佐久間 康成

OBJECTIVES: Cholestatic liver disease (CLD) is the main indication for liver transplantation in children. This retrospective study evaluated the outcomes of living donor liver transplantation (LDLT) in children with CLD. METHODS: One hundred fifty-nine children with CLD who underwent 164 LDLT between May 2001 and May 2011 were evaluated. Their original diseases were biliary atresia (n=145, 91%), Alagille syndrome (n=8, 5%), primary sclerosing cholangitis (n=2), and the others (n=4). The mean age and body weight of the recipients at LDLT was 42±53 months and 14.0±11.0 kg, respectively. RESULTS: Parents were living donors in 98%. The left lateral segment was the most common type of graft (77%). There were no reoperations and no mortality in any living donor. Recipients' postoperative surgical complications consisted mainly of hepatic arterial problems (7%), hepatic vein stenosis (5%), portal vein stenosis (13%), biliary stricture (18%), intestinal perforation (3%). The overall rejection rate was 31%. Cytomegalovirus infection and Epstein-Barr virus disease were observed in 26% and 5%, respectively. Retransplantation was performed five times in four patients; the main cause was hepatic vein stenosis (n=3). Four patients died; the main cause was gastrointestinal perforation (n=2). The body height of Alagille syndrome patients less than 2 years old significantly improved compared with older patients after LDLT. The 1-, 5-, and 10-year patient survival rates were 98%, 97%, and 97%, respectively. CONCLUSIONS: LDLT for CLD is an effective treatment with excellent long-term outcomes.

OBJECTIVE: The number of kidney transplantations (KTx) among patients on long-term hemodialysis (HD) is increasing due to the donor shortage in Japan. We investigated the outcomes of KTx among long-term (more than 15 years) patients on HD. METHODS: We performed 103 KTx between April 2003 and April 2010 including seven patients (one living and six deceased donor grafts), who had been treated with HD for more than 15 years (group 1) compared with 96 patients (94 living and two deceased donor grafts) treated for less than 15 years (group 2) before KTx. We examined the differences in patient and graft survivals and complication rates between the groups. RESULTS: Acute rejection episodes (ARE) occurred in 2 (29%) group 1 and 22 (22%) group 2 subjects. Urinary tract infections were diagnosed in 1 (14%) group 1 versus 8 (8%) group 2 cases. The incidence of perioperative complications, such as delayed graft function, cytomegalovirus infection, and surgical complications was higher among group 1. The serum creatinine at 1 year after KTx was the same (1.3 mg/dL). The patient/graft survivals were 100%/100% at 1 and 3 years in group 1 versus 100%/100% at 1 and 99%/98% at 3 years in group 2. CONCLUSION: The outcomes of KTx among long-term dialysis patients were similar to those in short-term dialysis patients.

INTRODUCTION: According to the Japanese renal transplant registry in 2009, there were 1123 living kidney transplantations (LKT), including 35% from spouses (husband/wife). Up to the present in Japan, biologically living unrelated donors (LURD) are most frequently spouses. This study summarized our experience with LURD, especially spousal, kidney transplantation. PATIENTS AND METHODS: We performed 112 cases of LKT between April 2003 and March 2011, including 44 (39%) from spouses and two from other LURD. The other 66 cases received kidneys from living related donors (LRD). We divided the patients into two groups: 44 patients (group 1) received kidneys from spouses (LURD) and 66 (group 2) from LRD. During the induction phase, tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone were prescribed for immunosuppression. Basiliximab was administered on postoperative days 0 and 4. In ABO-incompatible LKT, plasmapheresis was performed to remove anti-AB antibodies prior to LKT; splenectomy or rituximab administration, at the time of or before LKT. RESULTS: Among group 1, one patient died with a functioning graft and one lost her graft. Among group 2, one patient died with a functioning graft and one lost his graft. The incidences of an acute rejection episode were 31.8% and 24.2% in groups 1 and 2, respectively. There were three cases of antibody-mediated rejection in group 1. No patient experienced a lethal infectious complication. CONCLUSIONS: Our results demonstrated that spousal LKT (LURD) was equivalent to LKT from LRD. In response to the shortage of deceased donors, LKT between married couples and from ABO-incompatible donors will spread in Japan.

