Background Smaller size grafts for living donor liver transplantation (LDLT) can enhance donor safety and expand donor availability. We previously reported that modulation of portal venous pressure ...(PVP) was key for successful LDLT with small grafts, and that it actively lowered graft-to-recipient weight ratio (GRWR) for adult-to-adult LDLT. This retrospective study investigated the outcome of LDLT using small grafts with PVP modulation. Method This study analyzed 221 adult LDLT patients between March 2008 and December 2013 and divided them into 3 groups based on GRWR: large (L), GRWR ≥ 0.8% ( n = 154), medium (M), ≥ 0.7% GRWR < 0.8% ( n = 38); and small (S) GRWR < 0.7% ( n = 29). Donor and recipient factors, PVP, pressure gradient between PVP and central venous pressure (CVP), occurrence of small for size syndrome (SFSS), ascites, and posttransplant laboratory data were compared across the 3 groups. Patient and graft survival were compared using Kaplan–Meier methods. Results There was no difference in patient or graft survival between the 3 groups. Amount of posttransplant ascites and posttransplant International Normalized Ratio were similar, but the S and M groups had more prolonged cholestasis. SFSS was identified in 17%, 13%, and 13% in the S, M, and L groups, respectively ( P = NS). Patients with a final PVP of ≤15 mmHg had better survival than patients with a final PVP of >15 mmHg ( P < .001). Multivariate analysis showed that donor age >40 years old, final PVP of >15 mmHg, and pressure gradient of PVP-CVP >5 mmHg were risk factors for inferior patient survival. Conclusion We achieved satisfactory outcomes in LDLT with GRWR as low as 0.6% using PVP modulation. Thus, we currently set a lower limit of GRWR at 0.6% while protecting donor safety and expanding donor availability.
Background
Native liver survival after laparoscopic Kasai portoenterostomy (Lap-PE) for biliary atresia (BA) is controversial. We examined whether a jaundice-free native liver survival rate is ...comparable between conventional Kasai portoenterostomy (Open-PE) and Lap-PE. Then, the impact of the two types of PE on subsequent living-donor liver transplantation (LTx) was addressed in this study.
Methods
The jaundice-free rate in 1- and 2-year-old patients who underwent Open-PE and Lap-PE from January 2006 to December 2017 was investigated. Additionally, perioperative data (duration from the start of surgery to the completion of hepatectomy and others) of patients aged 2 years or younger who underwent LTx after either Open-PE or Lap-PE from 2006 to 2017 were evaluated.
Results
Thirty-one (67%) out of 46 Open-PE patients and 23 (77%) out of 30 Lap-PE patients showed native liver survival with jaundice-free status at 1 year of age (
p
= 0.384); 29 (63%) out of 46 Open-PE patients and 19 (70%) out of 27 Lap-PE patients showed native liver survival with jaundice-free status at 2 years of age (
p
= 0.524); there were no significant differences. Additionally, there were 37 LTx cases after PE within 2 years of birth, including 29 Open-PE and 8 Lap-PE cases. The patients in the Lap-PE group had fewer adhesions and significantly shorter durations of surgery up to the completion of the recipient’s hepatectomy and durations of post-LTx hospital stay compared to the Open-PE group. There were no differences in blood loss or duration of stay in intensive care unit between the Lap-PE and Open-PE groups.
Conclusions
Jaundice-free native liver survival rate has been comparable between Open-PE and Lap-PE. Lap-PE resulted in fewer adhesions, contributing to better outcomes of subsequent LTx compared to Open-PE.
Ischemic heart disease is the major cause of death in Western countries. CTRP9 (C1q/TNF-related protein 9) is a fat-derived plasma protein that has salutary effects on glucose metabolism and vascular ...function. However, the functional role of CTRP9 in ischemic heart disease has not been clarified. Here, we examined the regulation of CTRP9 in response to acute cardiac injury and investigated whether CTRP9 modulates cardiac damage after ischemia and reperfusion. Myocardial ischemia-reperfusion injury resulted in reduced plasma CTRP9 levels and increased plasma free fatty acid levels, which were accompanied by a decrease in CTRP9 expression and an increase in NADPH oxidase component expression in fat tissue. Treatment of cultured adipocytes with palmitic acid or hydrogen peroxide reduced CTRP9 expression. Systemic administration of CTRP9 to wild-type mice, before the induction of ischemia or at the time of reperfusion, led to a reduction in myocardial infarct size following ischemia-reperfusion. Administration of CTRP9 also attenuated myocyte apoptosis in ischemic heart, which was accompanied by increased phosphorylation of AMP-activated protein kinase (AMPK). Treatment of cardiac myocytes with CTRP9 protein reduced apoptosis in response to hypoxia/reoxygenation and stimulated AMPK phosphorylation. Blockade of AMPK activity reversed the suppressive actions of CTRP9 on cardiomyocyte apoptosis. Knockdown of adiponectin receptor 1 diminished CTRP9-induced increases in AMPK phosphorylation and survival of cardiac myocytes. Our data suggest that CTRP9 protects against acute cardiac injury following ischemia-reperfusion via an AMPK-dependent mechanism.
