OBJECTIVETo report the experience in surveillance and early detection of cholangiocarcinoma (CC) and in using en bloc total hepatectomy-pancreaticoduodenectomy-orthotopic liver transplantation (OLT-Whipple) to achieve complete eradication of early-stage CC complicating primary sclerosing cholangitis (PSC).

METHODSAsymptomatic PSC patients underwent surveillance using endoscopic ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) with multilevel brushings for cytological evaluation. Patients diagnosed with CC were treated with combined extra-beam radiotherapy, lesion-focused brachytherapy, and OLT-Whipple.

RESULTSBetween January 1988 and February 2001, 42 of 119 PSC patients were followed according to the surveillance protocol. CC was detected in 8 patients, 6 of whom underwent OLT-Whipple. Of those 6 patients, 4 had stage I CC, and 2 had stage II CC. All 6 OLT-Whipple patients received combined external-beam and brachytherapy radiotherapy. The median time from diagnosis to OLT-Whipple was 144 days. One patient died 55 months post-transplant of an unrelated cause, without tumor recurrence. The other 5 were well without recurrence at 79, 82, 108, 128, 129 and 145 months.

CONCLUSIONSFor patients with PSC, ERCP surveillance cytology and intralumenal endoscopic ultrasound examination allow for early detection of CC. Broad and lesion-focused radiotherapy combined with OLT-Whipple to remove the biliary epithelium en bloc offers promising long-term, tumor-free survival. All patients tolerated this extensive surgery well with good quality of life following surgery and recovery. These findings support consideration of the complete excision of an intact biliary tree via OLT-Whipple in patients with early-stage hilar CC complicating PSC.

Adolescent ; Adult ; Bile Duct Neoplasms ; diagnosis ; radiotherapy ; surgery ; Bile Ducts, Intrahepatic ; Cholangiocarcinoma ; diagnosis ; radiotherapy ; surgery ; Disease-Free Survival ; Early Diagnosis ; Female ; Follow-Up Studies ; Hepatectomy ; Humans ; Liver Transplantation ; Male ; Mass Screening ; Middle Aged ; Pancreaticoduodenectomy ; Retrospective Studies

INTRODUCTIONThe 2005 American Association for Study of Liver Diseases (AASLD) diagnostic criteria allow non-invasive diagnosis of hepatocellular carcinoma (HCC) based on their enhancement pattern but we have observed a high incidence of atypical enhancement characteristics in HCC associated with portal vein thrombosis. This study seeks to examine the radiological features of this particular subgroup.

MATERIALS AND METHODSPatients with HCC and portal vein thrombosis who underwent pre-treatment multiphasic CT imaging were drawn from a surgical database. The arterial, portal venous and delayed phase images were assessed qualitatively and quantitatively (with region of interest [ROI] analysis) for lesion hypervascularity and washout. The background enhancement of the left and right lobes of the liver was also quantifi ed by ROI analysis.

RESULTSTwenty-fi ve lesions in 25 patients were selected for analysis. Qualitative analysis showed that 10/25 (40%) lesions demonstrated arterial hypervascularity while 16/25 (64%) lesions showed washout. Ten out of 25 (40%) lesions demonstrated both arterial hypervascularity and washout. Quantitative analysis showed that the average absolute lesion enhancement from precontrast to arterial phases was 49.1 (± 17.1) HU for hypervascular lesions compared to 23.8 (± 16.6) HU for non-hypervascular lesions (P <0.01). The mean absolute enhancement of the background liver parenchyma in the arterial phase was 13.79 (± 7.9) HU for hypervascular lesions compared to 36.6 (± 30.6) HU for non-hypervascular lesions (P = 0.03).

CONCLUSIONA large proportion of HCC with portal vein thrombosis lack characteristic arterial hypervascularity, which may be secondary to compensatory increased arterial supply to the background liver. This is a potential pitfall when applying imaging criteria for diagnosis of HCC.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; complications ; diagnostic imaging ; Female ; Humans ; Liver Neoplasms ; complications ; diagnostic imaging ; Male ; Middle Aged ; Pattern Recognition, Automated ; Portal Vein ; diagnostic imaging ; physiopathology ; Retrospective Studies ; Tomography, X-Ray Computed ; methods ; Venous Thrombosis ; diagnostic imaging ; etiology

OBJECTIVETo explore the effects of periodontal inflammation on the functions of gut barrier (ecological barrier, mechanical barrier, and immune barrier) in mice.

