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Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC) but its use it is eventually limited by presence of esophagogastric varices (EGV) and bleeding-risk. This study aimed to assess prevalence and risk factors of EGV and bleeding in lenvatinib-treated patients with HCC. In this multicenter international retrospective study, cirrhotic patients treated with lenvatinib for aHCC with an upper-gastrointestinal endoscopy performed <6 months before treatment were enrolled. Primary endpoint: incidence and risk factors of EGV bleeding during treatment. Secondary endpoints: prevalence and risk factors for EGV and high-risk EGV (HR-EGV) at baseline. 535 patients were enrolled [median age 72 years, 78% male, 63% viral aetiology, 89% Child-Pugh-A, 16% neoplastic portal vein thrombosis (nPVT), 56% BCLC-C]: 301 (56%) patients were EGV-free, 234 had EGV (44%) and 70 (30%) HR-EGV. Presence of EGV and of HR-EGV were independently associated with Child-Pugh-B (OR 2.12; 95%CI 1.08-4.17, p=0.03), nPVT (OR 2.54; 95%CI 1.40-4.61, p=0.002) and platelets<150.000/uL (OR 2.47; 95%CI 1.35-4.50, p=0.003). During lenvatinib treatment, 17 patients bled from EGV, the 12-month cumulative incidence being 3%. The only independent predictor of bleeding was presence of HR-EGV (HR 6.94, 95% CI 2.23-21.57, p=0.001). Risk of EGV bleeding can be stratified according to Child-Pugh-B, presence of nPVT and platelets<150.000/uL into low (0/3 risk factors, 6-months cumulative incidence 0.77%), intermediate (1/3 risk factors, 6-months cumulative incidence 2.31%) and high (2/3 or 3/3 risk factors, 6-months cumulative incidence 7.40%). Among the 476 Child-Pugh-A patients, independent predictors of HR-EGV were nPVT (OR 2.53; 95%CI 1.24-5.16, p=0.008) and platelets<150.000/uL (OR 2.56; 95%CI 1.28-5.10, p=0.01). In HCC patients treated with lenvatinib, the risk of EGV bleeding is low but it increases in patients with HR-EGV at baseline. A risk stratification for HR-EGV can be applied according to liver reserve, platelet count and nPVT. [ABSTRACT FROM AUTHOR]

Background: Forced oscillometry is a non-invasive method to measure respiratory resistance and reactance. In this study, we investigated the characteristics of measurements obtained with an impulse oscillation system (IOS) for patients with interstitial lung disease (ILD). Method: IOS and spirometry were performed in 64 ILD patients, 54 asthma patients, 49 chronic obstructive pulmonary disease (COPD) patients, and 29 controls. Respiratory resistance and reactance were assessed as measurements averaged over several tidal breaths (whole-breath analysis) and as measurements separately averaged during inspiration and expiration (inspiratory-expiratory analysis). Results: Whole-breath IOS analyses for ILD patients showed increased resistance at 5 Hz and decreased reactance at 5 Hz (X5) compared with controls, although these features were also found in asthma and COPD patients. Inspiratory-expiratory analysis demonstrated that the changes in X5 and reactance area (AX) between inspiration and expiration (DX5 and ΔAX, respectively) were significantly different from those in asthma patients, COPD patients, and controls. However, multiple linear regression analysis showed that the presence of ILD was independently associated with ΔX5, but not with ΔAX. Furthermore, DX5 was inversely correlated with vital capacity and diffusing capacity of carbon monoxide in ILD patients. Conclusions: Our results suggest that DX5 is a characteristic feature of IOS measurements in ILD patients, which is clearly different from those in asthma and COPD patients. This within-breath X5 change in ILD might be associated with its severity and physiological abnormality, although further studies are needed to investigate its cause. [ABSTRACT FROM AUTHOR]