The functional role of the fat-derived plasma protein CTRP9 in ischemic heart disease is unknown.
Systemic delivery of CTRP9 reduces myocardial infarct size and apoptosis following ischemia-reperfusion in mice. CTRP9 protects cardiomyocyte from apoptosis through activation of AMP-activated protein kinase (AMPK).
CTRP9 prevents acute cardiac ischemic injury via an AMPK-dependent mechanism.
CTRP9 represents a novel target molecule for manipulation of myocardial ischemic injury.
Acute coronary syndrome is a leading cause of death in developed countries. Follistatin-like 1 (FSTL1) is a myocyte-derived secreted protein that is upregulated in the heart in response to ischemic ...insult. Here, we investigated the therapeutic impact of FSTL1 on acute cardiac injury in small and large preclinical animal models of ischemia/reperfusion and dissected its molecular mechanism.
Administration of human FSTL1 protein significantly attenuated myocardial infarct size in a mouse or pig model of ischemia/reperfusion, which was associated with a reduction of apoptosis and inflammatory responses in the ischemic heart. Administration of FSTL1 enhanced the phosphorylation of AMP-activated protein kinase in the ischemia/reperfusion-injured heart. In cultured cardiac myocytes, FSTL1 suppressed apoptosis in response to hypoxia/reoxygenation and lipopolysaccharide-stimulated expression of proinflammatory genes through its ability to activate AMP-activated protein kinase. Ischemia/reperfusion led to enhancement of bone morphogenetic protein-4 expression and Smad1/5/8 phosphorylation in the heart, and FSTL1 suppressed the increased phosphorylation of Smad1/5/8 in ischemic myocardium. Treating cardiac myocytes with FSTL1 abolished the bone morphogenetic protein-4-stimulated increase in apoptosis, Smad1/5/8 phosphorylation, and proinflammatory gene expression. In cultured macrophages, FSTL1 diminished lipopolysaccharide-stimulated expression of proinflammatory genes via activation of AMP-activated protein kinase and abolished bone morphogenetic protein-4-dependent induction of proinflammatory mediators.
Our data indicate that FSTL1 can prevent myocardial ischemia/reperfusion injury by inhibiting apoptosis and inflammatory response through modulation of AMP-activated protein kinase- and bone morphogenetic protein-4-dependent mechanisms, suggesting that FSTL1 could represent a novel therapeutic target for post-myocardial infarction, acute coronary syndrome.
Background
Intrahepatic cholangiocarcinoma had been considered a contraindication for liver transplantation because of poorer outcomes. However, incidental intrahepatic cholangiocarcinoma in the ...explanted liver has been reported because of the difficulty of obtaining an accurate diagnosis in cirrhotic livers on preoperative imaging.
Methods
We conducted a nationwide survey to analyze the incidence of incidental intrahepatic cholangiocarcinoma and outcomes after liver transplantation, in Japan.
Results
Forty‐five of 64 institutions (70%) responded to our initial investigation. Between January 2001 and December 2015, 6627 liver transplantations were performed in these 45 institutions, with 19 cases (0.3%) of incidental intrahepatic cholangiocarcinoma reported from 12 transplant centers. Six cases were diagnosed as hepatocellular carcinoma preoperatively. The 1‐, 3‐, and 5‐year recurrence‐free survival rates were 79%, 45%, and 45%, respectively. Tumor recurrence after liver transplantation was found in 10 patients (53%). The 1‐, 3‐, and 5‐year overall survival rates were 79%, 63%, and 46%, respectively.
