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Background Tuberculosis (TB) is a serious opportunistic infection in liver transplant (LT) recipients with a high rate of morbidity and mortality. This study aims to clarify the frequency and risk factors for tuberculosis in LT recipients. Methods A total of 884 LT recipients were investigated retrospectively at China Medical University Hospital, Taichung, Taiwan. We performed a case–control study (1:2) to investigate the potential risk factors and disease onset of TB after LT. Results Among the 884 LT recipients, 25 of TB cases (2.8%) were reported from 2009 to 2016. The overall incidence of TB was 744 cases per 100,000 patient-year, which was 18-fold higher than the general population in Taiwan. The median time to develop TB after liver transplant was 20 months. Of the TB cases, 15 were pulmonary TB and 10 were extra-pulmonary TB. Five cases of those extra-pulmonary TB occurred in the first post-transplant year. Overall five-year survival rate was 63.3%. Multivariate analyses identified apical fibrotic change in pre-transplant computed tomographic (CT) finding and the exposure to mammalian target of rapamycin (mTOR) inhibitors before TB event as independent risk factors for TB development (Odd ratio (OR) 10.79, 95% confidence interval (CI), 1.73–67.49, p = 0.01; OR 3.847, 95% CI 0.80–18.51, P = 0.09, respectively). Conclusion TB incidence in LT recipients is high in this study. Among those post-transplant recipients with long-term immunosuppression, abnormal CT finding and exposure to mTOR inhibitors before liver transplant might be the risk factors for TB.

Purpose Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), a leading cause of cancer-related death worldwide. The HCC patients who harbor HBV pre-S2 mutant, an oncoprotein that plays key roles in HCC development, have been closely associated with a worse prognosis after curative surgical resection, suggesting an urgent need for alternative therapeutic options to improve their survival. In this study, we aimed to evaluate the expression profiles of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), two of the most well-studied immune checkpoint molecules that promote tumor immune evasion, in tumor of the pre-S2 mutant-positive/high HCC patients. Methods We classified 40 HBV-related HCC patients into the pre-S2-positive/high and -negative/low groups by a next-generation sequencing-based approach. The fluorescent immunohistochemistry staining was performed to detect the expression of PD-1 and PD-L1 in HCC tissues of patients. Results We showed that patients with either deletion spanning pre-S2 gene segment or high percentage of pre-S2 plus pre-S1+pre-S2 deletion (the pre-S2 mutant-positive/high group) exhibited a significantly higher density of PD-L1-positive cells in HCC tissues than those without. Moreover, the percentage of pre-S2 plus pre-S1+pre-S2 deletion displayed a high positive correlation with the density of PD-L1-positive cells in HCC tissues. Conclusion The increased expression of PD-L1 in tumor tissues of the pre-S2 mutant-positive HCC patients suggest that pre-S2 mutant may play a potential role in dysregulation of tumor immune microenvironment in the progression of HBV-related HCC, implicating for the development of future therapeutic strategies.

To share our experience with hollow viscus migration of artificial vascular grafts (AVG) used for venous reconstruction of the right anterior sector in living donor liver transplantations (LDLT).Clinical, radiological, and endoscopic data of 13 right lobe LDLT patients (range: 26-67 years) with a diagnosis of postoperative AVG migration into adjacent hollow viscus were analyzed.Biliary complications were detected in 12 patients. A median of four times endoscopic retrograde cholangiopancreatography (ERCP) procedures were performed in 11 patients prior to AVG migration diagnosis. A median of 2.5 times various percutaneous radiological interventional procedures were performed in eight patients prior to AVG migration diagnosis. The site of migration was the duodenum in eight patients, gastric antrum in four, and Roux limb in the remaining one patient. The migrated AVS were made of polytetrafluoroethylene (PTFE) in 10 patients and polyethylene terephthalate (Dacron) in three. The migrated AVGs were endoscopically removed in seven patients and surgically removed in six. Only one patient died due to sepsis unrelated to AVG migration.AVG migration into the adjacent hollow viscus following right lobe LDLT is a rare and serious complication. Repetitive ERCP, interventional radiological procedures, infection related to biliary leakage, and thrombosis of AVGs are among the possible risk factors.

Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite remarkable advances in treatment, high mortality in HCC patients remains a big challenge. To develop novel therapeutic strategies for HCC is thus urgently needed to improve patient survival. Dendritic cells (DC)-based vaccines can induce tumor-specific immunity and have emerged as a promising approach for treating HCC patients; however, its effectiveness needs to be improved. Recently, blockade of programmed death ligand 1 (PD-L1) immune checkpoint pathway has been shown to enhance anti-tumor immune responses and exhibited great potential in HCC therapy.In this study, we generated DC vaccine by pulsing the C57BL/6J mouse bone marrow-derived DC with mouse hepatoma Hep-55.1C cell lysate. We developed a therapeutic strategy combining DC vaccine and PD-L1 inhibitor for HCC and evaluated its efficacy in an orthotopic HCC mouse model in which Hep-55.1C cells were directly injected into left liver lobe of C57BL/6J mouse.Compared with a control group of mice, groups of mice treated with DC vaccine or PD-L1 inhibitor had significantly improved overall survival, reduced tumor volume, and increased tumor cell apoptosis. Remarkably, combination treatment with DC vaccine and PD-L1 inhibitor led to considerably longer overall survival, smaller tumor volume, and higher tumor cell apoptosis of mice than either treatment alone in a dose-dependent manner through inducing a stronger anti-tumor cytotoxic T cell response.Our data suggested that combination therapy with DC vaccine and PD-L1 inhibitor might have great promise as a novel treatment strategy for HCC.

Hepatocellular carcinoma (HCC) is, globally, one of the most prevalent and deadly human cancers, despite curative surgical resection, its high recurrence rate after surgery remains a large threat, resulting in poor patient survival. The hepatitis B virus (HBV) pre-S2 mutant that harbors deletions spanning the pre-S2 gene segment has emerged as an important oncoprotein for HCC development and a valuable prognostic biomarker for HCC recurrence, however, its relationship with clinicopathological factors is largely unexplored. In this study, the correlation of the deletion spanning the pre-S2 gene segment with clinicopathological factors and the association of such correlation with HCC recurrence after curative surgical resection were examined in HBV-related HCC patients. Inverse correlation between serum albumin level and the deletion spanning the pre-S2 gene segment was identified. HCC patients with the presence of the deletion spanning the pre-S2 gene segment and a low serum albumin level were associated with higher HCC recurrence than patients with either factor alone or neither factor were. Moreover, a combination of the serum albumin level and the deletion spanning the pre-S2 gene segment exhibited better performance than that of either factor alone in predicting HCC recurrence. Collectively, this study shows an association of low serum albumin level with pre-S2 mutant-positive HCC patients, and validates the prognostic value of this association in identifying patients with higher HCC recurrence after curative surgical resection.

Hepatocellular carcinoma (HCC) is one of the most frequent and fatal human cancers worldwide and its development and prognosis are intimately associated with chronic infection with hepatitis B virus (HBV). The identification of genetic mutations and molecular mechanisms that mediate HBV-induced tumorigenesis therefore holds promise for the development of potential biomarkers and targets for HCC prevention and therapy. The presence of HBV pre-S gene deletions in the blood and the expression of pre-S deleted proteins in the liver tissues of patients with chronic hepatitis B and HBV-related HCC have emerged as valuable biomarkers for higher incidence rates of HCC development and a higher risk of HCC recurrence after curative surgical resection, respectively. Moreover, pre-S deleted proteins are regarded as important oncoproteins that activate multiple signaling pathways to induce DNA damage and promote growth and proliferation in hepatocytes, leading to HCC development. The signaling molecules dysregulated by pre-S deleted proteins have also been validated as potential targets for the prevention of HCC development. In this review, we summarize the clinical and molecular implications of HBV pre-S gene deletions and pre-S deleted proteins in HCC development and recurrence and highlight their potential applications in HCC prevention and therapy.