METHODSTwenty male C57BL/6J mice were randomly divided into perio-dontitis (P) or control (C) groups. The P group was subjected under a 10-day ligation with Porphyromonas gingivalis to induce periodontitis, whereas the C group was ligated with sham. Maxillae were obtained to assess alveolar bone loss. The phylogenetic structure and diversity of microbial communities in the gut were analyzed by 16s rRNA pyrosequencing. Immunohisto-chemical analysis was performed to determine the expressions of occludin, claudin2, and NOD2 in the ileum.

RESULTSCom-pared with the C group, the P group displayed significant alveolar bone loss (P<0.001). In addition, no significant influence on the main phyla and genus Parabacteroides of the two groups was observed (P>0.05). However, the ileum of the P group showed significantly upregulated occludin, claudin2, and NOD2 (P=0.039, P=0.011, and P=0.039, respectively).

CONCLUSIONSPeriodontal inflammation influences to some extent the mechanical and immune barrier functions of the mice gut. 
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Alveolar Bone Loss ; Animals ; Inflammation ; Male ; Mice ; Mice, Inbred C57BL ; Periodontitis ; Phylogeny ; Porphyromonas gingivalis ; RNA, Ribosomal, 16S

Objective: To understand the status, attitude and related risk factors on smoking among 18-65 years old patients with hypertension, diabetes, dyslipidemia, chronic obstructive pulmonary disease (COPD) or asthma in Beijing. Methods: Data was gathered from the 2014 Beijing Non-communicable and Chronic Disease Surveillance Program. Multiple classified cluster sampling method was used and 19 815 participants aged 18-65 were sampled from 16 districts in Beijing. Results: Among all the 18 405 participants, male hypertensive patients showed a higher rate on current smoking than the other groups (χ(2)=17.695, P<0.001). Male patients with dyslipidemia had higher current smoking rate than the other groups (χ(2)=39.292, P<0.001). However, female patients with COPD or with asthma showed higher rate on current smoking than the other groups (χ(2)=6.276, P=0.012), (χ(2)=8.245, P=0.004). Among the smokers, hypertensive patients presented lower rate (χ(2)=20.487, P<0.001) on intention of smoking concession, than the other groups. Patients with COPD showed greater intention in quitting smoking (χ(2)=6.085, P=0.048), than the other groups. Male patients with diabetes (χ(2)=9.219, P=0.010) or dyslipidemia (χ(2)=13.513, P=0.001) who had stopped smoking tobacco appeared having higher rates in keeping the current status. Results from logistic regression analyses showed that smoking was the risk factor for hypertension (OR=1.17), dyslipidemia (OR=1.25), COPD (OR=1.78), and asthma (OR=1.57). Conclusions: Patients with certain kinds of chronic diseases showed higher rate of current smoking and lower rate of quitting. Cigarette consumption appeared an important risk factor for patients with hypertension, dyslipidemia, COPD, or asthma in Beijing.
Adolescent ; Adult ; Aged ; Asthma/epidemiology* ; Beijing/epidemiology* ; Chronic Disease/epidemiology* ; Diabetes Mellitus/epidemiology* ; Female ; Humans ; Hypertension/epidemiology* ; Intention ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Risk Factors ; Smokers ; Smoking/psychology* ; Smoking Cessation ; Nicotiana/adverse effects*

BACKGROUNDIt has been reported that several baseline polymorphisms of direct-acting antivirals (DAAs) agents resistance-associated variants (RAVs) would affect the treatment outcomes of patients chronically infected with hepatitis C virus (CHC). The aim of this study is to investigate the prevalence of DAAs RAVs in treatment-naÏve GT1b CHC patients.

METHODSDirect sequencing and ultra-deep sequencing of the HCV NS3, NS5A, and NS5B gene were performed in baseline serum samples of treatment-naÏve patients infected with genotype 1b hepatitis C virus (HCVs).

RESULTSOne hundred and sixty CHC patients were studied. Complete sequence information was obtained for 145 patients (NS3), 148 patients (NS5A), and 137 patients (NS5B). Treatment-failure associated variants of DAAs were detected: 56.6% (82/145) of the patients presented S122G for simeprevir (NS3 protease inhibitor); 10.1% (14/148) of the patients presented Y93H for daclatasvir and ledipasvir (NS5A protein inhibitors); 94.2% (129/137) of the patients presented C316N for sofosbuvir (NS5B polymerase inhibitor). Nearly, all of the DAAs RAVs detected by ultra-deep sequencing could be detected by direct sequencing.

