Size selection of intrahepatic lesions for cryoablation contributes to abscopal effect and long-term survival in patients with liver metastatic melanoma receiving PD-1 blockade therapy.

OBJECTIVES: In this study, we aimed to examine parameters of cryoablation, tumor characteristics, and their correlations with distant tumor response and survival of liver metastatic melanoma patients receiving cryoablation and PD-1 blockade (cryo-PD-1) combination treatment. MATERIALS AND METHODS: A retrospective study was conducted among 45 melanoma patients who received combined PD-1 blockade therapy and cryoablation for liver metastasis from 2018 to 2022. Cox regression was utilized to determine the associations between factors and overall survival (OS). Changes in cytokines and immune cell compositions in peripheral blood samples following the combined treatment were investigated, along with their correlations with treatment response. RESULTS: The mean cycle of cryo-PD-1 combination treatment was 2.2 (range, 1-6), and the 3-month overall response rate (RECIST 1.1 criteria) was 26.7%. Of the 21 patients who failed previous PD-1 blockade therapy after diagnosis of liver metastasis, 4 (19.0%) achieved response within 3 months since combination treatment. The diameter of ablated lesion ≤ 30 mm, metastatic organs ≤ 2, and pre-treatment LDH level ≤ 300 U/L were independent prognostic factors for favorable OS. Further analysis showed patients with intrahepatic tumor size of 15-45 mm, and ablated lesion size of ≤ 30 mm had significantly higher 3-month response rate (42.9% vs 12.5%; P = 0.022) and survival time (30.5 vs 14.2 months; P = 0.045) than their counterparts. The average increase in NLR among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 3.59 ± 5.01 and 7.21 ± 12.57, respectively. The average increase in serum IL-6 levels among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 8.62 ± 7.95 pg/ml and 15.40 ± 11.43 pg/ml, respectively. CONCLUSION: Size selection of intrahepatic lesions for cryoablation is important in order to achieve abscopal effect and long-term survival among patients with liver metastatic melanoma receiving PD-1 blockade therapy.

Prevalence and risk factors of dental fluorosis among children aged 8-12 years in Shandong province of China.

This study was to investigate the prevalence and severity of children's dental fluorosis (DF) in Shandong and identified the potential risk factors for DF. A total of 87 villages in Shandong were investigated to calculate the prevalence of DF and Community Fluorosis Index (CFI) in 2018-2019. Six hundred and seventy children were enrolled to identify the potential risk factors using univariate and multivariate logistic regressions. Goodman-Kruskal Gamma was used to explore the factors related to the severity of DF. In 87 villages, 1249 of 8700 (14.36%) children still have DF. The prevalence of DF in most villages was below 40% in 2018-2019. Water fluorine concentration when selected for the study and urinary fluorine concentration were related to the risk of DF (P < 0.001). Some eating habits, like lower frequency of eating fresh vegetables, eggs, and beans, were associated with the risk of DF (P < 0.001). The high water fluorine concentration, and lower frequency of eating fresh vegetables, eggs, and beans were also related to the severity of DF (P < 0.001). DF in children in Shandong province is still a common endemic disease. This study tries to provide a useful guide for the prevention and control of DF.

An innovative experimental apparatus for the analysis of natural gas hydrate cavitation erosion process using laser-induced cavitation.

Natural gas hydrates (NGHs) are an emerging source of clean energy distributed in the pores of soil sediments in deep seabed and permafrost zones with abundant reserves. Cavitation contains enormous energy, thus allowing radial cavitation jets to improve drilling and production rates of NGHs. This paper presents an experimental apparatus that was developed to synthesize NGHs and generate cavitation bubbles by laser for the analysis of the erosion rules of NGHs by cavitation in a reservoir environment. The apparatus consists of a working fluid injection and pressure control system, a temperature control and circulation system, a laser-induced cavitation system, a visual reaction vessel, and a data acquisition and measurement system. The laser-induced cavitation erosion on NGHs and multi-bubble interaction experiments can be conducted over temperatures and pressures in the range of 0-20 °C and 0-12 MPa, respectively, in a visualized reaction vessel. Hydrophones and high-speed photography were utilized for monitoring and analyzing the erosion process within the visualized reaction vessel. In addition, bubble groups of different components in various environments can also be tested in this apparatus to obtain the interaction characteristics under different conditions. This paper discusses the basic structure and principle of the apparatus and conducts a series of experiments to verify the effect of cavitation erosion on hydrate and the feasibility of using cavitation to increase production in hydrate exploitation.

