Prognostic impact of pre- and postoperative tumor markers in patients with intrahepatic cholangiocarcinoma.

PURPOSE: The present study assessed the impact of pre- and postoperative tumor markers on the survival of patients with intrahepatic cholangiocarcinoma. METHODS: Medical records of 73 patients with intrahepatic cholangiocarcinoma were reviewed retrospectively. The pre- and postoperative carcinoembryonic antigen and carbohydrate antigen 19-9 levels were assessed. Patient characteristics, clinicopathological factors, and prognostic factors were analyzed. RESULTS: The median recurrence-free survival and overall survival were 30.0 and 90.9 months, respectively. A multivariate survival analysis revealed that elevated postoperative carbohydrate antigen 19-9 (p = 0.023) was the only independent poor prognostic factor. The median overall survival of patients with normal and elevated postoperative carbohydrate antigen 19-9 levels was 101.4 and 15.7 months (p < 0.001), respectively. Multivariate logistic regression identified elevated preoperative carbohydrate antigen 19-9 as an independent preoperative risk factor for elevated postoperative carbohydrate antigen 19-9. The optimal cutoff value of preoperative carbohydrate antigen 19-9 for predicting elevated postoperative carbohydrate antigen 19-9 was 40 U/mL, with a sensitivity and specificity of 92% and 87%, respectively (area under curve = 0.915). CONCLUSIONS: Elevated postoperative carbohydrate antigen 19-9 was an independent poor prognostic factor. Preoperative predictors, such as elevated preoperative carbohydrate antigen 19-9, may indicate the need for neoadjuvant therapies to improve the survival.

Surgery-related disseminated intravascular coagulation predicts postoperative complications.

PURPOSE: The rate of postoperative morbidity, including infectious complications, is still high after major hepatobiliary pancreatic (HBP) surgery. Although surgery-related disseminated intravascular coagulation (DIC) occurs in some cases, its significance has not been elucidated in HBP surgery. This study aimed to evaluate the influence of surgery-related DIC on the complication severity after HBP surgery. METHODS: We analyzed the records of 100 patients with hepatectomy in two or more segments, hepatectomy with biliary tract reconstruction, and pancreaticoduodenectomy. The baseline characteristics and complications were compared between patients with and without surgery-related DIC on postoperative day 1 (POD1) after HBP surgery between 2010 and 2018. Complication severity was assessed using the Comprehensive Complication Index (CCI). RESULTS: The DIC group (surgery-related DIC on POD1) had predictive factors, such as larger bleeding volume and higher liver enzyme levels. The DIC group exhibited significantly elevated rates of surgical site infection, sepsis, prolonged intensive care unit stay, more frequent blood transfusions, and higher CCI. Furthermore, compared with and without adjustment of DIC, odds ratio (OR) of AST level and operation time for  the risk of high CCI decreased (OR of AST level: 1.25 to 1.19 and OR of operation time: 1.30 to 1.23) and the significant differences had vanished. CONCLUSIONS: Surgery-related DIC on POD1 could be a partial mediator between AST level, operation time and higher CCI. The prevention or proper management of surgery-related DIC on POD1 can be an important target to reduce the severity of postoperative complications.

Adoptive immunotherapy overcomes genetic susceptibility to bloodstream infections due to fc-gamma receptor polymorphisms after liver transplantation.

Single nucleotide polymorphisms (SNPs) in FCGR3A can predict the susceptibility of liver transplant (LT) recipients to bloodstream infections (BSI) and clinical outcomes following living-donor LT (LDLT). Here, we retrospectively analyzed the relationship of adoptive immunotherapy with activated natural killer (NK) cells from perfusate effluents of liver allografts against BSI following LDLT. Higher BSI incidence and lower survival were observed in LT recipients with FcγRIIIa (158F/F or F/V) (n = 81) who did not receive adoptive immunotherapy (n = 55) than in those who did (n = 26) (BSI frequency, 36.4% vs. 11.5%; p = .033; log-rank p = .047). After matching patient background using propensity score, similar results were obtained (BSI ratio, 41.7% vs. 12.5%; p = .049; log-rank p = .039). The predominant BSI pathogens in patients who did and did not receive adoptive immunotherapy were gram-negative rods (n = 3, 100%) and gram-positive cocci (GPC) (n = 15, 65.2%), respectively. The proportion of NK cells administered to patients with BSI was significantly lower than that administered to patients without BSI (Number: 80.3 (29.9-239.2) × 106 cells vs. 37.1 (35.6-50.4) × 106 ; p = .033, percentage; 14.1 (13.3-17.8)% vs. 34.6 (16.5-47)%, p = .0078). Therefore, adoptive immunotherapy with NK cells was associated with the reduced post-transplant BSI related to GPCs due to FcγRIIIa SNP in LT recipients.

