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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.

Background: As the fight against the COVID-19 epidemic continues, medical workers may have allostatic load. Objective: During the reopening of society, medical and nonmedical workers were compared in terms of allostatic load. Methods: An online study was performed; 3,590 Chinese subjects were analyzed. Socio-demographic variables, allostatic load, stress, abnormal illness behavior, global well-being, mental status, and social support were assessed. Results: There was no difference in allostatic load in medical workers compared to nonmedical workers (15.8 vs. 17.8%; p = 0.22). Multivariate conditional logistic regression revealed that anxiety (OR = 1.24; 95% CI 1.18–1.31; p < 0.01), depression (OR = 1.23; 95% CI 1.17–1.29; p < 0.01), somatization (OR = 1.20; 95% CI 1.14–1.25; p < 0.01), hostility (OR = 1.24; 95% CI 1.18–1.30; p < 0.01), and abnormal illness behavior (OR = 1.49; 95% CI 1.34–1.66; p < 0.01) were positively associated with allostatic load, while objective support (OR = 0.84; 95% CI 0.78–0.89; p < 0.01), subjective support (OR = 0.84; 95% CI 0.80–0.88; p < 0.01), utilization of support (OR = 0.80; 95% CI 0.72–0.88; p < 0.01), social support (OR = 0.90; 95% CI 0.87–0.93; p < 0.01), and global well-being (OR = 0.30; 95% CI 0.22–0.41; p < 0.01) were negatively associated. Conclusions: In the post-COVID-19 epidemic time, medical and nonmedical workers had similar allostatic load. Psychological distress and abnormal illness behavior were risk factors for it, while social support could relieve it.

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.

More options regarding the choice of direct-acting antivirals (DAAs) are helpful for avoiding individual limitations in treating hepatitis C virus (HCV) infection. We aimed to assess the efficacy and tolerability of grazoprevir (GZR)/elbasvir (EBR) treatment in genotype-1b (GT-1b) HCV-infected liver or kidney transplant recipients. In this phase 4, single-arm, open-label, multicenter trial, patients received GZR 100 mg/EBR 50 mg daily for 12 weeks. Patients with any HCV infection other than GT-1b, liver decompensation, human immunodeficiency virus, or hepatitis B virus co-infection, a history of NS5A inhibitor exposure, or any severe drug–drug interactions (DDIs), was excluded. The primary endpoint was sustained virologic response at 12 weeks posttreatment (SVR12). Of the 14 patients (10 kidney and 4 liver transplant subjects) enrolled in this study, 9 (64%) were females; the median age was 64.0 (range: 43–73) years. The regularly used immunosuppressants were tacrolimus (93%), everolimus (29%), and sirolimus (7%), with patient blood levels easily managed and generally stable (all P > 0.05 in quantile regression analysis). The rate of SVR12 was 100% in intent-to-treat analysis. Only one patient discontinued GZR/EBR therapy at 6 weeks posttreatment, due to a treatment-unrelated adverse event (AE); however, this patient remained, achieving SVR12. Most AEs were mild in severity and deemed to be not treatment-related. No organ rejection episodes or deaths occurred during the study period. The single-tablet regimen of GZR/EBR for 12 weeks is highly effective and well tolerated in GT-1b HCV-infected liver or kidney transplant recipients, and its DDIs are generally easy to manage. (This study has been registered at ClinicalTrials.gov under identifier NCT03723824.)

Recurrent renal cell carcinoma(reRCC) is associated with poor prognosis and the underlying mechanism is not yet clear. A comprehensive understanding of tumor microenvironment (TME) of reRCC may aid in designing effective anticancer therapies, including immunotherapies. Single-cell transcriptomics holds great promise for investigating the TME, however, this technique has not been used in reRCC. Here, we aimed to explore the difference in the TME and gene expression pattern between primary RCC (pRCC) and reRCC at single-cell level.We performed single-cell RNA sequencing analyses of 32,073 cells from 2 pRCC, 2 reRCC, and 3 adjacent normal kidney samples. 41 pairs of pRCC and reRCC samples were collected as a validation cohort to assess differences observed in single-cell sequencing. The prognostic significance of related cells and markers were studied in 47 RCC patients underwent immunotherapy. The function of related cells and markers were validated via in vitro and in vivo experiments.reRCC had reduced CD8We delineated the heterogeneity of reRCC and highlighted an innovative mechanism that CAFs acted as a suppressor of CD8

