Lanthanum hydroxide@cellulose membranes with tunable pore sizes for selective removal of dyes with the same charges.

Adsorptive membranes for the efficient separation of dyes with the same charges are quite desirable. Herein, a novel membrane of lanthanum hydroxide/cellulose hydrogel coated filter paper (LC) was prepared through a facile strategy of dip-coating followed by freeze-shaping. With the aid of cellulose gel, the generated La(OH)3 achieved fine dispersion. In addition, the pore size of LC membrane could be regulated by altering the cellulose concentration or the lanthanum chloride dosage, which was crucial for its water flux. In particular, the obtained membrane possessed a high water flux (128.4 L m-2 h-1) and a high dye rejection (97.2 %) for anionic Congo red (CR) only driven by the gravity, which outperformed many previously reported membranes. More intriguingly, its dye rejection for anionic methyl orange (MO) was only 0.9 %, exhibiting high selectivity for dyes with the same charges. Single-solute adsorption experiments indicated that the CR adsorption on the membrane was best fitted by the pseudo-first-order kinetic model, and it followed the Langmuir monolayer adsorption mechanism.

Comprehensive analysis of coagulation indices for predicting survival in patients with biliary tract cancer.

BACKGROUND: Abnormal activation of the coagulation system has been reported in patients with malignancies, but its prognostic significance in biliary tract cancer (BTC) remains unclear. This study aims to analyze and compare the prognostic value of coagulation indices in patients with BTC. METHODS: The medical records of 450 patients with BTC who underwent surgical resection at our hospital between 2003 and 2017 were retrospectively analyzed. Time-dependent receiver operating characteristic curves were plotted to compare the predictive accuracy of coagulation indices. A predictive nomogram for overall survival (OS) was established based on the Cox regression analysis and validated in both the training and validation cohorts. A novel stratification model was created according to the total points of the nomogram. RESULTS: Fibrinogen and international normalized ratio (INR) had the best predictive accuracy among the coagulation indices considered and were also the independent prognostic factors for OS. The nomogram and the novel stratification model had satisfactory performance and outperformed TNM staging. CONCLUSIONS: The study demonstrated that coagulation indices are valuable in predicting OS in BTC, with fibrinogen and INR having the best predictive ability. The nomogram and the novel stratification model could be applied to predict survival for patients with BTC.

Public Psychosocial and Behavioral Responses in the First Wave of COVID-19 Pandemic: A Large Survey in China.

Background: The COVID-19 has grown into a global pandemic. This study investigated the public psychosocial and behavioral responses through different time periods of the pandemic, and assessed whether these changes are different in age, gender, and region. Methods: A three-phase survey was conducted through the DaDui Social Q&A Software for COVID-19. A total of 13,214 effective responses of COVID-19 were collected. Statistical analysis was performed based on their basic information and psychosocial responses. Results: The degree of attention, understanding, and cooperation with preventive and control measures of the disease increased and then decreased. The panic level gradually increased with the epidemic process. The degree of satisfaction with management measures and of confidence in defeating COVID-19 increased throughout the survey. Compared with residents in other areas, respondents from the COVID-19 epicenter (Wuhan) reported a higher degree of self-protection during the outbreak and a significantly lower degree of satisfaction with respect to government prevention and control measures during all phases. Shortages of medical supplies and low testing capacity were reported as the biggest shortcoming in the prevention and control strategies during COVID-19, and an abundance of disorderly and inaccurate information from different sources was the primary cause of panic. Conclusions and Relevance: Major public health events elicit psychosocial and behavioral changes that reflect the different phases of the biologic curve. Sufficient medical supplies and improved organization and accurate information during epidemics may reduce panic and improve compliance with requested changes in behavior. We need to recognize this natural phenomenon and our public policy preparedness should attempt to move the social/psychological curve to the left in order to minimize and flatten the biologic curve.

Prognostic Value of the Albumin-to-γ-glutamyltransferase Ratio for Gallbladder Cancer Patients and Establishing a Nomogram for Overall Survival.

