Hideki Ijichi

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.

Biliary strictures in living donor liver transplantation: Incidence, management, and technical evolution

Biliary complications, biliary strictures (BS) in particular, continue to be a significant cause of morbidity after LDLT despite technical refinement. In this study, we assessed the incidence of BS and their management in living donor liver transplantation (LDLT) with special reference to the type of biliary reconstruction. A total of 182 LDLTs performed at our institution for either adult (n = 157) or pediatric (n = 25) patients were included in the study. The duct‐to‐duct (DD) biliary reconstruction was performed for 106 cases, while the conventional Roux‐en‐Y hepaticojejunostomy (HJ) was utilized for the remaining 76 cases. Overall, BS developed in 46/182 (25.3%) of the cases (DD, 26.4%; HJ, 25.0%). The 1‐ and 3‐year cumulative incidences of BS were 22.9% and 31.9%, respectively, in the DD group, and 15.2% and 29.1%, respectively, in the HJ group (P= not significant). The left‐lobe LDLT was more prone to develop BS. Continuous anastomosis tended to be associated with the high incidence of BS in the DD group. The incidence of anastomotic leak was significantly lower in the DD group. Intervention via either precutaneous or endoscopic approach was successful in the majority of cases, although recurrence could occur in some patients. In conclusion, BS was not associated with the type of reconstruction in LDLT. The primary radiological or endoscopic interventions were satisfactory treatments of choice. Technical refinement is an important factor to reduce the incidence of BS. Liver Transpl 12:979–986, 2006.

Validity of preoperative volumetric analysis of congestion volume in living donor liver transplantation using three-dimensional computed tomography

Reconstruction of middle hepatic vein (MHV) tributaries is controversial in right‐lobe living donor liver transplantation (LDLT). This study aimed to evaluate the appropriateness of reconstructing MHV tributaries by volumetry using 3‐dimensional computed tomography (3D‐CT). Between November 2003 and January 2005, 42 donor livers (right‐lobe graft, n = 25; left‐lobe graft, n = 17) were evaluated using this software. The total congestion volume (CV) associated with the MHV tributaries and the inferior right hepatic vein (IRHV), and graft volume (GV) were calculated. In recipients with right‐lobe grafts, CV/(right liver volume [RLV]) and (GV − CV)/(standard liver volume [SLV]) were compared between 2 groups: with reconstruction (n = 16) and without reconstruction (n = 9). To evaluate the influence of CV on the remnant right lobe in donors, total bilirubin was compared between 2 groups: high CV (CV > 20%, n = 13) or low CV (CV ≤ 20%, n = 4). The mean CV/RLV ratio was 32.3 ± 17.1% (V5, 15.2 ± 9.9%; V8, 9.2 ± 4.1%; and IRHV, 8.5 ± 11.4%) and the maximum ratio was as high as 80.8%. The mean (GV − CV)/SLV ratio before reconstruction in patients with or without reconstruction resulted in 33.5 ± 12.8% and 55.4 ± 12.9%, respectively (P < 0.01). In donors, total bilirubin was significantly high in the high CV group on postoperative day 1 compared with the low CV group (P < 0.05). In conclusion, calculation of CV using 3D‐CT software proved to be very useful. We concluded that this evaluation should be an integral part of procedure planning, especially for right‐lobe LDLT. (Liver Transpl 2005;11:1556–1562.)

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.

Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver to minimize intraoperative bleeding.

PurposeAlthough laparoscopic liver resection has been widely adopted, performing a pure laparoscopic right hepatectomy remains a challenging procedure. The aim of this report is to evaluate the efficiency of a pure laparoscopic right hepatectomy (PLRH) in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver.MethodsPure laparoscopic right hepatectomy was performed in the semi-prone position with the use of an intrahepatic Glissonian approach and modified hanging maneuver for patients with primary liver cancer (n = 3) and metastatic liver cancer (n = 1).ResultsThe intraoperative total blood loss was only 95–140 g (mean: 126.2 g). None of the patients required a blood transfusion, and no serious complications were encountered. The durations of the surgeries ranged from were 308 to 445 min (mean: 394.8 min). The postoperative hospital stay was 8–11 days (mean 9.5 days).ConclusionPure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver is thus considered to be a safe modality, which minimizes intraoperative bleeding.

