Feasibility and Short-Term Stability of Portal Vein Infusion Port Placement by Transjugular Access.

Six pigs underwent implantation of a portal vein infusion port by transjugular access. The technical success rate was 100% (n = 6), with no surgical complications or deaths. At 1 month after implantation, the catheter tip had moved from the splenic vein to the main portal vein, while the catheter protruded into the right ventricle through the right atrium in all cases. Hence, the infusion port system has not been used in clinical practice due to its obvious displacement after implantation. However, this study provides a new idea for future exploration of portal vein infusion pathways.

Theory of Chiral p-Wave Superconductivity with Near Nodes for Sr_{2}RuO_{4}.

We use the functional renormalization group method to study a three-orbital model for superconducting Sr_{2}RuO_{4}. Although the pairing symmetry is found to be a chiral p wave, the atomic spin-orbit coupling induces near nodes for quasiparticle excitations. Our theory explains a major experimental puzzle between a d-wavelike feature observed in thermal experiments and the chiral p-wave triplet pairing revealed in nuclear-magnetic resonance and the Kerr effect.

High Epithelial Cell Adhesion Molecule-Positive Circulating Tumor Cell Count Predicts Poor Survival of Patients with Unresectable Hepatocellular Carcinoma Treated with Transcatheter Arterial Chemoembolization.

PURPOSE: To assess the role of epithelial cell adhesion molecule (EpCAM)-positive circulating tumor cell (CTC) count in predicting survival outcomes of transcatheter arterial chemoembolization in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: EpCAM-positive CTC counts were prospectively determined via CellSearch in peripheral blood of 97 patients with unresectable HCC treated with chemoembolization. The impact of each CTC cutoff point on overall survival (OS) was evaluated by univariate Cox regression analysis. Based on hazard ratio, patients were divided into 3 groups with low (CTC count 0/1), moderate (CTC count 2-5), and high (CTC count ≥ 6) levels. Correlation of CTC counts with survival was assessed by Cox proportional-hazards model. RESULTS: Eighty-nine patients met inclusion criteria and were enrolled. On multivariate Cox regression analysis, CTC count was found to be an independent predictor of OS (P = .049) and progression-free survival (PFS; P = .007) in patients treated with chemoembolization. After adjustment for confounding factors, mortality risks in the high- and moderate-level groups were 2.819 times (95% confidence interval [CI], 1.218-6.526; P = .016) and 1.301 times (95% CI, 0.630-2.685; P = .477) greater, respectively, than in the low-level group. The risk of progression was 3.705 fold higher in the high-level group (95% CI, 1.628-8.433; P = .002) and 1.648 fold higher in the moderate-level group (95% CI, 0.843-3.223; P = .144) vs the low-level group. CONCLUSIONS: High EpCAM-positive CTC count predicts poor survival of patients with unresectable HCC treated with chemoembolization.

[Effects of Different Altitudes and Sowing Dates on Direct Sowing Angelica sinensis Yield and Quality].