SurvivalPath:A R package for conducting personalized survival path mapping based on time-series survival data.

The survival path mapping approach has been proposed for dynamic prognostication of cancer patients using time-series survival data. The SurvivalPath R package was developed to facilitate building personalized survival path models. The package contains functions to convert time-series data into time-slices data by fixed interval based on time information of input medical records. After the pre-processing of data, under a user-defined parameters on covariates, significance level, minimum bifurcation sample size and number of time slices for analysis, survival paths can be computed using the main function, which can be visualized as a tree diagram, with important parameters annotated. The package also includes function for analyzing the connections between exposure/treatment and node transitions, and function for screening patient subgroup with specific features, which can be used for further exploration analysis. In this study, we demonstrate the application of this package in a large dataset of patients with hepatocellular carcinoma, which is embedded in the package. The SurvivalPath R package is freely available from CRAN, with source code and documentation hosted at https://github.com/zhangt369/SurvivalPath.

Black carbon-climate interactions regulate dust burdens over India revealed during COVID-19.

India as a hotspot for air pollution has heavy black carbon (BC) and dust (DU) loadings. BC has been identified to significantly impact the Indian climate. However, whether BC-climate interactions regulate Indian DU during the premonsoon season is unclear. Here, using long-term Reanalysis data, we show that Indian DU is positively correlated to northern Indian BC while negatively correlated to southern Indian BC. We further identify the mechanism of BC-dust-climate interactions revealed during COVID-19. BC reduction in northern India due to lockdown decreases solar heating in the atmosphere and increases surface albedo of the Tibetan Plateau (TP), inducing a descending atmospheric motion. Colder air from the TP together with warmer southern Indian air heated by biomass burning BC results in easterly wind anomalies, which reduces dust transport from the Middle East and Sahara and local dust emissions. The premonsoon aerosol-climate interactions delay the outbreak of the subsequent Indian summer monsoon.

Double Trouble of Air Pollution by Anthropogenic Dust.

With urbanization worldwide in recent decades, anthropogenic dust (AD) emissions due to heavy urban construction and off-road vehicle use have been increasing. Its perturbations on urban air pollution at the global scale are still unclear. Based on observations, we found that a high urban AD optical depth is often accompanied by severe non-dust aerosol optical depth in the planetary boundary layer (PBL), both magnitudes even comparable. To investigate the causes, an AD emission inventory constrained by satellite retrievals is implemented in a global climate model. The results show that AD-induced surface radiative cooling of up to -15.9 ± 4.0 W m-2 regionally leads to reduced PBL height, which deteriorates non-dust pollution, especially over India and northern China, in addition to the tremendous direct AD contribution to pollutants. The estimated global total premature mortality due to AD is 0.8 million deaths per year and is more severe in populous regions.

Investigating Mechanisms of Response or Resistance to Immune Checkpoint Inhibitors by Analyzing Cell-Cell Communications in Tumors Before and After Programmed Cell Death-1 (PD-1) Targeted Therapy: An Integrative Analysis Using Single-cell RNA and Bulk-RNA Sequencing Data.

Currently, a significant proportion of cancer patients do not benefit from programmed cell death-1 (PD-1)-targeted therapy. Overcoming drug resistance remains a challenge. In this study, single-cell RNA sequencing and bulk RNA sequencing data from samples collected before and after anti-PD-1 therapy were analyzed. Cell-cell interaction analyses were performed to determine the differences between pretreatment responders and nonresponders and the relative differences in changes from pretreatment to posttreatment status between responders and nonresponders to ultimately investigate the specific mechanisms underlying response and resistance to anti-PD-1 therapy. Bulk-RNA sequencing data were used to validate our results. Furthermore, we analyzed the evolutionary trajectory of ligands/receptors in specific cell types in responders and nonresponders. Based on pretreatment data from responders and nonresponders, we identified several different cell-cell interactions, like WNT5A-PTPRK, EGFR-AREG, AXL-GAS6 and ACKR3-CXCL12. Furthermore, relative differences in the changes from pretreatment to posttreatment status between responders and nonresponders existed in SELE-PSGL-1, CXCR3-CCL19, CCL4-SLC7A1, CXCL12-CXCR3, EGFR-AREG, THBS1-a3b1 complex, TNF-TNFRSF1A, TNF-FAS and TNFSF10-TNFRSF10D interactions. In trajectory analyses of tumor-specific exhausted CD8 T cells using ligand/receptor genes, we identified a cluster of T cells that presented a distinct pattern of ligand/receptor expression. They highly expressed suppressive genes like HAVCR2 and KLRC1, cytotoxic genes like GZMB and FASLG and the tissue-residence-related gene CCL5. These cells had increased expression of survival-related and tissue-residence-related genes, like heat shock protein genes and the interleukin-7 receptor (IL-7R), CACYBP and IFITM3 genes, after anti-PD-1 therapy. These results reveal the mechanisms underlying anti-PD-1 therapy response and offer abundant clues for potential strategies to improve immunotherapy.