Objectives In elderly kidney transplant (KT) recipients, the incidence of acute rejection is decreased, while that of fatal infections is increased. There are currently no guidelines for an upper age limit for KT, which is very difficult to determine. Here we examined several cases of elderly KT recipients. Methods We evaluated 127 KT patients treated at our department between 2003 and 2012 and followed them for 3 years post-transplant. The subjects were divided into two groups by age: ≥60 years (elderly group; n = 24); and <59 years (non-elderly group; n = 103). The presence or absence of acute rejection and infection, dose of immunosuppressive drugs, trough calcineurin inhibitor level, renal function, and graft and patient survival rates were retrospectively examined. Results Our basic immunosuppressive regimen was a combination of calcineurin inhibitor, methylprednisolone, mycophenolate mofetil, and basiliximab. At 1 year post-transplantation, the average tacrolimus and cyclosporine dose and trough levels were not significantly different. The mean dose of mycophenolate mofetil in the elderly group at 1 year post-transplantation was significantly lower than that of the non-elderly group. The incidences of cytomegalovirus infection and acute rejection during follow-up did not differ significantly between groups. There were no significant differences in creatinine level between the two groups. In the elderly group, the graft survival rates at 1 and 5 years were 100% and 95.4%, respectively, while those in the non-elderly group were 98.1% and 92.5%, respectively. Conclusion Using our current immunosuppressive protocol, the outcomes of patients in the elderly group were considered acceptable. [ABSTRACT FROM AUTHOR]

Abstract: Living donor liver transplantation (LDLT) offers timely transplantation for patients with hepatocellular carcinoma (HCC). If ABO-incompatible LDLT is feasible, the need for pretransplantation treatment may be eliminated, which may reduce overall morbidity. In this article, we have described 8 adult HCC patients who successfully underwent LDLT from ABO-incompatible donors. Antirejection therapy included multiple preoperative plasmaphereses, splenectomy, and an immunosuppressive regimen with tacrolimus, methylprednisolone, and mycophenolate mofetil. The maintenance dose of immunosuppression did not differ from that of the ABO-identical cases. In addition, we also performed intrahepatic arterial infusion of prostaglandin E1. In 5 patients, we administered a single dose of rituximab, a chimeric CD20 monoclonal antibody. As a result of this treatment, 6/8 patients are still alive. Our experience has shown that it is possible to control antibody-mediated humoral rejection and other complications in adult ABO-incompatible LDLT. [Copyright &y& Elsevier]

The relative distribution of types I and III collagens and collagen fibre architecture in the perimysium and endomysium were compared to the longissimus thoracis (LT) and pectoralis profundus (PP) muscles in pigs. The LT muscle was composed of type I myofibres 16.8%, IIA 12.9% and IIB 70.2%, and the PP muscle was 25.4, 23.1 and 51.5%, respectively. The total collagen amount differed significantly between the LT (2.66 mg/g) and PP (4.13 mg/g) muscle (P<0.001). On image analysis of the immunohistochemical preparations for types I and III collagens, the percentage area of the perimysium to the total collagen area showed significant differences between the muscles, where perimysial type I collagen occupied 25.4% of the total area in the LT muscle and 45.7% in the PP and perimysial type III 37.6 and 54.5%, respectively (P<0.001). In scanning electron microscopic photographs of the macerated preparation, very thick collagen layers composed of several fibre bands were observed in the perimysia of the PP muscle and appeared differently from the thinner perimysia with a few bands in the LT. Similar architecture of endomysial collagen fibres were observed around every myofibre type in the PP muscle and also in the LT. The fine surface cover of reticular collagen fibres around an adipocyte was shown as a global cast. These results suggested that the total collagen amount of the PP muscle was related mainly to the well developed perimysia composed of several collagen bands, indicating tougher meat compared with the LT muscle. [Copyright &y& Elsevier]