OBJECTIVE: To study the effects of different altitudes and sowing dates on direct sowing Angelica sinensis biomass, yield and quality, and to provide a theoretical basis for Angelica sinensis direct sowing cultivation techniques. METHODS: Two factors trials were used to research the influence of altitude and sowing dates on yield and quality of direct sowing Angelica sinensis. The altitudes were located at 2500, 2000 and 1500 m, and the sowing dates were set up at autumn August 29, and Spring April 3 and April 24. The experiments were designed with split plot. RESULTS: Under the same altitude, roots and aboveground biomass of direct sowing Angelica sinensis were higher when sowing earlier. In the same sowing date, the root and aboveground biomass was the maximum at 2 000 m altitude, followed by elevation of 1 500 m. At 2 500 m altitude, Angelica sinensis root and aboveground biomass was the minimum. Sowing at 2 000 m altitude at August 29 direct sowing Angelica sinensis showed the highest biomass and yield, reaching 13 840.95 kg/hm2, significantly higher than the other treatments. Compared with transplanting Angelica sinensis in this region, the production of direct sowing Angelica sinensis was also 15. 3% higher. Angelica sinensis medicinal grade was significantly higher than the rest of the process. Angelica sinensis extract, volatile oil and ferulic acid content had reached the standard of Chinese Pharmacopoeia. CONCLUSION: Angelica sinensis sowed in late August at 2000 m altitude has the best yield and quality on root length, root diameter, plant height, leaf number, dry and fresh matter accumulation, followed by 1500 m altitude, and 2500 m worst. Therefore, altitude range of Angelica sinensis direct sowing cultivation area can be reduced to 1500-2000 m. CONCLUSION: Angelica sinensis sowed in late August, at 2000 m altitude, the indicators like root length,root diameter,plant height,leaf number,and dry and fresh matter accumulation showed the best, followed by 1500 m altitude, 2500 m worst. Therefore, altitude range of Angelica sinensis direct sowing cultivation area can be reduced to 1500~2000 m.

Electroacupuncture and A-317491 depress the transmission of pain on primary afferent mediated by the P2X3 receptor in rats with chronic neuropathic pain states.

P2X is a family of ligand-gated ion channels that act through adenosine ATP. The P2X3 receptor plays a key role in the transmission of neuropathic pain at peripheral and spinal sites. Electroacupuncture (EA) has been used to treat neuropathic pain effectively. To determine the role of EA in neuropathic pain mediated through the P2X3 receptor in dorsal root ganglion neurons and the spinal cord, a chronic constriction injury (CCI) model was used. Sprague-Dawley rats were divided into four groups: sham CCI, CCI, CCI plus contralateral EA, and CCI plus ipsilateral EA. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were recorded. Furthermore, the expression of the P2X3 receptor was evaluated through Western blotting and immunofluorescence. The effects of EA and A-317491 were investigated through the whole-cell patch-clamp method and intrathecal administration. Our results show that the MWT and TWL of EA groups were higher than those in the CCI group, whereas the expression of the P2X3 receptor was lower than that in the CCI group. However, no significant difference was detected between the two EA groups. EA depressed the currents created by ATP and the upregulation of the P2X3 receptor in CCI rats. Additionally, EA was more potent in reducing mechanical allodynia and thermal hyperalgesia when combined with A-317491 through intrathecal administration. These results show that both contralateral and ipsilateral EA might inhibit the primary afferent transmission of neuropathic pain induced through the P2X3 receptor. In addition, EA and A-317491 might have an additive effect in inhibiting the transmission of pain mediated by the P2X3 receptor.

Subsequent Treatment after Transarterial Chemoembolization Failure/Refractoriness: A Review Based on Published Evidence.

Transarterial chemoembolization (TACE) is widely applied for the treatment of hepatocellular carcinoma. Repeat TACE is often required in clinical practice because a satisfactory tumor response may not be achieved with a single session. However, repeated TACE procedures can impair liver function and increase treatment-related adverse events, all of which prompted the introduction of the concept of "TACE failure/refractoriness". Mainly based on evidence from two retrospective studies conducted in Japan, sorafenib is recommended as the first choice for subsequent treatment after TACE failure/refractoriness. Several studies have investigated the outcomes of other subsequent treatments, including locoregional, other molecular targeted, anti-programmed death-1/anti-programed death ligand-1 therapies, and combination therapies after TACE failure/refractoriness. In this review, we summarize the up-to-date information about the outcomes of several subsequent treatment modalities after TACE failure/refractoriness.

Transarterial chemoembolization failure/refractoriness: A scientific concept or pseudo-proposition.

