Koji Natsuda

Hybrid procedure in living donor liver transplantation.

BACKGROUND We have previously reported a hybrid procedure that uses a combination of laparoscopic mobilization of the liver and subsequent hepatectomy under direct vision in living donor liver transplantation (LDLT). We present the details of this hybrid procedure and the outcomes of the procedure. METHODS Between January 1997 and August 2014, 204 LDLTs were performed at Nagasaki University Hospital. Among them, 67 recent donors underwent hybrid donor hepatectomy. Forty-one donors underwent left hemihepatectomy, 25 underwent right hemihepatectomy, and 1 underwent posterior sectionectomy. First, an 8-cm subxiphoid midline incision was made; laparoscopic mobilization of the liver was then achieved with a hand-assist through the midline incision under the pneumoperitoneum. Thereafter, the incision was extended up to 12 cm for the right lobe and posterior sector graft and 10 cm left lobe graft procurement. Under direct vision, parenchymal transection was performed by means of the liver-hanging maneuver. The hybrid procedure for LDLT recipients was indicated only for selected cases with atrophic liver cirrhosis without a history of upper abdominal surgery, significant retroperitoneal collateral vessels, or hypertrophic change of the liver (n = 29). For total hepatectomy and splenectomy, the midline incision was sufficiently extended. RESULTS All of the hybrid donor hepatectomies were completed without an extra subcostal incision. No significant differences were observed in the blood loss or length of the operation compared with conventional open procedures. All of the donors have returned to their preoperative activity level, with fewer wound-related complaints compared with those treated with the use of the conventional open procedure. In recipients treated with the hybrid procedure, no clinically relevant drawbacks were observed compared with the recipients treated with a regular Mercedes-Benz-type incision. CONCLUSIONS Our hybrid procedure was safely conducted with the same quality as the conventional open procedure in both LDLT donors and recipients.

Preoperative simulation with a 3-dimensional printed solid model for one-step reconstruction of multiple hepatic veins during living donor liver transplantation

Meticulous preoperative volumetry of the partial liver graft is essential for both assessing the postoperative graft function and to ensure the donor safety in the field of living donor liver transplantation (LDLT). We herein report the case of a 53-year-old patient who underwent LDLT for hepatitis C virusinfected liver cirrhosis complicated with hepatocellular carcinoma. Preoperative 3D images were obtained using a 3D image analysis system to evaluate the graft volume and possible congested volume after implantation in LDLT, which revealed that a large middle hepatic vein drained a vast area in the right lobe. The extended left graft was considered to be small for size of the recipient, with an estimated congested area of 407 ml, which was equivalent to 39% of the donor’s liver volume in the remnant right lobe. We decided to use a right lobe graft with the middle hepatic vein, because the volume was considered to be sufficient. A preoperative contrast-enhanced CT scan revealed a distance of 2 cm between the donor’s right hepatic vein and middle hepatic vein at the estimated Cantlie line. Because of the location, we planned to use autologous portal vein Y-graft interposition for the hepatic venous anastomosis. Three-dimensional printed solid models of the donor’s right lobe graft and the Y-graft from the recipient’s portal vein were also made for preoperative simulation using the Vincent program. Based on the estimation, we were able to evaluate whether to reconstruct the middle hepatic vein tributaries or anomalous hepatic veins in LDLT. The 3D solid model was effective for preoperative simulation and planning, which made it easy to imagine the reconstructed shape of the anastomosis with appropriate spatial perception.

Analysis of early relaparotomy following living donor liver transplantation

We retrospectively analyzed the causes, risk factors, and impact of early relaparotomy after adult‐to‐adult living donor liver transplantation (LDLT) on the posttransplant outcome. Adult recipients who underwent initial LDLT at our institution between August 1997 and August 2015 (n = 196) were included. Any patients who required early retransplantation were excluded. Early relaparotomy was defined as surgical treatment within 30 days after LDLT. Relaparotomy was performed 66 times in 52 recipients (a maximum of 4 times in 1 patient). The reasons for relaparotomy comprised postoperative bleeding (39.4%), vascular complications (27.3%), suspicion of abdominal sepsis or bile leakage (25.8%), and others (7.6%). A multivariate analysis revealed that previous upper abdominal surgery and prolonged operative time were independent risk factors for early relaparotomy. The overall survival rate in the relaparotomy group was worse than that in the nonrelaparotomy group (6 months, 67.3% versus 90.1%, P < 0.001; 1 year, 67.3% versus 88.6%, P < 0.001; and 5 years, 62.6% versus 70.6%, P = 0.06). The outcome of patients who underwent 2 or more relaparotomies was worse compared with patients who underwent only 1 relaparotomy. In a subgroup analysis according to the cause of initial relaparotomy, the survival rate of the postoperative bleeding group was comparable with the nonrelaparotomy group (P = 0.96). On the other hand, the survival rate of the vascular complication group was significantly worse than that of the nonrelaparotomy group (P = 0.001). Previous upper abdominal surgery is a risk factor for early relaparotomy after LDLT. A favorable longterm outcome is expected in patients who undergo early relaparotomy due to postoperative bleeding. Liver Transplantation 22 1519–1525 2016 AASLD.