Liver retransplantation (re-LT) is required in patients with irreversible graft failure, but it is a significant issue that remains medically, ethically, and economically controversial, especially in living donor liver transplantation (LDLT). The aim of this study was to evaluate the outcome, morbidity, mortality, safety and prognostic factors to improve the outcome of pediatric living donor liver retransplantation (re-LDLT). Six of 172 children that underwent LDLT between January 2001 and March 2010 received a re-LDLT and one received a second re-LDLT. The overall re-LDLT rate was 3.5%. All candidates had re-LDLT after the initial LDLT. The overall actuarial survival of these patients was 83.3% and 83.3% at one and five yr, respectively. These rates are significantly worse than the rates of pediatric first LDLT. Vascular complications occurred in four patients and were successfully treated by interventional radiologic therapy. There were no post-operative biliary complications. One case expired because of hemophagocytic syndrome after re-LDLT. Although pediatric re-LDLT is medically, ethically, and economically controversial, it is a feasible option and should be offered to children with irreversible graft failure. Further investigations, including multicenter studies, are therefore essential to identify any prognostic factors that may improve the present poor outcome after re-LDLT.

Carcinoma of the minor duodenal papilla is extremely rare. We present the case of a 69-year-old man diagnosed with a tumor of the second portion of the duodenum by upper gastrointestinal endoscopy, which revealed a 1.5-cm elevated tumor with slight ulceration at the minor duodenal papilla. Biopsy revealed adenocarcinoma, and a computed tomography scan showed an enhanced tumor in the duodenum, with no abnormality in the pancreatic head. A pancreas-sparing segmental duodenectomy was performed, and the duodenum reconstructed with an end-to-end anastomosis. Microscopically, the tumor was a well-differentiated adenocarcinoma, with no infiltration at the cut end of the accessory pancreatic duct. The postoperative course was uneventful and the patient discharged on postoperative day 11. We reviewed previously reported cases of carcinoma of the minor duodenal papilla. Early and exact preoperative diagnosis of duodenal neoplasms makes it possible to select a less invasive treatment, which also maintains curability.

血行郭清術を行った胃食道静脈瘤16例(男性10例、女性6例、平均61.4歳)を、2007年迄の大開腹手術9例(前期群)と2007年以降の正中切開3例・鏡視下手術4例の計7例(後期群)に分け検討した。疾患はB・C型肝炎11例、非アルコール性脂肪肝炎3例、アルコール性肝硬変、特発性門脈圧亢進症各1例、術前内視鏡的硬化療法7例、同内視鏡的静脈瘤結紮術3例、バルーン下逆行性経静脈的塞栓術適応外9例、無効7例であった。前期群と後期群の脾摘:3例、0例、LigaSure使用:3例、7例、手術時間:280.0分、207.9分、出血量:1578.9ml、204.3ml、在院日数:27.8日、14.0日、合併症:3例(創し開、胃内容停滞、難治性腹水)、0例、内視鏡治療追加(全例食道静脈瘤):2例、5例、手術死亡や重篤な合併症はなく全例軽快退院した。現在生存10例、死亡6例(肝細胞癌5例、多臓器不全1例)、平均生存期間44.9ヵ月であった。後期群で出血量、在院日数が有意に減少した。

PURPOSE: Hepatopulmonary syndrome (HPS) is a progressive, deteriorating complication of end-stage liver disease (ESLD) that occurs in 13-47% of liver transplant candidates. Although LT is the only therapeutic option for HPS, it has a high morbidity and mortality, especially in patients with severe hypoxemia before transplantation, but the course of HPS after living donor liver transplantation (LDLT), especially for biliary atresia (BA) patients is not well established. PATIENTS AND METHODS: The present study evaluated 122 patients who received an LDLT for BA and of these, 3 patients had HPS at the time of LDLT in a single-center series. RESULTS: Two patients of the HPS patients them had biliary and/or vascular complications, but they recovered uneventfully with interventional treatment. None of the patients required supplemental oxygen and had no residual cardiopulmonary abnormalities at a follow-up of more than 24 months. CONCLUSION: Although a series of three patients is too small for definitive conclusion and further investigations must be conducted, pediatric LDLT can be a favorable therapeutic option for HPS.