Background Sepsis is a highly heterogeneous syndrome with stratified severity levels and immune states. Even in patients with similar clinical appearances, the underlying signal transduction pathways are significantly different. To identify the heterogeneities of sepsis from multiple angles, we aimed to establish a combined risk model including the molecular risk score for rapid mortality prediction, pathway risk score for the identification of biological pathway variations, and immunity risk score for guidance with immune-modulation therapy. Methods We systematically searched and screened the mRNA expression profiles of patients with sepsis in the Gene Expression Omnibus public database. The screened datasets were divided into a training cohort and a validation cohort. In the training cohort, authentic prognostic predictor characteristics (differentially expressed mRNAs, pathway activity variations and immune cells) were screened for model construction through bioinformatics analysis and univariate Cox regression, and a P value less than 0.05 of univariate Cox regression on 28-day mortality was set as the cut-off value. The combined risk model was finally established by the decision tree algorithm. In the validation cohort, the model performance was assessed and validated by C statistics and the area under the receiver operating characteristic curve (AUC). Additionally, the current models were further compared in clinical value with traditional indicators, including procalcitonin (PCT) and interleukin-8 (IL-8). Results Datasets from two sepsis cohort studies with a total of 585 consecutive sepsis patients admitted to two intensive care units were downloaded as the training cohort (n = 479) and external validation cohort (n = 106). In the training cohort, 15 molecules, 20 pathways and 4 immune cells were eventually enrolled in model construction. These prognostic factors mainly reflected hypoxia, cellular injury, metabolic disorders and immune dysregulation in sepsis patients. In the validation cohort, the AUCs of the molecular model, pathway model, immune model, and combined model were 0.81, 0.82, 0.62 and 0.873, respectively. The AUCs of the traditional biomarkers (PCT and IL-8) were 0.565 and 0.585, respectively. The survival analysis indicated that patients in the high-risk group identified by models in the current study had a poor prognosis (P Conclusions In summary, the present study provides opportunities for bedside tests that could quantitatively and rapidly measure heterogeneous prognosis, underlying biological pathway variations and immune dysfunction in sepsis patients. Further therapeutic recommendations for patients with high risk scores could improve the therapeutic system for sepsis.

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 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.

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 and Aims: Improving liver regeneration (LR) capacity and thereby liver function reserve is a critical bridging strategy for managing liver failure patients. Since estrogen signaling may participate in LR, our aim was to characterize the roles of ERα and ERβ in LR. Methods: LR capacity and estradiol levels following 2/3rd partial hepatectomy (PHx) were compared in ERα-KO or ERβ-KO vs. wildtype mice. The ERα- or ERβ-related transcriptome and interactome were analyzed from regenerating livers, and then bioinformatics was used for pathway discovery and analysis of interactome-transcriptome relationships. Human hepatic progenitors (HepRG cells) and mouse Hepa1-6 hepatocytes were used to elucidate molecular interactions and functions. Results: This paper demonstrated that estrogen signals orchestrate hepatic repopulation and differentiation via distinct transcriptome patterns governed by ERα or ERβ. Cell repopulation pathway was associated with the ERα-transcriptome, but cell differentiation and metabolic function were associated with the ERβ transcriptome. Mechanistic studies linking ERs interactomes and transcriptomes discovered that ERα-Chd1 interaction promoted cell growth by upregulating Ssxb6, Crygc, and Cst1; and, ERβ-Ube3a interaction facilitated hepatic progenitor cell differentiation to hepatocytes and cholangiocytes, specifically by upregulating Ifna5. Conclusions: ERα and ERβ orchestrate liver cell proliferation and differentiation respectively, thereby promoting LR.

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.

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.

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

CENPU (centromere protein U), a centromere component essential for mitosis, relates with some cancers progression. However, it is not well illustrated in lung adenocarcinoma (LAC). Here, we aimed to investigate the potential effect of CENPU on LAC progression and prognosis. In this experiment, expression level of CENPU and association between its expression and LAC patients’ clinicopathological characteristics and prognosis were analyzed. The proliferation, migration and invasive abilities of LAC cells were determined by CCK-8, colony formation, transwell assays. Western blot was used to detect PI3K/AKT signaling key proteins. We found CENPU level was overexpressed in LAC tissues on comparing normal tissues. Moreover, CENPU overexpression correlated with clinicopathological variables and predicted an independent prognostic indicator in LAC patients. Functionally, CENPU downregulation significantly inhibited LAC cell proliferation, migration and invasion in, which was possibly mediated by PI3K/AKT pathway inactivation. Our findings insinuate targeting CENPU may be a potential therapeutic strategy for LAC.