A Donor Age-based and Graft Volume–based Analysis for Living Donor Liver Transplantation in Elderly Recipients

Background Given the expected increase in the number of elderly recipients, details regarding how clinical factors influence the outcome in living donor liver transplantation (LDLT) for the elderly remain unclear. We examined the survival outcomes according to the results of donor age-based and graft volume–based analyses and assessed the impact of prognostic factors on the survival after LDLT for elderly recipients. Methods The 198 adult recipients were classified into 2 groups: an elderly group (n = 70, E group; ≥ 60 years of age) and a younger group (n = 128, Y group; <60 years of age). We analyzed the prognostic factors for the survival in the E group and the survival rate for both groups at several follow-up points and conducted subgroup analyses in the E group by combining the donor age (≥50 vs <50 years) and graft weight (GW)/standard liver volume (SLV) (≥40% vs <40%). Results Donor age (hazard ratio [HR], 2.17; P = 0.062) and GW/SLV (HR, 1.80; P = 0.23) tended to have a high HR in the E group. The overall patient survival rates at 1, 3, and 5 years were 78.3%, 73.0%, and 61.0% in the E group, and 82.0%, 75.1%, and 69.2% in the Y group, respectively (P = 0.459). However, the outcomes tended to be worse in recipients of grafts from donors ≥50 years of age than in those with grafts from younger donors with GW/SLV < 40% (P = 0.048). Conclusions A worse outcome might be associated with aging of the donor, which leads to impairment of the graft function and liver regeneration. Both the graft volume and donor age should be considered when choosing grafts for LDLT in elderly patients.

The donor advocacy team: a risk management program for living organ, tissue, and cell transplant donors

AbstractBackground and PurposeAlthough the incidence of living donor death is low in Japan, statistics show one living liver donor death in more than 7000 living liver transplants. Thus, medical transplant personnel must recognize that the death of a living organ or tissue transplant donor can occur and develop an appropriate risk management program.Methods and resultsWe describe how Nagasaki University Hospital established and implemented a Donor Advocacy Team (DAT) program: a risk management program for initiation in the event of serious, persistent, or fatal impairment of an organ, tissue, or cell transplantation from a living donor.DiscussionThe purposes of the DAT program are as follows: 1.To disclose official information without delay.2.To provide physical and psychological care to the patient experiencing impairment and their family.3.To provide psychological care to the medical staff in charge of the transplant.4.To standardize the responses of the diagnosis and treatment department staff and other hospital staff.5.To minimize the damage that the whole medical transplantation system may suffer and leverage the occurrence for improvement. To address (1) and (5), actions, such as reporting and responses to the government, mass media, transplant-related societies, and organ transplant networks, have been established to ensure implementation.

The Kupffer Cell Number Affects the Outcome of Living Donor Liver Transplantation from Elderly Donors

Background There have been no previous reports how Kupffer cells affect the outcome of living donor liver transplantation (LDLT) with an elderly donor. The aim of this study was to elucidate the influence of Kupffer cells on LDLT. Methods A total of 161 adult recipients underwent LDLT. The graft survival, prognostic factors for survival, and graft failure after LDLT were examined between cases with a young donor (<50, n = 112) and an elderly donor (≥50, N = 49). The Kupffer cells, represented by CD68-positive cell in the graft, were examined in the young and elderly donors. Results In a multivariable analysis, a donor older than 50 years, sepsis, and diabetes mellitus were significant predictors of graft failure after LDLT. The CD68 in younger donors was significantly more expressed than that in elderly donors. The group with a less number of CD68-positive cells in the graft had a significantly poor survival in the elderly donor group and prognostic factor for graft failure. Conclusions The worse outcome of LDLT with elderly donors might be related to the lower number of Kupffer cells in the graft, which can lead to impaired recovery of the liver function and may predispose patients to infectious diseases after LDLT.