Multi-session transarterial chemoembolization (TACE) is usually needed for the treatment of intermediate-stage hepatocellular carcinoma (HCC), but it may not always have a positive influence on prognosis due to high heterogeneity of HCC. To avoid ineffective repeated TACE, the concept of TACE failure/refractoriness has been proposed by several organizations and is being addressed using tyrosine kinase inhibitors. The concept of TACE failure/refractoriness is controversial due to ambiguous definitions and low evidence-based data. To date, only a few studies have examined the rationality concerning the definition of TACE failure/refractoriness, although the concept has been introduced and applied in many TACE-related clinical trials. This review focuses on some of the issues related to different versions of TACE failure/refractoriness, the rationality of related definitions, and the feasibility of continuing TACE after so-called failure/refractoriness based on published evidence. A suggestion to re-define TAEC failure/refractoriness is also put forward.

Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response.

Background: Locoregional therapy combined with systemic therapy can further improve the prognoses for HCC. However, the efficacy of TACE combined with ICIs and TKIs for HCC and whether this triple therapy can activate systemic immune response are still unknown. Purpose: To identify the efficacy of TACE+ICIs+TKIs for unresectable hepatocellular carcinoma (uHCC) and its effect on systemic immunity. Materials and Methods: This single-center retrospective study was approved by the Institutional Review Board. From August 1, 2019, to March 30, 2021, patients with uHCC who received the combination therapy of TACE+ICIs+TKIs were included. Peripheral blood samples were collected at baseline and once a month for 4 months after treatment. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The dynamic change trend of circulating parameters was tested using simple linear regression. Results: Fifty-three patients with a mean age of 59 ± 10.6 years were included. TTP was 8.0 months (95% CI, 5.5-10.5) and PFS was 8.5 months (95% CI, 5.4-11.5). ORR was 52.8% and DCR was 81.1%. Twenty patients had completed analysis of biomarkers in peripheral blood. For cellular immune response, the level of circulating CD8+, CD3+ T cells and NK cells increased, the frequency of CD4+T cells and the CD4+/CD8+ ratio decreased, and among them, CD8+ T cells increased significantly. For humoral immune response, there was a significant decrease in B cells and a significant increase in Ig G, Ig κ, and Ig λ. Moreover, Ig G, Ig κ, and Ig λ were related to tumor response. Conclusion: TACE+ICIs+TKIs showed considerable efficacy in patients with uHCC. This triple therapy activated not only cell immune but also humoral immune activation. Circulating Ig G, Ig λ, and Ig κ can serve as potential biomarkers.

Transarterial Chemoembolization Combined with Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors versus Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors for Advanced Hepatocellular Carcinoma.

Objective: This study aimed to evaluate the effectiveness and safety of transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) (TACE+IT) versus ICIs plus TKIs (IT) for advanced hepatocellular carcinoma (HCC). Materials and Methods: Data of consecutive advanced HCC patients receiving TACE+IT or IT between January 2019 and December 2021 were included and were retrospectively analyzed. Propensity score matching (PSM) was performed to reduce bias due to confounding variables. The primary outcome of the study was overall survival (OS). The secondary outcomes were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs), respectively. Results: Sixty-four patients were enrolled in the study, among which 24 and 40 received TACE+IT and IT, respectively. The PSM cohort included 24 patients receiving TACE+IT (TACE+IT group) and 24 patients receiving IT (IT group) alone. During a median follow-up of 23 months, patients in TACE+IT group had significantly longer OS (median, 17.3 vs 11.8 months, P = 0.023), better ORR (41.7% vs 12.5%, P = 0.023) and DCR (79.2% vs 50.0%, P = 0.035) than those in the IT group, whereas a non-significant trend in PFS (median, 7.4 vs 6.7 months, P = 0.23) was observed. According to multivariable cox regression analysis, it was found that treatment modality was the only independent risk factor for OS (HR = 0.404, 95% CI = 0.179-0.911, P < 0.05). There were no remarkable differences in AEs associated with ICIs and TKIs between the two groups, with the exception of gastrointestinal reaction. Conclusion: TACE combined with ICIs plus TKIs significantly improved OS, ORR, and DCR and showed a relatively longer PFS trend over ICIs combined with TKIs for advanced HCC.