Downregulation of thrombomodulin contributes to ischemia-reperfusion injury in mice with steatotic liver.

AIM: Ischemia-reperfusion (IR) injury is one of the most critical complications commonly associated with liver surgery, including liver transplantation. Steatotic livers are particularly vulnerable to IR injury. However, the underlying mechanisms of this increased susceptibility have not fully been understood. In the present study, we used heterogeneous thrombomodulin (TM)-knockout (KO) (TM+/- ) mice, which express about 50% functional activity of TM as compared with wild type, to investigate whether dysregulation of TM enhances IR injury in steatotic livers. METHODS: Steatotic livers were induced using choline-deficient diets (CDD) in mice. The biological activity of TM was assessed using the productivity of protein C. Susceptibility to IR injury was compared between steatotic livers and non-steatotic livers and also assessed in TM-KO mice. We investigated whether recombinant TM (rTM) and the lectin-like domain of TM (rTM-D1) ameliorated IR injury in steatotic livers. RESULTS: Protein C activity was significantly decreased to less than 20% in CDD-fed mice compared with mice with non-steatotic livers. Steatotic livers showed exaggerated IR injury compared with non-steatotic livers. Recombinant TM (rTM) and the lectin-like domain of TM (rTM-D1), which has anti-inflammatory effects, ameliorated IR injury in steatotic livers. TM+/- mice showed increased susceptibility to IR injury, and rTM ameliorated the increased IR injury in TM+/- mice. CONCLUSION: We conclude that downregulation of TM increases susceptibility to hepatic IR injury in steatotic livers and that rTM ameliorates hepatic IR injury through anti-inflammatory action.

Protein Kinase N Family Negatively Regulates Constitutive Androstane Receptor-Mediated Transcriptional Induction of Cytochrome P450 2b10 in the Livers of Mice.

In receptor-type transcription factors-mediated cytochrome P450 (P450) induction, few studies have attempted to clarify the roles of protein kinase N (PKN) in the transcriptional regulation of P450s. This study aimed to examine the involvement of PKN in the transcriptional regulation of P450s by receptor-type transcription factors, including the aryl hydrocarbon receptor, constitutive androstane receptor (CAR), and pregnane X receptor. The mRNA and protein levels and metabolic activity of P450s in the livers of wild-type (WT) and double-mutant (D) mice harboring both PKN1 kinase-negative knock-in and PKN3 knockout mutations [PKN1 T778A/T778A; PKN3 -/-] were determined after treatment with activators for receptor-type transcription factors. mRNA and protein levels and metabolic activity of CYP2B10 were significantly higher in D mice treated with the CAR activator phenobarbital (PB) but not with 1,4-bis((3,5-dichloropyridin-2-yl)oxy)benzene compared with WT mice. We examined the CAR-dependent pathway regulated by PKN after PB treatment because the extent of CYP2B10 induction in WT and D mice was notably different in response to treatment with different CAR activators. The mRNA levels of Cyp2b10 in primary hepatocytes from WT and D mice treated with PB alone or in combination with Src kinase inhibitor 1 (SKI-1) or U0126 (a mitogen-activated protein kinase inhibitor) were evaluated. Treatment of hepatocytes from D mice with the combination of PB with U0126 but not SKI-1 significantly increased the mRNA levels of Cyp2b10 compared with those from the corresponding WT mice. These findings suggest that PKN may have inhibitory effects on the Src-receptor for activated C kinase 1 (RACK1) pathway in the CAR-mediated induction of Cyp2b10 in mice livers. SIGNIFICANCE STATEMENT: This is the first report of involvement of PKN in the transcriptional regulation of P450s. The elucidation of mechanisms responsible for induction of P450s could help optimize the pharmacotherapy and improve drug development. We examined whether the mRNA and protein levels and activities of P450s were altered in double-mutant mice harboring both PKN1 kinase-negative knock-in and PKN3 knockout mutations. PKN1/3 negatively regulates CAR-mediated induction of Cyp2b10 through phosphorylation of a signaling molecule in the Src-RACK1 pathway.

