S. Sekiguchi

Risks of donation and quality of donors’ life after living donor liver transplantation

The purpose is to clarify risks of donation and quality of the donors life after living‐related donor liver transplantation (LDLTx). Sixty‐eight donors were classified into four groups: lateral segment group (n = 30); left lobe group (n = 18); left lobe with the middle hepatic vein group (n = 11); right lobe group (n = 9). We investigated (i) the risks of donation, and evaluated the following: blood loss, operation time, postoperative liver function and duration of hospitalization; (ii) quality of donors’ life: donors were mailed a structured questionnaire and the Short‐Form Health Survey (SF‐36), a generic measure assessing quality of life using eight scales. The results were: (i) there were no differences in liver function and duration of hospitalization between four groups; (ii) 48 donors (71%) responded. All donors returned to normalcy. The donors did not regret their decision to donate except two cases whose recipients had died. The donors’ life was almost guaranteed regardless of the lobe we used as the graft.

Liver transplantation for severe hypoxemia caused by patent ductus venosus

The authors describe the case of a 9-year-old girl who underwent liver transplantation because she suffered from severe hypoxemia caused by patent ductus venosus (PDV). Generally, severe hypoxemia (PaO2 < 50 mm Hg in room air or < 300 mm Hg in pure oxygen) is not an indication for liver transplantation because the hypoxemia may not be improved, and may lead to a fatal outcome. PDV, which is associated with mild liver dysfunction, is not an indication for liver transplantation by itself. But in our patient, most of the mesenteric venous flow directly entered the systemic circulation through the PDV just like the portosystemic shunt, and this caused the pulmonary arteriovenous shunt and hypoxemia. Thus, the authors operated on the patient in an attempt to restore her pulmonary function. Nitric oxide (10 to 20 ppm) was added to the inhaled gas to dilate the functional pulmonary capillaries and to deliver sufficient oxygen after the transplantation. Although the patient suffered various complications after the operation, the final results were excellent.

Present Status of Pancreas Transplantation in Japan—Donation Predominantly From Marginal Donors and Modified Surgical Technique: Report of Japan Pancreas Transplantation Registry

In Japan, organ donation has been still limited because of the strict donor criteria. The aim of this study was to show the effectiveness of pancreas transplantation (PTx) by analyzing the outcomes even under poor donor conditions. Thirty-six cases of PTx (32 simultaneous pancreas and kidney transplantations [SPK], 4 pancreas after kidney transplantations) performed during the last 8 years were examined especially for donor characteristics. Mean donor age of 41.4 +/- 11.9 years was considerably older compared with that in the United States and Europe; donors aged over 40 years comprised 67% of the total. According to the criteria described by Kapur, 29 cases (81%) in our series would be considered marginal. Thus, to increase blood supply into the pancreatic head, the gastroduodenal artery (GDA) was anastomosed using donor artery to common hepatic artery or iliac Y graft. These procedures were performed in 16 of the 24 cases in which there was liver procurement. Eventually, 34 cases (94%) preserved GDA continuity. Mean total cold ischemic time of pancreatic grafts was 12 hours 15 minutes. Of 214 registrants, 17 patients on the waiting list for SPK died of diabetic complications. To date, patient survival remains 100% with a mean follow-up period of 33 months. Pancreas graft survivals at 1, 3, and 5 years posttransplantation were 92%, 80%, and 80%, respectively. In contrast, kidney survivals were 91%, 91%, and 91%, respectively. The integrity of the pancreas head and duodenum by preservation of the GDA continuity might have decreased the risk associated with the marginal donors.

Quality of Life and Problems Affecting Recipients More Than 10 Years After Living Donor Liver Transplantation

BACKGROUND We initiated living donor liver transplantation (LDLT) in 1991, allowing us to examine issues related to long-term survival. The aim of this study was to review the long-term outcomes of LDLT in children. PATIENTS AND METHODS We performed 116 LDLT from 1991 to present, including 17 recipients who survived >10 years. They were evaluated for growth, immunosuppressive therapy, complications, and quality of life (QOL). RESULTS The average age at LDLT was 5.4 years (range, 6 months to 17 years), with a present average age of 17.2 years (range, 11-28 years). At the time of LDLT, 6 recipients had growth retardation with body weights low for age by 2 standard deviations (SD). However, 4 of 6 recipients who underwent LDLT before age of 2 years caught up, reaching average heights and body weights for their ages. Among 6 recipients who were diagnosed with acute rejections by biopsy >5 years after LDLT, 5 improved after steroid pulse therapy. One recipient with a steroid-resistant acute rejection was administered deoxyspergualin after steroids. Chronic rejection was not observed in this series. One recipient has not required immunosuppressive therapy for >4 years with a good present condition. CONCLUSION The majority of LDLT recipients achieved a good QOL during long-term survival; they are pursuing normal studies.