Performance of artificial intelligence for prognostic prediction with the albumin-bilirubin and platelet-albumin-bilirubin for cirrhotic patients with acute variceal bleeding undergoing early transjugular intrahepatic portosystemic shunt.

PURPOSE: The aim of this study was to validate and compare the prognostic performance of the albumin-bilirubin (ALBI) grade, platelet-albumin-bilirubin (PALBI) grade, Child-Pugh (CP) grade, and Model for End-Stage Liver Disease (MELD) score in predicting the 1-year variceal rebleeding probability using artificial intelligence for patients with cirrhosis and variceal bleeding undergoing early transjugular intrahepatic portosystemic shunt (TIPS) procedures. MATERIALS AND METHODS: This dual-center retrospective study included two cohorts, with patients enrolled between January 2016 and September 2018 in the training cohort and January 2017 and September 2018 in the validation cohort. In the training cohort, independent risk factors associated with the 1-year variceal rebleeding probability were identified using univariate and multivariate logistic analyses. ALBI-, PALBI-, Child-Pugh-, and MELD-based nomograms and an artificial neural network (ANN) model were established and validated internally in the training cohort and externally in the validation cohort, which included patients with variceal bleeding who were treated with preventive TIPS. RESULTS: A total of 259 patients were included. The median follow-up periods were 24.1 and 18.9 months, and the 1-year variceal rebleeding rates were 12.3% (14/114) and 10.3% (15/145) in the training and validation cohorts, respectively. In the training cohort, all four variables were identified as independent risk factors. Four nomograms were then established and showed comparable prognostic performances after internal (C-index: 0.879, 0.829, 0.874, and 0.798) and external (C-index: 0.720, 0.719, 0.718, and 0.703) validation. The ANN demonstrated that these four variables had comparable importance in predicting the 1-year variceal rebleeding probability. CONCLUSION: None of the four variables are optimal in predicting the 1-year variceal rebleeding probability for patients with cirrhosis and variceal bleeding undergoing early TIPS.

Single-Centre Retrospective Training Cohort Using Artificial Intelligence for Prognostic Prediction of Encephalopathy, Mortality, and Liver Dysfunction after Early TIPS Creation.

OBJECTIVES: Based on an artificial intelligence approach, this study attempted to establish prognostic models to predict 3-month overt hepatic encephalopathy (OHE) occurrence, 1-year mortality, and liver dysfunction for cirrhotic patients with acute variceal bleeding (AVB) treated with early transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: This retrospective study included patients treated with early TIPS between January 2016 and November 2019. Independent risk factors associated with occurrence of OHE within 3 months, 1-year mortality, and liver dysfunction after early TIPS were identified using univariate and multivariate logistic analyses. Artificial neural network (ANN) models and prognostic nomograms based on the independent risk factors were established and validated internally. RESULTS: A total of 207 patients were included, with 33 (15.9%) experienced OHE within 3 months after TIPS creation. The albumin-bilirubin grade (P = 0.015), age (≤ 65, > 65 years) (P < 0.001), gender (P = 0.002), and alcoholic cirrhosis (P = 0.013) was identified as independent risk factors associated with 3-month OHE. Presence of portal vein thrombosis (P = 0.034) and model for end-stage liver disease score (P = 0.063) were identified as independent risk factors associated with 1-year mortality. The platelet-albumin-bilirubin grade (P = 0.041) and a history of hepatic encephalopathy (P = 0.018) were identified as independent risk factors associated with liver dysfunction after TIPS creation. Three ANN models and three nomograms were then established and validated with high accuracy. CONCLUSIONS: The ANN and nomogram models have potential to accurately predict early occurrence of OHE, mortality, and liver dysfunction after early TIPS creation for cirrhotic patients with AVB.

Safety and Efficacy of Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Hepatocellular Carcinoma.

