Abnormal phosphorylation / dephosphorylation and Ca2+ dysfunction in heart failure.

Heart failure (HF) can be caused by a variety of causes characterized by abnormal myocardial systole and diastole. Ca2+ current through the L-type calcium channel (LTCC) on the membrane is the initial trigger signal for a cardiac cycle. Declined systole and diastole in HF are associated with dysfunction of myocardial Ca2+ function. This disorder can be correlated with unbalanced levels of phosphorylation / dephosphorylation of LTCC, endoplasmic reticulum (ER), and myofilament. Kinase and phosphatase activity changes along with HF progress, resulting in phased changes in the degree of phosphorylation / dephosphorylation. It is important to realize the phosphorylation / dephosphorylation differences between a normal and a failing heart. This review focuses on phosphorylation / dephosphorylation changes in the progression of HF and summarizes the effects of phosphorylation / dephosphorylation of LTCC, ER function, and myofilament function in normal conditions and HF based on previous experiments and clinical research. Also, we summarize current therapeutic methods based on abnormal phosphorylation / dephosphorylation and clarify potential therapeutic directions.

Biological aging mediates the associations of metabolic score for insulin resistance with all-cause and cardiovascular disease mortality among US adults: A nationwide cohort study.

AIM: To investigate the associations of metabolic score for insulin resistance (METS-IR) with all-cause and cardiovascular disease (CVD)-specific mortality and the potential mediating role of biological ageing. METHODS: A cohort of 19 204 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 was recruited for this study. Cox regression models, restricted cubic splines, and Kaplan-Meier survival curves were used to determine the relationships of METS-IR with all-cause and CVD-specific mortality. Mediation analyses were performed to explore the possible intermediary role of biological ageing markers, including phenotypic age (PhenoAge) and biological age (BioAge). RESULTS: During a median follow-up of 9.17 years, we observed 2818 deaths, of which 875 were CVD-specific. Multivariable Cox regression showed that the highest METS-IR level (Q4) was associated with increased all-cause (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.14-1.67) and CVD mortality (HR 1.52, 95% CI 1.10-2.12) compared with the Q1 level. Restricted cubic splines showed a nonlinear relationship between METS-IR and all-cause mortality. Only METS-IR above the threshold (41.02 µg/L) was positively correlated with all-cause death. METS-IR had a linear positive relationship with CVD mortality. In mediation analyses, we found that PhenoAge mediated 51.32% (p < 0.001) and 41.77% (p < 0.001) of the association between METS-IR and all-cause and CVD-specific mortality, respectively. For BioAge, the mediating proportions of PhenoAge were 21.33% (p < 0.001) and 15.88% (p < 0.001), respectively. CONCLUSIONS: This study highlights the detrimental effects of insulin resistance, as measured by METS-IR, on all-cause and CVD mortality. Moreover, it underscores the role of biological ageing in mediating these associations, emphasizing the need for interventions targeting both insulin resistance and ageing processes to mitigate mortality risks in metabolic disorders.

TIPS plus sequential systemic therapy of advanced HCC patients with tumour thrombus-related symptomatic portal hypertension.

OBJECTIVES: Portal vein tumour thrombus (PVTT)-related symptomatic portal hypertension (SPH) leads to a poor prognosis in hepatocellular carcinoma (HCC) patients. A transjugular intrahepatic portosystemic shunt (TIPS) can effectively relieve SPH but its effect remains unclear in PVTT-related SPH. This study aimed to evaluate the clinical value of the TIPS procedure combined with sequential systemic therapy in advanced HCC patients with PVTT-related SPH. METHODS: After 1:1 propensity score matching (PSM), this retrospective study analysed 42 patients who underwent TIPS placement plus sequential systemic therapy (group A) and 42 patients who received only symptomatic and supportive treatment (group B). The evaluated outcomes were overall survival (OS) and SPH control rate. Cox proportional hazards regression analysis was used to compare OS in the two groups. RESULTS: In group A, the technical success rate of the TIPS procedure was 95.2%, and no severe complications occurred. The rebleeding rates in group A and group B were 5.0% and 73.7%, respectively (p < 0.001), and the ascites control rates were 92.0% and 28.0%, respectively (p < 0.001). The median OS of group A was significantly better than that of group B (9.6 [95% CI: 7.1, 12.0] vs. 4.9 [95% CI: 3.9, 5.8], months, p < 0.001). Multivariable analysis showed that TIPS plus sequential systemic therapy (hazard ratio [HR] = 5.799; 95% CI: 3.177, 10.585; p < 0.001) was an independent prognostic factor related to OS. Additionally, PVTT degree (I+II) (p = 0.008), AFP ≤ 400 ng/ml (p = 0.003), and Child-Pugh class A (p = 0.046) were significant predictors of OS. CONCLUSION: TIPS plus sequential systemic therapy is safe and feasible for treating advanced HCC with tumour thrombus-related SPH. KEY POINTS: • Portal vein tumour thrombus (PVTT) is common in advanced hepatocellular carcinoma (HCC) and transforms compensated portal hypertension into symptomatic portal hypertension (SPH). • HCC patients with PVTT-related SPH have a very poor prognosis, and there are no effective treatments recommended by the guidelines. • Therefore, a treatment strategy that utilises a transjugular intrahepatic portosystemic shunt (TIPS) to manage SPH combined with sequential systemic therapy in advanced HCC patients is explored in this study for its feasibility and clinical value. This research can fill the gap in current research data to provide clinically meaningful treatment options.