Microsurgical Back Wall Support Suture Technique With Double Needle Sutures on Hepatic Artery Reconstruction in Living Donor Liver Transplantation

OBJECTIVES In living-donor-liver transplantation (LDLT), microsurgical reconstruction of the hepatic artery is an essential but challenging issue. Especially using a living donor graft, the hepatic artery is short, the intimal damage may be severe, and the usable vessel grafts are limited compared with cadaveric donors. Thus, sometimes it is difficult to use a conventional twist reconstruction technique in which one needs to turn over the hepatic artery. METHODS To overcome these difficulties, we began to use a back wall support suture technique. From July 1991 to June 2007, we performed 110 LDLTs. In 87 cases, we used the conventional twist technique. In the most recent 23 cases, we used a back wall support suture technique. To put it briefly, we placed 2 sutures at the deepest, most difficult points in the artery for backside support. Each stitch was placed from the inner side of the arterial wall to the outer side with double needle sutures. The subsequent sutures were placed forward on either side adjacent to the previous suture. RESULTS The total ratio of hepatic artery thrombosis (HAT) was 8.2% (9/110). In the conventional twist technique group, HAT occurred in 8 cases (9.2%). In the new technique group, it occurred in only 1 case that had an intimal dissection in the recipient artery (4.3%). Thus there was no HAT associated with the arterial anastomosis in the new technique group. CONCLUSION Our technique allows for safe intimal adaptation without turning over the artery. In conclusion, this back wall support suture technique may contribute to more satisfactory results.

Risk Factors for Hepatic Artery Thrombosis After Microsurgical Vascular Reconstruction in Liver Transplantation

OBJECTIVE In liver transplantation, microsurgical reconstruction of a hepatic artery is essential but requires challenging techniques. Especially in living-donor liver transplantation, the recipient artery is short and located deep in the abdominal cavity. Furthermore, hepatic artery thrombosis (HAT) can be a lethal complication. This study sought to uncover the risk factors for HAT after microsurgical vascular reconstruction. METHODS From 1991 to 2011, we performed 151 microsurgical vascular reconstructions, including 3 deceased-donor liver transplantations. We retrospectively investigated the cases, performing univariate and multivariate analyses to identify independent risk factors for HAT. The patients had undergone ultrasonographic examinations for HAT over the first 14 days after transplantation. RESULTS Upon univariate analysis, the risk factors identified to be associated with P < .20 were young age (P = .0484), low body weight (P = .0466), short height (P = .0128), high graft-to-recipient weight ratio (P = .0031), small liver graft volume (P = .0416), small amounts of gabexate mesilate infusion (P = .0516), and the conventional technique (without a back-wall support suture; P = .1326). A multiple logistic regression analysis identified low body weight to be the only independent risk factor for HAT. CONCLUSION On the univariate analysis, we found that using the back-wall support suture technique contributed to the reduction of HAT, whereas on multivariate analysis, the only independent risk factor for HAT was low body weight.

The Use of Recipient Superficial Femoral Vein as a Venous Graft for Portal Vein Reconstruction in Right Lobe Living Donor Liver Transplantation

In living donor liver transplantation (LDLT), portal vein thrombosis (PVT) in the recipient is frequently regarded as a contraindication. To reconstruct the PV of a right-lobe liver graft (RLG) using an interposition or jump graft from the splenomesenteric junction, various vein grafts and technical modifications have been introduced. The internal jugular, external iliac, or great saphenous veins have been utilized in such reconstructive procedures. However, the superficial femoral vein (SFV) is preferable to the autologous vein grafts in terms of caliber, wall thickness, and length. We employed the recipient SFV to reconstruct PVT among 40 adult LDLT using RLG. Thirty-three were reconstructed by single end-to-end anastomosis with the right or left recipient PV. Three patients were transplanted with a RLG using 2 separated PVs reconstructed by double anastomoses with both the right and left PVs of the recipient. The remaining 4 patients required venous grafting for portal reconstruction. We used the recipient SFV as an interposition or jump graft from the splenomesenteric junction to the graft PV. There were 2 cases of anastomotic PV stenosis; 1 in portal reconstruction without a venous graft and the other with a SFV graft. Both were treated successfully by balloon angioplasty. The recipient SFV is an excellent size match for the PV reconstruction as a long interposition or jump conduit when the venous system from the deceased donor is not available. The indication for LDLT in patients with complete PVT should be carefully decided before transplantation in terms of portal reconstruction.

The relationship between recurrences and immunosuppression on living donor liver transplantation for hepatocellular carcinoma.