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.

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.

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 among the leading causes of cancer-related death worldwide. Patients with hepatitis B virus (HBV) pre-S mutants in liver tissues or blood have been regarded as a high-risk population for HCC development and recurrence. Detection of pre-S mutants in clinical specimens is thus important for early diagnosis and prognosis of HCC to improve patient survival. Recently, we have developed a next-generation sequencing (NGS)-based platform that can quantitatively detect pre-S mutants in patient plasma with superior sensitivity and accuracy. In this study, we compared the pre-S genotyping results from plasma by the NGS-based analysis with those from liver tissues by the immunohistochemistry (IHC)-based analysis in 30 HBV-related HCC patients. We demonstrated that the detection rate of pre-S mutants was significantly higher by NGS- than by IHC-based analysis. There was a moderate to good agreement between both analyses in detection of pre-S mutants. Compared with the IHC, the NGS-based detection of pre-S mutants in patient plasma could determine the patterns of pre-S mutants in liver tissues more efficiently in a noninvasive manner. Our data suggest that the NGS-based platform may represent a promising approach for detection of pre-S mutants as biomarkers of HBV-related HCC in clinical practice.

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

To evaluate the contribution of methylenetetrahydrofolate reductase (MTHFR) genotype to the risk of colorectal cancer (CRC) in Taiwan.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.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=4.32×10MTHFR 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.

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.

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.

Background:After living donor liver transplantation (LDLT), rising serum bilirubin levels commonly indicate insufficient numbers of hepatocytes are available to metabolize bilirubin into biliverdin. Recovery of bilirubin levels is an important marker of hepatocyte repopulation after LDLT. Cytochrome P450 (CYP) 2A6 in humans (or cyp2a4 in rodents) can function as “bilirubin oxidase.” Functional hepatocytes contain abundant CYP2A6, which is considered a marker for hepatocyte function recovery. The aim of our study was to determine the impact of estradiol/estrogen receptor signaling on bilirubin levels during liver function recovery.Methods:We conducted a hospital-based cohort study of bilirubin levels after LDLT surgery in both liver graft donors and recipients, performed a transcriptome comparison of wild-type versus estrogen receptor (ER)α knockout mice and a bioinformatics analysis of transcriptome changes in their regenerating liver after two-third partial hepatectomy (PHx), and assayed in vitro expression of cytochrome (CYP2A6) in human hepatic progenitor cells (HepRG) treated with 17β-estradiol (E2).Results:The latency of bilirubin level reduction was shorter in women than in men, suggesting that a female factor promotes bilirubin recovery after liver transplantation surgery. In the PHx mouse model, the expression of the cyp2a4 gene was significantly lower in livers from the knockout ERα mice than in livers from their wild-type littermates; but the expression of other bilirubin metabolism–related genes were similar between these groups. Moreover, E2 or bilirubin treatments significantly promoted CYP2A6 expression in hepatocyte progenitor cells (HepRG cells). Sequence analysis revealed similar levels of aryl hydrocarbon receptor (AhR; bilirubin responsive nuclear receptor) and ESR1 binding to the promoter region of CYP2A6.Conclusions:This is the first report to demonstrate, on a molecular level, that E2/ERα signaling facilitates bilirubin metabolism in regenerating liver. Our findings contribute new knowledge to our understanding of why the latency of improved bilirubin metabolism and thereby liver function recovery is shorter in females than in males.

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 Gastric cancer is a major public health concern as the fourth most common cancer, and it is of particular relevance as the second most common cause of cancer death worldwide. We caparisoned the urinary nucleoside concentrations between the gastric patients and healthy volunteers that try to evaluate the diagnostic value in the gastric cancer. Method Urinary nucleosides from 49 gastric patients and 40 healthy volunteers were evaluated by high-performance liquid chromatography/electrospray ionization–tandem mass spectrometry (HPLC/ESI–MS/MS) under optimized conditions as determined in our previous study. Results The mean concentrations of 5 urinary nucleosides, cytidine, 3-methylcytidine (m3C), 1-methyladenosine (m1A), adenosine, and inosine, were found to be elevated in cancer patients, but only cytidine showed a significant elevation. Moreover, cytidine concentrations were significantly elevated by an average of 1.42-fold in patients with late stage (S3 + 4) disease. Combining the determined concentrations of preoperative serum alpha-fetoprotein (AFP, cutoff of 20 μg/l) or carbohydrate antigen 19-9 (CA19-9, cutoff of 37 U/ml) with the mean urinary cytidine concentration was shown to improve the diagnostic ratio (sensitivity) for gastric cancer from 16.3% (8/49 patients) to 38.8% (8 + 11/49 patients) or from 28.6% (14/49 patients) to 51.0% (14 + 11/49 patients), respectively. Conclusions Urinary cytidine may be an important adjunct biomarker for gastric cancer.