CONCLUSIONSThe majority of genotype 1b CHC patients in China present a virus population carrying HCV DAAs RAVs. Pretreatment sequencing of HCV genome might need to be performed when patients infected with GT1b HCV receiving DAAs-containing regimens in China. Population sequencing would be quite quantified for the work.

Adult ; Aged ; Antiviral Agents ; therapeutic use ; Benzimidazoles ; therapeutic use ; China ; Drug Resistance, Viral ; genetics ; Female ; Fluorenes ; therapeutic use ; Genotype ; Hepacivirus ; drug effects ; pathogenicity ; Hepatitis C ; drug therapy ; High-Throughput Nucleotide Sequencing ; Humans ; Imidazoles ; therapeutic use ; Male ; Middle Aged ; Polymorphism, Genetic ; genetics ; Simeprevir ; therapeutic use

Humans ; Adenocarcinoma/pathology* ; Lung/pathology* ; Lung Neoplasms/pathology* ; Neoplasm Invasiveness ; Retrospective Studies

Background:Entecavir (ETV) has been shown to be effective in randomized controlled trials in highly selected patients with hepatitis B virus (HBV) infection. This study aimed to evaluate the efficacy of ETV in chronic hepatitis B (CHB) patients in the real-world setting.

Methods:A total of 233 treatment-naïve, CHB patients who received at least 12 months of ETV treatment were included in this retrospective study. Rates of virological response (VR), hepatitis B s antigen (HBsAg) loss, hepatitis B e antigen (HBeAg) clearance/seroconversion, virological breakthrough, cirrhosis, and hepatocellular carcinoma were evaluated.

Results:Of 233 patients, 175 patients were male, with mean age of 43 years old, and 135 patients were HBeAg positive. The mean baseline levels of serum alanine aminotransferase and HBV DNA in all patients were 230 U/L and 6.6 log 10 IU/ml, respectively. The mean follow-up period was 28 months. The cumulative rates of achieving VR increased from 3.4% at 3 months to 94.4% at 60 months. Primary nonresponse occurred in 3 (1.3%) patients. Partial VR (PVR) occurred in 61 (26.2%) patients at 12 months. The baseline serum HBV DNA level (hazard ratio [HR], 2.054; P < 0.001) was an independent risk factor for PVR. HBsAg loss did not occur. The cumulative rates of HBeAg clearance increased from 2.2% at 3 months to 28.2% at 60 months. PVR was the significant determinant of HBeAg clearance (HR, 0.341; P = 0.026). Age (HR, 1.072; P = 0.013) and PVR (HR, 5.131; P = 0.017) were the significant determinants of cirrhosis.

Conclusions:ETV treatment was effective for HBV DNA suppression in this study, but HBsAg loss and HBeAg clearance/seroconversion rates were lower compared with previous clinical trials. PVR was associated with HBeAg clearance and cirrhosis.

Background: DNA replication and sister chromatid cohesion 1 (DSCC1) (also called DCC1) is a component of an alternative replication factor C complex that loads proliferating cell nuclear antigen onto DNA during S phase of the cell cycle. It is located at 8q24 and frequently amplified in hepatocellular carcinoma (HCC). However, the role of DSCC1 in the carcinogenesis and progress of HCC has not been fully investigated. Here, we aimed to assert the importance of DSCC1 in the HCC. Methods: In this study, copy number variation data and RNA sequencing data were used to calculate the DNA copy number and mRNA expression of DSCC1 in HCC. Quantitative polymerase chain reaction, Western blotting, and immunohistochemistry analysis were used to determine the mRNA and protein level of DSCC1 in HCC. The Kaplan-Meier analysis and univariate and multivariate Cox regression analysis were used to assess the association of DSCC1 with the overall survival (OS) of HCC patients. Moreover, lentiviral shRNA was used to knockdown DSCC1, and then, colony-forming assay, cell cycle assay, and cell proliferation assay were performed to evaluate the impact of DSCC1 silencing on HCC cell lines. Results: We found that DSCC1 was amplified and highly expressed in HCC tumor tissues than in nontumor tissues. We then found that the overexpression of both mRNA and protein of DSCC1 was linked to the bad prognosis of HCC patients. Astonishingly, the protein level of DSCC1 was an independent prognostic factor for OS (hazard ratio, 1.79; 95% confidence interval, 1.17-2.74; P = 0.007). Furthermore, the clonogenic capacity of DSCC1-amplified HCC cell lines (MHCC-97H, MHCC-97L, and Hep3B) was significantly inhibited by transduction of a lentiviral shRNA that targets DSCC1. We also showed that knockdown of DSCC1 induced G0-G1 cell cycle arrest (increased from 60% to more than 80%) and greatly inhibited the proliferation of HCC cell lines. Conclusion These results suggest that DSCC1 is a putative HCC driver gene that promotes proliferation and is associated with poor prognosis in HCC.
Blotting, Western ; Carcinoma, Hepatocellular ; genetics ; pathology ; Cell Cycle ; genetics ; physiology ; Cell Cycle Checkpoints ; genetics ; physiology ; Cell Line, Tumor ; Cell Proliferation ; genetics ; physiology ; DNA Replication ; genetics ; physiology ; Female ; Hep G2 Cells ; Humans ; Immunohistochemistry ; Liver Neoplasms ; genetics ; pathology ; Male ; Middle Aged ; Multivariate Analysis ; Proportional Hazards Models ; Real-Time Polymerase Chain Reaction