Ornithine transcarbamylase deficiency, the most common urea cycle disorder, causes hyperammonemic encephalopathy and has a poor prognosis. Recently, LT was introduced as a radical OTCD treatment, yielding favorable outcomes. We retrospectively analyzed LT results for OTCD at our facility. Twelve children with OTCD (six boys and six girls) accounted for 7.1% of the 170 children who underwent LDLT at our department between May 2001 and April 2010. Ages at LT ranged from nine months to 11 yr seven months. Post-operative follow-up period was 3-97 months. The post-operative survival rate was 91.7%. One patient died. Two patients who had neurological impairment preoperatively showed no alleviation after LT. All patients other than those who died or failed to show recovery from impairment achieved satisfactory quality-of-life improvement after LT. The outcomes of LDLT as a radical OTCD treatment have been satisfactory. However, neurological impairment associated with hyperammonemia is unlikely to subside even after LT. It is desirable henceforth that more objective and concrete guidelines for OTCD management be established to facilitate LDLT with optimal timing while avoiding the risk of hyperammonemic episodes.

5歳9ヵ月女児。7ヵ月時、胆道閉鎖症術後肝硬変に対して母親の外側区域をグラフトとする生体部分肝移植術を施行し、術後にタクロリムスとメチルプレドニソロンによる免疫抑制療法を施行した。1年6ヵ月後にメチルプレドニソロンを漸減中止し、5年時はタクロリムス単剤で行っていた。今回、プロトコール肝生検で門脈域の拡大と形質細胞の浸潤を認めinterface hepatitisを呈し、門脈域の線維性拡大を認めbridging fibrosisへの進行が懸念され、タクロリムス増量、mycophenolate mofetil(MMF)を導入して免疫抑制療法を強化した。5年6ヵ月後のフォローアップ肝生検でinterface hepatitisと門脈域の形質細胞浸潤は改善傾向を認めたが、一部線維化を認めtacrolimusの継続とMMFの増量を行った。6年6ヵ月後のフォローアップ肝生検で門脈域の形質細胞浸潤は消失し、bridging fibrosisも改善したため、免疫抑制療法は変更せずに継続した。

症例は69歳，男性．CT，MRIで肝右葉に早期濃染される最大径15 cmの巨大腫瘍と外側区域と尾状葉に数個の小腫瘍を認め，PIVKAIIの高値と画像所見から肝細胞癌と診断した．総コレステロール855 mg/dl ，トリグリセリド753 mg/dl と著明な高脂血症も認めた．2年前の総コレステロールは250 mg/dl であった．胆汁うっ滞所見がなく，高脂血症の家族歴もなく，急激な上昇を認めていることから腫瘍随伴症候群による高脂血症と考えられた．右肝の主腫瘍切除後，総コレステロール・トリグリセリド値は急速に改善したが，術後早期に肝内再発をきたし，肝動脈化学塞栓療法を行うも著効なく，骨転移により急速な転帰をたどった．<br>

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.

PURPOSE: Bowel perforation after liver transplantation (LT) is a rare, but highly lethal complication with a poor prognosis. Here, we report the outcome of cases of bowel perforation after pediatric LT in our department. PATIENTS AND METHODS: The study subjects were 148 patients who underwent pediatric living donor liver transplantation. The 114 with biliary atresia (BA) were divided into two groups: those with associated bowel perforation (Group A) and those without (Group B). RESULTS: Four patients in all (2.5%) suffered bowel perforation. Their original disease was BA and emergency surgery was performed in all cases, with a mortality rate of 50.0%. Comparison of Groups A and B revealed significant differences in the patient age, body weight, duration of surgery, cold ischemic time, and blood loss volume. The survival rates in Groups A and B were 50.0 and 99.1%, respectively (p < 0.01). Duration of surgery was an independent risk factor (p = 0.05). CONCLUSION: Bowel perforation after LT is a potentially fatal complication. LT is a procedure that requires care and precision, and the possibility of bowel perforation should always be borne in mind during post-operative management, when the duration of surgery has been long.

