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The number of elderly patients with hepatocellular carcinoma (HCC) has been increasing, but it remains unclear whether hepatectomy can be performed using the same criteria as in younger patients. Furthermore, the appropriate preoperative evaluation for hepatectomy in elderly patients is not yet clearly defined. Here, we investigated the applicability of preoperative assessment using the Controlling Nutritional Status (CONUT) score to help improve hepatectomy outcomes in elderly patients with HCC. This was a single-center retrospective analysis, and the study population comprised 64 consecutive patients who underwent hepatectomy for HCC between January 2012 and August 2016. We compared the preoperative assessment and perioperative outcomes between elderly (≥ 75 years old) and younger (75 years old) patients. A total of 61 patients were reviewed. Poor preoperative CONUT score was associated with a longer postoperative hospital stay in elderly patients undergoing hepatectomy for HCC. In addition, although elderly patients had similar perioperative outcomes to younger patients, the incidence of delirium was significantly higher, and univariate analysis confirmed that old age is a risk factor for delirium among the preoperative factors. Hepatectomy for HCC in the elderly can be safely performed with appropriate preoperative nutritional assessment using CONUT score and prevention of postoperative delirium. Preoperative nutritional assessment using the CONUT score was useful in predicting prolonged hospitalization for elderly hepatectomy with HCC.

Background Liver transplantation from donors after cardiac death (DCD) might increase the pool of available organs. Recently, some investigators reported the potential use of mesenchymal stem cells (MSCs) to improve the outcome of liver transplantation from DCD. The aim of this study was to evaluate the cytoprotective effects and safety of MSC transplantation on liver grafts from DCD. Methods Rats were divided into 4 groups (n = 5) as follows: 1. the heart-beating group, in which liver grafts were retrieved from heart-beating donors; 2. the DCD group, in which liver grafts were retrieved from DCD that had experienced apnea-induced agonal conditions; 3. the MSC-1 group, and 4. the MSC-2 group, in which liver grafts were retrieved as with the DCD group, but were infused MSCs (2.0 × 105 or 1.0 × 106, respectively). The retrieved livers were perfused with oxygenated Krebs-Henseleit bicarbonate buffer (37°C) through the portal vein for 2 hours after 6 hours of cold preservation. Perfusate, bile, and liver tissues were then investigated. Results Bile production in the MSC-2 group was significantly improved compared with that in the DCD group. Based on histologic findings, narrowing of the sinusoidal space in the both MSC groups was improved compared with that in the DCD group. Conclusions MSCs could protect the function of liver grafts from warm ischemia-reperfusion injury and improve the viability of DCD liver grafts. In addition, we found that the infusion of 1.0 × 106 MSCs does not obstruct the hepatic sinusoids of grafts from DCD.

Background Liver transplantation from donors after cardiac death (DCD) provides a solution to the donor shortage. However, DCD liver grafts are associated with a high incidence of primary graft nonfunction. We investigated the effectiveness of subnormothermic porcine liver perfusion, before transplantation from DCD, on graft viability. Methods Landrace pigs (25–30 kg) were randomly allocated to 3 groups (5 per group): heart-beating (HB) graft, transplanted after a 4-hour period of cold storage (CS); DCD graft, retrieved 20 minutes after apnea-induced cardiac arrest (respiratory withdrawal) and transplanted after a 4-hour period of CS; and subnormothermic ex vivo liver perfusion (SELP) graft, retrieved in the same manner as the DCD graft but perfused with a subnormothermic oxygenated Krebs-Henseleit buffer (21–25°C, 10–15 cm H2O) for 30 minutes in a simplified dripping manner, without a machine perfusion system, after the 4-hour period of CS, and subsequently transplanted. Results Although all animals in the HB group survived for >7 days, all animals in the DCD group died within 12 hours after transplantation. In the SELP group, 2 recipients survived for >7 days and another 2 recipients were killed on day 5. The survival rate was significantly better for SELP than for DCD grafts (P = .0016). The values of tumor necrosis factor α were not significantly different between the SELP and HB groups. Preserved structure of the parenchyma was observed in the SELP group on histologic examination. Conclusions A simplified subnormothermic perfusion before liver transplantation is expected to improve graft viability and survival.

Key Clinical Message Performing resection of a biliary tract malignancy with a hepatic artery aneurysm is very challenging. Resection of the extrahepatic bile duct and extra-anatomical reconstruction can be successfully performed using free radial artery autografts from the aorta to the right hepatic artery. Hepatic artery thrombosis can be prevented with intimal preservation.

