Yuzo Umeda

Effects of prophylactic splenic artery modulation on portal overperfusion and liver regeneration in small-for-size graft.

Background. The small-for-size (SFS) syndrome is caused by excessive portal inflow into a small-sized liver graft. Various approaches for portal decompression have been used, but details of their impact on liver regeneration in SFS graft remain unclear. We examined the effect of prophylactic splenic artery modulation (SAM). Methods. We conducted a retrospective cohort study. The study group was 39 consecutive adult-to-adult living liver transplantation recipients, with a graft-to-recipient body weight ratio of less than 0.8. Patients were assigned into the non-SAM group (n=18, without any portal inflow attenuation) or SAM group (n=21, preoperative embolization in 15 patients and intraoperative ligation in 6 patients). Hepatic hemodynamics, graft function, liver regeneration, and outcome were evaluated. Results. In the SAM group, the excessive portal flow was significantly reduced (P<0.01) and the effect of embolization on portal decompression was equivalent to that of ligation. In the acute postoperative phase, serum transaminases, interleukin-6, and tumor necrosis factor-&agr;, were lower in the SAM group than in non-SAM group. In both groups, a negative correlation was observed between graft-to-recipient body weight ratio and liver regeneration rate at 2 weeks after living donor liver transplantation. Splenic artery modulation was advantageous for liver regeneration, and significantly improved clinical features, hyperbilirubinemia, and prolonged ascites. Small-for-size syndrome occurred in five patients of the non-SAM group, and only one of SAM group (P=0.038). Conclusion. In SFS graft with severe portal hypertension, prophylactic splenic embolization/ligation seems to relieve portal overperfusion injury and contributes in improvement of posttransplantation prognosis through liver regeneration.

Risk factors for major morbidity after liver resection for hepatocellular carcinoma

Bile leakage, and organ and/or space surgical‐site infection (SSI) are common causes of major morbidity after partial hepatectomy for hepatocellular carcinoma (HCC). The purpose of this study was to analyse risk factors for major morbidity and to explore strategies for its reduction after partial hepatectomy for HCC.

Risk factors for acute renal injury in living donor liver transplantation: evaluation of the RIFLE criteria.

Acute renal injury (ARI) is a serious complication after liver transplantation. This study investigated the usefulness of the RIFLE criteria in living donor liver transplantation (LDLT) and the prognostic impact of ARI after LDLT. We analyzed 200 consecutive adult LDLT patients, categorized as risk (R), injury (I), or failure (F), according to the RIFLE criteria. ARI occurred in 60.5% of patients: R‐class, 23.5%; I‐class, 21%; and F‐class, 16%. Four patients in Group‐A (normal renal function and R‐class) and 26 patients in Group‐B (severe ARI: I‐ and F‐class) required renal replacement therapy (P < 0.001). Mild ARI did not affect postoperative prognosis regarding hospital mortality rate in Group A (3.2%), which was superior to that in Group B (15.8%; P = 0.0015). Fourteen patients in Group B developed chronic kidney disease (KDIGO stage 3/4). The 1‐, 5‐ and 10‐year survival rates were 96.7%, 90.6%, and 88.1% for Group A and 71.1%, 65.9%, and 59.3% for Group B, respectively (P < 0.0001). Multivariate analysis revealed risk factors for severe ARI as MELD ≥20 [odds ratio (OR) 2.9], small‐for‐size graft (GW/RBW <0.7%; OR 3.1), blood loss/body weight >55 ml/kg (OR 3.7), overexposure to calcineurin inhibitor (OR 2.5), and preoperative diabetes mellitus (OR 3.2). The RIFLE criteria offer a useful predictive tool after LDLT. Severe ARI, defined beyond class‐I, could have negative prognostic impact in the acute and late postoperative phases. Perioperative treatment strategies should be designed and balanced based on the risk factors for the further improvement of transplant prognosis.

Preoperative proximal splenic artery embolization: a safe and efficacious portal decompression technique that improves the outcome of live donor liver transplantation.

Terminal liver cirrhosis is associated with marked severe portal hypertension, which increases the risk of intraoperative hemorrhage and graft hyper‐perfusion, especially, in small‐for‐size graft. In cases with developed collateral vessels, we often face difficulties in perihepatic dissection with blood stanching against bleeding during recipient hepatectomy. For aseptic preoperative portal decompression, we established the proximal splenic artery embolization (PSAE) technique. Sixty adult living donor liver transplantation recipients with viral/alcoholic hepatic failure were divided into two groups; PSAE group (n = 30) and non‐PSAE (n = 30). In the PSAE group, the splenic artery was embolized proximal to the splenic hilum 12–18 h before surgery. PSAE enabled shortening of operating time, reduced blood loss, led to less need for transfusion, and significantly reduced the post‐transplant portal venous velocity and ascites. PSAE was not associated with complications, e.g., splenic infarction, abscess, or portal thrombosis. Six of the non‐PSAE patients required additional surgical intervention to resolve postoperative hemorrhage and three patients required secondary PSAE for arterial‐steal‐syndrome. The hospital mortality rate of PSAE patients (3.3%) was significantly better than that of the PSAE group (13.3%, P < 0.05). Preoperative noninvasive PSAE makes more efficient use of portal decompression; thus, it can potentially contribute to improvement of outcome.