Supplemental Digital Content is available in the text., Background and Methods. Data from 2 randomized liver transplant trials (N = 772; H2304 [deceased donor, n = 488], H2307 [living donor, n = 284]) were pooled to further evaluate the efficacy and safety of everolimus with reduced tacrolimus (EVR + rTAC) versus standard tacrolimus (sTAC) regimen at month 24. Results. EVR + rTAC was comparable to sTAC for composite efficacy failure of treated biopsy-proven acute rejection, graft loss, or death (9.8% versus 10.8%; difference, −1.0%; 95% confidence interval, −5.4 to 3.4; P = 0.641) at month 24. EVR + rTAC was superior to sTAC for the mean change in estimated glomerular filtration rate (eGFR) from randomization to month 24 (−8.37 versus −13.40 mL/min/1.73 m2; P = 0.001). A subanalysis of renal function by chronic kidney disease (CKD) stage at randomization showed significantly lower decline in eGFR from randomization to month 24 for patients with CKD stage 1/2 (eGFR ≥ 60 mL/min/1.73 m2) in EVR + rTAC group versus sTAC (−12.82 versus −17.67 mL/min/1.73 m2, P = 0.009). In patients transplanted for hepatocellular carcinoma (HCC) beyond Milan criteria, HCC recurrence was numerically lower although not statistically significant with EVR + rTAC versus sTAC group (5.9% [1 of 17] versus 23.1% [6 of 26], P = 0.215), while comparable in patients within Milan criteria (2.9% [3 of 102] versus 2.1% [2 of 96], P = 1.000), irrespective of pretransplant alpha-fetoprotein levels. Conclusions. EVR + rTAC versus sTAC showed comparable efficacy and safety with significantly better renal function, particularly in patients with normal/mildly decreased renal function (CKD stage 1/2) at randomization and a trend toward lower HCC recurrence in patients transplanted with HCC beyond Milan at month 24. Further long-term data would be required to confirm these results.

Background There is an increased bleeding risk following hepatectomy either due to surgical complications or the nature of liver dysfunction among these patients. For better prevention of delayed bleeding in patients undergoing hepatectomy with different kinds of comorbidities and medications, we examined the risk of major bleeding up to 10 years following hepatectomy. Materials and methods This retrospective study used data from Taiwan's National Health Insurance Research Database. Patients who underwent hepatectomy between 2000 and 2012 were identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes. The non-hepatectomy cohort was defined as patients without any record of hepatectomy. Variables including gender, age, comorbidities, and prescribed medications were matched between the hepatectomy and non-hepatectomy cohorts. Results A total of 1155 patients with hepatectomy and 1155 matched non-hepatectomy subjects were included in this study. The risk of major bleeding was significantly higher in the hepatectomy cohort than that of the non-hepatectomy cohort (adjusted hazard ratio: 1.60). The gastrointestinal tract was the most common site of bleeding among patients with bleeding tendencies (adjusted hazard ratio: 1.93). Compared with the non-hepatectomy cohort, patients who underwent hepatectomy were at greater risk of delayed major bleeding in the first decade following surgery (adjusted hazard ratios ranged from 1.56 to 1.70). Conclusion Hepatectomy poses a significant risk of delayed major bleeding, especially in the first decade following surgery. Proper prevention methods and close monitoring for bleeding complications are indicated for patients undergoing hepatic surgeries.

Hepatocellular carcinoma (HCC) is a frequent and deadly human cancer worldwide that is intimately associated with chronic hepatitis B virus (HBV) infection. Pre-S2 mutant is a HBV oncoprotein that plays important roles in HCC development and is linked to poor prognosis in HCC patients. However, the profiles of tumor-infiltrating lymphocytes in HCC tissues of pre-S2 mutant-positive patients remain unknown. In this study, we performed fluorescent immunohistochemistry staining to detect the infiltration of ‘anti-tumor’ cytotoxic T lymphocytes (CTLs) and ‘pro-tumor’ regulatory T cells (Tregs) in pre-S2 mutant-positive and -negative HCC patients. We showed that pre-S2 mutant-positive patients had a significantly higher infiltration of CD4+CD25+ cells and forkhead box P3 (Foxp3)-expressing cells but similar CTLs and lower granzyme B-expressing cells in HCC tissues compared with pre-S2 mutant-negative patients. Moreover, the percentage of pre-S2 plus pre-S1 + pre-S2 deletion (pre-S2 mutant) was positively correlated with the density of CD4+CD25+ cells and Foxp3-expressing cells but negatively with granzyme B-expressing cells in HCC tissues. Considering that increased intratumoral Tregs have been shown to promote tumor immune evasion, our data may provide new insights into the pathogenesis of HBV pre-S2 mutant-induced HCC and suggest that therapeutics targeting Tregs may be a promising strategy for treating pre-S2 mutant-positive high-risk patient population.

Background and aim Hepatocellular carcinoma (HCC) remains a serious cause of cancer-related deaths worldwide. Developing new therapeutic strategies is urgently needed to improve the outcomes of HCC patients. Dendritic cell (DC)-based vaccines and programmed death 1 (PD-1) immune checkpoint inhibitors have been regarded as potential immunotherapeutics for HCC. However, the therapeutic efficacy of combining these two treatments for HCC remains to be evaluated. Methods In this study, DCs were derived from mouse bone marrow and pulsed with mouse HCC cell lysates to generate a DC vaccine. A monoclonal antibody that blocks the interaction of mouse PD-1 with its ligands was used as a PD-1 inhibitor. An orthotopic HCC mouse model was established to assess the effect of a DC vaccine in combination with a PD-1 inhibitor on overall survival and tumor volume. Results Compared with the untreated control, single treatment with a DC vaccine or PD-1 inhibitor prolonged the overall survival and reduced the tumor volume of HCC mice. Further, compared with the single treatment with the DC vaccine or the PD-1 inhibitor, a combination treatment using both agents elicited a higher cytotoxicity of T cells against HCC cells and resulted in a better overall survival, smaller tumor volume, and greater tumor cell apoptosis in HCC mice. Conclusions Our results suggest that a combination treatment with DC vaccine and PD-1 inhibitor may be a promising therapeutic strategy for HCC.

Objective To investigate the anti-carcinogenic effect of metronomic Celecoxib (i.e., frequent administration in clinically available doses) against hepatocellular carcinoma (HCC) in the perspective of metastasis, spontaneous hepatocarcinogenesis, cancer invasion, proliferation, and stemness in vivo and in vitro. Background Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is known to cause anti-carcinogenic effects for HCC in suprapharmacological doses. However, the effects of metronomic Celecoxib treatment on HCC cells remain unclear. Methods The in vivo chemopreventive effect of metronomic Celecoxib (10mg/kg/d) was investigated by the syngeneic HCC implantation model and spontaneous hepatocarcinogenesis in HBV-transgenic(HBVtg) mice individually. HCC cell lines were treated by either suprapharmacological (100 μM) or metronomic (4 μM) Celecoxib therapy. Anti-carcinogenic effects were evaluated using cell invasion, cancer proliferation, angiogenesis, and phenotype of cancer stem/progenitor cells (CSPC). The molecular mechanism of metronomic Celecoxib on HCC was dissected using Luciferase assay. Results In vivo metronomic Celecoxib exerted its chemopreventive effect by significantly reducing tumor growth of implanted syngeneic HCC and spontaneous hepatocarcinogenesis in HBVtg mice. Unlike suprapharmacological dose, metronomic Celecoxib can only inhibit HCC cell invasion after a 7-day course of treatment via NF-κB/MMP9 dependent, COX2/PGE2 independent pathway. Metronomic Celecoxib also significantly suppressed HCC cell proliferation after a 7-day or 30-day culture. Besides, metronomic Celecoxib reduced CSPC phenotype by diminishing sphere formation, percentage of CD90+ population in sphere cells, and expression of CSPC markers. Conclusions Metronomic Celecoxib should be investigated clinically as a chemopreventive agent for selected high-risk HCC patients (e.g., HCC patients after curative treatments).