Purpose: The albumin-to-γ-glutamyltransferase ratio (AGR), a novel inflammation-related index, has been reported to have prognostic importance in several malignancies but not yet in gallbladder cancer (GBC). This study intended to assess the prognostic value of AGR in GBC and to develop a nomogram based on AGR for predicting overall survival (OS) in GBC patients after surgery. Methods: Medical records of 140 qualified GBC patients between July 2003 and June 2017 were retrospectively analyzed. The function "surv_cutpoint" in the R package "survminer" was implemented to discover the optimal cut-off value of AGR. A nomogram on the fundamental of Cox model was established in the training cohort and was internally validated using calibration curves, Harrell's concordance index, time-dependent AUC plots and decisive curve analyses. Results: The optimal AGR cut-off value concerning overall survival was 2.050. Univariate and multivariate analyses demonstrated that AGR (HR=0.354, P=0.004), T stage (HR=3.114, P=0.004), R0 resection (HR=0.448, P=0.003), BMI (HR=0.470, P=0.002) and CA19-9 (HR=1.704, P=0.048) were independent predictors for OS. The nomogram combining these prognostic factors showed considerable prognostic performance in term of consistency, discrimination and net benefit. Conclusion: AGR has independent prognostic value for OS in GBC patients receiving surgery. A nomogram incorporating AGR, T stage, R0 resection, CA19-9 and BMI achieved enhanced prognostic ability.

Controlling nutritional status score as a prognostic marker to predict overall survival in resected biliary tract cancers.

BACKGROUND: The aim of our study was to explore the prognostic significance of the preoperative controlling nutritional status (CONUT) score and establish a nomogram to predict overall survival (OS) and to achieve a more accurate prognostic risk stratification. METHODS: Clinicopathological records of 371 patients who underwent surgical resection for biliary tract cancers (BTC) from December 2002 to December 2017 were reviewed retrospectively. The associations of the CONUT score with clinicopathological factors and OS were evaluated. Univariate and multivariable Cox regression analysis were used to screen out independent predictors. A nomogram was developed and validated to estimate OS. RESULTS: The CONUT score was an independent predictor of OS [hazard ratio 1.478, 95% confidence interval (CI), 1.078-2.025, P=0.015]. And patients with a high CONUT score tended to have a poor prognosis with poor differentiation (P=0.011) of tumor cells and longer hospital stays (P=0.046). Besides the CONUT score, carbohydrate antigen 19-9, surgical method, and the American Joint Committee on Cancer (AJCC; 7th edition) TNM stage were contained in the final prognostic model. An OS nomogram was generated to visually predict 1-, 3-, and 5-year OS. The C-index was 0.714 (95% CI, 0.673-0.755) and 0.679 (95% CI, 0.616-0.742) in the development and validation cohort respectively. The nomogram provided superior discriminative power than the AJCC TNM staging system. The nomogram also demonstrated good risk stratification power in the entire cohort of BTC patients as well as for both BTC and surgical method subgroups. CONCLUSIONS: The nomogram based on the CONUT score can predict OS in patients with BTCs, and it performed better than the AJCC TNM staging system.

Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure.