Abstract: Background: Posttransplant anemia (PTA) influences kidney graft function and prognosis; however, there is no consensus regarding target hemoglobin (Hb) levels. Methods: We examined several cases of PTA to identify any correlation between Hb levels and graft function. We evaluated 84 kidney transplant recipients (50 men and 34 women; mean age, 46.7 years) who were treated at our department between February 2004 and March 2012 and were available for a 2-year post-transplant follow-up. Results: Hb levels and serum creatinine levels before transplantation and at 1, 3, 6, 12, and 24 months after transplantation were compared. We examined the correlation between the degree of anemia and renal function among the patients. Data were analyzed using Spearman's rank correlation coefficient and Friedman tests. The mean pretransplantation Hb level was 10.4 g/dL, whereas Hb levels at 6, 12, and 24 months after transplantation were significantly increased to 11.6, 12.2, and 12.4 g/dL, respectively, suggesting an improvement in anemia after the transplantation. Correlation analysis between anemia and kidney graft dysfunction revealed significant correlations at 1, 3, 12, and 24 months after transplantation. Subjects were stratified for correlation analysis according to Hb level at 24 months after transplantation: <10, 10–10.9, 11.0–11.9, 12.0–12.9, and ≥13.0 g/dL. A significant improvement in kidney graft function was noted in patients with an Hb level ≥11 g/dL at 2 years after transplantation. Anemia improved significantly by 3 months after transplantation. Conclusions: A significant correlation between PTA and kidney graft function was apparent, and the prognosis for kidney graft function was poor in patients with Hb levels ≤11 g/dL. [Copyright &y& Elsevier]

Abstract: Background: Beneficial effects of protocols using minimal steroid exposure have been recently reported. The purpose of this study was to evaluate the outcomes of kidney transplantation recipients who received immunosuppression protocols with early steroid withdrawal (ESW) at our center. Methods: We retrospectively studied 84 kidney transplant recipients who had received ESW immunosuppressive protocols at our center from March 2005 to December 2010. The immunosuppressive regimen was a combination of calcineurin inhibitors (tacrolimus/cyclosporine), methylprednisolone, which was tapered and discontinued within 2 months, mycophenolate mofetil, and basiliximab (postoperative days 0 and 4). We compared the outcomes of our ESW recipients with those of a historical control group (February 2003 to January 2005; n = 18). Results: Clinical acute rejection episodes were observed in 15 (17.9%) and 5 (27.8%) cases in the ESW and control groups, respectively. Cytomegalovirus infection occurred in 12 (14.3%) and 5 (27.8%) cases in the ESW and control groups, respectively. The creatinine levels at 1 year after transplantation were 1.3 ± 0.4 mg/dL and 1.3 ± 0.5 mg/dL in the ESW and control groups, respectively. In the ESW group of 84 recipients, actuarial patient survival at 1 year was 94.0%. In the historical group of 18 recipients, the actuarial patient survival at 1 year was 100% (P = .76). In the ESW group the graft survival rate at 1 year was 95.2%. In the historical group, graft survival rate at 1 year was 100% (P = .65). There were no significant differences in the parameters between the groups. Conclusions: The outcomes from this study were considered to be acceptable; however, the possibility of improving the protocols exists. [Copyright &y& Elsevier]

Abstract: Objective: The incidence of biliary complications after adult living donor liver transplantation (ALDLT) are still high even though various devices have been reported to overcome them. Method: From October 2000 to April 2007, we performed 52 ALDLTs which included 15 ABO-incompatible grafts. Median follow-up was 565 days. In 49 procedures, we used duct-to-duct anastmosis with a stent inserted in the recipient duct and out through the common bile duct wall as an external stent, and in 3 procedures, we used duct-to-jejunostomy anastomosis. We investigated postoperative biliary complications and their management. Results: Forty-four patients received right lobe grafts and 8 received left lobe grafts. Among patients in whom duct-to-duct anastomosis was used, nine (20.5%) developed biliary complications including bile leakage in five and biliary strictures in four. All bile leakage was treated with reoperation. Three biliary strictures were treated with stent placement, and one biliary stricture was treated with magnetic compression anastomosis. Among the three patients in whom duct-to-jejunostomy was used, two (66.7%) had bile leakage and stricture, respectively. Two of four ABO-incompatible patients (50%) had hepatic artery thrombosis with biliary complications, a high incidence. Conclusion: In our series of ABO-incompatible patients undergoing ALDLT, those who developed hepatic artery thrombosis exhibited a high incidence of biliary complications. [Copyright &y& Elsevier]