BACKGROUND ABO-incompatible (ABO-i) living donor liver transplantation (LDLT) is a feasible alternative for donor liver allograft in emergency situations, especially in Asia, where deceased-donor organs remain scarce. The reported outcomes of ABO-i LDLT after optimal desensitization are comparable to those of ABO-compatible LDLT. In this retrospective study, we found improved outcomes after ABO-i LDLT with a low-dose rituximab in combination with double-filtration plasmapheresis (DFPP) and prophylactic antibiotic therapy. MATERIAL AND METHODS Between January 2006 and December 2018, a total of 65 recipients underwent ABO-i LDLT surgeries at our center. The study cohort consisted of 50 recipients (Era III) who underwent ABO-i LDLT using the recently updated desensitization protocol, which included rituximab 200 mg intravenous injection once a week prior to LDLT, 4 sessions of DFPP in all patients, and prophylactic antibiotics for 3 months. RESULTS The 3-year overall survival rate achieved in ABO-i LDLT patients was 72.7% (66.6% for Era I and 33.3% for Era II patients). In the study population, 11 patients developed complications due to infection. Five of these patients (10%) died due to overwhelming sepsis. Four patients (8%) were diagnosed with multiple strictures and diffusely scattered dilatation of intrahepatic bile ducts on computed tomography, without vascular complications. Three of them had evidence of antibody-mediated rejection (AMR). CONCLUSIONS Our experience shows that the ABO-i LDLT protocol of lowered rituximab combined with pre-transplant sessions of plasmapheresis and a quadruple immunosuppressive regimen can be effective in chronic liver failure patients with clinical urgency in the absence of an ABO-compatible donor. Fast-tracking the use of ABO-i LDLT is feasible in patients with an acute liver failure (ALF) and can safely increase the donor liver pool, with an acceptable outcome.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the current pandemic, coronavirus disease 2019 (COVID-19), has taken a huge toll on human lives and the global economy. Therefore, effective treatments against this disease are urgently needed. Here, we established a fluorescence resonance energy transfer (FRET)-based high-throughput screening platform to screen compound libraries to identify drugs targeting the SARS-CoV-2 main protease (Mpro), in particular those which are FDA-approved, to be used immediately to treat patients with COVID-19. Mpro has been shown to be one of the most important drug targets among SARS-related coronaviruses as impairment of Mproblocks processing of viral polyproteins which halts viral replication in host cells. Our findings indicate that the anti-malarial drug tafenoquine (TFQ) induces significant conformational change in SARS-CoV-2 Mproand diminishes its protease activity. Specifically, TFQ reduces the α-helical content of Mpro, which converts it into an inactive form. Moreover, TFQ greatly inhibits SARS-CoV-2 infection in cell culture system. Hence, the current study provides a mechanistic insight into the mode of action of TFQ against SARS-CoV-2 Mpro. Moreover, the low clinical toxicity of TFQ and its strong antiviral activity against SARS-CoV-2 should warrant further testing in clinical trials.

Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC), the leading cause of cancer-related death worldwide. Despite progress in the prevention and therapy of HCC, high incidence and recurrence rates of HCC remain big threats, resulting in poor patient survival. Effective biomarkers and targets of HCC are therefore urgently needed for better management and to improve patient outcomes. Pre-S mutants have been well demonstrated as HBV oncoproteins that play important roles in HCC development through activation of multiple oncogenic signal pathways in hepatocytes, in vitro and in vivo. The presence of pre-S mutants in patients with chronic HBV infection and HBV-related HCC has been associated with a significantly higher risk of HCC development and recurrence after curative surgical resection, respectively. In this review, we summarize the roles of pre-S mutants as biomarkers for predicting HBV-related HCC development and recurrence, and highlight the pre-S mutants-activated oncogenic signal pathways as potential targets for preventing HBV-related HCC development.

Background: Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite remarkable advances in treatment, high mortality in HCC patients remains a big challenge. To develop novel therapeutic strategies for HCC is thus urgently needed to improve patient survival. Dendritic cells (DC)-based vaccines can induce tumor-specific immunity and have emerged as a promising approach for treating HCC patients; however, its effectiveness needs to be improved. Recently, blockade of programmed death ligand 1 (PD-L1) immune checkpoint pathway has been shown to enhance anti-tumor immune responses and exhibited great potential in HCC therapy. Methods: In this study, we generated DC vaccine by pulsing the C57BL/6J mouse bone marrow-derived DC with mouse hepatoma Hep-55.1C cell lysate. We developed a therapeutic strategy combining DC vaccine and PD-L1 inhibitor for HCC and evaluated its efficacy in an orthotopic HCC mouse model in which Hep-55.1C cells were directly injected into left liver lobe of C57BL/6J mouse. Results: Compared with a control group of mice, groups of mice treated with DC vaccine or PD-L1 inhibitor had significantly improved overall survival, reduced tumor volume, and increased tumor cell apoptosis. Remarkably, combination treatment with DC vaccine and PD-L1 inhibitor led to considerably longer overall survival, smaller tumor volume, and higher tumor cell apoptosis of mice than either treatment alone in a dose-dependent manner through inducing a stronger anti-tumor cytotoxic T cell response. Conclusion: Our data suggested that combination therapy with DC vaccine and PD-L1 inhibitor might have great promise as a novel treatment strategy for HCC.

// Shih-Ting Huang 1, 2 , Ya-Wen Chuang 1 , Tung-Min Yu 1, 3 , Cheng-Li Lin 4, 5 and Long-Bin Jeng 3, 6 1 Division of Nephrology, Taichung Veterans General Hospital, Taichung, Taiwan 2 Graduate Institute of Public Health, China Medical University, Taichung, Taiwan 3 Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan 4 Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan 5 College of Medicine, China Medical University, Taichung, Taiwan 6 Department of Surgery, Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan Correspondence to: Long-Bin Jeng, email: otc.Jeng@gmail.com Keywords: bleeding, cholangitis, cirrhosis, pancreatitis, polycystic kidney disease Received: May 19, 2017 Accepted: August 07, 2017 Published: September 15, 2017 ABSTRACT Background: The objective of this study was to determine the incidence of major hepatointestinal complications in patients with polycystic kidney disease (PKD). Methods: We analyzed the Taiwan National Health Insurance claims data (2000–2010) of 6031 patients with PKD and 23,976 non-PKD hospitalized controls. The control cohort was propensity score matched with the PKD cohort at a 1:4 ratio. All patients were followed up from the index date to the first inpatient diagnosis of hepatointestinal complications, death, or 31 December, 2011. Cox proportional hazard regression models were used to identify the risk of outcome after adjustment for potential confounders. Results: The incidence rates of acute pancreatitis, cholangitis, peptic ulcer bleeding, and cirrhosis were 5.72, 4.01, 19.9, and 5.46 per 1000 person-years, respectively, in the PKD cohort. Compared with the non-PKD controls, patients with PKD exhibited an increased risk of hospitalization for acute pancreatitis, cholangitis, peptic ulcer bleeding, and cirrhosis (adjusted subhazard ratio [aSHR]: 2.36, 95% confidence interval [95% CI], 1.95–2.84]; 2.36, [95% CI, 1.95–2.84]; 2.41, [95% CI, 1.93–3.01]; 2.41, [95% CI, 2.17–2.67]; and 1.39, [95% CI, 1.16–1.66], respectively; all p < 0.001). PKD, chronic kidney disease, and alcoholism were independent predictors of all these hepatointestinal complications. Kaplan–Meier analysis revealed an increased overall mortality in patients with PKD who developed acute pancreatitis and peptic ulcer bleeding (log-rank p < 0.05). Conclusion: PKD is associated with clinically significant extrarenal complications including acute pancreatitis, cholangitis, peptic ulcer bleeding, and cirrhosis.

