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Background Myotubular myopathy is a rare disease sometimes accompanied by peliosis hepatis, a leading cause of fatal liver hemorrhage. Case Report We present a case of a 2-year-old boy with myotubular myopathy who developed liver hemorrhage because of peliosis hepatis and was successfully treated with living-donor liver transplant. The patient initially presented with fever, anemia, and liver dysfunction. A computed tomographic scan revealed hemorrhages in the liver, and the patient underwent hepatic artery embolization twice. After the second embolization, multiple peliosis hepatis cavities appeared in the left lobe of the liver that had increased in size. Therefore, the patient underwent ABO-incompatible living-donor liver transplant using a lateral segment graft from his father. The patient developed severe septic shock with an unknown focus on postoperative day 18, which resolved with antibiotic therapy. On postoperative day 62, he was discharged. Fourteen months after undergoing living-donor liver transplant, the patient showed no recurrence of peliosis hepatis. Conclusions Although the long-term prognosis of peliosis hepatis due to myotubular myopathy after living-donor liver transplant remains unclear, liver transplant may be a curative treatment for patients with myotubular myopathy who have uncontrollable peliosis hepatis.

Graft inflow modulation (GIM) during adult-to-adult living donor liver transplantation (LDLT) is a common strategy to avoid small-for-size syndrome, and some transplant surgeons attempt small size graft strategy with frequent GIM procedures, which are mostly performed by splenectomy, in LDLT. However, splenectomy can cause serious complications such as portal vein thrombosis and overwhelming postsplenectomy infection.Forty-eight adult-to-adult LDLT recipients were enrolled in this study and retrospectively reviewed. We applied the graft selection criteria, which routinely fulfill graft-to-recipient weight ratio ≥ 0.8%, and consider GIM as a backup strategy for high portal venous pressure (PVP).In our current strategy of LDLT, splenectomy was performed mostly due to hepatitis C and splenic arterial aneurysms, but splenectomy for GIM was intended to only one patient (2.1%). The final PVP values ≤ 20 mmHg were achieved in all recipients, and no significant difference was observed in patient survival or postoperative clinical course based on whether splenectomy was performed or not. However, 6 of 18 patients with splenectomy (33.3%) developed postsplenectomy portal vein thrombosis (PVT), while none of the 30 patients without splenectomy developed PVT after LDLT. Splenectomy was identified as a risk factor of PVT in this study (P0.001). Our study revealed that a lower final PVP could be risk factor of postsplenectomy PVT.Using sufficient size grafts was one of the direct solutions to control PVP, and allowed GIM to be reserved as a backup procedure. Splenectomy should be avoided as much as possible during LDLT because splenectomy was found to be a definite risk factor of PVT. In splenectomy cases with a lower final PVP, a close follow-up is required for early detection and treatment of PVT.

Early relaparotomy of adult recipients after living donor liver transplantation (LDLT) is significantly associated with poor prognosis. However, there are few reports focusing on pediatric recipients after LDLT. The aim of this study is to clarify the causes and outcomes of early relaparotomy after pediatric LDLT. A total of 265 pediatric recipients (272 LDLTs) transplanted from May 2001 to October 2015 were retrospectively analyzed. Early relaparotomy was defined as surgical intervention performed within 3 months after LDLT. Early relaparotomy was performed 49 times for 33 recipients (12.5%). The recipient and graft survival rates in the early relaparotomy group were significantly lower than those in the nonearly relaparotomy group, respectively (75.0% and 63.6% versus 96.6% and 95.8%; both P < 0.001). Left lateral segment grafts were used significantly more frequently in the nonrelaparotomy group (P = 0.01). According to the multivariate analysis, the preoperative Pediatric End-Stage Liver Disease (PELD)/Model for End-Stage Liver Disease (MELD) score of the early relaparotomy group was significantly higher than that of the nonearly relaparotomy group (13.7 versus 6.3; P = 0.04). According to the receiver operating characteristic curve, the preoperative PELD/MELD score cutoff point was 17.2. Early relaparotomy due to infectious causes led to significantly poorer graft survival than that due to noninfectious causes (P = 0.04). In conclusion, the recipient and graft survival rates of the early relaparotomy group were significantly lower than those of the nonearly relaparotomy group. A high preoperative PELD/MELD score was a risk factor for early relaparotomy. In particular, early relaparotomy due to infection showed a poor prognosis.

Patients with hepatitis-associated aplastic anemia (HAA) who undergo living-donor liver transplantation (LDLT) have a poor prognosis with infections and bleeding complications. Rapid recovery of blood cells is critical for preventing these complications and improving the outcome. Immunosuppressive therapy (IST) combined with thrombopoietin receptor agonists is considered effective for aplastic anemia. However, there are no data on the benefits of adding thrombopoietin receptor agonists to IST for HAA. We present the case of a child with severe HAA who underwent LDLT, and who achieved rapid blood cell recovery with IST combined with romiplostim, a thrombopoietin receptor agonist. In addition, despite having undergone LDLT, the patient had no adverse events such as serious liver dysfunction or thrombosis. This case suggests that IST combined with thrombopoietin receptor agonists may be a promising treatment option for HAA patients undergoing LDLT.

Objectives Predicting the risk of posthepatectomy liver failure is important when performing extended hepatectomy. However, there is no established method to evaluate liver function and improve preoperative liver function in pediatric patients. Materials and methods We show the clinical features of pediatric patients who underwent living donor liver transplant for posthepatectomy liver failure in hepatoblastoma. The subjects were 4 patients with hepatoblastoma who were classified as Pretreatment Extent of Disease III, 2 of whom had distal metastasis (chest wall and lung). Results Hepatic right trisegmentectomy was performed in 3 patients and extended left hepatectomy in 1 patient. The median alpha-fetoprotein level at the diagnosis of hepatoblastoma was 986300 ng/mL (range, 22500-2726350 ng/mL), and the median alpha-fetoprotein level before hepatectomy was 8489 ng/mL (range, 23-22500 ng/mL). The remnant liver volume after hepatectomy was 33.3% (range, 20% to 34.9%). Four patients had cholangitis after hepatectomy and progressed to posthepatectomy liver failure. The peak serum total bilirubin after hepatectomy was 11.4 mg/dL (range, 8.7-14.6 mg/dL). Living donor liver transplant was performed for these 4 patients with posthepatectomy liver failure, and they did not have a recurrence. Conclusions When the predictive remnant liver volume by computed tomography-volumetry before extended hepatectomy for patients with hepatoblastoma is less than 40%, the possibility of posthepatectomy liver failure should be recognized.

Background There have been no reports on the effectiveness of the administration of antithrombin III (AT III) for post-transplant portal vein thrombosis (PVT). We herein report a case of post-transplant PVT that was resolved by AT III treatment after living donor liver transplantation (LDLT). Case presentation The patient was a 57-year-old man who had been diagnosed with decompensate liver cirrhosis by hepatitis C virus infection. He presented with repeated hepatic coma and refractory ascites. Computed tomography (CT) revealed PVT of Yerdel classification grade II before LDLT. He underwent ABO-identical LDLT using a right lobe graft. A liver function test revealed elevated liver enzyme levels on post-operative day (POD) 14. The CT examination on POD 15 revealed PVT in the left side of the main portal vein at the side of left gastric vein ligation. AT III treatment from POD 15 to POD 24 was performed. Magnetic resonance imaging revealed that the PVT had decreased 10% on POD 27. Furthermore, AT III treatment from POD 28 to POD 32 was performed. The CT examination demonstrated the disappearance of PVT on POD 69 and thereafter, he had no recurrence of PVT on 10 post-operative month (POM). Conclusions The present case suggests that the administration of AT III is safe and suitable for the treatment of post-transplant PVT.