Transarterial chemoembolization (TACE) combined with apatinib versus TACE combined with sorafenib in advanced hepatocellular carcinoma patients: a multicenter retrospective study.

BACKGROUND: The combination of transarterial chemoembolization (TACE) with sorafenib has demonstrated superior efficacy over sorafenib and TACE monotherapy in hepatocellular carcinoma (HCC). Apatinib, a new targeted agent, has been recently reported to prolong the survival of HCC patients, either alone or in combination with TACE. However, the superior regimen between TACE-apatinib and TACE-sorafenib in HCC patients has not been determined. In this study, we compared the efficacy and safety of TACE-apatinib versus TACE-sorafenib in advanced stage HCC patients. METHODS: The data of 201 HCC patients who had received TACE-sorafenib or TACE-apatinib between January 2016 and June 2018 in three hospitals were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and adverse effects (AEs) between the two treatment groups were compared. A subgroup analysis based on the doses of targeted agents was also performed. RESULTS: No significant differences in baseline clinicopathological features were found between the two groups except for dose reduction. The TACE-apatinib group had higher incidences of hypertension, oral or anal ulcer and proteinuria, while the TACE-sorafenib group had higher incidences of diarrhea and alopecia. Grade 3/4 AEs occurred more frequently in the TACE-apatinib group than in the TACE-sorafenib group (52.3% vs. 22.6%, P<0.001). The TACE-sorafenib group had better PFS than the TACE-apatinib group (median PFS: 5.0 vs. 6.0 months, P=0.002) while the two groups showed no difference in OS (median OS: 13.0 vs. 13.0 months, P=0.448). The TACE-apatinib group had a higher rate of targeted agent dose reduction than the TACE-sorafenib group (53.5% vs. 17.4%, P<0.001). When the patients were stratified into normal and reduced-dose subgroups, those who received TACE-sorafenib exhibited improved PFS but similar OS compared with the patients who received TACE-apatinib in the reduced-dose subgroup (median OS: 12.0 vs. 13.3 months, P=0.614; median PFS: 3.0 vs. 7.0 months, P<0.001). Multivariable analysis validated that treatments and dose reduction were independent prognostic factors for PFS among all patients. CONCLUSIONS: Compared with TACE-sorafenib, the strategy of TACE-apatinib yielded shorter PFS in advanced HCC patients while no difference in OS was observed. A high rate of AE-related dose reduction of apatinib could account for the observed differences.

Preoperative identification of microvascular invasion in hepatocellular carcinoma by XGBoost and deep learning.

PURPOSE: Microvascular invasion (MVI) is a valuable predictor of survival in hepatocellular carcinoma (HCC) patients. This study developed predictive models using eXtreme Gradient Boosting (XGBoost) and deep learning based on CT images to predict MVI preoperatively. METHODS: In total, 405 patients were included. A total of 7302 radiomic features and 17 radiological features were extracted by a radiomics feature extraction package and radiologists, respectively. We developed a XGBoost model based on radiomics features, radiological features and clinical variables and a three-dimensional convolutional neural network (3D-CNN) to predict MVI status. Next, we compared the efficacy of the two models. RESULTS: Of the 405 patients, 220 (54.3%) were MVI positive, and 185 (45.7%) were MVI negative. The areas under the receiver operating characteristic curves (AUROCs) of the Radiomics-Radiological-Clinical (RRC) Model and 3D-CNN Model in the training set were 0.952 (95% confidence interval (CI) 0.923-0.973) and 0.980 (95% CI 0.959-0.993), respectively (p = 0.14). The AUROCs of the RRC Model and 3D-CNN Model in the validation set were 0.887 (95% CI 0.797-0.947) and 0.906 (95% CI 0.821-0.960), respectively (p = 0.83). Based on the MVI status predicted by the RRC and 3D-CNN Models, the mean recurrence-free survival (RFS) was significantly better in the predicted MVI-negative group than that in the predicted MVI-positive group (RRC Model: 69.95 vs. 24.80 months, p < 0.001; 3D-CNN Model: 64.06 vs. 31.05 months, p = 0.027). CONCLUSION: The RRC Model and 3D-CNN models showed considerable efficacy in identifying MVI preoperatively. These machine learning models may facilitate decision-making in HCC treatment but requires further validation.

