholangitis (nxa0=xa03), hepatopulmonary syndrome (nxa0=xa06), portopulmonary hypertension (nxa0=xa01), and intestinal bleeding (nxa0=xa01). Jaundice occurred more frequently in Groups 1 and 2 than in Groups 3 and 4 (pxa0=xa00.031). Survival rates were 81.5, 100, 90.9, and 80xa0% in Groups 1, 2, 3, and 4, respectively.ConclusionAlthough the overall LTx survival rate was satisfactory, some adult recipients experienced LTx-related difficulty. Close follow-up, meticulous assessment of physical and social conditions, presence of a multidisciplinary support system, and appropriate time course for LTx are all essential factors in the treatment of BA.

Technical standardization of Kasai portoenterostomy for biliary atresia

BACKGROUNDnThe purpose of this study was to assess the clinical outcome of patients treated with the current technique of Kasai procedure compared with that of those treated with previous procedures.nnnMETHODSnWe retrospectively assessed the outcomes of 256 patients with biliary atresia who underwent Kasai portoenterostomy at our hospital between 1972 and 2014. Patients were divided into four groups: group 1 (1972-1981, double Roux-en Y, n=91), group 2 (1982-1991, Suruga II, n=80), group 3 (1992-2000, double-valve Roux-en Y, n=46), and group 4 (2001-2014, total removal of the extrahepatic biliary remnants at hepatic capsule and Roux-en Y reconstruction with a spur valve, n=39). Clinical outcomes were compared between the four groups.nnnRESULTSnIn groups 1, 2, 3, and 4, the rate of jaundice clearance was 65.9%, 77.5%, 63.0%, and 87.2%, respectively; incidence of early cholangitis was 60.4%, 53.8%, 37.0%, and 23.1%, respectively; requirement for redo Kasai surgery was 15.4%, 37.5%, 17.4%, and 5.1%, respectively; 10-year native liver survival rate was 53.8%, 60.1%, 44.1%, and 73.7%, respectively; and 10-year overall survival rate was 55.0%, 72.3%, 86.7%, and 97.3%, respectively.nnnCONCLUSIONnThe standardized Kasai procedure was associated with favorable outcomes. Long-term outcomes remain to be evaluated.nnnLEVEL OF EVIDENCEnCase-control/treatment study, level III.

Effectiveness of Bortezomib in a Patient With Acute Rejection Associated With an Elevation of Donor-Specific HLA Antibodies After Small-Bowel Transplantation: Case Report

BACKGROUNDnA significant association between donor-specific antibody (DSA) and graft rejection has recently been documented. However, confirmed strategy has not been established for DSA-associated rejection after intestinal transplantation (ITx).nnnCASE REPORTnA 20-year-old male patient with chronic intestinal obstruction caused by hypoganglionosis of the entire intestine underwent cadaveric donor ITx with grafting performed on 232xa0cm of the small intestine, cecum, and a part of the ascending colon. On post-operative day (POD) 14, a histological evaluation showed an acute rejection of indeterminate grade. The patient had severe acute rejection on POD 16, which prompted us to administer bolus steroids and polyclonal anti-thymocyte antibody, along with baseline maintenance immunosuppression. The histopathological findings of the graft indicated typical acute cellular rejection, although C4d was positive. We then detected donor-specific HLA antibody. The patient initially responded well to the therapy and showed decreased histological rejection signs. However, the refractory low-grade rejection persisted in the graft. During this period, the patient showed increased levels of DSA, and we speculated that the persistent rejection was associated with DSA; thus, bortezomib was administered at this stage as a salvage therapy. This rejection was thereafter successfully controlled without severe adverse effect. Twenty-three months after ITx, the patient is currently alive with complete enteral autonomy.nnnCONCLUSIONSnA case of acute graft rejection followed by a marked elevation of DSA is presented. In this particular case, a modified treatment protocol using bortezomib in addition to the typical immunosuppressive agents was effective.

Aplasia of the dorsal pancreas and choledochal cyst

The authors describe a rare case of choledochal cyst and aplasia of the dorsal pancreas complicated with chronic pancreatitis. A 9-year-old boy presented with obstructive jaundice. After biliary drainage using pericutaneous transhepatic gallbladder drainage (PTGBD) technique, the patient underwent choledochal cyst excision with Roux-en-Y hepaticojejunostomy. The association of choledochal cyst and aplasia of the dorsal pancreas with chronic pancreatitis has never been reported previously.