The outcome of living donor liver transplantation with prior spontaneous large portasystemic shunts

We investigated the outcome of living donor liver transplantation (LDLT) with prior spontaneous large portasystemic shunts. Thirty‐three patients of 155 patients (21.2%) undergoing LDLT had spontaneous large portasystemic shunts. Portal venous hemodynamics, surgical procedures for shunts, and morbidity and mortality rates were investigated in three types of shunts: splenorenal shunt (SRS group; n = 11), shunt derived from coronary vein (CVS group; n = 6) and umbilical vein shunt (UVS group; n = 15). The two groups of patients (SRS/CVS) received prophylactic surgical repair of shunts during LDLT except for one patient in the SRS group. The flow direction of main portal vein and grade of steal of superior mesenteric vein flow by shunt were significantly different among three groups. No significant differences were observed among three groups in operative parameters, hospitalization and morbidity except for postoperative portal complication. There was no significant difference in the actuarial survival rate among three groups of SRS, CVS and UVS (81.8% vs. 83.3% vs. 86.6% at 1 year respectively). In the SRS group, two patients had postoperative steal of graft portal venous flow by residual SRS that needed further treatment. The outcome of LDLT with prior spontaneous large portasystemic shunts is satisfactory, despite the complexity of the transplant procedures.

Complications of Arterial Reconstruction in Living Donor Liver Transplantation: A Single-Center Experience

PurposeMicrosurgical reconstruction of the fine hepatic arteries (HA) reduces the chance of complications in living donor liver transplantation (LDLT). We reviewed HA reconstructions and analyzed their complications and treatment in a single center.MethodsBetween August 1996 and September 2004, we performed LDLT on 71 adults and 19 children. Patients received a lateral segment graft (n = 16), a left lobe graft (n = 11), an extended left lobe graft (n = 12), or a right lobe graft (n = 51).ResultsHepatic artery reconstruction was performed by end-to-end anastomosis under an operating microscope in all except five adults who received right lobe grafts with loupe magnification. Arterial complications developed in 5 (5.6%) of the 90 patients. Three patients required reanastomosis during their primary operation because of HA thrombosis, anastomotic kinking, and stenosis, respectively. There were three postoperative complications: an anastomotic stenosis, revised by percutaneous transluminal angioplasty; rupture of an HA pseudoaneurysm, treated by embolization; and anastomotic kinking, revised by reanastomosis. The patient with the pseudoaneurysm died of arterial complications. Multivariate analysis of cases before (4/13, 30.8%) and after 2000 (1/77, 1.3%) revealed that surgical experience was the only significant factor in reducing the incidence of HA complications (P = 0.007).ConclusionCase number-dependent anastomotic reliability using microsurgical techniques is important for safer arterial reconstruction.

The Impact of Donor Age on the Outcome of Adult Living Donor Liver Transplantation

Background. The negative effects of increased donor age on liver transplantation became evident in deceased donor liver transplantation. In living donor liver transplantation (LDLT), the details remain unclear. Methods. Initially, 137 adult LDLT recipients from August 1996 to May 2005 were divided into two groups (donors<50 years of age: n=99, donors≥50 years of age: n=38) for the retrospective study. Then, 24 recipients who received LDLT from June 2005 to July 2006 were divided into two groups: group 1 (donors<50 years of age, n=14) and group 2 (donors≥50 years of age, n=10) and enrolled in the prospective study to analyze their clinical course and prognostic factors in the aged graft. Results. In the retrospective study, the younger donor group had significantly better survival than that of the aged donor group (P=0.015, Log rank test). In the prospective study, the postoperative graft functions showed that the serum total bilirubin levels were significantly lower in group 1 (P<0.02, by ANOVA analysis). The phosphorylated-Signal Transducer and Activator of Transcription3 expression at 4 hr after reperfusion (RT2) in group 2 was significantly lower than that in group 1. At RT2, the expressions were up-regulated in group 1, but were down-regulated in group 2. The serum 8-hydroxydeoxyguanosine value became significantly higher in group 1 two weeks after LDLT. Conclusions. In the near term, Signal Transducer and Activator of Transcription3 gene induction during cold preservation may be of great use in improving the outcome of aged grafts in LDLT.