BACKGROUND Rituximab is commonly used to reduce the agglutinin titer in ABO-incompatible liver transplant recipients. Although well-tolerated, rituximab infusion therapy may result in severe pulmonary adverse effects such as drug-induced pneumonitis, leading to acute respiratory distress syndrome (ARDS), which has a high mortality rate. Management of such rare cases in an ABO-incompatible patient has never been described before. Herein, we present successful use of extracorporeal membrane oxygenation (ECMO) support for rituximab-induced ARDS in an ABO-incompatible living donor liver transplantation (LDLT) recipient. CASE REPORT A 57-year-old man patient presented with acute-on-chronic hepatic failure. Due to worsening clinical condition and unavailability of a deceased donor organ, ABO-incompatible LDLT was considered. The patient received rituximab therapy and plasmapheresis 1 week before the transplantation to reduce the B cell count. However, he suddenly developed acute respiratory distress-like symptoms, with a chest X-ray suggesting organized pneumonia. Infectious etiology was excluded as evidenced from negative sputum and blood culture, which were repeated after 48 h. LDLT was performed and ECMO support was instituted in the immediate postoperative period due to worsening of the ARDS. The pulmonary signs improved, with a chest X-ray showing clear lung fields on the 5th postoperative day. The patient recovered well and was discharged with normal liver functions in the 4th postoperative month. CONCLUSIONS This is first reported experience of successful use of ECMO in an ABO-incompatible liver transplant recipient with rituximab-induced ARDS. This experience shows the feasibility and effectiveness of ECMO support in liver transplant recipients with poor respiratory functions.

BACKGROUND Our recent studies have highlighted the importance and safety of backtable venoplasty for middle hepatic vein (MHV) and inferior right hepatic veins (IRHV) reconstruction using expanded polytetrafluoroethylene (ePTFE) vascular grafts. In this study, we aim to analyze the complications associated with ePTFE graft use and discuss the management of the rare, but, potentially life threatening complications directly related to ePTFE conduits. MATERIAL AND METHODS From January 2012 to October 2015 a total of 397 patients underwent living donor liver transplantation (LDLT). The ePTFE vascular grafts were used during the backtable venoplasty for outflow reconstruction in 262 of the liver allografts. Recipients who developed ePTFE-related complications were analyzed. RESULTS ePTFE-related complications developed in 1.52% (4/262) of the patients. One patient (0.38%) developed complete thrombosis with sepsis at 24 months post-transplantation and died due to multiorgan failure. Three patients (1.1%) developed graft migration into the second portion of the duodenum, without overt peritonitis. Surgical exploration and ePTFE graft removal was done in all the patients. One patient died due to overwhelming sepsis. CONCLUSIONS ePTFE graft migration into the duodenum causing perforation is a new set of complications that has been recently described in LDLT and can be treated effectively by surgical removal of the infected vascular graft and duodenal perforation closure. Despite of such complications, in our experience, ePTFE use in LDLT continues to have wide safety margin, with a complication rate of only 1.52%.

Background: The reconstruction of hepatic artery (HA) is most complex step in living donor liver transplantation (LDLT) due to smaller diameter of the artery and increased risk of HA related complications. Due to smaller diameter of the HA, many centres use microsurgical technique with interrupted sutures for arterial anastomosis. Aim of our study was to retrospectively investigate the outcomes after HA reconstruction performed under magnifying loupes using “parachute technique”. Materials and Methods: From August 2002 to 31st August 2016, LDLT was performed in 766 recipients. HA reconstruction for initial 25 LDLT surgeries was performed using microsurgery technique (Era I). From May 2007 till date, HA reconstruction was performed in 741 recipients by a “parachute technique” under surgical loupes (Era II). Results: HA reconstruction was performed using surgical loupes in 737 adults (Male:Female, 526:211) and 4 pediatric patients (Male:Female, 3:1). Average diameter of the donor graft HA was 2.8 mm (range,1 to 6.5 mm). The most notable factor in this era was quick HA anastomosis procedure with a mean time of 10 ± 5 minutes (range, 5-30 minutes). In Era II, nine patients (1.21%) developed hepatic artery thrombosis (HAT) whereas 2 patients developed non-thrombotic HA related complications. Extra-anatomic HA reconstruction was performed in 14 patients due to either primary HA anastomosis failure or poor caliber recipient HA. Conclusions: Use of magnifying surgical loupes to perform HA reconstruction is safe, feasible, and yields low incidence of HA related complications. The “Parachute Technique” for HA reconstruction can achieve a speedy reconstruction without increasing risk of HAT. This article is protected by copyright. All rights reserved.

BACKGROUND Positron emission tomography-computed tomography using F-fluorodeoxyglucose (F-FDG PET/CT) has been widely used in oncology. Vascular invasion of hepatocellular carcinoma (HCC) is associated with a high risk of tumor recurrence and low survival rates after liver transplantation (LT). This retrospective study determined the predictive value of F-FDG PET/CT for vascular invasion in patients with HCC before LT. METHODS Sixty-five patients with HCC who underwent F-FDG PET/CT before LT were retrospectively included between January 2010 and July 2012. Volumes of interest (VOIs) were drawn for the tumors and normal liver tissues, and the standardized uptake value (SUV) in each VOI was measured. The maximal SUV (SUVmax) of the tumor, the ratio of tumor SUVmax to normal liver SUVmax (TSUVmax/LSUVmax), and the ratio of tumor SUVmax to normal liver SUVmean (TSUVmax/LSUVmean) were measured. The predictive value of metabolic parameters and conventional prognostic factors were analyzed. RESULTS Vascular invasion was pathologically confirmed in 15 (23.08%) of 65 patients. Compared with patients without vascular invasion, patients with vascular invasion exhibited significantly higher serum alpha-fetoprotein (AFP) (P < 0.001), larger tumor size (P = 0.001), higher tumor number (P = 0.017), and higher SUVmax, TSUVmax/LSUVmax ratio, and higher TSUVmax/LSUVmean ratio (P = 0.008, P = 0.002, and P = 0.006, respectively). Univariate analysis revealed that SUVmax, TSUVmax/LSUVmax ratio, and TSUVmax/LSUVmean ratio of FDG PET/CT were significantly associated with vascular invasion in patients with HCC before LT (P = 0.019, P = 0.018, and P = 0.015, respectively). Multivariate analysis revealed that the TSUVmax/LSUVmean ratio of F-FDG PET/CT was a significant predictor of vascular invasion (P = 0.04) and that the TSUVmax/LSUVmax ratio of F-FDG PET/CT was an independent predictor of vascular invasion, although this finding demonstrated borderline statistical significance (P = 0.06) in patients with HCC before LT. CONCLUSIONS According to the study results, the TSUVmax/LSUVmean ratio is an independent and significant predictor of vascular invasion, and the TSUVmax/LSUVmax ratio of F-FDG PET/CT is an independent predictor of vascular invasion, which is the main negative outcome after LT. Therefore, FDG PET/CT can provide vital information for determining prognosis and selecting an optimal candidate of LT for HCC.