Significance of liver resection for intermediate stage hepatocellular carcinoma according to subclassification.

BACKGROUND: Patients diagnosed with Barcelona Clinic Liver Cancer (BCLC) intermediate stage hepatocellular carcinoma (HCC) encompass a broad clinical population. Kinki criteria subclassifications have been proposed to better predict prognoses and determine appropriate treatment strategies for these patients. This study validated the prognostic significance within the Kinki criteria substages and analyzed the role of liver resection in patients with intermediate stage HCC. METHODS: Patients with intermediate stage HCC (n = 378) were retrospectively subclassified according to the Kinki criteria (B1, n = 123; B2, n = 225; and B3, n = 30). We analyzed the overall survival (OS) and treatment methods. RESULTS: The OS was significantly different between adjacent substages. Patients in substage B1 who underwent liver resection had a significantly better prognosis than those who did not, even after propensity score matching (PSM). Patients in substage B2 who underwent liver resection had a significantly better prognosis than those who did not; however, there was no difference after PSM. There was no difference in prognosis based on treatments among patients in substage B3. CONCLUSIONS: The Kinki criteria clearly stratify patients with intermediate stage HCC by prognosis. For substage B1 HCC patients, liver resection provides a better prognosis than other treatment modalities. In patients with substage B2 and B3, an alternative approach is required.

A novel model for predicting posthepatectomy liver failure based on liver function and degree of liver resection in patients with hepatocellular carcinoma.

BACKGROUND: The permissible liver resection rate for preventing posthepatectomy liver failure (PHLF) remains unclear. We aimed to develop a novel PHLF-predicting model and to strategize hepatectomy for hepatocellular carcinoma (HCC). METHODS: This retrospective study included 335 HCC patients who underwent anatomical hepatectomy at eight institutions between 2013 and 2017. Risk factors, including volume-associated liver-estimating parameters, for PHLF grade B-C were analyzed in a training set (n = 122) via multivariate analysis, and a PHLF prediction model was developed. The utility of the model was evaluated in a validation set (n = 213). RESULTS: Our model was based on the three independent risk factors for PHLF identified in the training set: volume-associated indocyanine green retention rate at 15 min, platelet count, and prothrombin time index (the VIPP score). The areas under the receiver operating characteristic curve of the VIPP scores for severe PHLF in the training and validation sets were 0.864 and 0.794, respectively. In both sets, the VIPP score stratified patients at risk for severe PHLF, with a score of 3 (specificity, 0.92) indicating higher risk. CONCLUSION: Our model facilitates the selection of the appropriate hepatectomy procedure by providing permissible liver resection rates based on VIPP scores.

Impact on biliary complications of donor abdominal aortic calcification among living donor liver transplantation: a retrospective study.

Abdominal aortic calcification (AAC) was reported as a poor prognostic factor among liver transplantation. However, donor AAC is not enough discussed. We analyzed the impact of the donor AAC level on graft function on outcomes following living donor liver transplantation (LDLT). A total of 133 consecutive patients who had undergone LDLT were divided into two groups (non-AAC group and AAC group) according to their donor AAC level by plain computed tomography. The rate of postoperative biliary complications (BC) was significantly higher in AAC group (N = 17) than in non-AAC group (N = 116; HR, 2.77; 95% CI, 1.32-5.83; P = 0.0008). The Cox proportional hazards regression model revealed that donor AAC (HR, 4.15; 95% CI, 1.93-8.97; P = 0.0003) and right lobe graft (HR, 2.81; 95% CI, 1.41-5.61; P = 0.003) increased the risk of BC. Conversely, splenectomy (HR, 0.39; 95% CI, 0.16-0.92; P = 0.03) decreased the risk of BC after LDLT independently. The long-term survival was also significantly worse in AAC group than in non-AAC group (HR, 2.25; 95% CI, 1.04-4.89; P = 0.04). Donor AAC was an independent prognostic factor for BC among patients undergoing LDLT. Although further investigations are needed to verify our results, the levels of donor AAC could be a useful tool to identify the risks of BC and predict better outcomes following LDLT.

