Masashi Utsumi

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.

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.

Preventive effect of omental flap in pancreaticoduodenectomy against postoperative pseudoaneurysm formation.

BACKGROUND/AIMS An omental flap covering the splanchnic vessels might reduce postoperative intraabdominal hemorrhage after pancreaticoduodenectomy. However, the efficiency of such a procedure remains to be verified. The purpose of this study was to determine the effect of omental flap placement in pancreaticoduodenectomy on the incidence of postoperative pseudoaneurysms. METHODOLOGY Of 229 consecutive patients who underwent pancreaticoduodenectomy, the most recent 157 patients received the omental flap, while the initial 72 patients had no omental flap placement. Various preoperative factors were considered in the evaluation (age, gender, body mass index, primary disease and concurrent disease), as well as operative factors (operation time, blood loss, operative procedures, pancreatic texture, size of pancreatic duct and surgeons experience). RESULTS Eighty-one patients (35.4%) developed pancreatic fistula. Nine patients (3.9%) developed postoperative pseudoaneurysm. Among the patients with pancreatic fistula, those without omental flap developed pseudoaneurysms more frequently (21.7%) than those with omental flap placement (5.2%). Multivariate analysis identified pancreatic fistula, no use of omental flap and hypertension, in that order, as predisposing factors for a pseudoaneurysm. The omental flap significantly prevented pseudoaneurysms (p=0.021; OR=0.151; 95% CI, 0.030-0.751). CONCLUSIONS Omental flap placement over splanchnic vessels could be a feasible and efficient surgical procedure to prevent postoperative pseudoaneurysms following pancreaticoduodenectomy.

CD14 upregulation as a distinct feature of non-alcoholic fatty liver disease after pancreatoduodenectomy

AIM To investigate the pathogenesis of non-alcoholic fatty liver disease (NAFLD) after pancreatoduodenectomy (PD). METHODS A cohort of 82 patients who underwent PD at Okayama University Hospital between 2003 and 2009 was enrolled and the clinicopathological features were compared between patients with and without NAFLD after PD. Computed tomography (CT) images were evaluated every 6 mo after PD for follow-up. Hepatic steatosis was diagnosed on CT when hepatic attenuation values were 40 Hounsfield units. Liver biopsy was performed for 4 of 30 patients with NAFLD after PD who consented to undergo biopsies. To compare NAFLD after PD with NAFLD associated with metabolic syndrome, liver samples were obtained from 10 patients with NAFLD associated with metabolic syndrome [fatty liver, n = 5; non-alcoholic steatohepatitis (NASH), n = 5] by percutaneous ultrasonography-guided liver biopsy. Double-fluorescence immunohistochemistry was applied to examine CD14 expression as a marker of lipopolysaccharide (LPS)-sensitized macrophage cells (Kupffer cells) in liver biopsy specimens. RESULTS The incidence of postoperative NAFLD was 36.6% (30/82). Univariate analysis identified cancer of the pancreatic head, sex, diameter of the main pancreatic duct, and dissection of the nerve plexus as factors associated with the development of NAFLD after PD. Those patients who developed NAFLD after PD demonstrated significantly decreased levels of serum albumin, total protein, cholesterol and triglycerides compared to patients without NAFLD after PD, but no glucose intolerance or insulin resistance. Liver biopsy was performed in four patients with NAFLD after PD. All four patients showed moderate-to-severe steatosis and NASH was diagnosed in two. Numbers of cells positive for CD68 (a marker of Kupffer cells) and CD14 (a marker of LPS-sensitized Kupffer cells) were counted in all biopsy specimens. The number of CD68+ cells in specimens of NAFLD after PD was significantly increased from that in specimens of NAFLD associated with metabolic syndrome specimens, which indicated the presence of significantly more Kupffer cells in NAFLD after PD than in NAFLD associated with metabolic syndrome. Similarly, more CD14+ cells, namely, LPS-sensitized Kupffer cells, were observed in NAFLD after PD than in NAFLD associated with metabolic syndrome. Regarding NASH, more CD68+ cells and CD14+ cells were observed in NASH after PD specimens than in NASH associated with metabolic syndrome. This showed that more Kupffer cells and more LPS-sensitized Kupffer cells were present in NASH after PD than in NASH associated with metabolic syndrome. These observations suggest that after PD, Kupffer cells and LPS-sensitized Kupffer cells were significantly upregulated, not only in NASH, but also in simple fatty liver. CONCLUSION NAFLD after PD is characterized by both malnutrition and the up-regulation of CD14 on Kupffer cells. Gut-derived endotoxin appears central to the development of NAFLD after PD.

Anti–high mobility group box 1 monoclonal antibody improves ischemia/reperfusion injury and mode of liver regeneration after partial hepatectomy

BACKGROUND The purpose of this study is to determine the effects of anti-high mobility group box 1 (HMGB1) monoclonal antibody (mAb) on ischemia/reperfusion injury (IRI) and the mode of liver regeneration. METHODS Rats underwent 70% hepatectomy with IRI caused by clamping the hepatoduodenal ligament for 20 minutes, followed by the administration of anti-HMGB1 mAb immediately before declamping the hepatoduodenal ligament. Five animals were used for each time point. We then evaluated IRI, regeneration parameters and the status of HMGB1 in remnant livers. RESULTS The anti-HMGB1 mAb significantly ameliorated the degree of IRI in the remnant livers in association with the downregulation of HMGB1 protein. The ratio of Ki67-positive hepatocytes at 48 hours after 70% hepatectomy was significantly improved. Mean hepatocyte size was significantly reduced and cyclin-dependent kinase inhibitor 1 expression was significantly attenuated. CONCLUSIONS Anti-HMGB1 mAb ameliorated IRI and improved the mode of liver regeneration after IRI followed by 70% hepatectomy in rats.