OBJECTIVES In the Asian population, patterns and risk factors for de novo malignancies after solid-organ transplant are not well understood. MATERIALS AND METHODS Insurance claims from Taiwan's National Health Institute Research Database from 1997 to 2011 revealed 687 deceased-donor heart transplant recipients, 5038 kidney transplant recipients (50% living related-donor, 50% deceased-donor transplants), and 2127 liver transplant recipients (mainly living related-donor transplants, 30% deceased-donor transplants). During the follow-up period, rates of malignancy incidence were calculated with standardization based on national age, sex, and year-specific incidence. We used multivariate regression analyses to determine risk factors of posttransplant de novo malignancies. RESULTS Compared with the general population, several de novo cancers were more common posttransplant (P < .05): lung cancer (2.6-fold), non-melanoma skin cancer (5.8-fold), and non-Hodgkin lymphoma (5.4-fold) in heart recipients; transitional cell carcinoma (31.4-fold), renal cell carcinoma (37.3-fold), and non-Hodgkin lymphoma (3.6-fold) in kidney recipients; and gastric cancer (3.0-fold) and lymphatic-hematopoietic malignancy (4.5-fold) in liver recipients. Independent risk factors for posttransplant malignancy in kidney transplant recipients were increased age, female, hepatitis B virus, and mycophenolate use (adjusted hazard ratio 1.5; 95% confidence interval, 1.2-1.8; P < .001). In liver transplant recipients, old age was an independent risk factor. Kidney transplant recipients without diabetes or hypertension had higher risk of transitional cell carcinoma (adjusted hazard ratio 3.0; 95% confidence interval, 2.1-4.4; P < .001) and renal cell carcinoma (adjusted hazard ratio 1.9; 95% confidence interval, 1.1-3.3; P < .05). CONCLUSIONS Regional endemic epidemiologic factors play significant roles in the development of de novo cancers, particularly in kidney transplant recipients due to causes of renal failure other than diabetes and hypertension. Each regional organ transplant program should tailor and establish its surveillance protocol based on epidemiologic data. However, the type and intensity of surveillance require further and long-term investigations in this patient cohort.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Despite curative surgical resection, high recurrence of HCC after surgery results in poor patient survival. To develop prognostic markers is therefore important for better prevention and therapy of recurrent HCC to improve patient outcomes. Deletion mutations over the pre-S1 and pre-S2 gene segments of hepatitis B virus (HBV) have been closely associated with recurrence of HCC after curative surgical resection. In this study, we applied a next-generation sequencing-based approach to further evaluate the association of pre-S deletion regions with HCC recurrence. We demonstrated that the pre-S2 deletion (nucleotide 1 to 54) was the most predominant deletion regions of pre-S gene in plasma of HBV-related HCC patients. Moreover, patients with the pre-S2 deletion (nucleotide 1 to 54) exhibited a significantly higher risk of HCC recurrence after curative surgical resection than those without. The pre-S2 deletion (nucleotide 1 to 54) in plasma represented a prognostic factor that independently predicted HCC recurrence with greater performance than other clinicopathological and viral factors. Our data suggest that detection of the pre-S2 deletion (nucleotide 1 to 54) in plasma may be a promising noninvasive strategy for identifying patients at high risk for HCC recurrence after curative surgical resection.

BACKGROUND Liver allograft trauma resulting in subcapsular hematoma after living donor liver transplantation (LDLT), although rare, is a life-threatening condition and requires prompt management to avoid any catastrophe. Herein we describe our successful experience in dealing with liver allograft hematoma that developed in the post-operative period after LDLT. MATERIAL AND METHODS From January 2002 to May 2015, a total of 616 recipients underwent LDLT at our institute. The intra-operative and postoperative records of these patients were analyzed to study the cases of liver allograft hematoma. Four patients (n=4) who developed liver allograft subcapsular hematoma during the intra-operative and post-operative periods were included in study. The outcomes of these patients were studied after the administration of the medical, surgical, or combined modalities of treatment. RESULTS Out of 616 LDLT recipients, 4 (0.64%) developed subcapsular hematoma. Patients were managed by a stepwise approach: Initial non-operative management with transarterial embolization (if extravasation of the contrast was noticed during imaging studies) was performed (n=1). Three patients developed hemodynamic instability with signs of hematoma rupture and were successfully treated by surgical exploration. CONCLUSIONS Timely diagnosis and suitable management can successfully salvage a liver allograft even in the presence of massive subcapsular hematoma. Our emphasis is on perihepatic packing rather than open surgical drainage if exploration is required, which can achieve a 100% success rate.

Purpose: The purpose of this study was to study the safety of the major hepatectomy in female donors with ongoing menstruation in situations where the recipient needs urgent liver transplantation and its impact on menstrual bleeding and subsequent menstrual cycles. Materials and Methods: Fifty-eight female donors that underwent adult-to-adult living donor liver transplantation were enrolled in this study and were categorized into two groups. Group A comprised 49 female donors with normal physiological state and Group B comprised nine female donors with ongoing menstruation during the surgery. All the donors in the cohort underwent right hepatectomy including the middle hepatic vein without any blood transfusion in perioperative period. Results: Preoperative international normalized ratio (INR) in Group A and B was 1.05 ± 0.08 and 1.07 ± 0.08, respectively, while INR at postoperative day 7 in Group A donors was 1.72 ± 0.22 while in Group B donors, it was 1.75 ± 0.26. Perioperative hemoglobin drop in Group A and B was statistically insignificant (1.59 ± 0.83 g% vs 1.68 ± 1.51 g%, P = 0.78). The menstrual blood loss in both the groups was statistically comparable. Conclusions: Our study shows safety of right lobe living donation in female donors with ongoing menstruation with no increased risk of intraoperative excessive bleeding and postoperative physiological impact on their general health.

BACKGROUND Right lobe living donor liver transplantation (LDLT) remains the most common form of liver transplantation in Asia. However, reconstruction of the venous outflow in a right liver allograft may pose technical difficulties if hepatic venous variations are present. Recently, much emphasis has been given to the reconstruction of large and multiple inferior right hepatic veins (IRHVs). The method of reconstructive technique, type of vascular grafts, and the outcome after the procedure have been a point of debate. In this report we discuss the IRHV reconstruction techniques using expanded polytetrafluoroethylene (ePTFE) vascular grafts and the outcomes after such reconstruction. MATERIAL AND METHODS Out of 262 right liver allografts that underwent venous reconstruction using ePTFE vascular grafts, IRHVs required either venoplasty or second inferior vena cava (IVC) anastomosis in 99 recipients. Depending upon type of IRHV reconstruction, the recipients were divided in 2 groups: Group A (n=52): IRHV venoplasty using ePTFE graft, and group B (n=47): Direct IRHV-to-IVC anastomosis. The outcome after LDLT was compared for these 2 groups. RESULTS The ePTFE venoplasty group had significantly shorter warm ischemia time as compared to the direct to IVC anastomosis group (p

Patients with end-stage liver disease (ESLD) who develop hepatorenal syndrome (HRS) have very high mortality rates. For patients with HRS type I, median survival without specific therapy is only 2 weeks. Due to worsening clinical condition in such patients secondary to uremia and hepatic disease, some form of renal replacement therapy (RRT), either intermittent hemodialysis IHD or continuous veno−venous hemodialysis (CVVHD), must be instituted. However, the literature regarding the survival benefits of the hemodialysis for the worsening renal failure in liver cirrhotic patients remains limited. In this review, we performed a meta-analysis of nine different studies done in the last 2 decades that included 464 patients with end-stage liver disease with renal failure who received either pretransplantation or post-transplantation CVVHD. Survival of the patients was then analyzed with respect to patients with end-stage liver disease without renal failure that underwent liver transplantation (LT). Outcomes for the patients with pre-LT CVVHD were comparable with those of liver transplant recipients without renal failure. However, patients requiring post-LT hemodialysis for prolonged periods showed poor outcomes and a tendency to progress to chronic kidney disease. In all selected studies, patients with post-transplantation CVVHD for a prolonged period had a 3-year survival rate of ≤40%. This review highlights the role of pretransplantation CVVHD in selected patients with HRS who could achieve significantly better survival rates compared with patients without any renal replacement therapy or patients with post-transplantation CVVHD.