Assessment of Ablative Margin After Microwave Ablation for Hepatocellular Carcinoma Using Deep Learning-Based Deformable Image Registration.

Aim: To assess the ablative margin (AM) after microwave ablation (MWA) for hepatocellular carcinoma (HCC) with a deep learning-based deformable image registration (DIR) technique and analyze the relation between the AM and local tumor progression (LTP). Patients and Methods: From November 2012 to April 2019, 141 consecutive patients with single HCC (diameter ≤ 5 cm) who underwent MWA were reviewed. Baseline characteristics were collected to identify the risk factors for the determination of LTP after MWA. Contrast-enhanced magnetic resonance imaging scans were performed within 1 month before and 3 months after treatment. Complete ablation was confirmed for all lesions. The AM was measured based on the margin size between the tumor region and the deformed ablative region. To correct the misalignment, DIR between images before and after ablation was achieved by an unsupervised landmark-constrained convolutional neural network. The patients were classified into two groups according to their AMs: group A (AM ≤ 5 mm) and group B (AM > 5 mm). The cumulative LTP rates were compared between the two groups using Kaplan-Meier curves and the log-rank test. Multivariate analyses were performed on clinicopathological variables to identify factors affecting LTP. Results: After a median follow-up period of 28.9 months, LTP was found in 19 patients. The mean tumor and ablation zone sizes were 2.3 ± 0.9 cm and 3.8 ± 1.2 cm, respectively. The mean minimum ablation margin was 3.4 ± 0.7 mm (range, 0-16 mm). The DIR technique had higher AUC for 2-year LTP without a significant difference compared with the registration assessment without DL (P = 0.325). The 6-, 12-, and 24-month LTP rates were 9.9, 20.6, and 24.8%, respectively, in group A, and 4.0, 8.4, and 8.4%, respectively, in group B. There were significant differences between the two groups (P = 0.011). Multivariate analysis showed that being >65 years of age (P = 0.032, hazard ratio (HR): 2.463, 95% confidence interval (CI), 1.028-6.152) and AM ≤ 5 mm (P = 0.010, HR: 3.195, 95% CI, 1.324-7.752) were independent risk factors for LTP after MWA. Conclusion: The novel technology of unsupervised landmark-constrained convolutional neural network-based DIR is feasible and useful in evaluating the ablative effect of MWA for HCC.

Development and validation of a clinicopathological-based nomogram to predict seeding risk after percutaneous thermal ablation of primary liver carcinoma.

OBJECTIVES: To develop a clinicopathological-based nomogram to improve the prediction of the seeding risk of after percutaneous thermal ablation (PTA) in primary liver carcinoma (PLC). METHODS: A total of 2030 patients with PLC who underwent PTA were included between April 2009 and December 2018. The patients were grouped into a training dataset (n = 1024) and an external validation dataset (n = 1006). Baseline characteristics were collected to identify the risk factors of seeding after PTA. The multivariate Cox proportional hazards model based on the risk factors was used to develop the nomogram, which was used for assessment for its predictive accuracy using mainly the Harrell's C-index and receiver operating characteristic curve (AUC). RESULTS: The median follow-up time was 30.3 months (range, 3.2-115.7 months). The seeding risk was 0.89% per tumor and 1.5% per patient in the training set. The nomogram was developed based on tumor size, subcapsular, α-fetoprotein (AFP), and international normalized ratio (INR). The 1-, 2-, and 3-year cumulative seeding rates were 0.1%, 0.7% and 1.2% in the low-risk group, and 1.7%, 6.3% and 6.3% in the high-risk group, respectively, showing significant statistical difference (P < .001). The nomogram had good calibration and discriminatory abilities in the training set, with C-indexes of 0.722 (95% confidence interval [CI]: 0.661, 0.883) and AUC of 0.850 (95% CI: 0.767, 0.934). External validation with 1000 bootstrapped sample sets showed a good C-index of 0.706 (95% CI: 0.546, 0.866) and AUC of 0.736 (95% CI: 0. 646, 0.827). CONCLUSIONS: The clinicopathological-based nomogram could be used to quantify the probability of seeding risk after PTA in PLC.