BACKGROUND The number of pregnancies after liver transplantation (LT) is increasing; however, the safety and incidence of complications associated with these pregnancies are still unclear. In this report, we retrospectively assessed the influences and problems associated with post-transplant pregnancy on allografts, recipients, and fetuses. MATERIAL AND METHODS A total of 14 pregnancies were identified in 8 female recipients between 2005 and 2018. The original disease was biliary atresia in all recipients. We provide a basic guide for the management of planned pregnancies in female recipients. RESULTS Of the 7 planned pregnancies, no recipients took mycophenolate mofetil (MMF) or had allograft liver dysfunction. Among the 7 unplanned conceptions, we judged that the pregnancy was inadequate to continue in 4 recipients due to taking MMF and 2 recipients due to allograft liver dysfunction at conception. However, 4 recipients who immediately stopped taking MMF continued with their pregnancies. Ten pregnancies resulted in live 11 births. Among obstetric complications or fetal and neonatal complications, gestational diabetes mellitus in 3 recipients was the most common. There were 3 miscarriages and 1 planned termination because of MMF medication and liver dysfunction. CONCLUSIONS Planned pregnancies in LT recipients can lead to the birth of a healthy baby and no influence on either the allograft or the recipient. However, unplanned pregnancies in LT recipients, such as recipients who take MMF or have allograft liver dysfunction, may have an adverse influence on the fetus.

Background Aspartate transaminase–to–platelet ratio index (APRI) and fibrosis-4 (FIB-4) are well known as representative indirect serum biomarkers related to liver fibrosis. The usefulness of these markers for the diagnosis of liver fibrosis after liver transplantation (LT) in hepatitis C virus (HCV)–infected patients and the influence of splenectomy were investigated. Methods From June 2003 to May 2014, 31 HCV-infected patients who underwent LT and postoperative follow-up liver biopsies were included in this study. The association between liver fibrosis and serum biomarkers and the influence of splenectomy on APRI and FIB-4 were also investigated. Results A total of 195 biopsy specimens were collected, and liver fibrosis was identified as: F0, 59.7%; F1, 34.1%; and F2, 6.3%. Both APRI and FIB-4 were significantly higher in patients who showed F1 and F2 in liver biopsy specimen than F0 (P values, .009 and .022, respectively); sensitivity and specificity of APRI were, respectively, 63.4% and 66.7%, and those of FIB-4 were 57.7% and 69.6%. In 11 patients (35.5%) who underwent splenectomy at the time of LT, the cutoff values for APRI and FIB-4 were 0.61 and 1.41, which were significantly lower than the corresponding values (1.00 and 3.64) of patients without splenectomy. Conclusions APRI and FIB-4 could effectively estimate liver fibrosis after LT for HCV-related liver disease. For LT patients with splenectomy, APRI and FIB-4 were also useful to estimate liver fibrosis, but the standard values should be adjusted lower than those for patients without splenectomy.

We herein report a case of lung metastases with unusual radiological appearances that mimicked those of chronic airway infection, causing diagnostic difficulty. A 60-year-old woman who underwent liver transplantation from a living donor was incidentally diagnosed with bile duct adenocarcinoma after a histopathological analysis of her explanted liver. Six months later, chest computed tomography (CT) revealed bilateral bronchogenic dissemination that had gradually worsened, suggesting chronic airway infection. A biopsy with bronchoscopy from a mass lesion beyond a segmental bronchus revealed adenocarcinoma identical to that of her bile duct adenocarcinoma, leading to the diagnosis of multiple lung metastases from bile duct adenocarcinoma.

Highlights • We report a case in which a brain death donor, supported by a left ventricular assist device, with significant congestive fibrosis of the liver. • This case serves as a note of caution when addressing organ procurement from brain death donor with left ventricular assist device. • Exposure of the surgical fields was restricted by the device and drive lines. • It also should be noted that chronic heart failure can lead to subclinical advanced liver fibrosis., Instruction Organ transplantation from a brain death donor on mechanical circulatory support is rare. We report a case in which a brain death donor, supported by a left ventricular assist device (LVAD), unexpectedly displayed significant congestive fibrosis of the liver. Presentation of case The potential organ donor was diagnosed 23 years previously as having dilated-phase of hypertrophic cardiomyopathy. He had undergone implantation of an LVAD as a bridge to heart transplantation. Laboratory tests and imaging studies performed during the follow-up for his cardiac disease and donor evaluation confirmed that he was suitable for donation of liver. During organ procurement, special attention was paid to preserving LVAD and its device’s drive lines and the exposure of the surgical fields was restricted by those devices. Thoracotomy and laparotomy were performed, and the aorta and inferior vena cava were encircled successfully. The gross appearance of liver, however, suggested significant fibrosis. Therefore, the decision was made not to use this liver. Subsequent trichrome-stained permanent sections revealed advanced fibrosis (stage F3–4). Discussion As previously reported, organ procurement from donors with LVAD was thought to be demanding procedure because of the limited exposure of surgical field. In addition, it would be difficult to predict severe liver fibrosis in patients with an LVAD without a pathological examination. Conclusion Donors with mechanical circulatory support systems can be candidate to expand the donor pool, but technical difficulty should be expected owing limited exposure during the donor operation. For liver transplantation, subclinical advanced liver fibrosis should be noted.

Case series Patient: Male, 44 • Male, 44 • Female, 36 Final Diagnosis: Alcohol use disorders in sustained remission Symptoms: Relapse of alcohol use • stress-related anger/irritation • zolpidem abuse Medication: — Clinical Procedure: Psychiatric intervention Specialty: Transplantology Objective: Unusual setting of medical care Background: Around 20–30% of patients who undergo liver transplantation (LT) for alcoholic liver disease (ALD) will resume heavy drinking after LT. It is crucial to control post-transplant relapse of alcohol use, because alcoholic recidivism has been shown to have a negative impact on post-transplant compliance and long-term outcomes of LT recipients. However, there is currently no specific, effective psychiatric intervention for preventing additional alcohol consumption in clinical practice. Case Report: We present 3 patients who underwent LT for ALD at Nagoya University Hospital who were followed up for prolonged periods (7.2, 8.8, and 11.3 years, respectively), and review the psychiatric interventions employed to address critical situations. Additional alcohol consumption was noted in Case 1, but prompt collaborative care led to stable abstinence. In Case 2, marked anger and irritation were exacerbated as a result of work, but the anger was controlled by anger management. Case 3 abused a minor tranquilizer, but limit-setting resulted in adequate medical adherence. Conclusions: Transplant teams need to provide comprehensive treatment for alcoholic recidivism to improve long-term health after LT for ALD.