PURPOSE: To explore the safety and efficacy of transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the treatment of unresectable hepatocellular carcinoma (uHCC). MATERIALS AND METHODS: From August 2019 to July 2020, patients who received TACE combined with ICIs and TKIs were retrospectively analyzed. Treatment-related adverse events (AEs) were recorded. The Kaplan-Meier method was used to estimate time to progression (TTP) and progression-free survival (PFS). RESULTS: In total, 31 patients with uHCC were included. Eleven patients were classified as BCLC-C. Nineteen patients had multiple lesions, and the cumulative targeted lesions were 69 mm (range, 21-170 mm) according to mRECIST. Twenty-nine (93%) patients experienced at least one AE during the treatment. Four (12.9%) patients developed AEs of higher grade (grade≥3). The objective response rate (ORR) and disease control rate (DCR) were 64.5% and 77.4%, respectively. The median time to response was 7 weeks (range, 4-30 w), and the duration of response was 17.5 weeks (range, 2-46 w). From the first ICIs, TTP and PFS were 6.5 months (95% CI, 3.5-11) and 8.5 months (95% CI, 3.5-NE), respectively. CONCLUSIONS: TACE combined with ICIs and TKIs shows an acceptable safety profile and considerable efficacy in patients with HCC.

Re-evaluating Transarterial Chemoembolization Failure/Refractoriness: A Survey by Chinese College of Interventionalists.

BACKGROUND AND AIMS: The recognition of transarterial chemoembolization (TACE) failure/refractoriness among Chinese clinicians remains unclear. Using an online survey conducted by the Chinese College of Interventionalists (CCI), the aim of this study was to explore the recognition of TACE failure/refractoriness and review TACE application for hepatocellular carcinoma (HCC) treatment in clinical practice. METHODS: From 27 August 2020 to 30 August 2020 during the CCI 2020 annual meeting, a survey with 34 questions was sent by email to 264 CCI clinicians in China with more than 10 years of experience using TACE for HCC treatment. RESULTS: A total of 257 clinicians participated and responded to the survey. Most participants agreed that the concept of "TACE failure/refractoriness" has scientific and clinical significance (n=191, 74.3%). Nearly half of these participants chose TACE-based combination treatment as subsequent therapy after so-called TACE failure/refractoriness (n=88, 46.1%). None of the existing TACE failure/refractoriness definitions were widely accepted by the participants; thus, it is necessary to re-define this concept for the treatment of HCC in China (n=235, 91.4%). Most participants agreed that continuing TACE should be performed for patients with preserved liver function, presenting portal vein tumor thrombosis (n=242, 94.2%) or extrahepatic spread (n=253, 98.4%), after the previous TACE treatment to control intrahepatic lesion(s). CONCLUSIONS: There is an obvious difference in the recognition of TACE failure/refractoriness among Chinese clinicians based on existing definitions. Further work should be carried out to re-define TACE failure/refractoriness.

Prognosis Nomogram for Hepatocellular Carcinoma Patients with Portal Vein Invasion Undergoing Transarterial Chemoembolization Plus Sorafenib Treatment: A Retrospective Multicentre Study.

OBJECTIVES: To explore the outcomes of combined transarterial chemoembolization (TACE) with sorafenib in hepatocellular carcinoma (HCC) patients with portal vein tumour thrombus (PVTT) and to establish a prognostic prediction nomogram to differentiate target patients and stratify risk. MATERIALS AND METHODS: This multicentre, retrospective study consisted of 185 consecutive treatment-naïve patients with HCC and PVTT treated with TACE plus sorafenib from three institutions between January 1st, 2012 and December 31st, 2017. The primary outcome measurement of the study was overall survival (OS). The type of PVTT was classified by the Liver Cancer Study Group of Japan. The prognostic nomogram was established based on the predictors and was performed with interval validation. RESULTS: The median OS of the Vp1-3 and Vp4 groups was 12.4 months (11.7-18.9) and 8.5 months (7.6-11.2) (P = 0.00098), respectively, and there was a significant difference in the median OS between the Vp1-2 and Vp3 subgroups (16.4 months (12.2-27.9) vs. 10.9 months (8.4-18.1), P = 0.041). The multivariate Cox regression analysis suggested that tumour size, albumin-bilirubin grade, and PVTT type were independent prognostic factors. The C-index value of the nomogram based on these predictors in the entire cohort was 0.731 (0.628-0.833). CONCLUSIONS: After the combined therapy of TACE and sorafenib, advanced HCC patients with segmental or subsegmental PVTT showed better survival than those with main PVTT. The nomogram can be applied to identify advanced HCC patients with PVTT who may benefit most from the combination treatment and be helpful for making decision in clinical practice.