Sex differences in solid pseudopapillary neoplasm of the pancreas: A population-based study.

OBJECTIVE: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor. This study aims to examine the clinicopathological features and surgical treatments of SPN and compare the clinical behavior and prognosis between men and women with SPN. METHODS: We collected the population data of patients with SPN diagnosed between 2004 and 2017 from the SEER database. The Kaplan-Meier method was used to analyze overall survival (OS) and disease-specific survival (DSS), and log-rank tests were used to evaluate the differences between subgroups. Univariate and multivariate Cox regression analyses were performed to screen out prognostic risk factors of SPN. RESULTS: A total of 378 patients with SPN were included, with 246 (65.1%) female patients. 1-, 3-, and 5-year overall survival rates were 98.9%, 95.7%, and 93.7%, respectively. Survival analysis revealed that regardless of stage, patients with SPN who underwent surgical interventions still had a significantly better prognosis than those without surgical interventions (P < .001). The patients with lymphatic dissection had a significantly better prognosis than those without lymphatic dissection (P < .001). Moreover, compared with female patients, male patients had significantly poorer OS and DSS (P < .001). Female SPN showed a bimodal age-frequency distribution with early-onset incidence at 28 years and late-onset peak incidence at 62 years, while male SPN presented a unimodal distribution with peak incidence at approximately age 64 years. In female patients, the tumor size in premenopausal females (<65 years old) was significantly larger than that in postmenopausal females (≥65 years old) (P < .001). Clinicopathological characteristic profiles were different not only between male SPN and premenopausal female SPN but also between premenopausal and postmenopausal female SPN. CONCLUSION: SPN presents indolent behavior and predominantly occurs in young women. Regardless of stage, surgical intervention is recommended. Moreover, our study is the first large enough study to demonstrate sex-related discrepancies in SPN. Thus, different treatment strategies should be designed for patients of different sexes at different ages and hormone therapy is a promising approach for SPN.

Assessment in the Survival Outcome After Transarterial Chemoembolization Combined with Cryoablation for Hepatocellular Carcinoma (Diameter > 4cm) Based on the Albumin-Bilirubin Grade and Platelet-Albumin-Bilirubin grade: A Preliminary Study.

OBJECTIVE: Based on the albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grade to assess the long-term outcomes of patients with large hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with cryoablation (TACE-CRA). MATERIALS AND METHODS: We studied 86 patients with HCC nodules (up to 3 HCCs with maximum diameters of 4.1-12.0 cm) who subsequently underwent TACE-CRA from July 2007 to August 2018. The overall survival (OS) was compared between groups classified by ALBI and PALBI grade. Baseline characteristics were collected to identify the risk factors for determination of poor OS after TACE-CRA. The prognostic performances of CTP class, ALBI and PALBI grade were compared. RESULTS: After a median follow-up time of 33.8 months, 41 patients had died. The cumulative1-, 3- and 5-year OS rates were 74.5%, 38.0% and 29.3%, respectively. Stratified according to ALBI grade, the cumulative 3- and 5-year OS rates were 41.2% and 41.2% in grade 1, respectively, and 20.9% and 9.8% in grades 2-3, respectively (P < 0.001). Stratified according to PALBI grade, the cumulative 3- and 5-year OS rates were 41.2% and 37.5% in grade 1, respectively, and 36.3% and 21.2% in grades 2-3, respectively (P = 0.002). Multivariate analysis results showed that older age, and ALBI grade 2-3 were associated with overall mortality. ALBI grade demonstrated significantly greater area under the curve values than CTP class and PALBI in predicting 1-, 3- and 5-year OS. CONCLUSION: ALBI grade offers accurate prediction of long-term outcome for patients with HCC (diameter > 4 cm) after TACE-CRA.