Advances in interventional radiology (IVR) treatment have notably improved the prognosis of hepatic vein (HV) and portal vein (PV) complications following pediatric living donor liver transplantation (LDLT); however, graft failure may develop in refractory cases. Although endovascular stent placement is considered for recurrent stenosis, its indications are controversial. We enrolled 282 patients who underwent pediatric LDLT in our department from May 2001 to September 2016. 22 (7.8%) HV complications occurred after LDLT. Recurrence was observed in 45.5% of the patients after the initial treatment, and 2 patients (9.1%) underwent endovascular stent placement. The stents were inserted at 8 months and 3.8 years following LDLT, respectively. After stent placement, both patients developed thrombotic obstruction and are currently being considered for re-transplantation. 40 (14.2%) PV complications occurred after LDLT. Recurrence occurred in 27.5% of the patients after the initial treatment, and 4 patients (10.0%) underwent endovascular stent treatment. The stents of all the patients remained patent, with an average patency duration of 41 months. Endovascular stent placement is an effective treatment for intractable PV complications following pediatric LDLT. However, endovascular stent placement for HV complications should be carefully performed because of the risk of intrastent thrombotic occlusion and the possibility of immunological venous injury.

Background We present a retrospective analysis of our experience with pediatric liver transplantation (LT), focusing on the long-term outcome of percutaneous transhepatic biliary drainage (PTBD) for post-transplant biliary strictures. Methods Fifty-three PTBDs were performed for 41 pediatric recipients with biliary strictures. The median ages at LT and PTBD were 1.4 and 4.4 years, respectively. The median observation period was 10.6 years. Results Post-transplant biliary strictures comprised anastomotic stricture (AS) in 28 cases, nonanastomotic stricture (NAS) in 12, anastomotic obstruction (AO) in 8, and nonanastomotic obstruction (NAO) in 5. The success rate of PTBD was 90.6%, and the 15-year primary patency rate of PTBD was 52.6%. The recurrence rate of biliary strictures after PTBD was 18.8% (9/48), and among the four NAS cases with recurrence, two underwent re-LT. The biliary obstruction rate was 27.1% (13/48). Among the eight cases with AO, five underwent the rendezvous method and three underwent surgical re-anastomosis. Among the five cases with NAO, one underwent re-LT. The recipient survival rate of PTBD treatment was 100%. Conclusions The graft prognosis of AS by PTBD treatment is good and AO is curable by the rendezvous method and surgical re-anastomosis. However, the graft prognosis of NAS and NAO is poor.

Background Long-term outcomes after endoscopic treatment of post-transplant biliary complications have not been fully understood. This study aimed to evaluate the impact of biliary complications on graft survival after right-lobe living-donor liver transplantation (R-LDLT). Method From a single-institutional prospectively maintained database, all patients who underwent R-LDLT between 1999 and 2017 were included. Data on patient demographics, complications, endoscopic treatment, and graft survival were retrieved for analyses. Results Among 111 patients who underwent R-LDLT, 33 (29.7%) developed biliary complications; of these, 19 (17.1%) were treated with biliary stenting, and the stent was removed following resolution of biliary complications in 8 of the 19 (42.1%) patients. The graft survival rate was 88.0% and 85.6% at 5- and 10-year follow-up, respectively, in patients without biliary complications, which was similar to that of the patients with resolved biliary complications (81.3% at 5- and 10-year follow-up, P = .68) but higher than that of patients having persistent (unresolved) biliary complications (61.4% and 49.1% at 5- and 10-year follow-up, respectively, P = .04). Conclusion Post-transplant persistent biliary complications, unresolved after endoscopic management and requiring prolonged biliary stenting, are associated with inferior graft survival. However, patients with resolved biliary complications achieve a favorable long-term survival similar to patients without biliary complications.

Advanced liver cirrhosis is usually accompanied by portal hypertension. Long-term portal hypertension results in various vascular alterations. The systemic hemodynamic state in patients with cirrhosis is termed a hyperdynamic state. This peculiar hemodynamic state is characterized by an expanded blood volume, high cardiac output, and low total peripheral resistance. Vascular alterations do not disappear even long after liver transplantation (LT), and recipients with cirrhosis exhibit a persistent systemic hyperdynamic state even after LT. Stability of optimal systemic hemodynamics is indispensable for adequate portal venous flow (PVF) and successful LT, and reliable parameters for optimal systemic hemodynamics and adequate PVF are required. Even a subtle disorder in systemic hemodynamics is precisely indicated by the balance between cardiac output and blood volume. The indocyanine green (ICG) kinetics reflect the patient's functional hepatocytes and effective PVF, and PVF is a major determinant of the ICG elimination constant (kICG) in the well-preserved allograft. The kICG value is useful to set the optimal PVF during living-donor LT and to evaluate adequate PVF after LT. Perioperative management has a large influence on the postoperative course and outcome; therefore, key points and unexpected pitfalls for intensive management are herein summarized. Transplant physicians should fully understand the peculiar systemic hemodynamic behavior in LT recipients with cirrhosis and recognize the critical importance of PVF after LT.

Hepatitis C recurrence continues to present a major challenge in liver transplantation (LT). Approximately 10% of hepatitis C virus (HCV)-positive recipients will develop fibrosing cholestatic hepatitis (FCH) after LT. FCH is clinically characterized as marked jaundice with cholestatic hepatic dysfunction and high titers of viremia. Pathologically, FCH manifests as marked hepatocyte swelling, cholestasis, periportal peritrabecular fibrosis and only mild inflammation. This progressive form usually involves acute liver failure, and rapidly results in graft loss. A real-time and precise diagnosis based on histopathological examination and viral measurement is indispensable for the adequate treatment of FCH. Typical pathological findings of FCH are shown. Currently, carefully selected combinations of direct-acting antivirals (DAAs) offer the potential for highly effective and safe regimens for hepatitis C, both in the pre- and post-transplant settings. Here, we review FCH caused by HCV in LT recipients, and current strategies for sustained virological responses after LT. Only a few cases of successfully treated FCH C after LT by DAAs have been reported. The diagnostic findings and therapeutic dilemma are discussed based on a literature review.

Development of renal dysfunction, including acute kidney injury (AKI) and chronic kidney disease (CKD), after liver transplantation (LT) remains a critical issue adversely affecting patient survival in both the short and long term. Previous reports have suggested that inflammatory and antiinflammatory cytokines and their functionally relevant gene polymorphisms may play critical roles in the development of AKI and CKD. However, the involvement of these cytokines and their gene polymorphisms in renal deterioration following LT remains unclear. We examined 62 recipients who underwent LT at Nagoya University between 2004 and 2009 and who had survived for at least 1 year. The following gene polymorphisms in recipients were analyzed: tumor necrosis factor-A (TNFA) T-1031C, interleukin-2 (IL2) T-330G, IL10 C-819T, IL13 C-1111T, transforming growth factor-B (TGFB) T29C, and IL4 T-33C. Thirteen patients (21 %) developed AKI within 4 weeks after LT. Of the investigated gene polymorphisms, the IL4 -33 T/T genotype was significantly associated with higher incidence of AKI compared with the other two genotypes [hazard ratio (HR) = 5.48, 95 % confidence interval (CI) 1.18–25.52, p = 0.03]. On the other hand, 16 patients (26 %) had developed CKD at median follow-up of 9.2 years after LT. We showed the lack of association between investigated gene polymorphisms in recipients and CKD development. The IL4 -33 T/T genotype might be a risk factor for AKI in LT, and this might contribute to earlier withdrawal of immunosuppressive agents to minimize renal toxicity. In contrast, none of the investigated cytokine gene polymorphisms were associated with CKD.