OBJECTIVES: To describe our experience with 126 consecutive living-donor liver transplantation (LDLT) procedures performed because of biliary atresia and to evaluate the optimal timing of the operation. PATIENTS AND METHODS: Between May 2001 and January 2010,126 patients with biliary atresia underwent 130 LDLT procedures. Mean (SD) patient age was 3.3 (4.2) years, and body weight was 13.8 (10.7) kg. Donors included 64 fathers, 63 mothers, and 3 other individuals. The left lateral segment was the most commonly used graft (75%). Patients were divided into 3 groups according to body weight: group 1, less than 8 kg (n = 40); group 2,8 to 20 kg (n = 63); and group 3, more than 20 kg (n = 23). Medical records were reviewed retrospectively. Follow up was 4.5 (2.7) years. RESULTS: All group 3 donors underwent left lobectomy, and all group 1 donors underwent left lateral segmentectomy. No donors required a second operation or died. Comparison of the 3 groups demonstrated that recipient Pediatric End-Stage Liver Disease score in group 1 was highest, operative blood loss in group 2 was lowest (78 mL/kg), and operative time in group 3 was longest (1201 minutes). Hepatic artery complications occurred more frequently in group 1 (17.9%), and biliary stenosis (43.5%) and gastrointestinal perforation (8.7%) occurred more frequently in group 3. The overall patient survival rates at 1, 5, and 9 years was 98%, 97%, and 97%, respectively. Five-year patient survival rate in groups 1,2, and 3 were 92.5%, 100%, and 95.7%, respectively. Gastrointestinal perforation (n = 2) was the primary cause of death. CONCLUSIONS: Living-donor liver transplantation is an effective treatment of biliary atresia, with good long-term outcome. It seems that the most suitable time to perform LDLT to treat biliary atresia is when the patient weighs 8 to 20 kg.

BACKGROUND: There have been few reports on the management of intra-abdominal drains after living donor liver transplantation (LDLT). We retrospectively investigated changes in ascitic data related to management of an intra-abdominal drain. PATIENTS AND METHODS: Between March 2008 and June 2009, we performed 28 LDLT. On the first and the fifth postoperative day (POD) after LDLT, we examined the number of ascites cells and cell fractions as well as performed biochemical examination and cultures. RESULTS: The day of removal of the drain for massive ascites (10 mL/kg/d or more) was 14.2 ± 5.4 POD; for less than 10 mL/kg/d it was 8.7 ± 1.9 POD (P < .001). Nine patients were ascites culture positive; long-term placement of the drain caused an infection in two patients. CONCLUSIONS: When the amount of ascitic fluid on the fifth POD after LDLT was small, it was important to assess the properties of the ascitic fluid because of the possibility of a drain infection or of poor drainage. If the ascitic neutrophil count is less than 250/mm(3) or the examined ascites is normal, intra-abdominal drains should be removed.

Recent studies suggest that the overall survival and risk of end-stage renal disease among renal transplant donors are similar to those of the general population, but few studies focused on elderly donors. Among 88 donors who underwent retroperitoneoscopic live donor nephrectomies; 20 (22.7%) were elderly, namely, older than 65 years. Perioperative characteristics, such as sex, donor kidney side (left or right), body mass index, operative time, blood loss, and complication rate were not significantly different among groups classified by age: young (<50), middle (50-65), or elderly (>65). One month after kidney donation, the serum, creatinine values in the young, middle, and elderly groups increased to 1.05 ± 0.25, 0.96 ± 0.24, and 1.06 ± 0.15 mg/dL (P = .103) and the estimated glomerular filtration rate (eGFR) decrease to 63 ± 10, 63 ± 14, 56 ± 8 mL/min/1.73 m(2), respectively (P = .037). At three months and at three years after donation these parameters showed the same degree of improvement in all groups. Percentage of eGFR (% eGFR) of its pre-donation value in the young and middle groups improved up to 21% and up to 9%, respectively, until four years after donation, whereas that of the elderly group remained unchanged below 1%. In conclusion residual renal function after retroperitoneoscopic kidney donation in elderly donors was stable and acceptable during mid-term observation. Our retroperitoneoscopic approach was safe.