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.

Outcomes after surgeries involving physicians as patients have not been researched. This study compares postoperative adverse events between physicians as surgical patients and nonhealth professional controls. Using reimbursement claims data from Taiwan's National Health Insurance Program, we conducted a matched retrospective cohort study of 7973 physicians as surgical patients and 7973 propensity score–matched nonphysician controls receiving in-hospital major surgeries between 2004 and 2010. We compared postoperative major complications, length of hospital stay, intensive care unit (ICU), medical expenditure, and 30-day mortality. Compared with nonphysician controls, physicians as surgical patients had lower adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of postoperative deep wound infection (OR 0.63, 95% CI 0.40–0.99; P

Right lobe living donor liver transplantation form a major source of liver allografts in Asia because of the scarcity of deceased donation. However, the transplant surgeons often face challenges while managing right lobe liver allografts due to variations in vascular anatomy. Such variations have led the transplant team to adopt modifications in existing techniques of inflow and outflow reconstruction. One of such variations is presence of multiple draining inferior right hepatic veins (IRHVs). This hepatic venous anomaly pose a lot of technical difficulties in the outflow reconstruction as second and/or third anastomosis to inferior vena cava is not always possible in limited retrohepatic space. Herein, we describe the "Single oval ostium technique" using dual synthetic vascular grafts ensuring a common outflow channel for all the hepatic veins.

Objective To analyze the outcomes of patients with high Model for End-Stage Liver Disease (MELD) scores who underwent adult-to-adult live donor liver transplantation (A-A LDLT). Materials and Methods From September 2002 to October 2010, a total of 152 adult patients underwent A-A LDLT in our institution. Recipients were stratified into a low MELD score group (Group L; MELD score ≤30) and a high MELD score group (Group H; MELD score >30) to compare short-term and long-term outcomes. Results Of the 152 adult patients who underwent A-A LDLT, 9 were excluded from the analysis because they received ABO-incompatible grafts. Group H comprised 23 and Group L 120 patients. The median follow-up was 21.5 months (range, 3 to 102 m). The mean MELD score was 15.6 in Group L and 36.7 in Group H. There were no significant differences in the mean length of stay in the intensive care unit (Group L: 3.01 days vs Group H: 3.09 days, P = .932) or mean length of hospital stay (Group L: 17.89 days vs. Group H: 19.91 days, P = 0.409). There were no significant differences in 1-, 3-, or 5-year survivals between patients in Groups L versus H (91.5% vs 94.7%; 86.4% vs 94.7%; and 86.4% vs 94.7%; P = .3476, log rank). Conclusion The short-term and long-term outcomes of patients with high MELD scores who underwent A-A LDLT were similar to those of patients with low MELD scores. Therefore, we suggest that high MELD scores are not a contraindication to LDLT.

Alcoholic cirrhosis is generally accepted as a risk factor for hepatocellular carcinoma (HCC) development; however, little research has examined the relationship between nonalcoholic cirrhosis (NAC) and HCC. Thus, the aim of this study was to investigate whether NAC is associated with the risk of HCC and extrahepatic malignancies in Taiwan. We conducted a populated-based retrospective cohort study by using data from the Taiwan National Health Insurance (NHI) program. A total of 2109 patients with NAC were identified from the NHI database between 2000 and 2011. For a control group, 4 patients without NAC were frequency-matched with each NAC patient according to sex, age, and index year. We used Cox proportional hazards regression analysis to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) and determine the effects of NAC on cancer risk. The overall cancer risk was significantly higher in patients with NAC compared with those without NAC, and this association was consistent among age, sex, and comorbidity groups. The risk of developing HCC was remarkably high in the NAC group compared with in the control cohort (aHR = 122.7, 95% CI = 68.4–220.1); significantly higher risks of extrahepatic malignancies were observed in patients with digestive tract cancers and hematological malignancies. Further analyses stratified according sex, age, and follow-up duration revealed various patterns among the cancer types. The results indicate that patients with NAC in Taiwan have higher risks of HCC, digestive tract cancers, and hematological malignancies.