OBJECTIVE: Shortage of organ donors, a critical challenge for treatment of end-stage organ failure, has motivated the development of alternative strategies to generate organs in vitro. Here, we aim to describe the hepatorganoids, which is a liver tissue model generated by three-dimensional (3D) bioprinting of HepaRG cells and investigate its liver functions in vitro and in vivo. DESIGN: 3D bioprinted hepatorganoids (3DP-HOs) were constructed using HepaRG cells and bioink, according to specific 3D printing procedures. Liver functions of 3DP-HOs were detected after 7 days of differentiation in vitro, which were later transplanted into Fah-deficient mice. The in vivo liver functions of 3DP-HOs were evaluated by survival time and liver damage of mice, human liver function markers and human-specific debrisoquine metabolite production. RESULTS: 3DP-HOs broadly acquired liver functions, such as ALBUMIN secretion, drug metabolism and glycogen storage after 7 days of differentiation. After transplantation into abdominal cavity of Fah-/-Rag2-/- mouse model of liver injury, 3DP-HOs further matured and displayed increased synthesis of liver-specific proteins. Particularly, the mice acquired human-specific drug metabolism activities. Functional vascular systems were also formed in transplanted 3DP-HOs, further enhancing the material transport and liver functions of 3DP-HOs. Most importantly, transplantation of 3DP-HOs significantly improved the survival of mice. CONCLUSIONS: Our results demonstrated a comprehensive proof of principle, which indicated that 3DP-HO model of liver tissues possessed in vivo hepatic functions and alleviated liver failure after transplantation, suggesting that 3D bioprinting could be used to generate human liver tissues as the alternative transplantation donors for treatment of liver diseases.

Unique TP53 neoantigen and the immune microenvironment in long-term survivors of Hepatocellular carcinoma.

Neoantigens are T-cell antigens derived from protein-coding mutations in tumor cells. Although neoantigens have recently been linked to anti-tumor immunity in long-term survivors of cancers such as melanoma, their prognostic and immune-modulatory role in many cancer types remain unexplored. We investigate neoantigens in hepatocellular carcinoma (HCC) through a combination of whole exome sequencing (WES), RNA sequencing (RNA-seq), computational bioinformation, and immunohistochemistry. Our analysis reveals that patients carried with TP53 neoantigen have a longer overall survival than others (p = 0.0371) and they showed higher Immune score (p = 0.0441), higher cytotoxic lymphocytes infiltration (p = 0.0428), and higher CYT score (p = 0.0388). In contrast, the prognosis is not associated with TMB and neoantigen load. Our study draws a preliminary conclusion that it is not TMB or neoantigen load but the TP53 specific neoantigen is related to overall survival of HCC patients. We suggest that the TP53 neoantigen may affect prognosis by regulating anti-tumor immunity and that the TP53 neoantigen may be harnessed as potential targets for immunotherapies of HCC.

Three-dimensional bio-printing of primary human hepatocellular carcinoma for personalized medicine.

Hepatocellular carcinoma (HCC) is one of the most lethal tumors worldwide. This study aims to address the lack of faithful and available in vitro models for patient-specific drug screening for HCC. We recently established a novel modeling system using three-dimensional (3D) bioprinting technology and constructed hepatorganoids with HepaRG cells, which retain the liver function and prolong the survival of mice with liver failure after abdominal transplantation. Here we extend this modeling system to establish individualized model for hepatocellular carcinoma. HCC specimens were obtained from six patients after surgery. Primary HCC cells were isolated and mixed with gelatin and sodium alginate to form the bioink for printing. Patient-derived three-dimensional bio-printed HCC (3DP-HCC) models were successfully established afterward and grew well during long-term culture. These models retained the features of parental HCCs, including stable expression of the biomarker, stable maintenances of the genetic alterations and expression profiles. 3DP-HCC models are capable of displaying the results of drug screening intuitively and quantitatively. In conclusion, 3DP-HCC models are faithful in vitro models that are reliable in long-term culture and able to predict patient-specific drugs for personalized treatment.

Comparison of Prognostic Value of Red Cell-Related Parameters of Biliary Tract Cancer After Surgical Resection and Integration of a Prognostic Nomogram: A Retrospective Study.