Monolayer NbF4: a 4d1-analogue of cuprates.

The electronic structure and possible electronic orders in monolayer NbF4 are investigated by density functional theory and functional renormalization group. Because of the niobium-centered octahedra, the energy band near the Fermi level is found to derive from the 4dxy orbital, well separated from the other bands. Local Coulomb interaction drives the undoped system into an antiferromagnetic insulator. Upon suitable electron/hole doping, the system is found to develop [Formula: see text] -wave superconductivity with sizable transition temperature. Therefore, the monolayer NbF4 may be an exciting 4d1 analogue of cuprates, providing a new two-dimensional platform for high-Tc superconductivity.

Upregulation of PD-L1 expression promotes epithelial-to-mesenchymal transition in sorafenib-resistant hepatocellular carcinoma cells.

BACKGROUND: The epithelial-to-mesenchymal transition (EMT) status is associated with programmed death-1 ligand 1 (PD-L1) expression in various cancers. However, the role and molecular mechanism of PD-L1 in the EMT of sorafenib-resistant hepatocellular carcinoma (HCC) cells remain elusive. In this study, we aimed to investigate the regulation of PD-L1 on the EMT in sorafenib-resistant HCC cells. METHODS: Initially, the sorafenib-resistant HCC cell lines HepG2 SR and Huh7 SR were established. Western-blot assays were used to detect the expression of PD-L1, E-cadherin, and N-cadherin. The intervention and overexpression of PD-L1 were used to explore the role of PD-L1 in the regulation of EMT in HepG2 SR and Huh7 SR cells. Cell migration and invasion were assessed by transwell assays. PD-L1 or Sterol regulatory element-binding protein 1 (SREBP-1) overexpression and knock-down were performed in order to study the mechanism of PD-L1 in sorafenib-resistant HCC cells. RESULTS: PD-L1 expression was upregulated, whereas E-cadherin levels were downregulated and N-cadherin expression was increased in HepG2 SR and Huh7 SR cells. The cell viabilities of HepG2 and Huh7 cells were lower than those of HepG2 SR and Huh7 SR cells. PD-L1 overexpression reduced E-cadherin expression and increased N-cadherin levels, whereas PD-L1 knock-down increased E-cadherin expression and decreased N-cadherin expression. PD-L1 expression promoted EMT and the migratory and invasive abilities of HepG2 SR and Huh7 SR cells. PD-L1 promoted the EMT of sorafenib-resistant HCC cells via the PI3K/Akt pathway by activating SREBP-1 expression in HepG2 SR and Huh7 SR cells. CONCLUSIONS: The findings reveal that PD-L1 expression promotes EMT of sorafenib-resistant HCC cells.

Prognostic Performance of Albumin-Bilirubin Grade With Artificial Intelligence for Hepatocellular Carcinoma Treated With Transarterial Chemoembolization Combined With Sorafenib.