Role of PRDM1 in Tumor Immunity and Drug Response: A Pan-Cancer Analysis.

Background: PR domain zinc finger protein 1 (PRDM1) is a regulator of both B cell and T cell differentiation and plays a critical role in immunosuppression. Its role in tumor immunity and correlation with drug response remain unknown. Methods: This work comprehensively analyzed the transcriptional expression pattern of the PRDM1 among 33 types of malignancies from The Cancer Genome Atlas and the Genotype-Tissue Expression projects. Besides, correlation of the PRDM1 with cancer prognosis, immune infiltrates, checkpoint markers, cancer stemness and drug response were explored. Results: High expression level of PRDM1 were observed in ACC, COAD, LAML, LGG, LUAD, OV, PAAD, STAD, TGCT. Cox regression model showed high expression of PRDM1 in tumor samples correlates with poor prognosis in LGG, PAAD, UVM while favorable prognosis in KIRC, SKCM and THCA. PRDM1 expression positively correlates with the expression of LAG3, CTLA4, PDCD1 (PD-1), CD274 (PD-L1), PDCD1LG2 (PD-L2), TIGIT in the majority of 33 cancer types. PRDM1 positively correlated with TNFRSF14 in LGG and UVM among cancers with unfavorable prognosis; this correlation were weak or even negative in cancers with favorable prognosis. The top negatively enriched KEGG terms in high PRDM1 subgroup were B cell receptor signaling, T cell receptor signaling, and the top negatively enriched HALLMARK terms included IL-2-STAT5 signaling and allograft rejection. The expression of PRDM1 was found positively correlated with cancer stemness in CHOL, KIRP, TGCT, THYM and UVM. A series of targeted drugs and small-molecule drugs with promising efficacy predicted by PRDM1 level were identified. Conclusion: The clinical significance and biological impact of high transcriptional expression of PRDM1 differs across different cancers. Inhibiting the PRDM1-dependent signaling could be a novel and promising strategy of immunotherapy in cancers including LGG, PAAD and UVM.

Efficacy of Hepatic Resection vs. Radiofrequency Ablation for Patients With Very-Early-Stage or Early-Stage Hepatocellular Carcinoma: A Population-Based Study With Stratification by Age and Tumor Size.

Background: Because of the poor health conditions of elderly patients (age >65) with very-early-stage and early-stage hepatocellular carcinoma (HCC), primary treatment via hepatic resection (HR), or radiofrequency ablation (RFA) must be considered. However, few studies have examined this issue. Methods: A retrospective cohort was obtained from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Patients were grouped by tumor size (0-20, 21-30, 31-35, and 31-50 mm) and age (>65 and ≤65). Overall survival (OS) and disease-specific survival (DSS) were assessed. Results: In total, 1912 patients aged >65 and 2,784 patients aged ≤65 were analyzed after propensity score matching (PSM). For patients >65 with tumors ≤20 mm, OS and DSS did not differ significantly between the RFA and HR groups (p = 0.47 and p = 0.76, respectively). For patients with tumors measuring 21-30 mm, the HR group had better OS and a trend toward better DSS compared with the RFA group (p = 0.03 and p = 0.09, respectively). For patients with tumors measuring 31-50 mm, the HR group had better OS and DSS compared with the RFA group (p < 0.001 for both). For patients <65, the HR group had better OS and DSS compared with the RFA group for all tumor sizes. Conclusions: For elderly patients (age >65), RFA is recommended for tumors ≤20 mm. For patients older than 65 with tumors measuring 21-50 mm and for those younger than 65 with tumors of any size, HR is the better choice.

Two Nomograms to Select Hepatocellular Carcinoma Patients with Macroscopic Vascular Invasion for Hepatic Resection.