Antithrombin attenuates the progression of hepatocellular carcinoma by regulating neutrophil/interleukin-8 signaling.

AIM: Inflammation plays an important role in hepatocellular carcinoma (HCC) progression. Here, we examined whether antithrombin (AT) plays a role in attenuating HCC progression, via its anti-inflammatory effects. METHODS: HCCs were developed in AT-insufficient (AT+/- ) mice and wild-type (AT+/+ ) mice treated with diethyl nitrosamine and carbon tetrachloride. AT was administered to AT+/- mice. The development of HCC was compared between the three groups. In vitro study, migration assay was performed. The association of the prognosis of patients with HCC and plasma AT values was clinically examined. RESULTS: AT suppressed the release of interleukin (IL)-8 from lipopolysaccharide (LPS)-stimulated human neutrophils in vitro. Huh-7 cells that were co-cultured with neutrophils and stimulated with LPS showed significantly enhanced migration; however, Huh-7 cells co-cultured with LPS/AT-stimulated neutrophils showed significantly decreased migration. Moreover, the addition of anti-IL-8 antibodies to LPS-stimulated Huh-7 cells co-cultured with neutrophils also suppressed migration. AT+/- mice (AT plasma activity: 64%) promoted liver cancer, as compared with wild-type mice (AT plasma activity: 135%); AT administration attenuated liver cancer in AT+/- mice. Patients with HCC with a preoperative AT level of ≥70% showed better outcomes after liver resection, as compared with those with an AT level of <70%. IL-8 expression and neutrophil infiltration in HCC tissues were negatively correlated with the AT level. CONCLUSIONS: AT attenuates HCC progression by regulating neutrophil/IL-8 signaling.

Simulation and navigation of living donor hepatectomy using a unique three-dimensional printed liver model with soft and transparent parenchyma.

Three-dimensional printed liver models have been used for preoperative simulation. Unlike the standard three-dimensional system on a monitor, the three-dimensional printed model can be observed from any angle manually; therefore, surgeons can obtain a clear image directly from the model. We herein report the use of a unique three-dimensional liver model with a soft and transparent liver parenchyma. Through the parenchyma, the surgeons can observe the intrahepatic vessels and perform incisions in the model as a preoperative simulation. In this study, we applied this model to donor hepatectomy, which under most circumstances requires meticulous attention to detail. The actual processes and uses of a three-dimensional liver model in clinical surgery for liver transplantation are presented.

Impact of Abdominal Aortic Calcification Among Liver Transplantation Recipients.

Abdominal aortic calcification (AAC) is known as a risk factor of coronary artery disease, stroke, hyperphosphatemia, chronic inflammation, diabetes, and decreased estimated glomerular filtration rate. However, the clinical implications of incidental AAC findings in liver transplantation (LT) have not been evaluated in terms of posttransplantation survival and complications. Therefore, we analyzed the relationships between the AAC level and the outcomes following LT. A total of 156 consecutive patients who underwent LT between January 2007 and December 2014 were divided into 2 groups according to their AAC level (<100 mm3 or ≥100 mm3 ), as calculated using the Agatston method. Even after propensity matching, the survival time was significantly longer in the low-AAC group compared with that in the high-AAC group (median survival time, 4.5 versus 3.0 years; P < 0.01). A multivariate analysis identified high AAC level (hazard ratio, 2.2) and old donor age (hazard ratio, 2.2) as prognostic factors for overall survival. In conclusion, high AAC is an independent unfavorable prognostic factor in LT.

A Multicenter, Randomized, Controlled Trial Comparing Reinforced Staplers with Bare Staplers During Distal Pancreatectomy (HiSCO-07 Trial).