BACKGROUND Cytomegalovirus (CMV) remains a major cause of morbidity and mortality for liver transplant recipients. Although the CMV pp65 antigenemia (AG) assay has been widely used to monitor patients for CMV infection after liver transplantation, real-time PCR is becoming the standard procedure. The World Health Organization (WHO) International Reference Standard for CMV quantification has become available to standardize values diagnostic of CMV infection. MATERIAL AND METHODS Our in-house real-time PCR assay was standardized using the WHO standard reagents. Levels of CMV DNA in 1339 blood samples obtained from 190 liver transplant recipients were quantified and expressed in international units, and results were then compared with those of the CMV pp65 AG assay performed on the same blood samples. Correlation was assessed and receiver operating characteristic curves were analyzed to determine the optimal cut-off value for CMV DNA (IU/mL) PCR results. RESULTS Significant correlation was found between results of the 2 assay methods (p

Portal vein stenosis develops in 3.4–14% of split liver transplantation1–3 and its early detection and treatment are essential to achieve long-term graft survival,2–5 although the diagnostic capability of conventional modalities such as Doppler ultrasound and computed tomography is limited.1,4,5 This study used computational fluid dynamics to analyze portal vein hemodynamics in the management of post-transplant portal vein stenosis. To perform computational fluid dynamics analyses, three-dimensional portal vein model was created using computed tomographic DICOM data. The inlet flow condition was set according the flow velocity measured on Doppler ultrasonography. Finally, portal vein flow was simulated on a fluid analysis software (Software Cradle, Japan). An 18-month-old girl underwent liver transplantation using a left lateral graft for biliary atresia. At the post-transplant 1-week evaluation, the computational fluid dynamics streamline analysis visualized vortices and an accelerated flow with a velocity ratio 3:1).3,5 The pressure analysis revealed a positive pressure gradient of 3.8 mmHg across the stenotic site. Based on the findings, the patient underwent percutaneous transhepatic portal venoplasty with balloon dilation. The post-treatment analyses confirmed the improvement of a jet flow, vortices, a high wall shear stress, and a pressure gradient. The computational fluid dynamics analyses are useful for prediction, early detection, and follow-up of post-transplant portal vein stenosis and would be a promising technology in post-transplant management.

A 39-year-old man was diagnosed with allopurinol-induced hepatic injury. He did not show any sign of hepatic encephalopathy, but his serum total bilirubin level was >40 mg/dL when he visited the local hospital. The therapeutic effects of initial medical treatments were transient, and both renal function and coagulation ability were gradually deteriorated. Four months after the onset of hepatic injury, he was referred to our hospital for the purpose of liver transplantation (LT). Although he was wasting and severely jaundiced, his consciousness level was not disturbed at all, with normal serum ammonia blood concentration before LT. Owing to allopurinol-induced severe cholestatic liver failure, living-donor LT (LDLT) was performed with the use of a right lobe graft from his younger brother. The explanted liver was extremely enlarged, with a weight of 2,480 g, and severely cholestatic. Microscopic findings were also compatible with drug-induced cholestatic liver injury. He was discharged from hospital 55 days after LDLT, whereas his renal dysfunction remained at 6 months after LT. There are 3 types of pathophysiology of drug-induced hepatotoxicity: hepatocellular, cholestatic, and mixed liver injury. Although allopurinol hepatotoxicity is rare, it can be severe and even fatal. This is the 1st case report of successful LDLT for a patient who had developed allopurinol-induced cholestatic liver failure.

Background There are few reports on the short- and long-term follow-up of endoscopic retrograde cholangiography (ERC) in adult patients with hepaticojejunostomy (HJS) stricture after living-donor liver transplantation (LDLT). Methods Nine LDLT recipients underwent ERC with the use of double-balloon endoscopy (DBE) for HJS stricture at Nagoya University Hospital. We assessed the rate of reaching biliary anastomosis, procedure success rate, procedure duration, complications, improvement in liver function test results, and biliary anastomosis patency. Results In total, 19 ERC procedures with the use of DBE were performed for 9 adult LDLT recipients with HJS stricture from June 2006 to September 2014. Balloon dilation with the use of DBE was successfully performed in 5 of the 9 patients during the 1st procedure. Of the 4 patients in whom DBE-ERC failed to be completed, 3 patients underwent 2nd procedures successfully. Liver function test results were significantly improved in the successful cases. Four patients underwent 2nd DBE-ERC for stricture recurrence at a mean time of 2.3 years after the 1st successful procedure. Of those, 2 patients required 3rd procedures for stricture recurrence after the 2nd procedure. Conclusions DBE-ERC is promising as a treatment for HJS stricture in adult LDLT recipients in the short term. However, the DBE-ERC procedure may have a considerable risk of restenosis.

Highlights • Donor organ scarcity is the major problem in the field of liver transplantation. • Extended criteria donor for living donor liver transplantation (LDLT) is crucial. • This is the first adult-to-adult LDLT using liver allograft with benign hemangioma. • Liver allograft with hemangioma is a remarkable strategy to resolve organ shortage. • This case is so suggestive for a safe expansion of living donor pool in LDLT., Introduction Hepatic hemangioma is one of the most common benign liver tumors. There are few published reports regarding liver transplantation using liver allografts with hemangioma. Presentation of case A 45-year-old man was evaluated as a living donor for 19-year-old son with cirrhosis due to hepatic fibrosis. Preoperative investigations revealed 20 and 7 mm hemangiomas, at segment 2 (S2) and 4 (S4) respectively. Considering the anatomical relation of S2 hemangioma and Glisson 2, liver graft was designed as left lobe excluded S2 hemangioma by partial resection. Estimated graft recipient weight ratio (GRWR) even after partial resection of hemangioma was reasonable. During the donor operation, a partial hepatic resection of S2 hemangioma was performed. Intraoperative pathologic findings revealed a cavernous hemangioma, and then, the left hepatic graft with the caudate lobe was harvested. Actual GRWR was 0.90%. Donor's postoperative course was uneventful. Recipient’s post-operative course was almost uneventful. Postoperative computed tomography of the recipient showed the graft regeneration without increase or recurrence of hemangioma. Discussion Organ shortage is a major concern in the field of liver transplantation. A novel donor source with a further option is extremely crucial for a guarantee of liver transplantation. We experienced the first case of adult-to-adult living donor liver transplantation using liver allograft after the resection of hemangioma. Conclusion We advocate that the use of liver allograft with hemangiomas in adult-to-adult LDLT settings can be remarkable strategy to reduce the problem of organ shortage without any unfavorable consequences in both living donor and recipient.