Intractable Bile Leakage after Hepatectomy for Hepatocellular Carcinoma in 359 Recent Cases

Background/Aims: Bile leakage is still a common cause of major morbidity after hepatectomy for hepatocellular carcinoma (HCC). The purpose of this study was to identify characteristics and risk factors for intractable bile leakage after hepatectomy for HCC. Methods: Risk factors for bile leakage were analyzed in 359 patients who underwent hepatectomy for HCC between 2001 and 2010. The causes, management and outcomes of intractable bile leakage which needed endoscopic therapy or percutaneous transhepatic biliary drainage were investigated. Results: A total of 296 patients (82.5%) underwent an anatomic hepatectomy, and a repeat hepatectomy was carried out in 59 patients (16.4%). The prevalence of bile leakage was 12.8%, and 8 patients had intractable bile leakage. An operative time ≥300 min was an independent risk factor for bile leakage after hepatectomy for HCC. The main causes of intractable bile leakage were a latent stricture of the biliary anatomy caused by previous treatments for HCC and intraoperative injury of the hepatic duct related to repeat hepatectomy. Conclusion: To help prevent intractable bile leakage, a preoperative assessment of the biliary anatomy and surgical procedures to decrease the incidence of major bile leakage should be considered for selected patients with a high risk for intractable bile leakage.

Phase II clinical trial of peptide cocktail therapy for patients with advanced pancreatic cancer: VENUS-PC study

We previously conducted a phase I clinical trial combining the HLA‐A*2402‐restricted KIF20A‐derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single‐armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine. Chemotherapy naïve PC patients were enrolled to evaluate primarily the 1‐year survival rate, and secondarily overall survival (OS), progression free survival (PFS), response rate (RR), disease control rate (DCR) and the peptide‐specific immune responses. All enrolled patients received therapy without the HLA‐A information, and the HLA genotypes were used for classification of the patients. Between June 2012 and May 2013, a total of 68 patients were enrolled. No severe systemic adverse effects of Grade 3 or higher related to these three peptides were observed. The 1‐year survival rates between the HLA‐A*2402‐matched and ‐unmatched groups were not significantly different. In the HLA‐A*2402 matched group, patients showing peptide‐specific CTL induction for KIF20A or VEGFR1 showed a better prognosis compared to those without such induction (P = 0.023, P = 0.009, respectively). In the HLA‐A*2402‐matched group, the patients who showed a strong injection site reaction had a better survival rate (P = 0.017) compared to those with a weak or no injection site reaction. This phase II study demonstrated that this therapeutic peptide cocktail might be effective in patients who demonstrate peptide‐specific immune reactions although predictive biomarkers are needed for patient selection in its further clinical application.

Aggressive combined resection of hepatic inferior vena cava, with replacement by a ringed expanded polytetrafluoroethylene graft, in living-donor liver transplantation for hepatocellular carcinoma beyond the Milan criteria

Background/purposeWe present the cases of two patients with hepatocellular carcinoma (HCC) beyond the Milan criteria (MC) who underwent living-donor liver transplantation (LDLT) combined with aggressive hepatic venacaval resection and replacement of the hepatic inferior vena cava (IVC) by an artificial vascular graft. The aim of the resection and replacement of the hepatic IVC was to resect completely a latent cancer adjacent to the hepatic IVC and to avoid micrometastasis via the hepatic veins during increased manipulation of the native liver with HCC.MethodsFirst, the hepatic hilus was dissected and the infrahepatic IVC was encircled. After minimum mobilization of the liver, the common orifice of the middle and left hepatic veins and suprahepatic IVC was encircled. Venovenous bypass (VVB) was started to stabilize systemic hemodynamics. After cross-clamping of the infrahepatic and suprahepatic IVC, the IVC was divided at the site just below the confluence of the common orifice of the middle and left hepatic veins and its infrahepatic site. Then, all retroperitoneal attachments of the right lobe were dissected and the native liver was resected with the retrohepatic IVC. The IVC was replaced by a ringed expanded polytetrafluoroethylene (e-PTFE) graft. Infrahepatic venous recirculation ended the VVB. An extended left-lobe graft was implanted. The e-PTFE grafts were covered with the greater omentum to avoid infection.ResultsThe operations were completed safely. The postoperative courses were free of complications related to the reconstruction of the hepatic IVC. One patient developed recurrence in the left adrenal gland.ConclusionLDLT combined with hepatic venacaval resection and replacement by an e-PTFE graft for HCC beyond the MC could be safe and feasible under VVB. Further studies are needed to confirm to what extent this procedure could prevent post-transplant recurrence in HCC beyond the MC.