Background Liver transplantation from donors after cardiac death (DCD) could increase the pool of organs. We previously reported that oxygenated subnormothermic (20°C-25°C) ex vivo liver perfusion (SELP) improved the graft viability in rats. This study aimed to compare the effectiveness of SELP and normothermic (37°C) ex vivo liver perfusion (NELP) after cold storage (CS) in DCD liver grafts. Methods Male Wistar rats were used, and grafts were retrieved 30 minutes after cardiac arrest. We performed oxygenated NELP and SELP with a Krebs-Henseleit buffer for different time points and durations: Group 0, donation performed from heart-beating donors (control); Group 1 (DCD group), donation performed from DCD donors with no treatments; Group 2, NELP performed before CS (30 minutes); Group 3, NELP performed after CS (30 minutes); Group 4, SELP performed after CS (30 minutes); Group 5, SELP performed after CS (60 minutes); and Group 6, SELP performed after CS (90 minutes). After 15 minutes of incubation at room temperature, the grafts were reperfused under normothermic conditions for 60 minutes as a model of liver transplantation. Results No significant differences in body and liver weight were observed between all groups. In the SELP after CS groups, even 30 minutes of perfusion improved bile production, tumor necrosis factor-α, and interleukin-1β significantly compared with the DCD group (P Conclusion SELP rescued DCD livers from ischemia-reperfusion injury the same as the normothermic perfusion before or after CS groups. SELP after CS is more convenient than normothermic perfusion; hence, this technique may increase the organ pool.

In living donor liver transplantation (LDLT), a graft-to-recipient weight ratio (GRWR) of under 0.8 is recognized as the critical graft size. Our aim was to compare the survival rates of recipients with small-for-size grafts (SFSG: GRWR 0.8), normal-sized grafts (NSG), and large-for-size grafts (LFSG: GRWR ≥ 3.5) and to investigate the mortality risk with SFSG.Between 1991 and April 2019, we performed 188 LDLT surgeries. Recently, we added splenectomy when portal vein pressure is high (17 mm Hg) to interrupt the splenic bloodstream. We divided all LDLT cases retrospectively into 3 groups: an SFSG group (n = 22), NSG group (n = 154), and LFSG group (n = 12). We investigated the survival rates in these groups. Furthermore, we divided the SFSG group into 2 subgroups: an SFSG with splenectomy (SFSG+S) group (n = 7) and an SFSG without splenectomy group. We investigated the occurrence rates of lethal complications such as portal vein thrombosis, hepatic artery thrombosis, and hepatic vein thrombosis.The 5-year survival rate in the SFSG group was significantly lower (52.8%) than in the other groups (NSG: 84.5%; LFSG: 83.3%), but that of the SFSG+S group was similar (80.0%) to that of other groups. There was no difference in the occurrence of postoperative complications such as portal vein thrombosis, hepatic artery thrombosis, or hepatic vein thrombosis between the SFSG+S group and other groups.Graft survival of LDLT using SFSG+S was as good as that of normal-sized grafts. Reducing portal vein pressure was important for SFSG.

We previously reported that short oxygenated warm perfusion before cold storage (CS) had improved the graft viability of rat livers from donors after circulatory death (DCD). In this study, we investigated the effectiveness of short-term oxygenated subnormothermic perfusion for different durations after CS in a rat DCD model.We used an isolated perfused rat liver system. In study 1: the grafts were retrieved from Wistar rats 30 minutes after cardiac arrest (thoracotomy), preserved in CS for 6 hours, and perfused with oxygenated subnormothermic (20-25°C) Krebs-Henseleit buffer for different durations (0, 15, 30, 60, and 90 minutes groups; n = 5 in each). In study 2: in addition to subnormothermic ex vivo liver perfusion (SELP), after 15-minute incubation at room temperature, the grafts were reperfused under normothermic condition for 60 minutes as a model of liver transplantation (0, 30, 60, and 90 minutes groups; n = 5 in each).In study 1, portal flow, bile production and tissue adenosine triphosphate increased with perfusion duration. In study 2, SELP significantly improved portal flow volume (P0.05), and bile production (P0.05), decreased liver enzymes (P0.05) and cytokines (P0.0001), and increased tissue adenosine triphosphate (P0.01). Histological examinations showed that additional SELP ameliorated tissue deterioration, preserved the parenchymal structure, and decreased apoptosis (P0.01). Furthermore, scanning electron microscopy revealed that additional SELP alleviated sinusoidal endothelial cells and hepatic microvasculature.Even 30 minutes of SELP after CS rescued DCD livers from ischemia-reperfusion injury, which may help the viability of the grafts.

Objectives In adults undergoing living donor liver transplantation (LDLT), the transplanted livers are partial grafts, and the portal venous pressure is higher than that observed with whole liver grafts. In patients undergoing LDLT concomitant with splenomegaly, portal venous flow is often diverted to collateral vessels, leading to a high risk of portal vein thrombosis. In such cases, occlusion of the collateral veins is important; however, complete occlusion of all collaterals without blocking the blood flow through the splenic artery causes portal hypertension and liver failure. We aimed to examine the effect of performing a splenectomy concomitant with LDLT to reduce portal vein complications. Methods Between 1991 and 2017, we performed 170 LDLT operations, including 83 in adults. For this cohort study, adult cases were divided into 2 groups. Group I was those who underwent LDLT without splenectomy (n = 60); Group II was those who underwent LDLT with splenectomy for the reduction of portal hypertension (n = 23). We investigated the incident rates of complications, including blood loss, lethal portal vein thrombosis (intrahepatic thrombosis), acute rejection, and so on. We also investigated the survival rates in both groups. Results The incident rate of lethal portal vein thrombosis in Group II was significantly lower than that observed in Group I (4.4% vs 21.7%, respectively, P = .0363). There were no statistically significant differences observed between the groups with respect to blood loss, survival rates, and other such parameters. Conclusion LDLT concomitant with splenectomy might effectively reduce the occurrence of portal vein complications in adults.