Frequency of regulatory T-cell and hepatitis C viral antigen-specific immune response in recurrent hepatitis C after liver transplantation☆

INTRODUCTION Regulatory T (Treg) and type 1 regulatory T (Tr1) cells facilitate hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT). However, their frequencies and effects on HCV-specific immune responses have not been well investigated. METHODS We determined Treg and Tr1 frequencies in OLT patients with hepatitis C and assessed their associations with HCV-specific T cell responses. These patients comprised the following groups: an early post-transplantation group (n=14); an OLT-chronic active hepatitis C group (n=14) with active hepatitis C (alanine aminotransferase of>upper limit of normal/positive for HCV-RNA); an OLT-persistently normal alanine aminotransferase group (n=12) without active hepatitis C (not interferon/positive for HCV-RNA); and an OLT-sustained viral response group (n=6) with sustained viral responses using interferon treatment (negative for HCV-RNA). The frequencies of HCV-specific CD4+ T cells that secreted interferon-γ were determined by enzyme-linked immunosorbent spot assay (except for the OLT early group). RESULTS Treg and Tr1 frequencies were low during the early post-transplantation period. OLT patients with sustained viral responses had lower Treg frequencies than those with chronic hepatitis C, whereas Tr1 frequencies were significantly reduced in OLT patients with persistently normal alanine aminotransferase levels compared to those with chronic hepatitis C (p<0.05). Treg frequencies positively correlated with HCV NS3 antigen-specific interferon-γ responses, which corresponded to HCV clearance. CONCLUSIONS Increased Treg frequencies and reduced HCV-NS3 antigen-specific responses recovered after viral eradication in post-OLT chronic hepatitis C patients. Reduced Tr1 frequencies were associated with hepatitis activity control, which may facilitate controlling chronic hepatitis C in patients after OLT.

First successful case of simultaneous liver and kidney transplantation for patients with chronic liver and renal failure in Japan.

Establishment of a preferential liver allocation rule for simultaneous liver and kidney transplantation (SLK) and revisions of laws regarding organ transplants from deceased donors have paved the way for SLK in Japan. Very few cases of SLK have been attempted in Japan, and no such recipients have survived for longer than 40 days. The present report describes a case of a 50‐year‐old woman who had undergone living donor liver transplantation at the age of 38 years for management of post‐partum liver failure. After the first transplant surgery, she developed hepatic vein stenosis and severe hypersplenism requiring splenectomy. She was then initiated on hemodialysis (HD) due to the deterioration of renal function after insertion of a hepatic vein stent. She was listed as a candidate for SLK in 2011 because she required frequent plasma exchange for hepatic coma. When her Model for End‐stage Liver Disease score reached 46, the new liver was donated 46 days after registration. The reduced trisegment liver and the kidney grafts were simultaneously transplanted under veno‐venous bypass and intraoperative HD. The hepatic artery was reconstructed prior to portal reconstruction in order to shorten anhepatic time. Although she developed subcapsular bleeding caused by hepatic contusion on the next day, subsequent hemostasis was obtained by transcatheter embolization. Thereafter, her recovery was uneventful, except for mild rejection and renal tubular acidosis of the kidney graft. This case highlights the need to establish Japanese criteria for SLK.

Bloodless Donor Hepatectomy in Living Donor Liver Transplantation: Counterclockwise Liver Rotation and Early Hanging Maneuver

IntroductionLiving donor hepatectomy is important because it determines donor safety and recipient outcome.MethodsWe applied the counter-clockwise liver rotation method and the hanging maneuver from an early stage in two major types of living donor operations.ResultTwenty-eight living donors underwent these procedures with significant reduction in blood loss. Right hepatectomy was performed in 14 of the donors and extended left hepatectomy was performed in the other 14 donors.ConclusionThese techniques facilitate safe and bloodless living donor hepatectomy.

Surgical rationalization of living donor liver transplantation by abolition of hepatic artery reconstruction under a fixed microscope

The small diameter of the hepatic artery is one of the complexities of living donor liver transplantation (LDLT). We analyzed whether the direct suture technique using surgical loupes can simplify the operative process for LDLT compared with fixed microscopic reconstruction. We applied the direct technique to rationalize the operative process and abolished routine microsurgery from 2004. Two hundred and nine LDLT with a postoperative period over 34 months were carried out from 1996 to 2008. The patients were divided into two groups: the micro group (children: 20, adults: 72) and the non‐micro group (children: 12, adults: 97). Running anastomosis was undertaken in the non‐micro group. The anastomotic size of the children was significantly smaller than that of the adults, but larger than 2 mm (2.38 ± 0.4 vs. 2.7 ± 0.47 mm, p = 0.0005). By appropriate choice of the proximal artery, direct anastomosis is possible even in children. Early complications occurred in seven cases in the micro group, but none occurred in the non‐micro group (p < 0.05). Significant reductions were observed in operation time (p < 0.0001), blood loss (p < 0.05), and hospital stay (p < 0.01) in the non‐micro group. Non‐microscopic anastomosis is useful for the rationalization of LDLT.