PURPOSE: To establish albumin-bilirubin (ALBI) grade-based and Child-Turcotte-Pugh (CTP) grade-based nomograms, as well as to develop an artificial neural network (ANN) model to compare the prognostic performance and discrimination of these two grades for hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) combined with sorafenib as an initial treatment. METHODS: This multicenter retrospective study included patients from three hospitals between January 2013 and August 2018. In the training cohort, independent risk factors associated with overall survival (OS) were identified by univariate and multivariate analyses. The nomograms and ANN were established and then validated in two validation cohorts. RESULTS: A total of 504 patients (319, 61, and 124 patients from hospitals A, B, and C, respectively) were included. The median OS was 15.2, 26.9, and 14.8 months in the training cohort and validation cohorts 1 and 2, respectively (P = 0.218). In the training cohort, both ALBI grade and CTP grade were identified as independent risk factors. The ALBI grade-based and CTP grade-based nomograms were established separately and showed similar prognostic performance and discrimination when validated in the validation cohorts (C-index in validation cohort 1: 0.799 vs. 0.779, P = 0.762; in validation cohort 2: 0.700 vs. 0.693, P = 0.803). The ANN model showed that the ALBI grade had higher importance in survival prediction than the CTP grade. CONCLUSIONS: The ALBI grade and CTP grade have comparable prognostic performance for HCC patients treated with TACE combined with sorafenib. ALBI grades 1 and 2 have the potential to act as a stratification factor for clinical trials on the combination therapy of TACE and systemic therapy.

Deep Learning Predicts Overall Survival of Patients With Unresectable Hepatocellular Carcinoma Treated by Transarterial Chemoembolization Plus Sorafenib.

OBJECTIVES: To develop and validate a deep learning-based overall survival (OS) prediction model in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) plus sorafenib. METHODS: This retrospective multicenter study consisted of 201 patients with treatment-naïve, unresectable HCC who were treated with TACE plus sorafenib. Data from 120 patients were used as the training set for model development. A deep learning signature was constructed using the deep image features from preoperative contrast-enhanced computed tomography images. An integrated nomogram was built using Cox regression by combining the deep learning signature and clinical features. The deep learning signature and nomograms were also externally validated in an independent validation set of 81 patients. C-index was used to evaluate the performance of OS prediction. RESULTS: The median OS of the entire set was 19.2 months and no significant difference was found between the training and validation cohort (18.6 months vs. 19.5 months, P = 0.45). The deep learning signature achieved good prediction performance with a C-index of 0.717 in the training set and 0.714 in the validation set. The integrated nomogram showed significantly better prediction performance than the clinical nomogram in the training set (0.739 vs. 0.664, P = 0.002) and validation set (0.730 vs. 0.679, P = 0.023). CONCLUSION: The deep learning signature provided significant added value to clinical features in the development of an integrated nomogram which may act as a potential tool for individual prognosis prediction and identifying HCC patients who may benefit from the combination therapy of TACE plus sorafenib.

ROR1 is highly expressed in circulating tumor cells and promotes invasion of pancreatic cancer.

Pancreatic cancer (PaC) is an aggressive malignancy, which is associated with high levels of metastasis. Circulating tumor cells (CTCs), which may be considered a functional biomarker and promising treatment strategy for metastasis, are associated with the prognosis and progression of various metastatic cancers, including PaC. Receptor tyrosine kinase­like orphan receptor 1 (ROR1) expression contributes to cell metastasis and poor clinical outcomes in malignant tumors. The present study aimed to explore the function of ROR1 in PaC CTCs. Reverse transcription­quantitative polymerase chain reaction and western blot analysis were used to examine the expression of ROR1, E­cadherin and N­cadherin. Cell proliferative and invasive ability was assessed by MTT and Transwell assays, respectively. The results revealed that the mRNA and protein expression levels of ROR1 were augmented in PaC tissues. Furthermore, the mRNA expression levels of ROR1 were higher in CTCs compared with in peripheral blood cells, and ROR1 was more highly expressed in CTCs than in cells. Notably, CTCs exhibited a markedly greater proliferative and invasive capacity than PANC­1 and SW­1990 cells, whereas knockdown of endogenous ROR1 by small interfering RNA led to suppression of the invasion of CTCs. In addition, it was revealed that the mechanism underlying the effects of ROR1 on PaC CTC metastasis may involve the epithelial­mesenchymal transition process. In conclusion, ROR1 may be considered a potential biomarker and therapeutic target for the treatment of PaC.