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.

A 35-year-old mother was scheduled to be the living donor for liver transplantation to her second son, who suffered from biliary atresia complicated with biliary cirrhosis at the age of 2 years. The operative plan was to recover the left lateral segment of the mother's liver for living donor transplantation. With the use of cholangiography at the time of surgery, we found the right anterior segmental duct (RASD) emptying directly into the cystic duct, and the catheter passed into the RASD. After repairing the incision in the cystic duct, transplantation was successfully performed. Her postoperative course was uneventful. Biliary anatomical variations were frequently encountered, however, this variation has very rarely been reported. If the RASD was divided, the repair would be very difficult because the duct will not dilate sufficiently in an otherwise healthy donor. Meticulous preoperative evaluation of the living donor's biliary anatomy, especially using magnetic resonance cholangiography and careful intraoperative techniques, is important to prevent bile duct injury and avoid the risk to the healthy donor.

OBJECTIVES: Recent studies demonstrated that prolactin (PRL) has beneficial effects on beta cells for islet transplantation. We examined the effect of human recombinant PRL (rhPRL) supplementation to the culture media to determine its potential use in the context of clinical islet transplantation. MATERIALS AND METHODS: Each human islet isolated from 14 deceased multiorgan donors was cultured in Miami modified media-1 supplemented with or without rhPRL (500 microg/L) for 48 hr. beta-Cell survival and proliferation (BrdU and Ki-67) were determined by laser scanning cytometry. The cytoprotective effects of rhPRL against noxious stimuli were assessed by flow cytometry (tetramethylrhodamine ethyl ester). Cytokine/chemokine and tissue factor productions were measured in vitro, and islet potency was assessed in vivo in diabetic immunodeficient mice. RESULTS: beta-Cell survival during culture was 37% higher in the rhPRL group than in control (P=0.029). rhPRL protected beta cells in vitro from cytokines, Nitric oxide donor, and H2O2. The exposure to rhPRL did not affect human beta-cell proliferation with our protocol. rhPRL treatment did not alter cytokine/chemokine and tissue factor production in vitro or affected human islet functionality in vivo: recipient mice achieved normoglycemia with a comparable tempo, whereas loss of graft function was observed in two of the seven mice in the control group and in none of the rhPRL group (p=n.s.). CONCLUSION: rhPRL supplementation to islet culture media improved human beta-cell-specific survival without altering islet quality. Addition of rhPRL to cultured islets may grant a more viable beta-cell mass in culture. The development of beta-cell cytoprotective strategies will be of assistance in improving islet transplantation outcomes.

8歳女児。胆道閉鎖症術後胆汁うっ滞性肝硬変に対し、1歳時に父親をドナーとする生体肝移植術を施行した。術後経過は良好で、第65病日に退院となった。外来フォロー中に門脈吻合部の狭窄を合併し、2歳時と4歳時にバルーン拡張術を施行した。しかし、8歳頃から再々狭窄を認めるようになった。全身麻酔下にバルーン拡張術を施行し、門脈の狭窄を解除後、プロトコール肝生検を超音波ガイド下に実施した。手技中のトラブルはなかった。また、術直前と術後8時間時に、予防的に抗生を投与した。40℃台の発熱が出現し、肝胆道系酵素の上昇を認めた。敗血症と診断し抗生剤、γグロブリン製剤の投与を開始した。敗血症の原因は肝生検による胆管炎が考えられた。術後3日目には解熱傾向に転じ、炎症反応や黄疸の改善もみられ、その後は速やかに状態の改善を得て、術後10日目に退院となった。