Purpose The purpose of the study is to evaluate the impact of fatty liver on maximum standard uptake value (SUVmax) of liver on 2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET). Materials and methods A total of 173 consecutive healthy subjects were retrospectively recruited for analysis. Subjects with acute renal disease, chronic renal disease, or malignancy were excluded. Demographic data were collected from chart records. All subjects performed whole-body FDG PET, sonography of liver, and glutamic pyruvic transaminase (GPT) level. The SUVmax of liver on FDG PET was calculated. The relationship between the severity of fatty liver and SUVmax of liver on FDG PET was analyzed. Results There were significant differences in SUVmax of liver on FDG PET in four groups: no fatty liver, mild-degree, moderate-degree, and severe-degree fatty liver on sonography diagnosis ( P =.041). After adjusting for possible covariates age, sex, body mass index, and GPT, there was a significantly negative correlation between the severity of fatty liver and SUVmax of liver on FDG PET ( β =−.20, P Conclusion Based on the results of this study, the liver cannot be used as a comparator of extrahepatic foci of equivocal increased FDG activity in patients with fatty liver disease.

Breast cancer is the most common female cancer and the fourth leading cause of cancer death among women in Taiwan. We measured urinary nucleoside levels in female breast cancer patients (n=36) to evaluate the diagnostic value of nucleosides as potential tumor markers.Purification of urinary nucleosides was performed using a 96-well solid phase extraction (SPE, cation-exchange column) procedure to decrease the variation between the single column preparations and to shorten the pretreatment time. Cation-exchange allows for the comprehensive purification of modified nucleosides, such as 2-deoxynucleosides, that are not purifiable by phenylboronic acid-based SPE. High-performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) in selected reaction monitoring (SRM) mode was used to quantify multiple nucleosides. Tubercidin was used as an internal standard. The qualitative parameters, retention time, and the parent and daughter ions used revealed that the method was more specific and sensitive than traditional UV detection.Urinary levels of 3 nucleosides, cytidine, 3-methylcytidine, and inosine were significantly higher in breast cancer patients than in normal controls (p0.01). The discriminative powers of cytidine, 3-methylcytidine, and inosine were 58%, 58%, and 62%, respectively.LC/MS/MS is a highly specific and sensitive method for rapidly screening a large number of urinary nucleosides that may be potential cancer markers. The 3-methylcytidine may be a candidate marker for breast cancer.

Since the introduction of laparoscopic colectomy, improved short-term surgical results have been noted in the literature. Therefore, efforts have shifted to reducing the invasiveness of laparoscopic surgery, resulting in the invention of single-incision laparoscopic surgery (SILS). Due to its comparable capabilities and feasibility, the implementation of SILS has rapidly grown in different fields. However, few studies discuss its true benefit compared with conventional laparoscopy. This study is the first to use SILS colectomy as an approach for malignant colon cancer. The goal of this cohort series is to compare the short-term surgical outcomes between SILS and conventional right hemicolectomy.This was a case-control study comparing SILS right hemicolectomy patients to traditional laparoscopic right hemicolectomy. The inclusion criteria were only ascending colon cecal lesions. Cases of obstruction or perforation that required emergent operation or previous abdominal surgery were excluded. These patients were specifically matched in regard to patient's age, gender, perioperative condition, surgical indication, and tumor size. No consideration or analysis of operative parameters and outcomes was made until this group was definitively selected as the best comparison cohort based on preoperative variables only.A total of 18 patients were included for SILS and the other 21 patients were completed by conventional laparoscopic right hemicolectomy. The SILS and traditional laparoscopic groups were similar in regard to age, gender, body mass index, and perioperation outcomes. Initial oncologic results were no different, including equal length of distal cut margin, numbers of harvested lymph nodes, and TMN stage. Three patients in the SILS colectomy group were converted (16.6%), and there were no conversions in the traditional laparoscopic colectomy group.Our preliminary experience with SILS right hemicolectomy demonstrated the safety of the procedure and its feasibility in malignant colon cancer. Although SILS right hemicolectomy may provide a subjective cosmetic advantage, there was no benefit in the short-term surgical outcomes. SILS is very situational, requires more effort from the surgeon, and may not offer more patient comfort. More experience with SILS and prospective trials are needed to validate it as a more favorable alternative to conventional laparoscopic colectomy.