BACKGROUND: Although distal pancreatectomy (DP) using a reinforced stapler is expected to reduce PF, no multicenter RCT has been performed. To investigate whether reinforced staplers reduce the incidence of clinically relevant pancreatic fistula (PF) after DP compared with staplers without reinforcement. METHODS: Between July 2016 and December 2017, patients scheduled for DP were enrolled in a multicenter, randomized, controlled trial (RCT) at nine hospitals in Hiroshima Japan. Patients were randomized either to reinforced stapler or bare stapler. The primary endpoint was incidence of clinically relevant PF. This RCT was registered with UMIN Clinical Trial Registry (UMIN000022341). RESULTS: A total of 122 patients were assigned to reinforced stapler (n = 61) or bare stapler (n = 61), and 119 patients (61 reinforced stapler and 59 bare stapler) were analyzed. There was no significant difference in the incidence of clinically relevant PF between the reinforced stapler and bare stapler groups (16.3% vs. 27.1%, p = 0.15). Furthermore, the rates of major complication (16.3% vs. 18.6%, p = 0.74), postpancreatectomy hemorrhage (0% vs. 3.4%, p = 0.08), and median postoperative in-hospital days (19 days vs. 20 days, p = 0.78) did not differ between the two groups. Within a subset of 82 patients in whom the thickness of pancreatic transection line was less than 14 mm, a significant difference was found in the incidence of clinically relevant PF (4.5% vs. 21.0% in the reinforced stapler vs. bare stapler groups, respectively, p = 0.01). CONCLUSIONS: Reinforced stapler for pancreatic transection during DP does not reduce the incidence of clinically relevant PF compared to stapler without reinforcement.

Antithrombin Insufficiency Promotes Susceptibility to Liver Tumorigenesis.

BACKGROUND: Antithrombin (AT) is not only a major regulator of hemostasis, but it shows anti-inflammatory properties as well. We aimed to investigate whether AT-insufficient mice increase susceptibility to liver tumorigenesis. METHODS: We induced the development of liver tumor in AT-insufficient (AT+/-) mice and wild-type (AT+/+) mice by treating them with diethylnitrosamine (DEN) and CCl4. The development of liver tumors and liver inflammation were compared between these mouse groups. Following this, AT was administered to the AT-insufficient mice treated with DEN and CCl4. RESULTS: Tumor size and the number of DEN and CCl4-induced liver tumors significantly increased in AT-insufficient mice compared with the wild-type mice. Serum transaminase levels, cell death, and the expression of cleaved caspase-3 in liver were increased in AT+/-. Furthermore, hepatic neutrophil infiltrations and serum interleukin 6 and tumor necrosis factor-α levels were significantly elevated in AT-insufficient mice. The levels of 8-OHdG, oxidative DNA damage marker, in liver were significantly increased in AT-insufficient mice. Administration of AT led to a significant decrease in DEN- and CCl4-induced liver injury and inflammation in AT-insufficient mice, compared with the wild-type group. CONCLUSIONS: AT insufficiency led to increased susceptibility to liver tumorigenesis by increasing hepatic inflammation.

Vitamin A-coupled liposomal Rho-kinase inhibitor ameliorates liver fibrosis without systemic adverse effects.

AIM: Rho-kinase (ROCK) inhibitor could ameliorate liver fibrosis by suppressing hepatic stellate cell (HSC) activation. However, because systemic administration of ROCK inhibitor causes serious adverse effects, we developed a drug delivery system selectively delivering ROCK inhibitor to HSCs. Here, we examined whether our developed vitamin A (VA)-coupled liposomal ROCK inhibitor reduced liver fibrosis in rats without causing systemic adverse effects. METHODS: LX-2 HSCs were analyzed for morphological changes and the expression of profibrotic proteins. The inhibitory effects of VA-coupled liposomal ROCK inhibitor on liver fibrosis were confirmed in a rat model of liver fibrosis induced by i.p. injection of carbon tetrachloride. The degree of liver fibrosis, biochemical changes, and survival rates were also investigated. RESULTS: Vitamin A-coupled liposomal ROCK inhibitor had an effect at approximately 1/100 the amount of the free ROCK inhibitor for inhibiting the activation of LX-2 cells and caused significant decreases in the expression levels of α-smooth muscle actin (SMA) and transforming growth factor (TGF)-ß1. The degree of liver fibrosis was suppressed by treatment with VA-coupled liposomal ROCK inhibitor, and the expression of α-SMA and TGF-ß1 in liver tissues was also significantly suppressed. In addition, serum levels of alanine aminotransferase and hyaluronic acid were significantly reduced, and there was no decline in kidney function, which has been noted as a systemic adverse effect of ROCK inhibitor. Furthermore, VA-coupled liposomal ROCK inhibitor improved survival rates in rats with liver fibrosis. CONCLUSION: Vitamin A-coupled liposomal ROCK inhibitor efficiently suppressed liver fibrosis without causing systemic adverse effects.