Introduction The risk of complications and transplant renal function increases in multiple arterial renal transplantations compared with single arterial renal transplantations. Even when multiple arteries are involved, with the introduction of laparoscopic nephrectomy, I mainly choose the left side kidney. Therefore, the number of renal artery reconstructions is increasing, and simultaneous imaging of arterial rebuilding during the donor nephrectomy is important. Material Between 2006 and 2015, we performed 132 living donor kidney transplantations at our center and analyzed 32 cases that were diagnosed pre- and intraoperatively. Method We compared the single renal artery (SRA) and multiple renal arteries (MRA) groups and analyzed the number of renal arteries, reconstruction methods, donor and recipient ages, sex, total ischemic times, and 1-month serum creatinine values. Result In the MRA and SRA groups, the average recipient age was 52.3 and 47.0 years, respectively, while the average donor age was 52.9 and 53.1 years, respectively. In SRA and MRA groups, total ischemic time (TIT) was 96.1 and 143.6 min ( P < .01). Serum creatinine level 1 month post-transplantation was 1.54 and 1.25, respectively ( P < .001). Here we experienced 12 cases of living renal donor nephrectomy with multiple vessels in which the vascular supply territory was first assessed in April 2013 using an intraoperative near-infrared fluorescence camera system. In addition, regarding TIT, it is possible to shorten surgery by using individual anastomosis and ligation. Conclusion By managing multiple donors; arteries by nephrectomy, it is possible to improve kidney transplantation results. [ABSTRACT FROM AUTHOR]

Abstract: The early results of liver transplantations (OLT) in patients with advanced hepatocellular carcinoma (HCC) were poor because of frequent tumor recurrence. However, OLT has significant, theoretical advantage that it removes both the tumor and the organ that is at a risk of malignancy. The Japanese law on organ transplantation limited the availability of cadaveric liver donors until its revision on July 17, 2011. ABO-incompatible OLT was formerly contraindicated because performed anti-A/B antibodies on recipient endothelial cells raised the risk of antibody-mediated humoral graft rejection. We have herein described four successful cases of steroid withdrawal among adult patients who underwent living donor OLT from ABO-incompatible donors. In addition, we transplanted a liver from a living donor into an ABO-incompatible recipient on August 9, 2004. The 55-year-old man with HCC due to hepatitis B virus (HBV) a cirrhosis had a Child-Pugh score of C, and Model for End-stage Liver Disease score of 22. Two tumors greater than 5 cm, exceeded the Milan criteria. His des-gamma-carboxy prothrombin level was 6 mAu/mL, and alpha-fetoprotein, 18.78 ng/mL. Antirejection therapy included multiple perioperative plasmaphereses and splenectomy; with an immunosuppressive regimen consisting of tacrolimus, methylprednisolone, and mycophenolate mofetil. The maintenance dose of immunosuppression did not differ from that of ABO-identical cases. After transplantation, we used intrahepatic arterial infusion therapy with prostaglandin E1 (PG E1). The patient had complications of portal vein thrombosis, hepatic artery thrombosis, and acute myocardial infarction, which were treated by interventional radiology in the posttransplantation period. We controlled the HBsAb titer by administering hepatitis B immunoglobulin and lamivudine (200 IU/L doses) for 1 year after OLT and 100 IU/L doses thereafter. As a result, the patient achieved long-term, disease-free graft survival without steroids. He currently has good liver function and leads a normal lifestyle. Our results suggested the feasibility of controlling antibody-mediated humoral rejection and other complications in living donor liver transplantations into ABO-incompatible adults via intrahepatic arterial PG E1 infusion splenectomy, and plasmapheresis with regular immunosuppression. Withdrawal of steroids, HBV vaccination, and lamivudine, an nucleoside analog reverse transcriptase inhibitor, have achieved long-term (7 years) survival without recurrent HBV infection or tumor. [Copyright &y& Elsevier]