Serial monitoring of Epstein-Barr virus (EBV) reveals that certain pediatric liver transplant (LT) recipients exhibit high EBV loads for long periods. We investigated the incidence and risk factors of chronic high EBV (CHEBV) loads (continuous EBV DNA10 000 IU/mL of whole blood for ≥6 months) and long-term outcomes.This single center, retrospective observational study investigated pediatric LT recipients who survived ≥6 months. We quantitated EBV DNA weekly during hospitalization and subsequently every 4 or 6 weeks at the outpatient clinic. Tacrolimus was maintained at a low trough level (3 ng/mL, EBV DNA load5000 IU/mL).Thirty-one of 77 LT recipients developed CHEBV. Univariate analysis revealed that age2 years and body weight10 kg upon LT, operation time700 minutes, warm ischemia time (WIT)35 minutes, graft-to-recipient weight ratio (GRWR)2.7%, and preoperative EBV seronegativity were significantly associated with the development of CHEBV loads. Multivariate analysis identified significant associations of CHEBV with WIT35 minutes, GRWR2.7%, and preoperative seronegative. None of the recipients developed post-transplantation lymphoproliferative disorder. Survival rates of patients with and without CHEBV loads were not significantly different.A significant number of pediatric LT recipients developed CHEBV loads. Long WIT, high GRWR, and preoperative EBV seronegativity were significantly associated with the development of CHEBV loads. Although the long-term outcomes of patients with or without CHEBV loads were not significantly different, further studies of more subjects are warranted.

The combination of nucleos(t)ide analogues (NAs) and hepatitis B immune globulin has been established as safe and effective prophylaxis against hepatitis B virus (HBV) reactivation after liver transplantation (LT). However, the essential weak point of this regimen is its high cost. The hepatitis B (HB) vaccine is an attractive alternative that costs less, and it enables some patients to have sufficiently high hepatitis B surface antibody (HBsAb) titers. Almost no data exist on whether NAs can be stopped safely in such successfully vaccinated patients. We investigated the incidence of HB vaccine escape mutants in liver recipients who had sufficient HBsAb titers after LT and stopped NAs. Among 18 HBV carriers and 7 non-HBV patients who received grafts from hepatitis B core antibody-positive donors, 2 HBV carriers and 6 non-HBV patients who achieved HBsAb titers >100 IU/L for >3 months after posttransplant vaccination were weaned from NAs. For the patients who showed viremia, we analyzed amino acid sequences of the HB envelope protein, and we performed a statistical analysis for the factors associated with viremia. In 4 of the 8 patients who achieved sufficient HBsAb levels after vaccination and stopped NAs, HBV DNA appeared after a median of 12 months. A sequence analysis showed various amino acid mutations, including the a-determinant, in the HB envelope region. Frequent vaccination was shown to be a statistically significant risk factor for inducing viremia. In conclusion, although the HB vaccine is an effective substitute for prophylaxis against HBV reactivation in some patients after LT, frequent vaccination could be a risk factor for producing escape mutants. Our data demonstrate not only that caution must be exercised in stopping NAs in effectively vaccinated patients (especially in patients vaccinated frequently) but also that it is important to set stopping rules for vaccination in transplant patients.

Living donor liver transplantation (LDLT) using a right liver graft with additional vein reconstructions has not been previously reported in a situs inversus (SI) patient. A 60-year-old man with SI was referred for LDLT for end-stage cirrhosis secondary to hepatitis B. The calculated regional volumes of the individual hepatic vein territories in the right liver graft suggested that the middle hepatic vein (MHV) tributaries and the inferior right hepatic veins (IRHVs) should be reconstructed in addition to the right hepatic vein (RHV). On the back-table, the recipient's recanalized umbilical vein graft was anastomosed to the V5 opening, and the other side of vein graft was anastomosed to the RHV and V8 opening to create a large single orifice. After total hepatectomy, the right liver graft was placed in the left subphrenic space at the reversed position. The common orifice of hepatic venous drainage from RHV, V8 and V5 was anastomosed to the anatomical RHV conduit of the recipient, followed by IRHV anastomosis to the inferior vena cava. Postoperative course was almost uneventful, and no vascular complications were experienced. Even for SI patients, LDLT using a right liver graft with reconstructions of the MHV tributaries and the IRHVs is feasible.

BACKGROUND Intracranial and pulmonary vascular anomalies are well-known complications and causes of mortality in AGS; however, visceral artery anomalies are less commonly recognized. Herein, we present a retrospective analysis of our experience with pediatric LDLT that focuses on the current problems with and treatments for visceral artery anomalies in AGS after LDLT. METHODS Between May 2001 and December 2017, 294 LDLTs were performed for 285 pediatric recipients. Of these, 13 LDLTs (4.4%) for 12 AGS patients were performed. We classified the visceral artery anomalies into aneurysms and stenosis. RESULTS The overall incidence of visceral aneurysm was 2 of 12 recipients (16.7%) and included a SMA aneurysm in one patient and an IPDA aneurysm with a subsequent SPA aneurysm in one patient; the ages of the diagnosis of visceral aneurysm were 16.3, 21.1, and 21.7 y, respectively. An endovascular treatment was performed for a progressive IPDA saccular aneurysm (12.0 × 14.5 × 15.0 mm). The overall incidence of visceral artery stenosis was 7 of 12 recipients (58.3%) and the median age at the diagnosis of visceral artery stenosis was 15.5 y (range 1.7-22.9 y). All 3 AGS patients with RA stenosis suffered from renal dysfunction (eGFR of 51, 78, and 51 mL/min/1.73m2 ). CONCLUSION The morbidity of visceral artery anomalies is not negligible. The performance of periodic imaging examinations is necessary, even for infants, because it is difficult to detect visceral vascular anomalies in the infant stage.

Objective To elucidate the effect of liver transplantation (LT) on brain dysfunctions in cirrhotic patients who had no clinical evidence of hepatic encephalopathy (HE), we performed a prospective study of voxel-based diffusion tensor imaging (DTI) and detailed cognitive examination. Methods We assessed 12 consecutive patients as transplant candidates by DTI, with neurological and cognitive examinations just before and at 6 months after LT. Results After LT, cirrhotic patients showed significant improvement in visual reproduction, digit symbol, digit span, Stroop test, and Trail-making test scores, suggesting recovery of frontal-temporal function. As for voxel-based DTI, increased mean diffusivity (MD) and reduced fractional anisotropy (FA) values were found before LT in the frontal and temporal lobes of cirrhotic patients. After LT, the unusual FA and MD values observed in the frontal and temporal lobes preoperatively were significantly reduced. Conclusion End-stage cirrhotic patients without clinical evidence of HE showed increased MD and decreased FA values in both frontal and temporal lobes. These parameters improved after LT, in line with cognitive function. MD and FA values might be of value as a biomarker in end-stage cirrhotic patients for investigating brain tissue dysfunctions and evaluating the efficacy of LT.