Background The prognosis of hepatocellular carcinoma (HCC) relies mainly on histopathological imaging examinations after surgical removal of the tumor. However, the rate of tumor recurrence is still high. Defining molecular signatures comprised of a number of distinct peptide ions specific for various tumor regions may improve the classification and prognosis of HCC patients. Methods MALDI imaging technology, cluster analysis and classification software were applied to investigate patients with hepatitis B virus (HBV)-related HCC to obtain differences in protein abundance and distribution from non-tumor to tumor regions. Results A number of mass spectra obtained from non-tumor and HCC tumor sections were readily distinguishable. Progressive change was found in a distance-dependent manner from non-tumor to tumor regions within the junction section of HCC. Fourteen of the peaks were determined from non-tumor and tumor sections as classifiers to classify various non-tumor and tumor regions of the junction section of HCC. The performance of the classification test for the tumor region with a coefficient of variation (CV) of 0.16 was better than the non-tumor region, which reached a CV of 0.53. Conclusions Our findings provide peptide information pertaining to the classification of various tumor regions to supplement current histopathological analysis in tumor margins.

Hemorrhoids are very common in adults. The data regarding the incidence of high 2-fluoro-2-deoxy-D: -glucose (FDG) uptake in hemorrhoids is incomplete. In this study, we evaluated FDG uptake in hemorrhoids and calculated the rate of high FDG uptake in these lesions.One hundred and seventy six subjects who undertook whole body FDG-PET for health screening examination were investigated retrospectively. All patients had colonoscopy and 156 subjects were found to have hemorrhoids and 20 had no hemorrhoids. Quantitative analysis of FDG uptake in the anal region was performed by calculating the maximum standard uptake value (SUV(max)).The SUV(max) ranged from 1.8 to 4.1 (2.8 ± 0.6) for normal subjects and ranged from 1.4 to 8.3 (2.9 ± 0.8) for patients with hemorrhoids. No statistical difference was noted between these two groups using a Student's t-tests. If the highest SUV(max), which was 4.1 in normal subjects, was used as a cutoff, 5.1% (8/156) hemorrhoid patients had a SUV(max) greater than 4.1.Hemorrhoids can be one possible cause of focal high FDG uptake in the rectum.

Background: Mobile-bearing total ankle arthroplasty designs have achieved good clinical results for the treatment of ankle osteoarthritis. However, no direct comparison of the outcomes of total ankle arthroplasty has been made between posttraumatic and primary osteoarthritis. The purpose of the present study was to compare the clinical and radiographic outcomes of total ankle arthroplasty in patients with posttraumatic and primary osteoarthritis. Materials and Methods: The HINTEGRA total ankle arthroplasty was carried out in 65 patients (67 ankles) with symptomatic ankle osteoarthritis. Group A included 37 patients (37 ankles) with post-traumatic osteoarthritis, whereas Group B included 28 patients (30 ankles) with primary osteoarthritis. Patients were assessed clinically and radiographically at a mean followup of 38 months. Results: No significant differences were found between the two study groups in terms of American Orthopaedic Foot and Ankle Society ankle-hindfoot scales, range of motion, or radiographic values at final followup ( p > 0.05). The incidence of complications (38% in Group A, 27% in Group B) and additional procedures (54% in Group A, 27% in Group B) was significantly higher in Group A ( p = 0.014 for complications, p = 0.013 for additional procedures). One ankle was revised in Group A for a deep infection. Conclusion: The clinical and radiographic outcomes of total ankle arthroplasty for post-traumatic and primary osteoarthritis were comparable, although the incidence of complications after total ankle arthroplasty was higher in the post-traumatic osteoarthritis group. More preceding or concomitant surgeries were required in order to make the posttraumatic cases suitable for total ankle arthroplasty. Level of Evidence: III, Retrospective Comparative Series