Background: Hepatocellular carcinoma (HCC) patients with macroscopic vascular invasion (MaVI) have limited lifespans. According to recent studies, surgical treatment may be the most promising option. However, the current staging system does not select patients who will benefit most from hepatic resection. Study design: A total of 123 patients undergoing hepatic resection for HCC with macroscopic vascular invasion (MaVI) between 2010 and 2014 at The Third Affiliated Hospital of Sun Yat-sen University were selected. We developed nomograms for overall survival (OS) and recurrence-free survival (RFS) using a Cox proportional hazards model. We assessed nomogram model performance based on the concordance index (C-index) and a calibration plot. Results: The 1- and 3-year overall survival (OS) rates for all patients were 84% and 71%, respectively. Correspondingly, the 1- and 3-year recurrence-free survival (RFS) rates were 55% and 35%, respectively. In the multivariate Cox model, the extent of vascular invasion, tumour count, fibrinogen, HBV DNA load and serum potassium significantly affected prognosis. The C-index of the two nomograms were 0.80 and 0.69 for OS and RFS respectively. Based on our nomogram, patients predicted to have 1-year and 3-year RFS rates of more than 80% and 56% had actual 1-year and 3-year RFS rates of 81.8% and 57.1%, respectively, including 9.0% and 17.1% of the HCC patients with MaVI in our database. Conclusion: Surgical treatments are a therapeutic option that can provide more survival benefit for HCC patients with MaVI. With the help of our nomograms, selected HCC patients with MaVI can benefit from hepatic resection and have the same survival rate as that for early-stage HCC patients.

Refining the American Joint Committee on Cancer Staging Scheme For Resectable Pancreatic Ductal Adenocarcinoma Using Recursive Partitioning Analysis.

Purpose: It remains unclear whether the recently proposed 8th edition of the American Joint Committee on Cancer (AJCC) staging scheme for pancreatic ductal adenocarcinoma (PDAC) outperforms the 7th edition. We assessed the prognostic performance of both these schemes and performed recursive partitioning analysis (RPA) to objectively regroup the 7th and 8th AJCC stages and derive a refined staging scheme. Methods: We examined 8542 patients with resectable PDAC from the 2004-2012 Surveillance, Epidemiology, and End Results database. The dataset was randomly divided into training and validation sets. The performance of different staging schemes was evaluated in terms of prognostic stratification, discriminatory ability, and prognostic homogeneity. Results: The 7th and 8th T classifications showed prominent heterogeneity within each subcategory when assessed against each other in the case of node-negative disease. RPA divided resectable PDAC into RPA-IA (8th T1N0 limited to the pancreas), RPA-IB (8th T1N0 extending beyond the pancreas, or 8th T2-T3N0 limited to the pancreas), RPA-IIA (8th T2N0 extending beyond the pancreas, or 8th T1N1-N2), RPA-IIB (8th T3N0 extending beyond the pancreas, or 8th T2-T3N1), and RPA-III stages (8th T2-T3N2) (median survival in the training set: 47, 28, 20, 16, and 14 months, respectively; P < 0.001). The RPA staging scheme outperformed the 7th and 8th AJCC classifications in terms of prognostic stratification, discriminatory ability, and prognostic homogeneity for both the training and validation sets. Conclusions: The proposed RPA staging is a superior risk-stratified tool to the 7th and 8th AJCC classifications and is not substantially more complex.

Alcohol drinking as an unfavorable prognostic factor for male patients with nasopharyngeal carcinoma.

The relationship between alcohol drinking and the prognosis of nasopharyngeal carcinoma (NPC) is unknown. To investigate the prognostic value of alcohol drinking on NPC, this retrospective study was conducted on 1923 male NPC patients. Patients were classified as current, former and non-drinkers according to their drinking status. Furthermore, they were categorized as heavy drinkers and mild/none drinkers based on the intensity and duration of alcohol drinking. Survival outcomes were compared using Kaplan-Meier analysis and Cox proportional hazards model. We found that current drinkers had significantly lower overall survival (OS) rate (5-year OS: 70.2% vs. 76.4%, P < 0.001) and locoregional recurrence-free survival (LRFS) rate (5-year LRFS: 69.3% vs. 77.5%, P < 0.001) compared with non-drinkers. Drinking ≥14 drinks/week, and drinking ≥20 years were both independent unfavorable prognostic factors for OS (hazard ratio [HR] = 1.38, 95% confidence interval [CI] 1.05-1.81, P = 0.022; HR = 1.38, 95% CI 1.09-1.75, P = 0.007). Stratified analyses further revealed that the negative impacts of alcohol were manifested mainly among older patients and among smokers. In conclusion, alcohol drinking is a useful predictor of prognosis in male NPC patients; drinkers, especially heavy drinkers have poorer prognosis.