Immunological responses to influenza vaccination administered to liver transplantation recipients are not fully elucidated. To compare inactivated influenza vaccine's immunogenicity between adult and pediatric recipients, 16 adult and 15 pediatric living donor liver transplantation recipients in the 2010–11 influenza season, and 53 adult and 21 pediatric recipients in the 2011–12 season, were investigated. Seroprotection rates (hemagglutinin-inhibition [HI] antibody titer 1:40) were 50–94% to all three antigens among adults and 27–80% among children in both seasons. Seroconversion rates (fourfold or more HI antibody rise) were 32–56% among adults and 13–67% among children in both seasons. No significant differences were observed between the two groups. In addition, 20/53 adult and 13/21 pediatric recipients received a vaccine containing identical antigens in both of these seasons. Geometric mean titer fold increases of all three antigens in adult recipients were significantly lower than those in recipients who had not received a preceding vaccination. In contrast, in pediatric recipients, there were no significant differences between the groups who had and had not received preceding vaccinations. The number of patients with rejection did not differ significantly between the two groups (0/53 vs. 1/21) in the 2011–12 season. The incidence of influenza after vaccination was significantly different between adult and pediatric recipients (0/16 vs. 5/15 in 2010–11 and 0/53 vs. 3/21 in 2011–12, respectively). Overall, there were no significant differences in antibody responses between adult and pediatric groups. Influenza infection was more frequent in pediatric recipients. Long-term response to preceding vaccinations appeared to be insufficient in both groups.

Patient: Male, 66 Final Diagnosis: Fibrosing cholestatic hepatitis Symptoms: Prolonged jaundice and intractable ascites Medication: Steroid pulse therapy and direct-acting antivirals Clinical Procedure: Liver transplantation Specialty: Transplantology Objective: Challenging differential diagnosis Background: Hepatitis C recurrence is a serious matter after liver transplantation (LT). Approximately 10% of hepatitis C virus (HCV) positive recipients develop fibrosing cholestatic hepatitis (FCH). FCH rapidly results in graft loss. Currently, direct-acting antivirals (DAAs) are effective and safe for hepatitis C, even after LT. However, only a few cases of successfully treated FCH after LT have been reported. We present FCH in a complicated case with sepsis and portal flow obstruction after LT. Case Report: A 66-year-old man underwent cadaveric LT. Liver function disorders were observed from post-operative day (POD) 22. Sepsis repeated on POD 38, 74, and 101. Steroid pulse therapy was given from POD 40 to 54. The infectious focus was surgically removed on POD 89. Interventional radiology for portal venous obstruction was completed on POD 96. To make a real-time diagnosis and to investigate the graft condition, repeat liver needle biopsies (LNBs) were taken. Although there was a combined impact of sepsis, portal flow decrease, and recurrent hepatitis C on graft failure, it was interesting that recurrent hepatitis C was consistently detectable from the first LNB. HCV-ribonucleic acid increased on POD 68. Liver function disorders peaked on POD 71 and 72. Jaundice peaked on POD 82. DAA induction was regrettably delayed because of a reluctance to introduce DAAs under conditions of graft dysfunction. DAAs were administered after hospital discharge. Conclusions: A real-time and precise diagnosis based on histopathological examination and viral measurement is important for FCH treatment. Well-considered therapy with DAAs should be aggressively introduced for potentially fatal FCH after LT.

BACKGROUND Prolonged-release tacrolimus (Tac QD) is widely used in organ transplantation. However, the conversion from twice-daily tacrolimus (Tac BID) to Tac QD in Japan is usually done in stable patients months or years after liver transplantation. The aim of this study was to assess the early conversion of Tac QD during liver transplant hospital stay. MATERIAL AND METHODS Eighteen liver transplants (excluding pediatric) were performed during 2014-2015. All cases except 2 early-expired patients were enrolled. Our standard immunosuppression is oral Tac BID and steroid taper, and we add mycophenolate mofetil if indicated. Conversion criteria from Tac BID to Tac QD were: 1) relatively stable liver function with stable trough level by oral Tac BID, and 2) good general condition (no or well-controlled complications). We did not fix the exact conversion date because each patient's recovery was different. Dose conversion rate from Tac BID to Tac QD was set at 1:1. RESULTS The median number of conversion days after liver transplant was 27 days. Sixty-two percent of patients were converted within 4 weeks after liver transplant, and 56% were discharged from the hospital within 2 weeks after conversion. The comparison of the last week of Tac BID and the first week of Tac QD revealed that the mean tacrolimus trough level declined by 30.4%, resulting in the 26.2% tacrolimus dose increase during the first 2 weeks after conversion. Adverse events after conversion were limited, and all patients show normal liver function to date. CONCLUSIONS Early Tac QD conversion is safe and feasible, but its long-term effects need further investigation.

Background Impaired exercise capacity and muscle weakness are important characteristics of liver transplantation recipients. Perioperative rehabilitation has been introduced to promote early mobilization of patients and to prevent postoperative pulmonary complications. However, it is unknown how physical status recovers during the hospital stay after a liver transplant. The purpose of this study was to evaluate the changes in clinical indicators that represent the functional exercise capacity and muscle strength before and after living donor liver transplantation (LDLT). Methods We retrospectively reviewed 21 consecutive patients who underwent LDLT with perioperative rehabilitation from April 2014 to December 2015. Twelve patients who were tested for 6-minute walk distance, hand-grip strength, and isometric knee extensor muscle strength before and 4 weeks after LDLT were enrolled. Results At the preoperative baseline, the 6-minute walk distance significantly correlated with the Model for End-stage Liver Disease score and pulmonary functions (vital capacity, forced vital capacity, and forced expiratory volume in 1 second of predictive values). Comparisons between the preoperative and postoperative values revealed significant decreases in weight, Barthel Index, hand-grip strength, and isometric knee extensor muscle strength. Changes in hand-grip strength and isometric knee extensor muscle strength after LDLT correlated with the preoperative Model for End-stage Liver Disease score. Conclusions Physical functional status had not been fully recovered 4 weeks after LDLT. Further investigation regarding developing a strategy for prevention of muscle atrophy before LDLT and recovery of physical fitness after LDLT would be helpful.

Aim: We investigated a protocol that lowered the necessary dose of anti-hepatitis B surface immunoglobulin (HBIg) with frequent monitoring of hepatitis B surface antigen (HBsAg) and antibody (HBsAb) levels in the early post-transplant period. Methods: Fifteen hepatitis B virus (HBV)-positive patients were studied. We administered a nucleoside analog from the preoperative period, high dose HBIg was used intraoperatively (200 IU/kg in the patients who weighed less than 50 kg, and 10 000 IU in those who weighed more than or equal to 50 kg) and was continued every day (5000–10 000 IU/day). Thereafter, HBIg was administered to keep the target trough titers. We evaluated the effectiveness and safety of this protocol for preventing HBV reactivation. Results: The average use of HBIg during the first three postoperative months (POM) was 27.9 ± 9.6 Kilo International Units. The average cost was $US11 800 in the first three postoperative months, compared with other previously reported protocols (about $20 000–40 000). HBV reactivation was detected in only one patient (6.7%) during the median follow up of 64 months (range: 12–86 months). Conclusions: The present protocol for HBIg administration, which used frequent monitoring of HBsAg and HBsAb levels to determine the minimum required dose, was both safe and effective, and contributed to overall cost saving after liver transplantation.