Conclusions
Intrahepatic cholangiocarcinoma at liver transplantation is associated with a high risk of recurrence and poor prognosis, even these tumors are detected incidentally in the explanted liver.
Highlight
Incidental intrahepatic cholangiocarcinoma in the explanted liver has been reported because of the difficulty of accurate diagnosis in cirrhotic livers on preoperative imaging. Hara and colleagues report the results of a nationwide Japanese survey. The incidence was 0.3% and the 1‐, 3‐ and 5‐year recurrence‐free survival rates were 79%, 45% and 45%, respectively.
Seeking empirical support for the Porter hypothesis (PH) applied to the trade of photovoltaic (PV) and wind energy components, this study examines effects of the interaction between innovative ...capacity and two kinds of renewable energy (RE) policies, feed-in tariff (FIT) and renewable portfolio standards (RPS), on export in OECD and BRICS countries. Meanwhile, the effect of such policies in import countries is estimated given prominent growth in RE component export by emerging economies and trade disputes with developed countries. The result reveals exporter innovative capacity as negatively correlated with their export when it is interacted with RPS dummy, suggesting inverse evidence for PH. On the other hand, importer annual PV share, which proxies demand for components, was positively associated with their import provided the presence of FIT/RPS. Overall, policies in importer countries exert a robust influence over their import growth, while those in exporter countries may not facilitate or have a negative effect on their export. The result above is in line with the theoretical implication on the effect of RE policy, while it contradicts to the narrowly strong version of PH. This indicates that positive effect of the interaction between policy and innovative capacity on export performance might depend on the distribution of the additional surplus from FIT/RPS.
•Interactional effect of innovative capacity and RE policies on export is examined.•Results support the theoretical view of economics on static reaction to FIT and RPS.•Inverse evidence of dynamic policy effect on PV/wind components export is found.•Robust evidence of importer policies is found on positive effect on their import.•The distribution of profit by RE policy is suggested to matter its effect on trade.
Background
Portal vein stenosis develops in 3.4–14% of split liver transplantation
1
–
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
Methods
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).
Results
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 < 2 around the anastomotic site. The wall shear stress analysis revealed a high wall shear stress area within the post-anastomotic portal vein. At the post-transplant 6-month evaluation, the streamline analysis illustrated the increased vortices and worsening flow acceleration to reach the proposed diagnostic criteria (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.
Discussion
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.
We present a case of a patient who underwent portal vein (PV) stenting for PV stenosis after a living-donor liver transplantation. A pretreatment 3D cine phase-contrast (4D-flow) MRI showed ...decreased, though hepatopetal, blood flow in the PV. After stenting, 4D-flow MRI confirmed an improvement in PV flow, with a more homogeneous flow distribution to each hepatic segment. 4D-flow MRI are valuable for understanding the hemodynamics of this area, planning for treatments, and evaluating the outcome of the interventions.
Background
In this study, we investigated long‐term survival of cirrhotic patients without hepatocellular carcinoma (HCC) and the proper timing of liver transplantation in the era with recent ...progress of management.
Methods
We first classified 217 non‐transplant cirrhotic patients without HCC according to the long‐term survival based on Child‐Turcotte‐Pugh (CTP) scores and the MELD scores. We then compared them with the survival after liver transplantation in 114 patients with liver cirrhosis.
Results
We classified into four groups (class A as CTP score of 5,6, B as 7,8, C as 9‐12, D as 13‐15) according to the long‐term survival of the patients, the survivals of patients with class C and D were significantly worse compared with transplant patients (P < 0.001 in each group). And we also classified into four groups based on the MELD scores (class A as MELD score of −8, B as 9‐12, C as 13‐19, D as 19‐), the survivals of patients with class C and D were significantly worse compared with those of transplant patients (P < 0.001 in each group).
Conclusions
Considering the long‐term survival of patients with liver cirrhosis, CTP score of 9 and/or MELD score of 13 could be a proper timing for liver transplantation.
Highlight
Focusing on the long‐term survival of patients with cirrhosis without hepatocellular carcinoma, Ishigami and colleagues reconsidered the indications of liver transplantation. Considering recent progress in liver cirrhosis management, they suggest a Child‐Turcotte‐Pugh score of 9 and Model for End‐Stage Liver Disease score of 13 as proper timing for liver transplantation.
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 (P < 0.001). 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.
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