Abstract: Background: In Japan ABO-incompatible liver transplantation has been done on >100 occasions up to 2003. However, <30% are cases involving adults. The difficultly of ABO-incompatible liver transplantation is associated with the high frequency of humoral rejection and local disseminated intravascular coagulation (DIC), leading to many postoperative complications. We report a successful case of adult ABO-incompatible liver transplantation with the use of an intrahepatic artery infusion. Methods: A 36-year-old man with Wilson disease, underwent living donor liver transplantation from an ABO-incompatible donor. The immunosuppressive therapy included multiple perioperative plasmaphereses, splenectomy, and treatment with tacrolimus, methylprednisolone, and cyclophosphamide. The dose and blood level of tacrolimus were the same as in ABO-compatible cases. In addition to these therapies, we administered an intrahepatic arterial infusion with prostaglandin (PG) E1 alone. Results: After perioperative plasmapheresis and cyclophosphamide, antidonor blood group antibody titers remained undiluted and without vascular complications throughout the postoperative course, but there was a tendency for bleeding that continued for 10 days after transplantation. On postoperative day 10, a reexploration was performed for intraabdominal bleeding. During another operation on postoperative day 59 a biloma was found and drained. The patient has now survived for 120 days after transplantation with normal liver function. Conclusions: Beneficial effect of intrahepatic artery infusion with PGE1 seems to be useful in adult ABO-incompatible liver transplantation. [Copyright &y& Elsevier]

Abstract Background Extended-release tacrolimus (TacER), administered once daily, offers improved adherence with reduced side effects while still maintaining an immunosuppressive potency equivalent to that of conventional tacrolimus preparations. Methods The study included 83 patients who received consecutive living-donor kidney transplants at our facility from June 2013 to December 2016. Comparisons were made between 48 cases of induction with TacER and 35 cases of induction with cyclosporine (CyA). The observation period was 3 months after transplantation. Transplanted kidney function, rejection, infectious disease, lipid abnormalities, and glucose tolerance were compared. Results The 2 groups showed no significant difference in donor background or transplanted kidney function. Within the 3-month observation period, an acute rejection response was observed in 2 cases in the TacER group and in 8 cases in the CyA group. After transplantation, hyperlipidemia requiring medication was observed more frequently in the CyA group. The 2 groups did not show a marked difference in systemic infection or renal calcineurin inhibitor toxicity in histopathologic examination of the transplanted kidneys 3 months after surgery. Discussion Proactive use of TacER leads to improved adherence while yielding immunosuppressive potency equivalent to that of conventional tacrolimus preparations; however, tacrolimus has a potent blood sugar-elevating effect; thus, direct comparison with the CyA group is important for assessing the side effects. Conclusion TacER has the potential to also reduce side effects in the early stages after surgery, suggesting its potential as a drug of first choice. Highlights • TacER effectively suppressed acute rejection in the early postoperative stages of kidney transplantation. • Diabetes and CyA administration were independent variables for acute rejection. • There is no need to worry about delayed absorption in evening for TacER. • We observed 2 cases of TacER had CNI toxicity without deterioration in serum creatinine levels. • TacER should be selected for kidney transplant recipients with diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Abstract Background To increase the number of cadaveric kidney transplants in Japan, it is necessary to proactively use organs from all donors. Since the revision of the Organ Transplant Law, the number of organ donors after cardiac death (DCD) has decreased but the number of organ donors after brain death (DBD) has increased; however, the number of donor organs and awareness of cadaveric transplantation have increased. Methods At our institution, 28 patients underwent cadaveric kidney transplantation from January 2001 to December 2016. These patients were classified into 2 groups according to DBD or DCD. Furthermore, 10 patients received transplants from expanded criteria donors (ECD) and 18 received them from standard criteria donors (SCD). Results Kidney graft survival and engraftment were observed for all patients. There were no significant differences in renal function at 6 months for DBD and DCD transplant recipients. Renal function at 1, 3, and 5 years and serum creatinine levels were better for the ECD group. Renal function at 5 years after transplantation was significantly better for the SCD group than for the ECD group; however, there was no difference in delayed graft function between the SCD and ECD groups. Comparisons of the 3 groups showed good renal function for transplants from DBDs, but there was no significant difference in survival rates. Conclusions Results were good for all patients. There were no significant differences in outcomes of our patients who received transplants from ECD or SCD. Highlights • Similar outcomes were found between kidney transplantations using organs from donors after cardiac death and donors after brain death. [ABSTRACT FROM AUTHOR]