Prediction of recurrence following hepatectomy in patients with hepatitis C virus infection-related hepatocellular carcinoma who achieved a sustained virological response.

AIM: The risk of hepatitis C virus infection-related hepatocellular carcinoma (HCC) is lower, with a better prognosis, in patients who achieve a sustained virological response (SVR) than in those who do not. We aimed to identify risk factors of post-hepatectomy HCC recurrence in patients who achieved a SVR. METHODS: This retrospective study included 349 HCC patients who underwent an initial radical hepatectomy at our institution between January 2005 and December 2014. Sixty-eight patients had achieved a SVR (the SVR group) and 281 patients had not (the non-SVR group). Clinical characteristics and long-term outcomes were compared between the two groups. Univariate and multivariate analyses identified variables associated with recurrence-free survival in the SVR group. RESULTS: Post-hepatectomy overall and recurrence-free survival rates were significantly higher in the SVR group than the non-SVR group (P < 0.01 and <0.05, respectively). Univariate analysis of post-hepatectomy recurrence-free survival in the SVR group revealed multiple significant factors: aspartate aminotransferase, 25 IU/L or more (P = 0.01); indocyanine green retention rate at 15 min, 20.0% or less (P < 0.05); hepatic vascular invasion (P < 0.05); and an interval of months or less between achieving a SVR and hepatectomy (P < 0.01). Multivariate analysis confirmed an interval of 30 months or less between achieving a SVR and hepatectomy as an independent prognostic factor of recurrence-free survival (hazard ratio, 2.30; 95.0% confidence interval, 1.04-5.13; P < 0.05). CONCLUSION: The interval between achieving a SVR and hepatectomy is an important predictor of recurrence in hepatitis C virus infection-related HCC patients who achieved a SVR.

Glasgow Prognostic Score and Prognosis After Hepatectomy for Hepatocellular Carcinoma.

BACKGROUND: Systemic inflammation can promote tumor growth. The Glasgow Prognostic Score (GPS), a simple assessment of systemic inflammation status, could be useful to predict the prognosis of hepatocellular carcinoma (HCC) patients after hepatectomy. METHODS: Consecutive HCC patients were enrolled following hepatectomy at our institution between 2005 and 2012. Univariate and multivariate analyses were performed to identify variables associated with overall survival (OS) and recurrence-free survival. Patients were stratified according to the GPS. To minimize selection bias, propensity score analysis was performed. RESULTS: An elevated GPS (1-2), des-gamma carboxyprothrombin levels (≥40 mAU/mL), and the presence of multiple tumors were significantly associated with a poor OS. Alpha-fetoprotein levels (≥20.0 ng/mL), des-gamma carboxyprothrombin levels (≥40 mAU/mL), and the presence of multiple tumors were independent risk factors for a poor recurrence-free survival. After one-to-one matching, 92 patients each with a normal GPS (0) and an elevated GPS (1-2) had similar preoperative and operative characteristics. Poorer OS times in patients with an elevated GPS were confirmed by excluding possible misinterpretation. CONCLUSIONS: An elevated GPS was an independent prognostic indicator for OS after hepatectomy in HCC patients. The GPS, which employs inexpensive and readily available biomarkers, could be a novel tool for predicting survival in such patients.

Influence of higher BMI for hepatitis B- and C-related hepatocellular carcinomas.