We encountered a patient with previously well-controlled Wilson disease who experienced fulminant hepatic failure with hemolytic anemia, possibly caused by the dietary supplement Health Proportion(®) (Jubilant Co., Ltd., Ehime, Japan). A 21-year-old woman was admitted to our hospital with marked liver dysfunction and severe hemolytic anemia. Free serum copper level was elevated at 101 μg/dl, and urinary copper excretion was extremely increased (25,600 μg/day). Plasma exchange and continuous hemodiafiltration were performed to remove serum copper and to treat the hemolytic anemia. However, liver function did not improve, and she underwent liver transplantation on 28th day after admission. Copper and iron contents in the resected liver were high at 851.9 μg and 551.7 μg/dry liver weight (g), respectively, despite the patient having regularly taken D-penicillamine since diagnosis and having a well-controlled copper level 1 year before her admission. Two months before admission, the patient had taken a dietary supplement made from soybeans for 1 month. This supplement was labeled as containing large amounts of copper and iron, and we assume that this caused fulminant hepatic failure with hemolytic crisis in this patient. It is important to be mindful of the micronutrient content of dietary supplements, especially for metabolic disorder patients.

Background Despite of recent development of imaging modalities, congenital intrahepatic portosystemic shunt (IPSS) is rarely diagnosed. Therefore, living donor liver transplantation using a liver graft with IPSS has not been previously published. Materials and Methods We report a 28-year-old male patient with end-stage liver disease secondary to Wilson disease. His 26-year-old brother was a potential living donor, who had an IPSS of 25 mm in diameter at segment 6 as shown by computed tomography. Liver function tests were normal, and blood ammonia concentration was in the upper limit of normal. Results Living donor liver transplantation was uneventfully performed. After surgery, a recipient liver function tests showed a quick recovery, and serum ammonia levels were consistently normal. Although thrombosis inside the IPSS was confirmed by computed tomography on postoperative day 21, this thrombosis disappeared at 3 months posttransplant with anticoagulants. Currently (12 months posttransplant), the patient has fully recovered, and the IPSS is still the same size. Conclusions Based on our experience, liver allografts with IPSS can be accepted as potential liver allografts.

Background To understand the impact of psychologic variables on donor quality of life, we studied long-term data on postoperative psychiatric complications in living liver donors. This study is a focused psychological investigation of diagnoses, treatments, and long-term clinical courses of living liver donors with psychiatric complications. Methods Of the 142 donors who underwent live-donor liver transplantation at Nagoya University Hospital between April 2004 and July 2014, we investigated those without a history of mental illness who had developed such illness after transplantation and required psychiatric treatment. Results A total of 6 (4.2%) donors developed the following psychiatric complications after transplantation: major depressive disorder (n = 2), panic disorder (n = 2), conversion disorder (n = 1), and substance use disorder (n = 1). Concerning psychiatric treatment, all donors received antianxiety drugs, 3 took antidepressants, and supportive psychiatric therapy was concomitantly provided to all subjects. The average treatment period was 53.3 months. Regarding subject outcomes, 3 donors achieved remission, and the other 3 continued treatment. All subjects showed improvement in Global Assessment of Functioning Scale. Conclusion It is important to accurately diagnose postoperative psychiatric complications and provide long-term treatment in close coordination with transplant surgeons.

自然壊死をきたした稀な肝細胞癌症例を経験したので報告する.症例は71歳の男性. C型慢性肝炎の診断で近医通院中であった.肝S5領域に腫瘤性病変を認め,肝細胞癌の診断で当科へ紹介入院の後,肝S5の部分切除術を施行した.肉眼的に病変は線維組織で取り囲まれた黄色の結節であり,病理学的所見では内部の組織は完全に壊死に陥っていた.術前の画像所見と腫瘍マーカーの推移に加え,標本の鍍銀染色に細網線維の残存が観察されたことや,抗ヘパトサイト抗体の陽性像などより,この壊死組織は自然壊死をきたした肝細胞癌であると考えられた.その機序として,血管造影に伴う内膜損傷による肝への血流の低下,免疫学的反応の関与が考えられた.文献上,同様な症例は6例であった.

AIM To investigate factors, including psychosocial factors, associated with alcoholic use relapse after liver transplantation (LT) for alcoholic liver disease (ALD). METHODS The clinical records of 102 patients with ALD who were referred to Nagoya University Hospital for LT between May 2003 and March 2015 were retrospectively evaluated. History of alcohol intake was obtained from their clinical records and scored according to the High-Risk Alcoholism Relapse scale, which includes duration of heavy drinking, types and amount of alcohol usually consumed, and previous inpatient treatment history for alcoholism. All patients were assessed for eligibility for LT according to comprehensive criteria, including Child-Pugh score, Model for End-Stage Liver Disease score, and psychosocial criteria. RESULTS Of the 102 patients with ALD referred for LT, seven (6.9%) underwent LT. One (14.3%) of these seven patients returned to heavy drinking, but that patient was able to successfully quit drinking following an immediate intervention, consisting of psychotherapeutic education and supportive psychotherapy, by a psychiatrist. A comparison between the transplantation/registration (T/R) group, consisting of the seven patients who underwent LT and 10 patients listed for deceased donor LT, and 50 patients who did not undergo LT and were not listed for deceased donor LT (non-T/R group), showed statistically significant differences in duration of abstinence period (P < 0.01), duration of heavy drinking (P < 0.05), adherence to medical treatment (P < 0.01), and declaration of abstinence (P < 0.05). CONCLUSION Patients with ALD referred for LT require comprehensive evaluation, including evaluation of psychosocial criteria, to prevent alcoholic recidivism.

The phrase small-for-size (SFS) graft came into use in clinical liver transplantation in the 1980s. There had already been discussions about graft size mismatching in liver transplantation in the era of whole or split liver transplantation, in which initially right trisegments were used for adults. Interest in the issue flourished when living donor liver transplantation (LDLT) was extended to adult patients. Controversies included the pathogenesis and clinical manifestations of SFS grafts and strategies for successful SFS graft transplantation. On the other hand, the definition of SFS graft has always been ambiguous, and it has been defined tentatively in respective studies by the graft weight relative to the body weight or to the estimated whole liver weight (a value derived from the body size). Furthermore, the phrase SFS syndrome, which is also ambiguous and is often defined arbitrarily, is widely used to define SFS graft (and vice versa). One of the early clinical studies attempting to elucidate the impact of graft size mismatching in LDLT has been frequently cited in later articles on the topic: it has been cited 350 times for 11 years according to the Web of Science. This study used 0.8%, 1.0%, 3.0%, and 5.0% of the recipient body weight as graft size category borders to show the prognostic impact. However, the study design had several pitfalls. Children younger than 15 years composed the vast majority of the study population; older patients represented only 10%. The graft sizes encountered in pediatric LDLT are highly variable, in contrast to adult LDLT, in which the range is relatively narrow (0.5%-1.5% of the body weight). Furthermore, the body weight of patients with end-stage liver disease fluctuates with the occurrence of ascites or edema or the use of diuretics. Even the actual graft weight is potentially influenced by the presence of blood or preservation solution with a high viscosity. Hence, it was uncertain whether the impact of small differences in the graft weight was not masked by the wide range of variables in the recipients, donors, and surgical techniques in adult LDLT. Actually, multiple successive clinical studies of adult LDLT have failed to demonstrate a negative prognostic impact of small differences in the graft weight, although the concept of SFS graft or syndrome has survived. This is partly because most clinical studies are performed in an intent-to-treat fashion; that is, a clinical practice is coupled with appropriate safety measures for graft selection and technical modifications, including outflow maximization and inflow modification. Many confounding factors potentially interfere with the true negative effect of SFS grafts. In this context, Moon et al. should be congratulated for their article. They have shown that older donor age, presumably accompanied by low adaptability of the graft tissue, affects graft prognosis only when it is combined with an SFS graft. Unfortunately, there remains some room for discussion concerning their analytical method. They censored patient death due to pneumonia as unrelated to graft function and included graft failure due to surgical complications or disease recurrence as potential results of graft function. The definition of graft loss