Background: Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC. Methods: RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development. Results: RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC. Conclusion RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.

BACKGROUNDBoth real-time three-dimensional echocardiography (RT3DE) and myocardial contrast echocardiography (MCE) are novel imaging techniques. The purpose of this study was to confirm the feasibility and accuracy of RT3DE combined with MCE for quantitative evaluation of myocardial perfusion defects.

METHODSThirteen dogs underwent ligation of the left anterior descending artery (LAD, n = 6) or distal branch of the left circumflex artery (LCX, n = 7) under general anaesthesia. Three to four ml of a perfluoropropane (C3F8) microbubble contrast agent was injected intravenously to assess the resulting myocardial perfusion defects with a commercially available Philips SONOS-7500 ultrasound system. After removal of the dog hearts, Evans blue dye was injected via the left and right coronary arteries to stain the myocardium at risk. In vitro anatomic measurements of myocardial mass after removal of the animals' hearts were used as controls.

RESULTSLeft ventricular (LV) mass determined by RT3DE ranged 36.7 - 68.9 g [mean, (54.6 +/- 9.6) g] before coronary artery ligation, and correlated highly (r = 0.99) with in vitro measurement of LV mass [range, 38.9 - 71.1 g; mean, (55.6 +/- 9.3) g]. There was no significant difference between RT3DE and in vitro measurements of LV mass [range, 36.7 - 68.9 g; mean, (51.3 +/- 12.5) g. Or range, 38.9 - 71.1 g; mean, (53.7 +/- 12.3) g, respectively] and under-perfused mass [range, 0 - 21.4 g; mean, (12.0 +/- 6.9) g. Or range, 0 - 19.8 g; mean, (10.8 +/- 6.3) g, respectively] after the LAD ligation (P > 0.05). Likewise, no significant difference was present between RT3DE and in vitro measurements of LV mass [range, 50.1 - 65.4 g; mean, (57.5 +/- 5.9) g. Or range, 51.5 - 65.8 g; mean, (57.3 +/- 6.4) g, respectively] and under-perfused mass [range, 0 - 25.6 g; mean, (13.3 +/- 9.6) g. Or range, 0 - 22.7 g; mean, (12.8 +/- 8.1) g, respectively] after the LCX ligation (P > 0.05). For all the animals with coronary ligation, LV mass measured by RT3DE ranged 35.9 - 68.6 g [mean, (54.8 +/- 10.0) g] and there was no significant difference between RT3DE and in vitro measurements of LV mass and under-perfused mass (P > 0.05, r = 0.99). Further, the under-perfused mass derived from RT3DE [range, 0 - 25.6 g; mean, (12.7 +/- 8.2) g] correlated strongly with the in vitro measurements [range, 0 - 22.7 g; mean, (11.9 +/- 7.2) g] (r = 0.96).

CONCLUSIONRT3DE with MCE is a rapid and accurate method for estimating LV myocardial mass and quantifying perfusion defects.

Animals ; Coronary Disease ; diagnostic imaging ; Dogs ; Echocardiography ; Echocardiography, Three-Dimensional ; Feasibility Studies ; Fluorocarbons