OBJECTIVES Living donor liver transplantation (LDLT) offers timely transplantation for patients with hepatocellular carcinoma (HCC). If ABO-incompatible LDLT is feasible, the needs for pretransplantation treatments may be eliminated. It is known that negative impacts of immunosuppression are limited among LDLT for HCC, however, we believe that excessive immunosuppression is one of the risk factors for recurrence. We compared the impacts of immunosuppression for LDLT with hepatectomy outcomes for HCC. METHODS From 1991 to 2010, we performed 144 LDLTs including 14 patients with HCC. Seven met the Milan criteria. Immunosuppressive therapies were based on tacrolimus plus methylprednisolone plus CD25 antibody. For ABO-incompatible cases, we also used mycophenolate mofetil and rituximab. Five cases underwent strong imunosuppressive therapy (steroid pulse or rituximab) within 180 days. In addition, we performed hepatectomy for 180 HCC cases from 1997 to 2010. RESULTS Overall survival rates of the LDLT cohort and hepatectomy groups were similar, but disease-free 5-year survival rates (DFS) of the LDLT cohort were significantly better than those of the hepatectomy group (total = 54.4% versus 27.4%, within the Milan criteria cases, 71.4% versus 33.8%). Thus, the negative impact of immunosuppression on recurrence was less than the benefit of a whole liver resection. Among strongly immunosuppressed cases, 5-years DFS rates were significantly worse than among other immunosuppressed cases (20.0% versus 76.2%). Upon univariate analysis, the factors associated with HCC recurrence were alpha-fetoprotein levels and steroid doses within 180 days, but multivariate analysis did not show a predictor for recurrence. CONCLUSION Patients who are strongly immunosuppressed may have several negative impacts for recurrences. More careful indications must be selected for ABO-incompatible cases.

Recombinant Human Soluble Thrombomodulin (ART-123) Prevents Warm Ischemia-Reperfusion Injury in Liver Grafts from Non-Heart- Beating Donors

BACKGROUND Liver transplantation is an established treatment for end-stage liver disease. However, an ongoing problem worldwide concerning this treatment is the shortage of grafts. Although transplantation using grafts from non-heart-beating donors (NHBDs) is considered a promising solution, some researchers have reported that these liver grafts are associated with primary graft nonfunction and biliary complications. The purpose of this study was to establish a safe technique procuring liver grafts from marginal donors such as NHBDs. MATERIALS AND METHODS Male Wistar rats were divided into three groups: (1) the heart-beating (HB) group, whose livers were retrieved from HB donors; (2) the non-HB (NHB) group, whose livers were retrieved from NHBDs that had experienced an apnea-induced agonal condition (for this group, livers were subjected to warm ischemia for 30 minutes after cardiac arrest); and (3) the recombinant human soluble thrombomodulin (ART-123) group, whose livers were retrieved in the same manner as the NHB group but pretreated with ART-123 (1 mg/kg) at the agonal stage. The livers were reperfused for 60 minutes with oxygenated Krebs-Henseleit bicarbonate buffer after cold preservation for 6 hours. RESULTS Bile production and portal flow volume in the ART-123 group were significantly higher than those in the NHB group. Alanine aminotransferase levels in the ART-123 group were significantly lower than those in the NHB group. Histological findings showed the narrowing of sinusoidal spaces and necroses in the NHB group were more severe than those in the ART-123 group. CONCLUSIONS These results suggest that thrombomodulin may improve the viability of liver grafts from NHBDs.

A Free Radical Scavenger, Edaravone, Prevents Ischemia-Reperfusion Injury in Liver Grafts From Non–Heart-Beating Donors

BACKGROUND Due to the increase in liver transplantation, the donor shortage has become a serious problem, requiring marginal, non-heart-beating donors (NHBDs). The aims of this study were to evaluate the cytoprotective effect of edaravone, a free radical scavenger, on warm ischemia-reperfusion (I/R) injury of liver grafts from NHBDs. METHODS Rat livers were harvested from heart-beating donors (HB group) or from NHBDs undergoing cardiac arrest for 30 minutes led by thoracotomy (NHB group), and reperfused for 60 minutes with Krebs-Henseleit bicarbonate buffer after cold preservation for 6 hours. In another group (ED group), warm ischemic livers from NHBDs were reperfused with buffer containing edaravone (1 mg/L) after cold preservation. RESULTS In the ED group, portal flow volume, bile production, and energy charge were significantly ameliorated. Lipid peroxidation, elevation of hepatic enzymes, and release of tumor necrosis factor-alpha and interleukin-1 beta were significantly alleviated, compared with the NHB group. CONCLUSIONS These results suggested that edaravone has suppressive effects on warm I/R injury in liver grafts from NHBDs.