PURPOSE: Although obesity is associated with hepatocellular carcinoma (HCC) development, its impact on the surgical outcomes of patients with hepatitis B virus (HBV)-and hepatitis C virus (HCV)-related HCC remains unclear. METHODS: We retrospectively analyzed 714 patients with HCC who underwent curative hepatectomy. Among them, the HBV-related HCC group (n = 125) and HCV-related HCC group (n = 426) were subdivided according to the presence of body mass index (BMI) ≥ 25 kg/m2. The surgical outcomes were compared. RESULTS: The 5-year overall survival rate after hepatectomy in the HBV-related HCC group was significantly better than that in the HCV-related HCC group. The 5-year overall survival rates of the HBV-related HCC with and without BMI ≥ 25 kg/m2 groups were 65 and 85%, respectively. The 5-year overall survival rates in the HCV-related HCC with and without BMI ≥ 25 kg/m2 groups were 75 and 65%, respectively. The HBV-related HCC with BMI ≥ 25 kg/m2 groups had a significantly worse prognosis than the HBV-related HCC without BMI ≥ 25 kg/m2 groups, while the HCV-related HCC with BMI ≥ 25 kg/m2 groups had a significantly better prognosis than the HCV-related HCC without BMI ≥ 25 kg/m2 groups. Multivariate analysis revealed that BMI ≥ 25 kg/m2 was the positive and negative prognostic factor for the surgical outcomes of patients with HBV- and HCV-related HCC, respectively. CONCLUSIONS: BMI ≥ 25 kg/m2 negatively affected the surgical outcomes of patients with HBV-related HCC and positively affected those of patients with HCV-related HCC.

Hybrid Surgery for Portosystemic Encephalopathy in a Patient with Liver Cirrhosis: a case report.

Regarding the treatment for a portosystemic shunt, surgical or interventional radiological closure of the shunt was established. Interventional radiology including balloon-occluded retrograde transvenous obliteration can worsen portal hypertension and create a large thrombus close to the major venous system in the case of a huge portosystemic shunt. In contrast, it is also difficult to treat some cases through surgery alone when huge complicated shunts exist very deep in the body. Herein, we report a successful case of surgical shunt ligation for portosystemic encephalopathy in a hybrid operation room that enabled intraoperative angiography and computed tomography. A 62-year-old woman with chronic hepatitis C was referred to our hospital due to high levels of serum ammonia and hepatic encephalopathy. She had a massive, complicated portosystemic shunt from the inferior mesenteric vein to the left renal vein but did not have esophageal or gastric varices. It was difficult to occlude the portosystemic shunt by interventional radiologic techniques because the shunt had an extremely large amount of blood flow and many collateral routes. We performed the shunt ligation in the hybrid operation room. Intraoperative angiography provided detailed information about the portosystemic shunt, such as direction or volume of blood flow and collateral routes in real time. Her encephalopathy disappeared completely and she remains healthy with improved liver functional reserve to date. In conclusion, this is a successful case of a hybrid operation for an extremely large and complicated portosystemic shunt, providing for intraoperative angiography as a safe and reliable surgical treatment for portosystemic encephalopathy in patients with liver cirrhosis.

Prediction of long-term survival by using the Glasgow Prognostic Score in patients with hepatocellular carcinoma after liver transplantation.

AIM: This study aimed to validate the prognostic value of the Glasgow Prognostic Score (GPS) in patients who underwent living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). METHODS: Data were retrospectively collected for HCC patients who underwent LDLT. Univariate and multivariate analyses were performed to identify variables associated with overall and recurrence-free survival. Patients were separated into two groups based on the GPS. The predictive ability of the GPS was compared with other variable scores (modified GPS and hepatic GPS) to identify the most accurate test for this population. RESULTS: Univariate analysis identified a GPS of 1 or 2 (P = 0.018), multiple tumors (P = 0.032) and HCC beyond the Milan criteria (P = 0.015) as factors significantly associated with poor overall survival. Hepatitis B negative status (P = 0.034), a GPS of 1 or 2 (P = 0.030), α-fetoprotein of 20.0 ng/mL or more (P = 0.042) and HCC beyond the Milan criteria (P = 0.002) were identified as factors significantly associated with poor recurrence-free survival. Multivariate analysis indicated that HCC beyond the Milan criteria and a GPS of 1 or 2 were independent risk factors for long-term outcomes. Among the scoring systems evaluated in this study, the GPS was the best predictive system in our population. Moreover, a new scoring system that combined the GPS and the Milan criteria showed the highest prognostic values. CONCLUSION: Novel prediction scores combining the GPS and the Milan criteria provide a precise, objective, and quick approach for selecting appropriate HCC patients for LDLT.