We encountered a case of hypercobalaminemia induced by oral intake of an energy drink after total gastrectomy. The patient was referred to our hospital due to findings suspicious for gastric cancer on screening. A 20 mm type 0-IIc lesion was detected in the gastric subcardia on esophagogastroduodenoscopy. Total gastrectomy followed by Roux-en-Y reconstruction was performed. He was discharged without complications. His basal serum vitamin B12 level was initially maintained with monthly intramuscular injections of vitamin B12. After 9 months, his serum vitamin B12 level suddenly increased up to 36-fold higher than the normal range and persisted there for one year without vitamin B12 injections. The patient ultimately reported consuming half a bottle of an energy drink each day during this time period. This case demonstrates the risk of unexpected hypervitaminemia resulting from self-administration of nutritional supplements.

The mortality of patients on the waiting list for deceased donor liver transplantation (DDLT) is high, especially in countries where donation rates are low. Thus, living donor liver transplantation (LDLT) is an attractive option. However, compared with DDLT, LDLT is associated with increased rates of arterial and biliary complications. We examined the rates of complications and risk factors following LDLT. We retrospectively investigated and compared the rates of complications of DDLT and LDLT in our institute. We also performed univariate and multivariate analyses to identify the independent risk factors for these complications. The complications and specific disadvantages of LDLT were reviewed and discussed. The incidence rate of arterial complications in LDLT was 6.0%, compared with 3.2% (13/441) in DDLT. A multivariate analysis identified low body weight (P = 0.032) as the only independent risk factor for hepatic artery thrombosis. The rate of all biliary complications in LDLT was 17.3%, compared with 18.7% in DDLT. The risk factors for biliary stricture identified by the multivariate analysis were recurrent cholangitis and the number of bile ducts. The durations of hospital stay and overall survival rates were similar between the two groups. Given the shortage of deceased donor organs, we believe that LDLT is acceptable in an attempt to meet demand.

Dendritic cells (DC) play pivotal roles in the induction and regulation of both innate and acquired immunity. DC express several cell-surface immune inhibitory receptors. However, little is known about their potential immunoregulatory functions in the context of T-cell activation. Here we report that murine gp49B, a member of the immunoglobulin superfamily, harboring immunoreceptor tyrosine-based inhibitory motifs, is expressed on DC and downregulates cellular activity to prevent the excessive activation of T cells in vitro and in vivo. Bone marrow-derived DC (BMDC) from newly generated gp49B-deficient (gp49B(-/-)) mice induced enhanced proliferation and IL-2 release of antigen-specific CD4(+) and CD8(+) T cells compared with BMDC from wild-type mice, in a cell-cell contact manner. The enhanced proliferation by gp49B(-/-) BMDC was also observed in allogeneic CD4(+) and CD8(+) T cells. Moreover, the transfer of allogeneic BALB/c splenocytes into C57BL/6 gp49B(-/-) mice induced severe acute graft-versus-host disease with an augmented upregulation of CD86 on CD11c(+) splenic gp49B(-/-) DC, while transfer of C57BL/6 gp49B(-/-) splenocytes into BALB/c mice did not, suggesting the exacerbation of the disease was due, at least in part, to augmented activation of recipient gp49B(-/-) DC. These findings demonstrate a novel regulatory role of gp49B in the function of DC.

Objectives: In living-donor liver transplantation (LDLT), microsurgical reconstruction of a hepatic artery is essential but requires challenging techniques, because graft arteries are short and usable vessel grafts are limited. Furthermore, hepatic artery thrombosis can be a lethal complication. Extra-anatomical jump graft reconstruction using free grafts is reported to have a high reocclusion rate. However, this technique is necessary when there is no other option. We report 4 cases of LDLT that required extra-anatomical reconstruction technique using free autografting from the aorta to the hepatic artery. In this technique, we used the systemic administration of gabexate mesilate that is the strong serine protease inhibitor. Methods: From 1991 to 2015, we performed 164 LDLTs. We retrospectively investigated 4 cases of extraanatomical reconstruction of the hepatic artery using free autografting from the aorta to the hepatic artery. Results: Two cases initially underwent anatomical reconstruction, but the arteries occluded early, because of the dissection of recipient’s artery. There was no arterial graft, so we performed extra-anatomical reconstruction by using free autografting from the aorta to the hepatic artery. In the other two cases, the recipient arteries could not be used. Therefore, we initially performed extra-anatomical reconstruction by using radial artery free autografting as jump grafts from the aorta to the hepatic artery. In all cases, we used the systemic administration of gabexate mesilate, and could rescue all cases. Conclusion: We experienced and were able to salvage 4 cases that required free autografts. When there is no other means of reconstructing arteries, it is necessary to perform this procedure, depending on the condition of the intima of the recipient artery.