Nao Kinjo

Long‐term results of balloon‐occluded retrograde transvenous obliteration for gastric variceal bleeding and risky gastric varices: A 10‐year experience

Background and Aim:  Balloon‐occluded retrograde transvenous obliteration (B‐RTO) is a new alternative treatment for gastric varices (GVx), but the long‐term efficacy is not known. We investigated the long‐term effects of B‐RTO on rebleeding, prevention of first bleeding, mortality and occurrence of risky esophageal varices (EVx).

Construct validity for eye-hand coordination skill on a virtual reality laparoscopic surgical simulator.

BackgroundThis study was carried out to investigate whether eye-hand coordination skill on a virtual reality laparoscopic surgical simulator (the LAP Mentor) was able to differentiate among subjects with different laparoscopic experience and thus confirm its construct validity.MethodsA total of 31 surgeons, who were all right-handed, were divided into the following two groups according to their experience as an operator in laparoscopic surgery: experienced surgeons (more than 50 laparoscopic procedures) and novice surgeons (fewer than 10 laparoscopic procedures). The subjects were tested using the eye-hand coordination task of the LAP Mentor, and performance was compared between the two groups. Assessment of the laparoscopic skills was based on parameters measured by the simulator.ResultsThe experienced surgeons completed the task significantly faster than the novice surgeons. The experienced surgeons also achieved a lower number of movements (NOM), better economy of movement (EOM) and faster average speed of the left instrument than the novice surgeons, whereas there were no significant differences between the two groups for the NOM, EOM and average speed of the right instrument.ConclusionsEye-hand coordination skill of the nondominant hand, but not the dominant hand, measured using the LAP Mentor was able to differentiate between subjects with different laparoscopic experience. This study also provides evidence of construct validity for eye-hand coordination skill on the LAP Mentor.

Impact of Antithrombin III Concentrates on Portal Vein Thrombosis After Splenectomy in Patients With Liver Cirrhosis and Hypersplenism

Objective:The aim of this study was to determine the role of antithrombin III (AT-III) in portal vein thrombosis (PVT) after splenectomy in cirrhotic patients. Summary Background Data:There is no standard treatment for PVT after splenectomy in liver cirrhosis. Methods:A total of 50 consecutive cirrhotic patients who underwent laparoscopic splenectomy for hypersplenism were enrolled into this study. From January 2005 to December 2005, 25 cirrhotic patients received no prophylactic anticoagulation therapy after the operation (AT-III [−] group). From January 2006 to July 2006, 25 cirrhotic patients received prophylactic administration of AT-III concentrates (1500 U/d) on postoperative day (POD) 1, 2, and 3 (AT-III [+] group). Results:In AT-III (−) group, 9 (36.0%) patients developed PVT up to POD 7, and risk factors for PVT were identified as: low platelet counts, low AT-III activity, and increased spleen weight. Although there were no significant differences in the clinical characteristics, including the above risk factors, between the 2 groups, only 1 (4.0%) patient developed PVT on POD 30 in AT-III (+) group, and the incidence of PVT was significantly lower than in AT-III (−) group (P = 0.01). In AT-III (−) group, AT-III activity was significantly decreased from POD 1 to POD 7, as compared with the preoperative level, whereas AT-III concentrates prevented the postoperative decrease in AT-III activity. Conclusions:These results demonstrate that low AT-III activity and further decreases in this activity are associated with PVT after splenectomy in cirrhotic patients, and that treatment with AT-III concentrates is likely to prevent the development of PVT in these patients.

Risk factors for portal venous thrombosis after splenectomy in patients with cirrhosis and portal hypertension.

Portal venous thrombosis (PVT) is a potentially fatal complication following splenectomy. Its mechanisms and risk factors are poorly understood, especially in patients with cirrhosis and portal hypertension. This study investigated risk factors for PVT following splenectomy in such patients.

Technical standardization of laparoscopic splenectomy harmonized with hand‐assisted laparoscopic surgery for patients with liver cirrhosis and hypersplenism

BACKGROUND/PURPOSE The aims of this study were to standardize the techniques of laparoscopic splenectomy (LS) to improve safety in liver cirrhosis patients with portal hypertension. METHODS From 1993 to 2008, 265 cirrhotic patients underwent LS. Child-Pugh class was A in 112 patients, B in 124, and C in 29. Since January 2005, we have adopted the standardized LS including the following three points: hand-assisted laparoscopic surgery (HALS) should be performed in patients with splenomegaly (> or =1,000 mL), perisplenic collateral vessels, or Child-Pugh score 9 or more; complete division and sufficient elevation of the upper pole of the spleen should be performed before the splenic hilar division; and when surgeons feel the division of the upper pole of the spleen is too difficult, conversion to HALS should be performed. RESULTS There were no deaths related to LS in this study. After the standardization, conversion to open surgery significantly reduced from 11 (10.3%) of 106 to 3 (1.9%) of 159 patients (P < 0.05). The average operation time and blood loss significantly reduced from 259 to 234 min (P < 0.01) and from 506 to 171 g (P < 0.01), respectively. CONCLUSIONS With the technical standardization, LS becomes a feasible and safe approach in the setting of liver cirrhosis and portal hypertension.