Up-regulated extracellular matrix components and inflammatory chemokines may impair the regeneration of cholestatic liver.

Although the healthy liver is known to have high regenerative potential, poor liver regeneration under pathological conditions remains a substantial problem. We investigated the key molecules that impair the regeneration of cholestatic liver. C57BL/6 mice were randomly subjected to partial hepatectomy and bile duct ligation (PH+BDL group, n = 16), partial hepatectomy only (PH group, n = 16), or sham operation (Sham group, n = 16). The liver sizes and histological findings were similar in the PH and sham groups 14 days after operation. However, compared with those in the sham group, the livers in mice in the PH+BDL group had a smaller size, a lower cell proliferative activity, and more fibrotic tissue 14 days after the operation, suggesting the insufficient regeneration of the cholestatic liver. Pathway-focused array analysis showed that many genes were up- or down-regulated over 1.5-fold in both PH+BDL and PH groups at 1, 3, 7, and 14 days after treatment. Interestingly, more genes that were functionally related to the extracellular matrix and inflammatory chemokines were found in the PH+BDL group than in the PH group at 7 and 14 days after treatment. Our data suggest that up-regulated extracellular matrix components and inflammatory chemokines may impair the regeneration of cholestatic liver.

The first case of deceased donor liver transplantation for a patient with end-stage liver cirrhosis due to human immunodeficiency virus and hepatitis C virus coinfection in Japan

We previously reported that progression of liver cirrhosis is quicker and survival is dismal in patients with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection, especially when acquired in childhood through contaminated blood products. Recently, we performed the first deceased donor liver transplantation (DDLT) for an HIV/HCV-coinfected hemophilic patient in Japan. A 40-year-old man was referred to our hospital for liver transplantation. Regular DDLT was performed using the piggyback technique with a full-sized liver graft. Cold ischemia time was 465 min, and the graft liver weighed 1,590 g. The antiretroviral therapy (ART) was switched from darunavir/ritonavir to raltegravir before the transplant for flexible usage of calcineurin inhibitors postoperatively; tenofovir was used as the baseline treatment. The postoperative course was uneventful, and the patient was discharged home on day 43. He started receiving anti-HCV treatment on day 110 with pegylated interferon, ribavirin, and simeprevir after the DDLT. Herein, we report the first case of DDLT in Japan. Meticulous management of ART and clotting factors could lead to the success of DDLT.

Standardized hybrid living donor hemihepatectomy in adult‐to‐adult living donor liver transplantation

The aim of this study was to analyze the outcomes of the most updated version and largest group of our standardized hybrid (laparoscopic mobilization and hepatectomy through midline incision) living donor (LD) hemihepatectomy compared with those from a conventional laparotomy in adult‐to‐adult living donor liver transplantation (LDLT). Of 237 adult‐to‐adult LDLTs from August 1997 to March 2017, 110 LDs underwent the hybrid procedure. Preoperative and operative factors were analyzed and compared with conventional laparotomy (n = 126). The median duration of laparoscopic usage was 26 minutes in the hybrid group. Although there was improvement in applying this procedure over time from the beginning of the series of cases studied, blood loss and operative duration were still smaller and shorter in the hybrid group. There was no significant difference between the groups in the incidence of postoperative complications greater than or equal to Clavien‐Dindo class III. There was no difference in recipient outcome between the groups. Our standardized procedure of hybrid LD hepatectomy is applicable and safe for all types of LD hepatectomies, and it enables the benefit of both the laparoscopic and the open approach in a transplant center without a laparoscopic expert. Liver Transplantation 24 363–368 2018 AASLD.

Aspartate transaminase–platelet ratio and Fibrosis-4 indices as effective markers for monitoring esophageal varices in HIV/hepatitis C virus co-infected patients due to contaminated blood products for hemophilia

We examined the feasibility of the aspartate transaminase (AST)–platelet ratio index (APRI) and Fibrosis‐4 (FIB4) score, which are well‐established markers for liver fibrosis, as indicators for monitoring esophageal varices in patients who were co‐infected with HIV and hepatitis C virus (HCV) due to contaminated blood products for hemophilia in Japan.