Y. Soejima

Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma

Sarcopenia was identified recently as a poor prognostic factor in patients with cancer. The present study investigated the effect of sarcopenia on short‐ and long‐term outcomes following partial hepatectomy for hepatocellular carcinoma (HCC), and aimed to identify prognostic factors.

Feasibility of left lobe living donor liver transplantation between adults: An 8-year, single-center experience of 107 cases

Operative mortality for a right lobe (RL) donor in adult living donor liver transplantation (LDLT) is estimated to be as high as 0.5–1%. To minimize the risk to the donor, left lobe (LL)‐LDLT might be an ideal option in adult LDLT. The aim of the study was to assess the feasibility of LL‐LDLT between adults based on a single‐center experience of 107 LL‐LDLTs performed over 8 years. The mean graft weight of LL grafts was 452 g, which amounted to 40.5% of the estimated standard liver volume of the recipients. The overall 1‐, 3‐ and 5‐year patient survival rates in LL‐LDLT were 81.4, 76.9 and 74.7%, respectively, which were comparable to those of RL‐LDLT. Twenty‐six grafts (24.3%) were lost for various reasons with three losses directly attributable to small‐for‐size graft syndrome. Post‐operative liver function and hospital stay in LL donors were significantly better and shorter than that in RL donors, while the incidence of donor morbidity was comparable between LL and RL donors. In conclusion, LL‐LDLT was found to be a feasible option in adult‐to‐adult LDLT. Further utilization of LL grafts should be undertaken to keep the chance of donor morbidity and mortality minimal.

Left Lobe Living Donor Liver Transplantation in Adults

Adult left lobe (LL) living donor liver transplantation (LDLT) has not generally been recognized as a feasible procedure because of the problem of graft size. The objectives of this study were to assess the feasibility and short‐ and long‐term results of adult LL LDLT in comparison with right lobe (RL) LDLT. Data on 200 consecutive LL LDLTs, including five retransplants, were retrospectively compared with those of 112 RL LDLTs, in terms of survival, complications and donor morbidity. The mean graft weight to standard volume ratio of LL grafts was 38.7% whereas that of RL grafts was 47.6% (p < 0.0001). The 1‐, 5‐ and 10‐year patient survival rates of LL LDLT were 85.6%, 77.9% and 69.5%, respectively, which were comparable to those of RL LDLT (89.8%, 71.3% and 70.7%, respectively). The incidence of small‐for‐size syndrome was higher in LL LDLT (19.5%) than in RL LDLT (7.1%) (p < 0.01). The overall donor morbidity rates were comparable between LL (36.0%) and RL (34.8%), whereas postoperative liver function tests and hospital stay were significantly better (p < 0.0001) in LL donors. In conclusion, adult LL LDLT has comparable outcomes to that of RL LDLT. LL LDLT is viable and is the first choice in adult LDLT.

Deceleration of regenerative response improves the outcome of rat with massive hepatectomy.

Small residual liver volume after massive hepatectomy or partial liver transplantation is a major cause of subsequent liver dysfunction. We hypothesize that the abrupt regenerative response of small remnant liver is responsible for subsequent deleterious outcome. To slow down the regenerative speed, NS‐398 (ERK1/2 inhibitor) or PD98059 (selective MEK inhibitor) was administered after 70% or 90% partial hepatectomy (PH). The effects of regenerative speed on liver morphology, portal pressure and survival were assessed. In the 70% PH model, NS‐398 treatment suppressed the abrupt replicative response of hepatocytes during the early phase of regeneration, although liver volume on day 7 was not significantly different from that of the control group. Immunohistochemical analysis for CD31 (for sinusoids) and AGp110 (for bile canaliculi) revealed that lobular architectural disturbance was alleviated by NS‐398 treatment. In the 90% PH model, administration of NS‐398 or PD98059, but not hepatocyte growth factor, significantly enhanced survival. The abrupt regenerative response of small remnant liver is suggested to be responsible for intensive lobular derangement and subsequent liver dysfunction. The suppression of MEK/ERK signaling pathway during the early phase after hepatectomy makes the regenerative response linear, and improves the prognosis for animals bearing a small remnant liver.

Primary Graft Dysfunction After Living Donor Liver Transplantation Is Characterized by Delayed Functional Hyperbilirubinemia

The purpose of this study is to propose a new concept of primary graft dysfunction (PGD) after living donor liver transplantation (LDLT), characterized by delayed functional hyperbilirubinemia (DFH) and a high early graft mortality rate. A total of 210 adult‐to‐adult LDLT grafts without anatomical, immunological or hepatitis‐related issues were included. All of the grafts with early mortality (n = 13) caused by PGD in LDLT had maximum total bilirubin levels >20 mg/dL after postoperative day 7 (p < 0.001). No other factors, including prothrombin time, ammonia level or ascites output after surgery were associated with early mortality. Thus, DFH of >20 mg/dL for >seven consecutive days occurring after postoperative day 7 (DFH‐20) was used to characterize PGD. DFH‐20 showed high sensitivity (100%) and specificity (95.4%) for PGD with early mortality. Among the grafts with DFH‐20 (n = 22), those with early mortality (n = 13) showed coagulopathy (PT‐INR > 2), compared with those without mortality (p = 0.002). Pathological findings in the grafts with DFH‐20 included hepatocyte ballooning and cholestasis, which were particularly prominent in the centrilobular zone. PGD after LDLT is associated with DFH‐20 caused by graft, recipient and surgical factors, and increases the risk of early graft mortality.