INTRODUCTION: Biliary tract cancer (BTC) comprises infrequently occurring neoplasms with poor prognoses. Red blood cell-related parameters are commonly reported prognostic factors. We aimed to compare and evaluate the clinical value of red blood cell-related parameters and develop a prognostic nomogram. METHODS: The analysis involved 418 patients with BTC who underwent surgery from December 2003 to April 2017. Patients were divided into training and validation cohorts. Red blood cell-related parameters were compared using Kaplan-Meier analysis, the area under receiver-operating characteristic curve (AUC), and C-index. Predictive abilities were evaluated using Cox regression. We developed a nomogram incorporating superior parameters verified using calibration curves, internal validation, and subgroup analysis. The nomogram was compared with the tumour-node-metastasis staging system through ROC, C-index, and Kaplan-Meier analysis. RESULTS: A combined parameter comprising haemoglobin, albumin, lymphocytes, and platelets (HALP), which was superior to other red blood cell-related parameters, indicated a high risk of worse overall survival when low. Univariate analysis revealed that HALP together with other clinical characteristics was associated with overall survival. Multivariate analysis revealed that HALP, tumour-node-metastasis staging, and operative outcome were independent predictors of poor overall survival. Internal validation proved the predictive value of the nomogram. Additional statistical analyses established the advantages of the nomogram vs. tumour-node-metastasis staging. CONCLUSION: HALP was a superior red blood cell-related parameter and an independent predictor of prognosis. Our nomogram based on HALP, tumour-node-metastasis staging, and operative outcome is a promising model for predicting overall survival.

Comparison of the Prognostic Value of Platelet-Related Indices in Biliary Tract Cancer Undergoing Surgical Resection.

PURPOSE: Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. MATERIALS AND METHODS: Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell's C-statistics, calibration curves, and decisive curve analysis were used to assess the model. RESULTS: MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. CONCLUSION: MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.

Preoperative Immune Prognostic Index Can Predict the Clinical Outcomes of Patients with Gallbladder Cancer: Single-Center Experience.

PURPOSE: The immune prognostic index (IPI) has been used as a prognostic biomarker in various cancers. However, the prognostic value of the IPI in gallbladder cancer remains to be determined. PATIENTS AND METHODS: This study included 139 patients who were diagnosed with gallbladder cancer after surgical resection from 2003 to 2017. We used a Kaplan-Meier curve analysis to evaluate the overall survival (OS). Cox proportional hazards regression methodology was used to identify significant independent prognostic factors. Prognostic nomograms for predicting OS were established to achieve superior discriminatory abilities. The prognostic nomograms were verified according to the concordance index, calibration curves, and decision curve analyses in the training cohort and validation cohort. RESULTS: Of all 139 patients, 87 (62.6%) patients accepted R0 resection, 32% and 68% were stratified into the good and poor IPI group, respectively. The median OS was 55.9 (range, 5.93-182.7) months in the good IPI group and 15.47 (range, 0.29-190.37) months in the poor IPI group (P < 0.001). In the multivariate Cox model, the IPI was an independent predictor of OS along with the CA19-9, curative resection, and postoperative chemoradiotherapy. A nomogram based on these factors was efficient in predicting 1-, 3-, and 5-year survival probabilities. The nomogram showed higher sensitivity and specificity than the current cancer TNM staging system in the training cohort and validation cohort. CONCLUSION: The IPI is an independent prognostic factor in gallbladder cancer. Our IPI-based nomogram can serve as a useful and convenient prognostic tool for gallbladder cancer.

The Impacts of Systemic Immune-Inflammation Index on Clinical Outcomes in Gallbladder Carcinoma.