Background Arthroscopic microfracture is frequently used to repair osteochondral lesions of the talus. However, despite the popularity of this technique, no study has been conducted on cartilage repair after microfracture by second-look arthroscopy. Purpose The purpose of the present study was to evaluate cartilage repair in osteochondral lesions of the talus by second-look arthroscopy and to compare arthroscopic findings with clinical outcomes 12 months postoperatively. Study Design Case series; Level of evidence, 4. Methods Second-look arthroscopies were performed in 20 ankles of 19 patients at 12 months postoperatively. Arthroscopic findings were classified using the Ferkel and Cheng staging system, and cartilage repair was assessed using the International Cartilage Repair System (ICRS). Clinical outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale. Results According to the Ferkel and Cheng staging at second-look arthroscopy, 7 of the 20 ankles (35%) showed incomplete healing (stage D). In terms of ICRS overall repair grades, 8 ankles (40%) were abnormal (grade III). Mean AOFAS scores for Ferkel and Cheng stages A to C (n 5 13) and stage D (n 5 7) were 88.5 and 82.0 points, and those for ICRS repair grades I and II (n 5 12) and grade III (n 5 8) were 88.7 and 82.5, respectively. Good correlations were found between AOFAS scores and Ferkel and Cheng stages and ICRS grades. Overall, 90% of ankles achieved an excellent or good AOFAS score of over 80 points. Conclusion Second-look arthroscopic findings at 12 months postoperatively after microfracture for osteochondral lesions of the talus revealed that 40% of lesions were incompletely healed. Nevertheless, the majority of patients achieved a good clinical outcome. Furthermore, postoperative clinical scores were found to be correlated with ICRS repair grades.

Increased levels of modified nucleosides have been observed in urine from patients suffering from several cancers. In this study, we evaluated whether urinary nucleosides can serve as potential tumor markers for colorectal cancer by high performance liquid chromatography-electrospray/tandem mass spectrometry (HPLC/ESI-MS/MS).A simple and specific method based on HPLC/ESI-MS/MS was developed to determine the urinary nucleosides from patients with colorectal cancer. We studied the excretion patterns of nucleosides in urine from 26 patients with colorectal cancer and 18 healthy controls.The LC/MS/MS approach with selective reaction monitoring (SRM) allowed for the sensitive determination of nucleosides in human urine samples with colorectal cancer. The mean levels of 5 urinary nucleosides (adenosine, cytidine, N(2),N(2)-dimethylguanine, 8-hydroxy-2'-deoxyguanosine and uridine) were significantly higher in the patients with colorectal cancer than in the healthy adults.The results indicate that urinary nucleosides determined by LC/MS/MS may be useful as biological markers for colorectal cancer. Our findings suggest that LC/MS/MS is a highly specific and sensitive method for rapidly screening a large number of nucleoside that may be useful as markers for cancer in humans.

Background: pyogenic liver abscess (PLA) is a potentially life-threatening disease in middle-to-old aged persons. Objective: to compare the differences in clinical features and outcomes between older and younger PLA patients, and to identify predictors of outcomes in older patients. Design: retrospective chart review of all PLA patients between July 1999 and June 2007. Setting: a 1,600-bed primary and tertiary care centre. Subjects: in total, 339 patients were enrolled and included 118 ≥65 years of age (the elderly group) and 221 patients

Acute appendicitis may become life threatening if it is complicated by retroperitoneal abscess. To the best of our knowledge, only case reports have been documented; thus, we analyzed the published experiences and reviewed this issue.In addition to two patients treated at our institution, a PubMed search identified 22 cases of acute appendicitis, complicated by retroperitoneal abscess, reported by 18 authors between 1955 and 2005. The patients' characteristics, onset of symptoms, timing and methods of diagnosis and management, and outcome are reviewed and analyzed.Most of the patients were adults (21/24, 87.5%), of whom seven were older than 65 years. None of the patients presented with the classical symptoms of acute appendicitis at the onset of the disease, and less than half (9/24) reported abdominal pain. The average interval between the onset of symptoms and diagnosis was 16 days, and the most effective diagnostic tool was computed tomography. Pathogens were usually polymicrobial, and appendectomy followed by adequate drainage of the abscess was the best treatment. The mortality rate was 16.7% (4/24), and all deaths were caused by profound sepsis. According to the available data, the average hospital stay was 27.3 days for the survivors.The formation of complicated retroperitoneal abscesses involving thigh, psoas muscle, perinephric space, or even the lateral abdominal wall is a serious complication of perforated acute appendicitis. An intra-abdominal pathological abnormality cannot be excluded in a patient presenting without abdominal symptoms. The mortality rate can only be reduced by a high index of suspicion, accurate diagnosis, and appropriate treatment.