Accuracy of an age‐adjusted formula in assessing the graft volume in living donor liver transplantation

In living donor liver transplantation, the estimated graft volume (GV) from young donors tends to be overestimated. One reason for this error may be a decrease in GV due to dehydration by University of Wisconsin (UW) solution. The aim of this study was to clarify (1) the usefulness of an age‐adjusted formula and (2) the correlation between the decrease in GV and donor age. First, we created the age‐adjusted formula using regression analysis retrospectively in 167 donors, and we evaluated the difference in the error ratio of GV from the age‐adjusted formula and 3‐dimensional computed tomography (3D‐CT) prospectively in 49 donors. Second, we measured intraoperative GV both before and after flushing with UW solution and calculated the decrease ratio, and we then evaluated the difference in the decrease ratio between young donors and older donors prospectively in 41 donors. The age‐adjusted formula was created as follows: age‐adjusted GV = 70.767 + (0.703 × GV estimated with 3D‐CT volumetry) + (1.298 × donor age). The mean error ratio for the age‐adjusted formula (9.6%) was significantly lower than that from 3D‐CT (14.0%). The mean decrease ratio in all 41 donors was 5.4%, and that in young donors (6.9%) was significantly higher than that in older donors (4.4%). In conclusion, although younger donor age is a major factor for estimation errors in hepatic volumetry, our age‐adjusted formula is very useful in reducing the error in estimating GV. Liver Transpl 14:1366–1371, 2008.

Tumor-infiltrating lymphocytes and hepatocellular carcinoma: pathology and clinical management

The presence of tumor-infiltrating lymphocytes (TILs) in hepatocellular carcinoma (HCC) is relatively rare. The prognosis of patients with HCC and marked TILs is better than that of patients with HCC without TILs. TILs in HCC tissues are mainly T cells, and previous reports suggested that TILs might be important antitumor effector cells. TILs have been extensively analyzed, and subpopulations of CD3+, CD4+, and CD8+ T cells are often present in HCC. Some studies have reported that the percentage of CD8+ T cells, which might have cytotoxic activity, is decreased in tumors with TILs, as compared with noncancerous tissues. Although the antitumor effects of TILs seem to be impaired in HCCs, the underlying mechanism has remained unclear until quite recently. Pathological and in vitro studies have now shown that regulatory T cells play important roles in the deterioration of the antitumor effects of TILs. The aim of this review is to introduce recent pathological findings for TILs in HCC and to evaluate new therapeutic strategies in this field.

Sustained spatial disturbance of bile canalicular networks during regeneration of the steatotic rat liver.

Background. Although it is generally considered that livers with moderate steatosis can be safely used in the setting of living-donor liver transplantation, the effect of the regenerative process of such a graft on postoperative liver function is incompletely understood. We assessed the morphologic and functional alterations during the regeneration of fatty liver, with special reference to the biliary system. Methods. Wistar rats with normal or fatty livers induced by a choline-deficient diet were subjected to 70% partial hepatectomy (PH). The regenerated liver weight and serum parameters were compared. Furthermore, to assess the spatial alterations of bile canalicular networks, the distribution of AGp110, a fibronectin receptor that localizes on the apical (bile canalicular) membrane of the hepatocytes, was analyzed immunohistochemically. Results. The serum albumin levels of the fatty-liver rats decreased significantly after 24 hours, and this continued until day 7. The increase in the total bile acid levels of the fatty-liver group was higher and more prolonged compared with that of the normal-liver group. At 24 hours after PH, discontinuity of the AGp110-positive canalicular network was evident in both groups. At 7 days after PH, the typical AGp110-positive canalicular network was almost restored in the normal-liver group. In contrast, the fatty-liver group showed sustained discontinuity of canalicular networks at the same time point. Conclusions. The livers with moderate steatosis are associated with prolonged cholestasis after 70% PH, and this was caused, in part, by sustained spatial disturbance of bile canalicular networks during the regenerative process.

Risk factors that increase mortality after living donor liver transplantation.

Background. Female liver to male recipient is a well-accepted risk factor for graft loss in cadaveric liver transplantation. However, gender matching is infeasible because of an insufficient number of available donors. No studies have been performed on the role of gender in the field of living donor liver transplantation. This report investigates the effect of gender mismatch on the outcome of living donor liver transplantation. Methods. A total of 335 patients and donors were classified into four groups according to the following gender combinations: male donor to male recipient group (n=104), male donor to female recipient group (n=120), female donor to male recipient (FM) group (n=59), and female donor to female recipient group (n=52). Patient and graft survival were compared among the groups. We performed a multivariable analysis to identify the factors associated with patient mortality. Results. The 1-, 3-, 5-, and 10-year patient survival rates in the FM group were 80.6%, 66.8%, 61.8%, and 47.7%, respectively. The FM group showed significantly shorter patient survival compared with the other three groups. Independent risk factors for patient mortality were: FM group (P=0.006), pretransplant diabetes mellitus (P=0.001), and a model for end-stage liver disease score more than or equal to 20 (P=0.004). Conclusions. Male recipients of transplants from female donors, pretransplant diabetes mellitus, and a model for end-stage liver disease score more than or equal to 20 have poor survival rates.