// Wei-Chun Chang 1, 2 , Shang-Fen Huang 1 , Yang-Ming Lee 2, 3 , Hsueh-Chou Lai 1, 2 , Bi-Hua Cheng 4 , Wei-Chung Cheng 1, 2 , Jason Yen-Ping Ho 1 , Long-Bin Jeng 1 , Wen-Lung Ma 1, 2, 5 1 Sex Hormone Research Center, Department of Obstetrics and Gynecology, Department of Gastroenterology, Research Center for Tumor Medical Science, and Organ Transplantation Center, China Medical University/Hospital, Taichung, Taiwan 2 Graduate Institute of Biomedical Sciences/Clinical Medical Science, School of Medicine, China Medical University, Taichung, Taiwan 3 Department of Endocrinology and Metabolism, Changhua Christian Hospital, Changhua, Taiwan 4 Department of OBs& GYN, Chia-Yi Chang-Gong Memorial Hospital, Chia-Yi, Taiwan 5 Department of Nursing, Asia University, Taichung Taiwan Correspondence to: Wen-Lung Ma, email: maverick@mail.cmu.edu.tw Keywords: cholesterol, steroidogenesis, gastric cancer, CYP19A1 Received: March 24, 2016 Accepted: November 11, 2016 Published: November 23, 2016 ABSTRACT Androgens, estrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or in vivo studies. This report used a web-based gene survival analyzer to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and estrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients. The AR, PR, ESR1 and ESR2 are progression promoters, as are the L/R route LDLR, LRP6, SR-B1 and LPL. It was found that CYP11A1, HSD3B1, CYP17, HSD17B1 and CYP19A1 promote progression, but dihydrotestosterone (DHT) converting enzyme SRD5A1 suppresses progression. Analyzing steroidogenic lipidome with a hazard ratio score algorithm found that CYP19A1 is the progression confounder in surgery, HER2 positive or negative patients. Finally, in the other patient cohort from TCGA, CYP19A1 was expressed higher in the tumor compared to that in normal counterparts, and also promoted progression. Lastly, exemestrane (type II aromatase inhibitor) dramatically suppress GCa cell growth in pharmacological tolerable doses in vitro . This work depicts a route-specific outside-in delivery of cholesterol to promote disease progression, implicating a host-to-tumor macroenvironmental regulation. The result indicating lipoprotein-mediated cholesterol entry and steroidogenesis are GCa progression biosignatures. And the exemestrane clinical trial in GCa patients of unmet medical needs is suggested.

The objective of this nationwide cohort study was to investigate the risk of peptic ulcer disease (PUD) in living liver donors (LDs). A total of 1333 LDs and 5332 matched nondonors were identified during 2003-2011. Hospitalized patients identified as LDs were assigned to the LD cohort, and the non-LD comparison cohort comprised age- and sex-matched nondonors. Cumulative incidences and hazard ratios (HRs) were calculated. The overall incidence of PUD was 1.74-fold higher in the LD cohort than in the non-LD cohort (2.14 vs. 1.48 per 1000 person-years). After adjustment for age, sex, monthly income and comorbidities, we determined that the LD cohort exhibited a higher risk of PUD than did the non-LD cohort (adjusted HR 1.74, 95% confidence interval [CI] 1.45-2.09). The incidence of PUD increased with age; the risk of PUD was 2.53-fold higher in patients aged ≥35 years (95% CI 2.14-2.99) than in those aged ≤34 years. LDs with comorbidities of osteopathies, chondropathies and acquired musculoskeletal deformities exhibited a higher risk of PUD (adjusted HR 3.93, 95% CI 2.64-5.86) compared with those without these comorbidities. LDs are associated with an increased risk of PUD after hepatectomy.

// Hsueh-Chou Lai 1, 2 , Chun-Chieh Yeh 1, 2 , Long-Bin Jeng 1 , Shang-Fen Huang 2 , Pei-Ying Liao 2 , Fu-Ju Lei 1, 2 , Wei-Chun Cheng 1, 2 , Cheng-Lung Hsu 3 , Xiujun Cai 4 , Chawnshang Chang 2, 4, 5 , Wen-Lung Ma 1, 2 1 Graduate Institution of Clinical Medical Science, and Graduate Institution of Cancer Biology, China Medical University, Taichung 40403, Taiwan 2 Sex Hormone Research Center, Organ Transplantation Center, Research Center for Tumor Medical Science, and Department of Gastroenterology, China Medical University/Hospital, Taichung 40403, Taiwan 3 Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung University/Memorial Hospital, Taoyuan 333, Taiwan 4 Chawnshang Chang Liver Cancer Center, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China 5 George Whipple Laboratory for Cancer Research, Department of Pathology, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14623, USA Correspondence to: Wen-Lung Ma, email: maverick@mail.cmu.edu.tw Chawnshang Chang, email: chang@urmc.rochester.edu Keywords: AR, HCC recurrence, CTC, CD90, anoikis Received: December 15, 2015 Accepted: May 28, 2016 Published: June 20, 2016 ABSTRACT Purpose: Although hepatectomy and liver transplantation surgery for hepatocellular carcinoma (HCC) are effective treatment modalities, the risk of recurrence remains high, particularly in patients with a high number of circulating tumor cells (CTCs) expressing cancer stem/progenitor cell markers. Androgen receptor (AR) signaling has been shown to suppress HCC metastasis in rodent models of HCC. In this study, we investigated whether AR is associated with postoperative HCC recurrence. Experimental Design: CTCs were obtained from patients with HCC who had undergone hepatectomy to investigate whether they are associated with disease outcome. AR knockout was introduced in two mouse models of spontaneous HCC (carcinogen- and hepatitis B virus-related HCC) to delineate the role that AR plays in HCC recurrence. Biological systems analysis was used to investigate the cellular and molecular mechanisms. Results: We found that the expression of AR in CTCs was negatively associated with HCC recurrence/progression after hepatectomy. Our results suggest that AR-mediated suppression of HCC recurrence/progression is governed by a three-pronged mechanism. First, AR suppresses the expression of CD90 in CTCs by upregulating Histone 3H2A. Second, AR suppresses cell migration at the transcriptome level. Third, AR promotes anoikis of CTCs via dysregulation of cytoskeletal adsorption. Conclusions: The results indicate that AR expression may be the gatekeeper of postoperative HCC recurrence. Therefore, targeting AR in presurgical down-staging procedures may serve as a secondary prevention measure against HCC recurrence in the future.

Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite curative resection, high recurrence of HCC remains a big threat, leading to poor patient outcomes. Hepatitis B virus (HBV) pre-S mutants, which harbor deletions over pre-S1 and pre-S2 gene segments of large surface proteins, have been implicated in HCC recurrence. Therefore, a reliable approach for detection of pre-S mutants is urgently needed for predicting HCC recurrence to improve patient survival. In this study, we used a next-generation sequencing (NGS)-based platform for quantitative detection of pre-S mutants in the plasma of HBV-related HCC patients and evaluated their prognostic values in HCC recurrence. We demonstrated that the presence of deletions spanning the pre-S2 gene segment and the high percentage of pre-S2 plus pre-S1 + pre-S2 deletions, either alone or in combination, was significantly and independently associated with poor recurrence-free survival and had greater prognostic performance than other clinicopathological and viral factors in predicting HCC recurrence. Our data suggest that the NGS-based quantitative detection of pre-S mutants in plasma represents a promising approach for identifying patients at high risk for HBV-related HCC recurrence after surgical resection in a noninvasive manner.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Early diagnosis and treatment of HCC remain a key goal for improving patient survival. Chronic hepatitis B virus (HBV) infection is a major risk factor for HCC development. Pre-S mutants harboring deletions in HBV large surface antigen have been well demonstrated as HBV oncoproteins that dysregulate multiple signaling pathways in hepatocytes, leading to HCC formation. The presence of pre-S mutants in plasma represents important predictive and prognostic markers for HCC in patients with chronic HBV infection. However, the method to detect pre-S mutants remains to be optimized. In this study, we developed a platform, based on the next-generation sequencing (NGS) technology, for detection of pre-S mutants in plasma of HBV-related HCC patients. Compared to the current TA cloning-based analysis, the NGS-based analysis could detect pre-S deletion quantitatively, and the detection rate was significantly more sensitive in 49 plasma analyzed (McNemar’s paired proportion test, P value