Living Donor Liver Transplantation Using Dual Grafts from Two Donors: A Feasible Option to Overcome Small-for-Size Graft Problems?

Living donor liver transplantation (LDLT) between adults inevitably implies two potential risks associated with a small‐for‐size graft for the recipient and small remnant liver for the donor. To overcome these problems, LDLT using dual grafts from two independent donors can be a solution, in which sufficient graft volume can be obtained while preserving donor safety. We present a case of LDLT that was managed successfully by using right and left lobe dual grafts from two donors. The recipient was a large‐size male with hepatitis C cirrhosis complicated by multiple hepatocellular carcinomas (HCCs). The first donor donated a right lobe graft and the second donor donated a left lobe plus caudate lobe graft with the middle hepatic vein. Graft function was excellent throughout the course without evidence of small‐for‐size syndrome. In conclusion, LDLT using dual grafts can be justified in a selected case to avoid small‐for‐size graft problems without increasing independent donor risks.

The hydroxyl radical scavenger MCI-186 protects the liver from experimental cold ischaemia-reperfusion injury

Oxidative stress contributes to hepatic ischaemia–reperfusion (IR) injury in a biphasic pattern. In addition to direct cytotoxic effects, oxidative stress also initiates the signal transduction processes that promote second‐phase liver injury. The present study investigated the effects of the hydroxyl radical scavenger MCI‐186 on the biphasic process of hepatic cold IR injury.

Revisiting the Safety of Living Liver Donors by Reassessing 441 Donor Hepatectomies: Is a Larger Hepatectomy Complication‐Prone?

Donor safety is of paramount importance in performing living donor liver transplantation (LDLT). We retrospectively reviewed donor medical records to confirm whether larger donor hepatectomy is absolutely complication‐prone. A total of 441 living donor hepatectomies were performed between October 1996 and July 2012 in our institute, which were divided into three eras (Era I, October 1996 to March 2004; Era II, April 2004 to March 2008; Era III, April 2008 to July 2012) and the incidences of postoperative complications were compared among the three types of hepatectomy—right hepatectomy (RH), left hepatectomy (LH) and left lateral segmentectomy (LLS). Although severe complications (Claviens grade 3 or more) frequently occurred in RH in Eras I and II (15.4% and 10.7%, respectively), the incidence in Era III decreased to the comparable level observed in LH and LLS (5.4% in RH, 2.3% in LH and 5.3% in LLS). The incidence of postoperative complications did not relate to the type of hepatectomy selected in the latest era. Since most complications after hepatectomy were considered preventable, step‐by‐step meticulous surgical procedures are a prerequisite for further assuring donor safety irrespective of the type of hepatectomy selected.

Prognostic importance of the gross classification of hepatocellular carcinoma in living donor-related liver transplantation

The gross classification of hepatocellular carcinoma (HCC) has been reported to be a significant prognostic factor for patients with HCC undergoing partial hepatectomy. The present study investigated whether the gross classification of HCC is also a prognostic factor in living donor‐related liver transplantation (LDLT).

Estimation of standard liver volume for Japanese adults.

INTRODUCTION Accurate pretransplant estimation of the recipients standard liver volume (SLV) is important. The purpose of this study was to compare reported formulas for clinical estimation of liver volume among Japanese adults. METHODS We reviewed data on 70 healthy adults (46 men, 24 women, ages 20 to 65 years old) evaluated for living donor liver transplantation. Liver volume (LV) was measured using two- or three-dimensional computed tomography volumetry (CTV). The formulas of DeLand (LV = 1020 x body surface area [BSA] - 220), Urata (LV = 706.2 x BSA + 2.4), Noda (LV = 50.12 x BW(0.78)), Heinemann (LV = 1072.8 x BSA - 345.7), Vauthey (LV = 18.51 x BW + 191.8) and Yoshizumi (LV = 772 x BSA) were applied to estimate LV. We calculated the differences for individual donors betwen CTV and LV estimated by each formula. RESULTS Mean LVs as estimated by the formulae of DeLand and Heinemann et al were significantly greater (P < .01) than the mean CTV, while LV estimated by the formula of Urata was significantly less (P < .05) than the CTV. The formulas of DeLand and Heinemann overestimated LV, while the formula of Urata underestimated it. The formulae of Noda et al and Yoshizumi et al tended to underestimate the LV when the CTV was greater than 1600 cm(3). When the Yoshizumi formula was applied, the number of donors with an acceptable difference (+/-15%) between CTV and estimated LV was 55 (78.6%). CONCLUSIONS The Yoshizumi formula was applicable, especially for patients with a BSA < 2.0, whereas the well-known Urata formula made LV underestimates.