Background: Systemic immune-inflammation index (SII) is considered to be a prognostic marker in several cancers. However, the prognostic value of baseline pre-operative SII in gallbladder carcinoma (GBC) has not been evaluated. This study aimed to determine the prognostic significance of SII and generate a predictive nomogram. Methods: We retrospectively studied 142 GBC patients who underwent surgical resection at the Peking Union Medical College Hospital between 2003 and 2017. SII, neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR) were evaluated for their prognostic values. A multivariate Cox proportional hazards model was used for the recognition of significant factors. Then, the cohort was randomly divided into the training and the validation set. A nomogram was constructed using SII and other selected indicators in the training set. C-index, calibration plots, and decision curve analysis were performed to assess the nomogram's clinical utility in both the training and the validation set. Results: The predictive accuracy of SII (Harrell's concordance index [C-index]: 0.624), NLR (C-index: 0.626), and LMR (C-index: 0.622) was evaluated. The multivariate Cox model showed that SII was a superior independent predictor than NLR and LMR. SII level (≥600) (hazard ratio [HR]: 1.694, 95% confidence interval [CI]: 1.069-2.684, p = 0.024), carbohydrate antigen (CA) 19-9 level (≥37 U/ml) (HR: 2.407, 95% CI: 1.472-3.933, p < 0.001), and TNM stage (p = 0.026) were selected to construct a nomogram for predicting overall survival (OS). The predictive ability of this model was assessed by C-index (0.755 in the training set, 0.754 in the validation set). Good performance was demonstrated by the calibration plot. A high net benefit was proven by decision curve analysis (DCA). Conclusion: SII is an independent prognostic indicator in GBC patients after surgical resection, and the nomogram based on it is a useful tool for predicting OS.

Integrated analysis of serum lipid profile for predicting clinical outcomes of patients with malignant biliary tumor.

BACKGROUND: Serum lipids were reported to be the prognostic factors of various cancers, but their prognostic value in malignant biliary tumor (MBT) patients remains unclear. Thus we aim to assess and compare prognosis values of different serum lipids, and construct a novel prognostic nomogram based on serum lipids. METHODS: Patients with a confirmed diagnosis of MBT at our institute from 2003 to 2017 were retrospectively reviewed. Prognosis-related factors were identified via univariate and multivariate Cox regression analyses. Then the novel prognostic nomogram and a 3-tier staging system were constructed based on these factors and further compared to the TNM staging system. RESULTS: A total of 368 patients were included in this study. Seven optimal survival-related factors-TC/HDL >  10.08, apolipoprotein B >  0.9 g/L, lipoprotein> 72 mg/L, lymph node metastasis, radical cure, CA199 > 37 U/mL, and tumor differentiation -were included to construct the prognostic nomogram. The C-indexes in training and validation sets were 0.738 and 0.721, respectively. Besides, ROC curves, calibration plots, and decision curve analysis all suggested favorable discrimination and predictive ability. The nomogram also performed better predictive ability than the TNM system and nomogram without lipid parameters. And the staging system based on nomogram also presented better discriminative ability than TNM system (P < 0.001). CONCLUSIONS: The promising prognostic nomogram based on lipid parameters provided an intuitive method for performing survival prediction and facilitating individualized treatment and was a great complement to the TNM staging system in predicting overall survival.

High Systemic Inflammation Response Index (SIRI) Indicates Poor Outcome in Gallbladder Cancer Patients with Surgical Resection: A Single Institution Experience in China.

PURPOSE: The systemic inflammation response index (SIRI) has been reported to have prognostic ability in various solid tumors but has not been studied in gallbladder cancer (GBC). We aimed to determine its prognostic value in GBC. MATERIALS AND METHODS: From 2003 to 2017, patients with confirmed GBC were recruited. To determine the SIRI's optimal cutoff value, a time-dependent receiver operating characteristic curve was applied. Univariate and multivariate Cox analyses were performed for the recognition of significant factors. Then the cohort was randomly divided into the training and the validation set. A nomogram was constructed using the SIRI and other selected indicators in the training set, and compared with the TNM staging system. C-index, calibration plots, and decision curve analysis were performed to assess the nomogram's clinical utility. RESULTS: One hundred twenty-four patients were included. The SIRI's optimal cutoff value divided patients into high (≥ 0.89) and low SIRI (< 0.89) groups. Kaplan-Meier curves according to SIRI levels were significantly different (p < 0.001). The high SIRI group tended to stay longer in hospital and lost more blood during surgery. SIRI, body mass index, weight loss, carbohydrate antigen 19-9, radical surgery, and TNM stage were combined to generate a nomogram (C-index, 0.821 in the training cohort, 0.828 in the validation cohort) that was significantly superior to the TNM staging system both in the training (C-index, 0.655) and validation cohort (C-index, 0.649). CONCLUSION: The SIRI is an independent predictor of prognosis in GBC. A nomogram based on the SIRI may help physicians to precisely stratify patients and implement individualized treatment.

