Hiroyoshi Matsukawa

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.

Short-term high-dose followed by long-term low-dose hepatitis B immunoglobulin and lamivudine therapy prevented recurrent hepatitis B after liver transplantation.

Hepatitis B immunoglobulin (HBIg) and lamivudine combination has been accepted as the best way to control hepatitis B recurrence after liver transplantation. However, the optimal dose of HBIg and the target titer of hepatitis B surface antibody (HBsAb) remain unclear. We report our satisfactory experience with high-dose HBIg in the early period followed by low-dose HBIg with lamivudine. Subjects comprised five patients with fulminant hepatitis (FH) and 18 patients with liver cirrhosis (LC) who underwent liver transplantation. HBIg at a dosage of 200 IU/kg per day was administered for one week postoperatively. Thereafter, HBIg was administered only for HBsAb titer <100 IU/L. After six months, HBIg was withdrawn in FH and administered in LC only for HBsAb titer <10 IU/L. Lamivudine was administered to two FH and all LC cases. Although two patients with LC showed transient hepatitis B surface antigen (HBsAg) recurrence, all patients remained HBsAg-negative at the final follow-up date. This method allows reliable and cost-effective control of hepatitis B recurrence.

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.

Mechanism of impaired regeneration of fatty liver in mouse partial hepatectomy model

Background and Aim:  The mechanism of injury in steatotic liver under pathological conditions been extensively examined. However, the mechanism of an impaired regeneration is still not well understood. The aim of this study was to analyze the mechanism of impaired regeneration of steatotic liver after partial hepatectomy (PH).

Milk-based test as a preventive method for chylous ascites following pancreatic resection.

Background/Purpose: The incidence and natural history of postoperative chylous ascites are not well understood. This complication causes malnutrition and prolonged hospital stay. We investigated our institution’s experience involving chylous ascites, especially following pancreatectomy. Additionally, we designed a new intraoperative method dubbed the ‘milk test’ for preventing chylous ascites. Methods: Five cases of chylous ascites following pancreatectomy from April 2001 through March 2004 were studied retrospectively. The milk test was carried out prospectively. Such rates as positivity and incidence of ascites were examined. Results: Of 65 cases (40 pancreatoduodenectomy; 25 distal pancreatectomy), 5 (7.7%) developed chylous ascites following pancreatic resection. All cases underwent octreotide and total parenteral nutrition treatment. From April 2004 through March 2009, the milk test was used in 104 cases. Surgical procedures comprised pancreatoduodenectomy (n = 78) and distal pancreatectomy (n = 23). Of these cases, 23 (22.1%) tested positive. No significant difference in positive rates was observed between the procedures and diseases. After initiation of the milk test, chylous ascites incidence decreased from 7.7 to 2.9%. Conclusions: For chylous ascites, octreotide and total parenteral nutrition treatments are useful. However, the milk test was found to be a safe and effective method for prevention of chylous ascites following pancreatectomy.

Analysis of host response to hepatectomy by simultaneous measurement of cytokines in the portal vein, caval vein and radial artery.

We analysed the host response to hepatectomy by simultaneous measurement of various cytokines and their antagonists in the portal vein, caval vein and radial artery in 10 patients with hepatocellular carcinoma. Concentrations of tumour necrosis factor-α (TNF), interleukin (IL) 1β, IL-2, IL-6, IL-10, soluble TNF receptor type I (sTNF-R), soluble IL-2 receptor (sIL-2R), IL-1 receptor antagonist (IL-1ra), soluble CD14 (sCD14) and endotoxin were determined just before and 1 h after hepatectomy. The values of IL-6, sTNF-R and IL-1ra were significantly increased after hepatectomy at each sampling site. In contrast, the levels of sIL-2R and sCD14 after hepatectomy were significantly decreased, and the levels of IL-1β, IL-2 and IL-10 were below the detection limits. Differences in cytokine concentrations between sampling sites revealed that the surgical stress of hepatectomy induced significant IL-1ra production in the liver and sTNF-R and IL-6 production in the lungs. These results suggest that hepatic resection is followed by the production of cytokine antagonists, such as IL-1ra, sTNF-R and IL-6, which could represent an important regulatory mechanism against surgical stress.

The analysis of the usefulness of laparoscopic microwave coagulation therapy for hepatocellular carcinoma in patients with poor hepatic reserve by serial measurements of IL-6, cytokine antagonists, and C-reactive protein

Background: Little is known about the effectiveness of laparoscopic microwave coagulation therapy (L-MCT) for hepatocellular carcinoma (HCC) in patients with liver cirrhosis and poor hepatic reserve. Here, we analyzed the usefulness of laparoscopic MCT by comparing the serum levels of IL-6, cytokine antagonists, and C-reactive protein (CRP) following L-MCT with those following MCT with the open method (O-MCT). Methods: Sixteen patients with hepatocellular carcinoma (HCC) were separated into L-MCT and O-MCT groups according to ICGR15 (ICGR15 30%<:L-MCT, 30%> :O-MCT). Nine patients with poorer hepatic reserve received L-MCT, while seven patients with relatively good hepatic reserve received O-MCT. Serum levels of cytokine antagonists (interleukin-6, IL-6; interleukin-1 receptor antagonist, IL-1ra; soluble tumor necrosis factor receptor type I, sTNF-R55) and C-reactive protein (CRP) were simultaneously measured on serial postoperative days (POD) by immunoassay. Results: Postoperative serum levels of IL-6, IL-1ra, and CRP were significantly elevated on POD-1 and returned to the preoperative levels on POD-7 in both L-MCT and O-MCT groups. In contrast, no significant elevation of sTNF-R55 was found during the period in both groups. In addition, no statistical differences were found in the levels of IL-6, IL-1ra, sTNF-R, and CRP between the groups, except that the level of IL-6 on POD-1 in L-MCT group was significantly lower than that in the O-MCT group. Conclusion: These results suggested that the surgical stress by L-MCT in patients with poorer hepatic reserve were almost equal to that by O-MCT in patients with relatively good hepatic reserve, indicating the usefulness of L-MCT for HCC patients with poorer hepatic reserve. We recommend the laparoscopic approach for future patients with the criterion that ICGR15 is over 30%.