To report experience of laparoscopic liver resection (LLR) in one center. We retrospectively reviewed 436 consecutive LLRs in 411 patients between December 2010 and December 2016. On the basis of the 2008 Louisville Statement, we divided the 436 cases into two groups: Simple Group (n = 203) and Difficult Group (n = 233). The indications were HCC (n = 194), colorectal cancer liver metastasis (n = 156), benign tumors (n = 62), hepatolithiasis (n = 2), and other malignant lesions (n = 22). The median tumor size was 24 mm (range 3 to 130). Procedures of LLR included wedge resection (n = 230), one segmentectomy (n = 8), two segmentectomies (n = 12), left lateral sectionectomy (n = 75), right hepatectomy (n = 52), left hepatectomy (n = 31), extended right hepatectomy (n = 2), extended left hepatectomy (n = 5), central bisectionectomy (n = 3), right posterior sectionectomy (n = 12), and right anterior sectionectomy (n = 6). The median operative time was 228 min (range 9–843) and median blood loss was 150 ml (range 2–3500). Twenty-five cases required blood transfusion (5.7%). Conversion to open surgery was required in six cases (1.4%). The mean length of stay was 6.4 ± 2.9 days. Overall complication rate was 9.4% and major complication rate was 5%. One patient died of liver failure on the thirtieth postoperative day after a right hepatectomy. We had higher median blood loss (200 vs. 100 ml; p

Outflow reconstruction in living donor liver transplantation (LDLT) is certainly difficult in limited retrohepatic space with using right liver grafts with venous anomalies. Venoplasty of the inferior right hepatic veins (IRHVs) and middle hepatic vein (MHV) reconstruction using synthetic grafts to form a common outflow channel or a second venocaval anastomosis are available options. We aim to compare outcomes of LDLT recipients who underwent outflow reconstruction with a "V-Plasty" technique and outcomes of patients who underwent a second venocaval anastomosis. Out of 325 recipients who underwent LDLT from March 2011 to September 2014, 45 received right liver allografts that were devoid of MHV with multiple draining IRHVs (2 or more). Group A (n = 16) comprised the recipients with outflow reconstruction with a V-Plasty, and group B (n = 29) included the recipients with a second venocaval anastomosis. Group A recipients (male:female, 10:6; median age, 50.5 years) had a mean Model for End-Stage Liver Disease score of 14.7, whereas for group B recipients (male:female, 20:9; median age, 52.0 years) it was 17.2. The mean IRHV diameter for group A and B grafts was 8.3 mm each. Mean warm ischemia time for group A was significantly lower (25.2 minutes) as compared to group B recipients (34.6 minutes) with P < 0.001. The 2-month patency rates of vascular grafts were 100% for group A recipients with no evidence of thrombosis. In conclusion, the V-Plasty technique of MHV and IRHV reconstruction to form a common outflow is a new concept that proves to be a safe and feasible alternative for second venocaval anastomosis.

Background The reconstruction of outflow is a crucial step in living donor liver transplantation. This study describes a suitable technique that uses synthetic vascular conduits in presence of multiple draining veins of right lobe of liver and the outcome of the recipients to evaluate safety of using multiple synthetic grafts. Methods From March 2011 to September 2014, 325 patients underwent right lobe living donor liver transplantation. Expanded polytetra-fluoroethylene (ePTFE) grafts were used in total 155 of the liver allografts. Among these, 16 liver grafts required dual ePTFE grafts to reconstruct the outflow due to presence of multiple hepatic veins. Results The mean diameters for venous branches of segment 5 (V5) and 8 (V8) were 5 mm (range, 4–8 mm) and 7 mm (range, 5–9 mm). The mean diameter of inferior right hepatic veins was 8 mm (7–10 mm). All the recipients who received the right liver with dual ePTFE grafts showed satisfactory inflow and outflow immediately after reconstruction as measured by Doppler flowmetry. Postoperative ultrasonographic studies showed no disturbances in outflow. Protocol dynamic computed tomography performed in the second postoperative month showed 100% patency rates of the artificial grafts. At median follow-up of 24 months graft survival was achieved in 88%, whereas the patency rates of the ePTFE grafts were 100%. Conclusion The use of “V-Plasty” technique using dual artificial vascular grafts is a safe and feasible technique in the presence of various allograft venous anomalies & ensures a single venous channel for outflow reconstruction. Our study also suggests that ePTFE graft may be a useful interposition material without serious complications.

Background Splenectomy has been suggested to have an impact on immunological function, and subsequent development of cancer has been recognized as a possible adverse effect of splenectomy. This study evaluated the possible association between splenectomy and malignancy in Taiwan. Methods A cohort study consisted of including 2,603 patients with nontraumatic and 2,295 patients with traumatic splenectomy, and then randomly frequency matched with 4 participants without splenectomy. The Cox proportional hazard regression analysis was conducted to estimate the influence of splenectomy on cancer risk. Results Both nontraumatic and traumatic splenectomy had a significantly higher risk for overall cancer development (adjusted hazard ratios are 2.64 and 1.29 for nontraumatic and traumatic reasons, respectively). After adjusting for age, sex, and comorbidities, patients with splenectomy were associated with significantly higher risks for developing certain gastrointestinal tract cancers, other head and neck cancers, and hematological malignancies, and the phenomenon is more prominent in nontraumatic splenectomy group. Conclusion This nationwide population-based study found that people with splenectomy have higher risks of developing overall cancer, as well as certain site-specific cancers, especially for patients with nontraumatic reasons.

Background Whether diabetes mellitus (DM) is associated with a higher risk of perioperative mortality and mortality after liver transplantation (LTx) remains unclear. Methods We compared the risk of postoperative mortality and morbidity in DM and non-DM patients undergoing LTx. We enrolled 558 DM patients who underwent LTx from 2000 to 2010. Results DM was associated with elevated 90-day risk of post-LTx stroke. Otherwise, the DM cohort did not exhibit significantly higher risks of postoperative morbidities, such as septicemia, pneumonia, and wound infection, than the non-DM cohort. Cox proportional hazards regression model showed that patients with DM with coexisting renal manifestations were at a significantly high risk of 30-day and 90-day postoperative mortality. Further comorbidity stratification analysis showed that DM cohort exhibited higher risk of mortality than the non-DM cohort if the patients had liver cancer, or did not have hypertension, ischemic heart disease, and chronic obstructive pulmonary disease. Conclusion DM is associated with elevated risk of 90-day post-LTx. Moreover, DM patients with coexisting renal manifestations exhibited an increased postoperative risk of mortality after LTx.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, the prevalence and mortality rates of which are very high in Taiwan. The study aimed at evaluating the contribution of XRCC7 G6721T, together with cigarette smoking and alcohol drinking lifestyles, to the risk of HCC. In this hospital-based case-control study, the association of XRCC7 single nucleotide polymorphism G6721T with HCC risk was examined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) among 298 HCC patients and 889 age- and gender-matched healthy controls. The results showed that the percentages of TT, GT, and GG XRCC7 G6721T were 53.0, 41.3, and 5.7 % in the HCC patient group and 48.9, 43.1, and 8.0 % in the non-cancer control group, respectively. We have further stratified the populations by genders, cigarette smoking, and alcohol drinking status to investigate their combinative contributions with XRCC7 G6721T genotype to HCC risk. The results showed that the GG genotype of XRCC7 G6721T conducted a protective effect on HCC susceptibility which was obvious among males and drinkers, but not females, smokers, non-smokers, or non-drinkers (p = 0.0058, 0.0069, 0.1564, 0.2469, 0.9354, and 0.3416, respectively). Our results suggested that the GG and GT genotypes of X-ray repair cross-complementing group 7 (XRCC7) G6721T had no effect on HCC risk to the whole population, but had a protective effect on HCC risk among males and alcohol drinkers.

AIM To evaluate the contribution of methylenetetrahydrofolate reductase (MTHFR) genotype to the risk of colorectal cancer (CRC) in Taiwan. MATERIALS AND METHODS In this hospital-based case-control study, the role of MTHFR C677T (rs1801133) and A1298C (rs1801131) genotypes in determining CRC risk were investigated among 362 patients with CRC and an equal number of age- and gender-matched healthy individuals. RESULTS The percentages of CC, CT and TT genotypes for MTHFR rs1801133 were 64.1%, 29.8% and 6.1% in the CRC group and 51.1%, 37.0% and 11.9% in the control group, respectively (p for trend=0.0006). Analysis of the allelic frequency distribution showed that the variant T allele of MTHFR rs1801133 conferred a lower CRC susceptibility than did the wild-type C allele (odds ratio(OR)=0.66, 95% confidence interval(CI)=0.52-0.84, p=4.32×10-5). For the gene-lifestyle interaction, there were obvious protective effects of MTHFR rs1801133 T allele on the risk of CRC among non-smokers, ever smokers and non-alcohol drinkers, but not drinkers. CONCLUSION MTHFR rs1801133 T allele serves as a predictive marker for CRC risk and future studies with larger samples and functional evaluation are warranted to validate the current findings.