We have previously shown that expression of costimulatory ligand B7-1 on MHC class I+ tumor cells (B16-BL6 melanoma) resulted in marked reduction of lung metastasis caused by i.v. injection into immunocompetent syngeneic mice and led to induction of immunity to the challenge by the parental B7-1 negative tumor. Here we investigated the effectiveness of irradiated B7-1 transfected tumor cells as a vaccine on established tumor metastasis and whether or not expression of B7-1 molecule on tumor cells in combination with administration of anti-adhesion peptide FC-336 can augment the antimetastatic efficacy. Immunization with X-irradiated B7-1 transfectants after i.v. injection of B7-1− parental B16-BL6 cells was effective in inhibiting lung metastasis. We also found that vaccination with irradiated B7-1 transfectants after excision of primary tumor on day 21 resulted in significant inhibition of spontaneous lung metastasis by intrafootpad injection of viable parental B16-BL6 melanoma, as compared with the untreated control. However, immunizing twice with mock transfectants did not affect inhibition of spontaneous lung metastasis of wild-type tumors. On the other hand, multiple administration of a pseudo-peptide of RGD sequence (FC-336) after tumor inoculation inhibited spontaneous lung metastasis through the interference of tumor invasion, migration and adhesion. Combined treatment of B7-1 transfected tumor vaccine and anti-adhesive therapy with FC-336 led to the augmentation of the antimetastatic effect in both experimental and spontaneous metastasis models, as compared with either treatment alone. B7-1- and FC-336-mediated inhibition of tumor metastasis may be mediated by different mechanisms at various steps of metastasis, based on the regulation (promotion or inhibition) of tumor interaction with host cells and components.

We investigated the inhibitory effect of oral administration of Juzen-taiho-to, a Kampo Japanese herbal medicine, and its related formulations on the experimental liver and lung metastasis of tumor cells in vivo. Oral administration of Juzen-taiho-to for 7 d before tumor inoculation significantly reduced the number of liver metastatic colonies of colon 26-L5 carcinoma cells and attenuated the increase of liver weight in a dose-dependent manner ranging from 4 to 40 mg/d. Its oral administration for this same period before tumor inoculation also significantly inhibited lung metastasis of B16-BL6 melanoma cells. Juzen-taiho-to originally consisted of 8 crude drugs derived from Shimotsu-to and Shikunshi-to prescriptions together with two crude drugs (Cinnamomi Cortex and Astragali Radix). Oral administration of Shimotsu-to as well as Juzen-taiho-to for 7 d before tumor inoculation resulted in a significant reduction in the number of metastatic colonies and the liver weight as compared with the control, whereas Shikunshi-to did not exhibit such an inhibitory effect. Unsei-in containing four Shimotsu-to constituents was also active in inhibiting liver metastasis. Toki-shakuyaku-san and Ninjin-yoei-to, which include all Shimotsu-to constituents except Rehmanniae Radix and Cnidii Rhizoma, respectively, did not show a significant anti-metastatic effect. Rikkunshi-to and Ninjin-yoei-to, which contain Shikunshi-to constituents, did not affect the inhibition of liver metastasis. Hochu-ekki-to treatment before tumor inoculation also led to a significant inhibition of liver metastasis, probably through an inhibitory mechanism different from Juzen-taiho-to. These results suggest that the anti-metastatic effect of Juzen-taiho-to is partly associated with its Shimotsu-to-derived constituents.

Background Hypersplenism is a common complication in cirrhotic patients, and liver transplantation would be one of the effective treatments. However, detailed dynamics, especially over a long term, are not fully understood. We investigated the long-term dynamics of hematological data and spleen volumes, as well as their correlation in cirrhotic patients who underwent liver transplantation. Patients and methods We studied 53 cirrhotic patients who underwent liver transplantation at our institute and followed for more than 1 year. Hematological data were collected from medical records, while spleen volumes were determined by CT volumetry at 0, 1, 3, 6, 12, 24, 36, 48, 60 postoperative months (POM). Results (1) Platelet (Plt) and hemoglobin (Hb) levels were gradually increased up to 18 and 10 POM, respectively, in contrast with white blood cells (WBC), which remained mostly unchanged from pretransplantation levels. (2) Spleen volume was sharply decreased in the first POM, then showed a slower but steady decline up to 48 POM. (3) Spleen volume was significantly correlated with hematological data, though the levels were generally weak (Plt: r = 0.433, p

AIM: Recently, knowledge for indications of living donor liver transplantation (LDLT) has been robustly accumulated in. For further improvement, risks should be reexamined in recent cases. In this study, we investigated preoperative risk factors in cirrhotic patients who underwent LDLT in recent era. METHODS: Seventy-four cirrhotic patients who underwent LDLT at our institution between 2003 and 2011 were included. Recipient and donor age and sex, existence of hepatocellular carcinoma (HCC), preoperative Model for End-Stage Liver Disease score, fasting blood glucose (FBG), triglyceride, total cholesterol, serum creatinine, hemoglobin A1c, graft : recipient weight ratio, ABO compatibility and choice of calcineurin inhibitor were analyzed. A proportional hazard model was applied and P

Anti-epidermal growth factor receptor monoclonal antibodies are approved and effective only in KRAS wild-type patients with advanced colorectal carcinoma. The present retrospective study investigated the role of KRAS gene

Highlights • We report a case of IVC thrombosis caused by ligation of large mesenteric-caval shunt. • This case serves as a note of caution when addressing a major portosystemic shunts in LT. • The position of large collateral ligation should be carefully considered in LT., Instruction Inferior vena cava (IVC) thrombosis can be a life-threatening complication after liver transplantation (LT). Although this complication is usually related to technical problems associated with vascular anastomosis, we report a case of IVC thrombosis which developed from a ligated large mesenteric-caval shunt. Presentation of case A 35-year-old man underwent LT from a brain-dead donor for primary sclerosing cholangitis. Enhanced computed tomography (CT) before LT showed a huge collateral vessel of the inferior mesenteric vein (IMV) draining into the infra-renal IVC directly. To obtain sufficient portal vein (PV) flow, the dilated IMV collateral was ligated. A routine Doppler ultrasound study on post-operative day 1 showed thrombus inside the infra-hepatic IVC. Enhanced CT showed that this thrombus originated from a ligated collateral vessel of the IMV and extended into the IVC. He was hemodynamically stable and liver function was consistently stable. The size of IVC thrombus slowly reduced and he is currently in good condition without any symptoms. Discussion To obtain adequate PV flow, ligation of a major PSS at the time of LT has been suggested. However, where it should be occluded has not been discussed. We should occlude a mesenteric-caval shunt not only at the upper side, but at the IVC side, based on findings from the current case. Conclusion To obtain appropriate PV flow toward a liver graft, occlusion of portosystemic shunts during LT is recommended. However, the position of ligation should be carefully considered to avoid extension of thrombus to major vessels.