Defective endothelial nitric oxide synthase signaling is mediated by rho‐kinase activation in rats with secondary biliary cirrhosis

In liver cirrhosis, down‐regulation of endothelial nitric oxide synthase (eNOS) has been implicated as a cause of increased intrahepatic resistance. We investigated whether Rho‐kinase activation is one of the molecular mechanisms involved in defective eNOS signaling in secondary biliary cirrhosis. Liver cirrhosis was induced by bile duct ligation (BDL). We measured mean arterial pressure (MAP), portal venous pressure (PVP), and hepatic tissue blood flow (HTBF) during intravenous infusion of saline (control), 0.3, 1, or 2 mg/kg/hour fasudil for 60 minutes. In BDL rats, 1 and 2 mg/kg/hour fasudil significantly reduced PVP by 20% compared with controls but had no effect on HTBF. MAP was significantly reduced in response to 2 mg/kg/hour fasudil. In the livers of BDL rats, 1 and 2 mg/kg/hour fasudil significantly suppressed Rho‐kinase activity and significantly increased eNOS phosphorylation, compared with controls. Fasudil significantly reduced the binding of serine/threonine Akt/PKB (Akt) to Rho‐kinase and increased the binding of Akt to eNOS. These results show in secondary biliary cirrhosis that (1) Rho‐kinase activation with resultant eNOS down‐regulation is substantially involved in the pathogenesis of portal hypertension and (2) Rho‐kinase might interact with Akt and subsequently inhibit the binding of Akt to eNOS. (HEPATOLOGY 2008.)

Portal vein thrombosis in liver cirrhosis

Portal vein thrombosis (PVT) is considered to be a frequent complication of liver cirrhosis. However, unlike PVT in patients without cirrhosis, very few data are available on the natural history and management of PVT in cirrhosis, despite its association with potentially life-threatening conditions, such as gastroesophageal bleeding and acute intestinal ischemia. Moreover, no consensus regarding PVT in cirrhosis exists. Suggested causes of PVT in cirrhosis include reduced portal blood flow velocity, multiple congenital or acquired thrombophilic factors, inherited or acquired conditions, and derangement of liver architecture. However, the understanding of PVT in cirrhosis is incomplete. In addition, information on the management of PVT in cirrhosis is inadequate. The aims of this review are to: (1) assemble data on the physiopathological mechanism, clinical findings, diagnosis and management of PVT in cirrhosis; (2) describe the principal factors most frequently involved in PVT development; and (3) summarize the recent knowledge concerning diagnostic and therapeutic procedures.

Significance of ERK nitration in portal hypertensive gastropathy and its therapeutic implications

Portal hypertensive (PHT) gastric mucosa increases susceptibility to injury and delayed mucosal healing. It is possible that nitration of ERK by peroxynitrite might alter MAPK (ERK) signaling in PHT gastric mucosa, leading to delayed mucosal healing, since excessive nitric oxide production is implicated in PHT gastric mucosa and MAPK (ERK) signaling induces cell proliferation and leads to gastric mucosal healing in response to injury. Portal hypertension was produced by staged portal vein ligation, and sham-operation (SO) rats served as controls. Lipid peroxide (LPO) and nitrotyrosine increased significantly in PHT gastric mucosa compared with SO rats. ERK activation was impaired in PHT gastric mucosa in response to ethanol injury, whereas no significant difference in the phosphorylation of MEK, an upstream molecule of ERK, was seen between the two groups. The nitration of ERK by peroxynitrite, as detected by the coimmunoprecipitation of ERK and nitrotyrosine, was significantly enhanced in PHT gastric mucosa. Administration of rebamipide, a gastroprotective drug that acts as an oxygen-derived free radical scavenger, significantly decreased LPO and nitrotyrosine as well as the nitration of ERK by peroxynitrite in PHT gastric mucosa, therefore normalizing ERK activation and restoring the gastric mucosal healing response to ethanol injury. Enhanced nitration of ERK by peroxynitrite is involved in the impaired MAPK (ERK) signaling in PHT gastric mucosa. These findings demonstrate a new molecular mechanism in which PHT gastric mucosa is predisposed to injury and impaired healing.

Laparoscopic splenectomy with interferon therapy in 100 hepatitis-C-virus-cirrhotic patients with hypersplenism and thrombocytopenia.

Background and Aim:  We intended to determine whether laparoscopic splenectomy (Lap‐Sp) contributes to treatment with interferon therapy in hepatitis C virus (HCV)‐cirrhotic patients with thrombocytopenia caused by hypersplenism.

Modulation of CD4+ T cell responses following splenectomy in hepatitis C virus-related liver cirrhosis

Dysfunction of T cells is a common feature in chronic persistent viral infections, including hepatitis C virus (HCV), and although hepatic and peripheral T cells have been studied extensively in chronic HCV hepatitis, the role of splenic T cell responses in such patients is poorly defined. This is an important issue, as thrombocytopenia is a complication of HCV‐related liver cirrhosis (LC), due to splenic platelet sequestration and bone marrow suppression; splenectomy has been proposed to treat such patients. Herein, we studied peripheral blood mononuclear cells (PBMC) and splenic lymphoid subpopulations from a total of 22 patients, including 15 with HCV‐related LC with marked thrombocytopenia treated with splenectomy, and seven controls. CD4+ T cells from peripheral blood and spleen were isolated and phenotype and function evaluated. Splenic CD4+ T cells in patients with LC expressed molecules associated with inhibitory signalling, including increased frequency of negative markers such as cytotoxic T lymphocyte associated antigen‐4 (CTLA‐4) and programmed death 1 (PD‐1) and decreased production of cytokines. Patients with LC manifest higher levels of splenic CD4+ regulatory T cells and PD‐L1‐ and PD‐L2‐expressing cells than controls. Blocking of PD‐1/PD‐1 ligand interaction reconstituted proliferative and cytokine responses of splenic mononuclear cells (SMC) from patients with LC. Splenectomy was followed by an increase in the ratio of interferon (IFN)‐γ to interleukin (IL)‐10 and a reduction of PD‐1‐expressing CD4+ T cells in peripheral blood. Our data suggest that peripheral tolerance is promoted by the spleen in LC via the up‐regulated expression of PD‐1 ligands.