Purpose Chronic pancreatitis (CP) can cause fat or bile acid malabsorption due to exocrine insufficiency. Fat or bile acid malabsorption has been reported to increase the risk of urolithiasis through increased intestinal oxalate absorption. However, no studies have reported an association between CP and urolithiasis. Methods We identified 15,848 patients (age: ≥20 years) diagnosed as having CP between 2000 and 2010 from the National Health Insurance Research Database as the study cohort. Beneficiaries without a history of CP were randomly selected and propensity-matched with the study cohort in a 1:4 ratio according to age; sex; comorbidities of hyperlipidemia, diabetes, obesity, hypertension, chronic obstructive pulmonary disease, alcohol-related illness, stroke, and coronary artery disease; and the index date. The prevalence of inflammatory bowel disease (0.44%), hyperparathyroidism (0.10%), or end stage renal disease (1.55%) in CP patients was low, but these comorbidities were also considered in the analysis. All patients were followed until the end of 2011 or withdrawal from the National Health Insurance program to determine the incidence of urolithiasis. Results The cumulative incidence of urolithiasis was higher in the CP cohort than that in the non-CP cohort (log-rank test, P < 0.001) with a 1.89-fold risk of urolithiasis (95% confidence interval [CI] = 1.74–2.06). The prevalence of CP was higher in men (81.9%) and in patients younger than 49 years (63.5%; mean age: 48.5 ± 15.3 years). CP was associated with the development of urolithiasis in each age group (≤49 years: aHR = 2.00, 95% CI = 1.81–2.22; 50–64 years: aHR = 1.71, 95% CI = 1.40–2.09; ≥65 years: aHR = 1.54, 95% CI = 1.20–1.98) and each sex (women: aHR = 2.10, 95% CI = 1.67–2.66; men; aHR = 1.86, 95% CI = 1.70–2.04). Among the patients without comorbidities, the rate of urolithiasis increased from 2.93/1,000 person-years in non-CP patients to 8.28/1,000 person-years in CP patients. Among the patients with comorbidities, the rate of urolithiasis increased from 6.12/1,000 person-years in non-CP patients to 10.9/1,000 person-years in CP patients. The contribution of CP to the relative risk of urolithiasis was greater in patients without comorbidities (without comorbidities: aHR = 2.81, 95% CI = 2.30–3.44) than in those with comorbidities (aHR = 1.76, 95% CI = 1.61–1.94). Conclusion CP is associated with urolithiasis in this population-based cohort study. The contribution of CP to the relative risk of urolithiasis was even greater in patients with a lower risk of urolithiasis, such as those without other comorbidities. Our findings warrant a survey and education on urolithiasis for patients with CP.

Objective We retrospectively investigate the prevalence of gynecomastia as false-positive 2-[ 18 F]fluoro-2-deoxy-d-glucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging in patients with hepatocellular carcinoma (HCC). Methods Among the 127 male HCC patients who underwent 18 F-FDG PET/CT scan, the 18 FDG uptakes at the bilateral breasts in 9 patients with gynecomastia were recorded as standard uptake value (SUVmax) and the visual interpretation in both early and delayed images. Results The mean early SUVmax was 1.58/1.57 (right/left breast) in nine gynecomastia patients. The three patients with early visual score of 3 had higher early SUVmaxs. Conclusion Gynecomastia is a possible cause of false-positive uptake on 18 F-FDG PET/CT images.

The association between uremia and survival outcomes of patients undergoing hepatic resection for hepatocellular carcinoma (HCC) has not been well investigated, particularly for perioperative complications. This nationwide cohort study aimed to compare survival outcomes as well as perioperative mortality and complications between uremia-HCC patients and non-uremia-HCC patients who underwent hepatic resection. Using Taiwan’s National Health Institute Research Database, 149 uremia-HCC patients who underwent hepatic resection between 1996 and 2008 were enrolled. The control group comprised 596 HCC patients who also received hepatic resection during the same time period. The two groups were matched for age, gender, viral hepatitis status, and underlying liver cirrhosis. Disease-free survival, overall survival, and perioperative complications were compared between the two groups. For the uremia-HCC cohort, the 1-, 5-, and 10-year overall and disease-free survival rates were 86, 52, and 38 %, as well as 77, 27, and 18 %, respectively. The survival outcomes were comparable between uremia-HCC cohort and the HCC cohort, regardless of extent of hepatic resection. As for perioperative complications, the uremia-HCC cohort had a higher risk of postoperative infections requiring invasive interventions as well as an increased risk of life-threatening heart-associated complications, compared to the HCC cohort. Uremia did not influence survival outcomes between the uremia-HCC and the HCC cohorts, irrespective of extent of hepatic resection. This study urges a better perioperative care strategy to avoid potential cardiac and infectious complications in uremia-HCC patients.

We assessed the risk of coronary heart disease (CHD) after subtotal gastrectomy with Billroth II anastomosis (SGBIIA) for peptic ulcer disease (PUD). The Taiwan National Health Insurance Research Database was used, and 6160 patients undergoing SGBIIA for PUD were identified as the surgical cohort. A total of 24,540 patients from the PUD population not undergoing surgery selected by frequency-matching were identified as the non-surgical cohort. All patients were followed until the end of 2011 to measure the incidence of CHD. The cumulative incidence of CHD was lower in patients with SGBIIA than in those without surgery (16.9 vs 22.9 per 1000 person-year, adjusted hazard ratio [aHR] = 0.79, 95% confidence interval [CI] = 0.71–0.88). The risk of CHD, either acute coronary syndrome (ACS) (aHR = 0.83, 95% CI = 0.75–0.91) or other non-ACS CHD (aHR = 0.78, 95% CI = 0.68–0.88), was lower for the SGBIIA cohort than for the non-surgery cohort (aHR = 0.79, 95% CI = 0.71–0.88) after adjusting for age and the comorbidities of hypertension, diabetes mellitus, hyperlipidemia, stroke, congestive heart failure, chronic kidney disease, and chronic obstructive pulmonary disease. We found SGBIIA is associated with a reduced risk of CHD for PUD patients.

BACKGROUND: The aim of this study was to identify predictors of treatment failure of percutaneous catheter drainage (PCD) in patients with hepatobiliary-pancreatic cancer with pyogenic liver abscess (PLA). METHODS: Medical records of 44 patients with PLA with underlying hepatobiliary-pancreatic cancer who underwent PCD under computed tomographic guidance as primary treatment between January 2001 and December 2010 were collected and reviewed. Included patients were diagnosed with cholangiocarcinoma (n 16), hepatocellular carcinoma (n 12), pancreatic carcinoma (n 9), carcinoma of the ampulla of Vater (n 6), and gallbladder cancer (n 1). The clinical factors related to failure of PCD were determined using logistic regression. RESULTS: The median age of the 44 patients with PLA was 68 years, and 48% were men. PCD failed in 15 patients (34%). Of the 15 patients with PCD failure, 12 subsequently required surgical intervention because of either clinical deterioration or imaging that demonstrated failure of abscess resolution with PCD. Three of these patients died with the initial drain in place before resolution of the abscess. In patients requiring surgery after PCD failure, the frequency of cure or abscess resolution reached 67%. Fourteen patients (32%) died during hospitalization. Multivariate analysis identified that multiloculated abscesses (P .005) and abscesses with biliary communication (P .036) were associated with failure of PCD. CONCLUSIONS: Multiloculated abscesses and lesions with biliary communication pose a greater likelihood of failure of PCD in patients with hepatobiliary-pancreatic cancer with PLA. Early surgical intervention after PCD failure should be considered for these patients.