Time-restricted feeding causes irreversible metabolic disorders and gut microbiota shift in pediatric mice.

BACKGROUND: Time-restricted feeding regimen (TRF), that is, no food consumption for 14-16 h during the light phase per day, attenuates the fattening traits and metabolic disorders in adults. This study aims to further investigate whether TRF would be protective against similar nutritional challenges in juvenile mice. METHODS: Mice in the experimental group were treated with TRF during the first 4 weeks (considered to be the childhood phase of mice) before switching to ad libitum (AD) feeding pattern as adults; the control group with all subjects sticks to AD mode. Body weight was monitored, and serum biochemistry, sexual maturity, immune function, and gut microbiota were assessed at a certain timing. RESULTS: Mice treated with TRF during the childhood period (from weaning age) but went through AD feeding pattern as adults demonstrated the tendency of higher body weight, higher levels of serum glucose, shrunken Langerhans islets, fatty liver disease, thickening of aortic walls, delayed sexual development, increased proportion of T regulatory cells, and unhealthy gut microbiota. CONCLUSION: Childhood TRF causes pleiotropic adverse effects, including severe irreversible metabolic disorders, depressed immune function, and retarded puberty. Microbiota set the stage for TRF to employ downstream reactions on the above changes.

Alteration in gut microbiota caused by time-restricted feeding alleviate hepatic ischaemia reperfusion injury in mice.

Time-restricted feeding (TRF), that is, no caloric intake for 14-16 hours each day leads to favourable nutritional outcomes. This study is the first to investigate TRF through a surgical perspective verifying its efficacy against liver ischaemia reperfusion (I/R) injury. We randomly assigned 100 10-week-old wild-type male C57BL/6 mice into two feeding regimens: TRF and ad libitum access to food. Main outcomes were evaluated at 6, 12 and 24 hours post-I/R surgery after 12 weeks of intervention. TRF group demonstrated minor liver injury via histological study; lower serum levels of liver enzymes, glucose and lipids; higher concentrations of free fatty acid and ß-hydroxybutyrate; decreased oxidative stress and inflammatory biomarkers; as well as less severe cell apoptosis and proliferation. Further exploration indicated better gut microenvironment and intestinal epithelial tight junction function. TRF employed its positive influence on a wide spectrum of biochemical pathways and ultimately revealed protective effect against hepatic I/R injury possibly through adjusting the gut microbiota. The results referred to a strong indication of adopting better feeding pattern for surgical patients.

Reassessment of different criteria for diagnosing post-hepatectomy liver failure: a single-center study of 1683 hepatectomy.

Assessing the incidence and severity of post-hepatectomy liver failure (PHLF) can be based on different criteria, and we wished to compare the diagnostic efficiency and specificity of different PHLF criteria. Data from patients (n=1683) who received hepatectomies in the liver surgery department of Peking Union Medical College Hospital from April 2008 to August 2014 were retrospectively analyzed. Possible PHLF patients were screened according to the criteria of the International Study Group of Liver Surgery (ISGLS). Subsequently, other PHLF evaluation methods, including Child-Pugh score, "50-50" criteria, Model for End-Stage Liver Disease (MELD) score, and Clavien-Dindo classification were used to assess the suspected PHLF patients, and statistical analysis was performed for correlation of these methods with clinical prognoses. Using ISGLS grading, 40 cases (2.38%) were suspected to have PHLF, among whom 5 (0.30%) patients died. Of the 40 cases there were 9 patients of ISGLS grade A, 21 of grade B, and 10 of grade C. Among the entire group, Child-Pugh scoring showed 3 patients in grade A, 35 in grade B, and 2 in grade C, while only 5 patients met the "50-50" criteria. Interestingly, MELD scores ≥11 points were found only in 3 cases. Twenty-eight patients were classified as Clavien-Dindo grade I, 8 as grade II, 3 as grade III, and 1 as grade IV. Prothrombin time on postoperative day 5 (PT5), ISGLS, and Clavien-Dindo were found to have significant correlation with the prognosis of PHLF (r>0.5, p <0.05), thus can be used as prognosis predictors for PHLF patients.