Analysis of the prognostic factors of long-term native liver survival in survivors of biliary atresia.

PurposeLong-term survivors of biliary atresia (BA) sometimes experience liver dysfunction. We evaluated the prognostic factors for long-term native liver survival (NLS) in BA patients after the Kasai procedure.MethodsThis study included 67 patients with jaundice disappearance after the Kasai procedure performed between 1972 and 1995, and NLS for over 10xa0years. We retrospectively evaluated the clinical parameters, including the type of BA, age at the Kasai procedure, medical conditions, and treatments. The adjusted odds ratios (aOR) were obtained for 20-year NLS using logistic regression analysis.ResultsThe median age of the patients at the Kasai procedure was 63xa0days. Of the 67 study patients, 62 patients (92.5xa0%) had jaundice-free NLS at the age of 20xa0years, 4 patients died before the age of 20xa0years from liver failure, and 1 patient underwent living related liver transplantation. The presence of gastro-esophageal varices requiring endoscopic injection sclerotherapy was a significant factor (aOR 33.8; pxa0=xa00.0033), while hypersplenism and cholangitis were not identified as significant factors.ConclusionsThe existence of symptomatic portal hypertension would influence long-term NLS in BA patients after the Kasai procedure. In such patients, accurate evaluation of hepatic function and adequate treatment for sequelae are needed.

Using 99mTc-DTPA galactosyl human serum albumin liver scintigraphy as a prognostic indicator in jaundice-free patients with biliary atresia

BACKGROUNDnWe evaluated the clinical significance of follow-up data, including 99mTc-DTPA galactosyl human serum albumin (99mTc-GSA) liver scintigraphy data, as prognostic indicators for jaundice-free patients with biliary atresia (BA).nnnMETHODSnOf 87 patients who underwent Kasai portoenterostomy (KP) between 1991 and 2012, 45 jaundice-free patients aged 1-2u202fyears underwent 99mTc-GSA scintigraphy and were classified into 2 groups: those who survived with a native liver (Group A, nu202f=u202f34) and those who required liver transplantation (LTx) (Group B, nu202f=u202f11). We compared 99mTc-GSA scintigraphy data (HH15, LHL15, and HH15/LHL15 [H/L15]) and liver function test (LFT) results between the groups. The patients underwent a second 99mTc-GSA scintigraphy at approximately 5u202fyears of age.nnnRESULTSnAll patients survived. HH15, H/L15, total bilirubin, direct bilirubin, gamma-glutamyl transpeptidase, and alanine transaminase levels were higher in Group B than in Group A (p<0.05). Total and direct bilirubin levels were associated with H/L15 (p<0.05). There were no significant changes in results between the first and second 99mTc-GSA scintigraphy in Group A.nnnCONCLUSIONSnMid- and long-term prognoses may be predicted using 99mTc-GSA scintigraphy data and LFTs in patients aged 1-2u202fyears. We recommend regular monitoring of postoperative data following KP, even in jaundice-free patients.nnnLEVEL OF EVIDENCEnIII.

Mediastinal tumor resection via open or video-assisted surgery in 31 pediatric cases: Experiences at a single institution

BACKGROUNDnVideo-assisted thoracic surgery (VATS) has been increasingly used for the diagnosis and treatment of thoracic diseases. Pediatric mediastinal tumors are often difficult to resect because of their proximity to important organs. For this reason, VATS is not established as a standard surgical approach for such tumors. We compared the efficacy and safety of mediastinal tumor resection in children using open thoracotomy (OT) and VATS.nnnMETHODSnA total of 31 children underwent mediastinal tumor resection (21 by VATS and 10 by OT). These nonrandomized approaches were retrospectively compared for incidence of operative complications, morbidity, and mortality.nnnRESULTSnTumor sizes and operation times were similar between groups. However, the VATS group required significantly fewer blood transfusions and shorter durations of thoracic drainage and hospital stays (p<0.05). Complications greater than grade 2 on the Clavien-Dindo classification occurred in four patients treated by VATS and OT. No delayed effects were noted in the survivors of either group. A patient with clear cell sarcoma of the kidney who underwent OT relapsed and died.nnnCONCLUSIONnAlthough complication rates were similar between the two approaches, VATS was suggested as less invasive because of fewer blood transfusions required, and shorter thoracic drainage and hospital stay durations.