Abstract Introduction The number of young women who wish to become pregnant opting for kidney transplants is increasing, as becoming pregnant under hemodialysis or peritoneal dialysis is associated with many risks. However, there have been reports indicating that these patients are subject to a higher risk of miscarriage compared to women with normal renal function. We examine and report cases of patients that experienced pregnancy after undergoing kidney transplantation at our hospital. Subjects and method Of the kidney transplantation cases that were performed at our hospital between 1985 and 2016, there were 7 cases of pregnancy. The serum creatinine levels, urine protein findings, etc, of these 7 cases were examined during the pre-pregnancy, pregnancy, childbirth, and postpartum periods. Results All 7 cases were able to give birth. There were two cases of transient postpartum hypertension. There were no cases of obvious pregnancy toxemia or fetal growth retardation. Two of the cases resulted in the failure of the transplanted kidneys. Discussion According to previous studies on pregnancy and childbirth after kidney transplantation, the presence of high blood pressure and proteinuria as well as the renal function at the time of pregnancy is closely associated with postpartum renal function. Urine protein was detected prior to pregnancy in both cases and resulted in the failure of the transplanted kidneys. The influence of immunosuppressants on the mother and fetus is also an important consideration. Conclusion We believe it is extremely important to ensure a thorough informed consent process prior to pregnancy and systematic use of immunosuppressants for young female transplant recipients. Highlights • Women with renal transplants are reported to have a higher rate of miscarriage than women with normal renal function. • Pregnancy and delivery after renal transplantation suggests that hypertension, albuminuria, and renal function during pregnancy affect postnatal renal function, and may be associated with serious maternal and fetal complications. • It is extremely important to ensure a thorough informed consent process prior to pregnancy and systematic use of immunosuppressants for young female recipients. [ABSTRACT FROM AUTHOR]

Objectives ABO-incompatible kidney transplantation has increased the possibility of finding suitable living donors for patients with renal failure. However, there are inevitable immunological risks, including a high risk of early post-transplantation complications. The purpose of this study was to evaluate recipient outcomes following ABO-incompatible kidney transplantation. Methods Seventy-one patients who had undergone living-donor kidney transplantation (LDKT) at our center between January 2008 and December 2013 were divided into ABO-incompatible (ABOi; n = 21) and ABO-compatible (ABOc; n = 50) groups. Baseline data, graft function, immunosuppressant use, and the results of biopsy 1 year after LDKT were compared between the groups. Results Recipient preemptive LDKT rates were significantly different between groups ( P = .017). Graft function, incidence of infection, and rates of T-cell-mediated rejection and borderline changes requiring medication were not significantly different. There was no acute antibody-mediated rejection. Selectivity of the immunosuppressant, tacrolimus, was significantly different between groups ( P < .01); however, steroid withdrawal rates, mycophenolate mofetil doses, and calcineurin inhibitor trough levels were not different. Regarding biopsy data, interstitial fibrosis scores were significantly different between groups ( P = .011), as were interstitial fibrosis and tubular atrophy scores ( P = .045) and arteriolar hyalinosis score ( P = .022). Conclusion ABOi LDKT was relatively safe, with no significant difference in the incidence of rejection compared to ABOc LDKT. Managing chronic pathological changes and arteriolar hyalinosis prophylaxis after ABOi LDKT may result in more successful outcomes. [ABSTRACT FROM AUTHOR]

Background To increase the number of cadaveric kidney transplants in Japan, it is necessary to proactively perform transplantation from marginal donors. We had the opportunity to frequently perform kidney transplantation from expanded-criteria donors (ECDs), and it is anticipated that there will be increases in the number of ECD kidney transplants. Methods In our institution, 18 patients underwent cadaveric kidney transplantation from January 2001 to December 2011. Sixteen of those patients were classified into 2 groups according to donation after brain death (BD) or after cardiac death (CD). We also classified donors as ECDs or standard-criteria donors (SCDs). Results Kidney graft survival and engraftment were observed in all of the patients. Renal function at 1 year after transplantation was significantly better in the BD group than in the CD group. However, there was no significant difference between the groups in renal function at 3 and 5 years. Renal function at 1 and 3 years after transplantation was significantly better in the SCD group than in the ECD group, but there was no difference in renal function between the SDC and ECD groups at 5 years. Conclusions The results were good for all of the patients. There are many reports that graft survival rate at 3–5 years after transplantation from ECDs is poorer than from SCDs. However, no statistically significant difference was found in kidney function at ≥5 years between the ECD and SCD groups in our patients. [ABSTRACT FROM AUTHOR]