Potential application of neogalactosylalbumin in positron emission tomography evaluation of liver function.

AIM: To investigate the evaluation of neogalactosylalbumin (NGA) for liver function assessment based on positron emission tomography technology. METHODS: Female Kunming mice were assigned randomly to two groups: fibrosis group and normal control group. A murine hepatic fibrosis model was generated by intraperitoneal injection of 10% carbon tetrachloride (CCl4) at 0.4 mL every 48 h for 42 d. 18F-labeled NGA ([18F]FNGA) was synthesized and administered at a dosage of 3.7 MBq/mouse to both fibrosis mice and normal control mice. Distribution of [18F]FNGA amongst organs was examined, and dynamic scanning was performed. Parameters were set up to compare the uptake of tracers by fibrotic liver and healthy liver. Serologic tests for liver function were also performed. RESULTS: The liver function of the fibrosis model mice was significantly impaired by the use of CCl4. In the fibrosis model mice, hepatic fibrosis was verified by naked eye assessment and pathological analysis. [18F]FNGA was found to predominantly accumulate in liver and kidneys in both control group (n = 21) and fibrosis group (n = 23). The liver uptake ability (LUA), peak time (Tp), and uptake rate (LUR) of [18F]FNGA between healthy liver (n = 8) and fibrosis liver (n = 10) were significantly different (P < 0.05, < 0.01, and < 0.05, respectively). LUA was significantly correlated with total serum protein level (TP) (P < 0.05). Tp was significantly correlated with both TP and glucose (Glu) concentration (P < 0.05 both), and LUR was significantly correlated with both total bile acid and Glu concentration (P < 0.01 and < 0.05, respectively). CONCLUSION: [18F]FNGA mainly accumulated in liver and remained for sufficient time. Functionally-impaired liver showed a significant different uptake pattern of [18F]FNGA compared to the controls.

Edmondson grade predicts survival of patients with primary clear cell carcinoma of liver after curative resection: A retrospective study with long-term follow-up.

AIM: Primary clear cell carcinoma of liver (PCCCL) is a specific and rare subtype of primary hepatocellular carcinoma (HCC). We performed a retrospective study with long-term follow-up to investigate predictive factors and prognosis of intrahepatic recurrences of PCCCL after radical resection. METHODS: We retrospectively analyzed records of 38 patients with PCCCL who were diagnosed at Peking Union Medical College Hospital between January 1989 and September 2010, with a long-term follow up to January 2015, to determine their clinical characteristics and postoperative survival. The data were compared with 400 patients received radical hepatectomy for common type hepatocellular carcinoma (CHCC) during the study period. RESULTS: PCCCL tumors were smaller than those of CHCC (P < 0.001) and the incidence of vascular invasion of tumors in PCCCL group was significantly lower than that in CHCC (P = 0.029). The 1-, 3-, and 5-year overall survival (OS) for PCCCL patients were 94.6%, 67.3%, and 58.5%, respectively; 1-, 3-, and 5-year disease-free survival (DFS) were 89.2%, 54.1%, and 48.6%, respectively. Both OS and DFS were significantly better for PCCCL patients than for CHCC (P = 0.039 and 0.044). Cox modeling showed high Edmondson grade to be the only independent predictive factor for survival of PCCCL patients, which were different from those of CHCC. CONCLUSIONS: PCCCL is a less malignant subtype of HCC than CHCC, patients with PCCCL likely have later intrahepatic recurrences and a better prognosis. Edmondson grade predicts survival of patients with PCCCL after curative resection; those with higher Edmondson grades may require more careful follow-up and aggressive post-hepatectomy therapy.