Case report: Drug-eluting bead transcatheter arterial chemoembolization in liver metastasis and retroperitoneal lymph node metastases of renal cell carcinoma: effective local therapy with the first report.

The liver is the fourth most common site of metastasis in renal cell carcinoma (RCC), which is usually treated with systemic therapies and local treatments. However, local treatments are challenging in RCC patients with liver metastasis who failed in first-line systemic therapy. Here, we report a case of a patient with both liver-dominant RCC metastasis and recurrence in the operative site who had failed in first-line targeted therapy plus immunotherapy, received drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE), and achieved a complete response.

Association between dietary supplement use and mortality in cancer survivors with different body mass index and frailty status: a cohort study.

Background: The association between Body Mass Index (BMI), frailty index (FI), and dietary supplement in cancer survivors has been a subject of growing interest. This study investigates the relationship of BMI and FI with mortality in American cancer survivors and explores the impact of dietary supplement usage on different BMI and FI groups. Methods: Three thousand nine hundred and thirty-two cancer patients from the National Health and Nutrition Examination Survey (NHANES) database were included in the analyses. BMI, FI, and supplement usage were obtained through the NHANES structured survey and the 49-item FI tool. Weighted logistic and Cox proportional hazards models, Kaplan-Meier survival analyses, and propensity score matching (PSM) were used to elucidate the relationships between BMI, FI, dietary supplement, and mortality outcomes. Results: The study found significant associations between higher BMI and increased frailty (Odds ratio [OR] = 1.04, 95% confidence interval [95% CI], 1.02-1.06). BMI < 25 kg/m2 and FI > 0.2 are associated with an increased mortality rate. Dietary supplement use can reduce all-cause and cancer mortality in cancer patients with BMI < 25 kg/m2 (Hazard ratio [HR] = 0.63, 95% CI, 0.47-0.84; HR = 0.48, 95% CI, 0.29-0.80) or FI ≤ 0.2 (HR = 0.77, 95% CI, 0.60-0.99; HR = 0.59, 95% CI, 0.39-0.89). In cancer patients with BMI < 25 kg/m2 and FI ≤ 0.2, dietary supplement users had lower all-cause and cancer mortality (HR = 0.49, 95% CI, 0.30-0.79; HR = 0.25, 95% CI, 0.10-0.60). Conclusion: The study revealed a negative correlation between BMI and the FI among the cancer patient cohort as well as their complex impact on mortality and highlighted the role of dietary supplement in cancer prognosis, indicating benefits for non-frail patients with BMI < 25 kg/m2.

Outcomes of two types of iodine-125 seed delivery with metal stents in treating malignant biliary obstruction: a systematic review and meta-analysis.

PURPOSE: To conduct a meta-analysis comparing the efficacy and safety of two types of iodine-125 (I-125) seed delivery with metal stents (the study group) versus conventional metal stents (the control group) in patients with malignant biliary obstruction (MBO). METHODS: Our team systematically searched the PubMed, Embase, and Cochrane Library databases for relevant studies published from January 2012 up to July 2021. Survival time and stent dysfunction were the primary measured outcomes. Subgroup analyses were conducted according to the type of I-125 seed delivery. RESULTS: Eleven studies, including 1057 patients in total, were pooled for stent dysfunction. The study group showed a lower risk of stent dysfunction than the control group [odds ratio (OR): 0.61, 95% confidence interval (CI) 0.46-0.81, P = 0.001]. The pooled results of six studies reporting overall survival (OS) showed that the study group had a better survival outcome than the control group [hazard ratio (HR): 0.34, 95% CI: 0.28-0.42, P < 0.001]. In the subgroup analyses, the I-125 seed stent group had significantly less stent dysfunction than the control group (OR: 0.49, 95% CI: 0.31-0.76, P = 0.002). Meanwhile, the metal stents + I-125 radioactive seed strand group showed significantly more improvement in OS than the control group (HR: 0.33, 95% CI: 0.26-0.42, P < 0.001). Moreover, our analysis suggests that using I-125 seeds did not result in increasing related adverse events compared with using metal stents alone (all P > 0.05). The study group was significantly superior to the control group, with better survival and decreased stent dysfunction. Meanwhile, the delivery of I-125 seeds did not increase adverse events. CONCLUSION: The delivery of I-125 with metal stents may be considered a preferable technique for MBO.

Locoregional therapy combined with systemic therapy (LRT + ST) for unresectable and metastatic intrahepatic cholangiocarcinoma: a systematic review and meta-analysis.

BACKGROUND: The outcome of systemic therapy (ST) for unresectable and metastatic intrahepatic cholangiocarcinoma (iCCA) is poor. This study aims to further evaluate the efficacy and safety of locoregional therapy combined with systemic therapy (LRT + ST) compared with only ST in unresectable and metastatic iCCA by performing a systematic literature review and meta-analysis. METHODS: A comprehensive search was performed in PubMed, Web of Science, EMBASE, and the Cochrane Library up to November 3, 2022. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). RESULTS: Ten retrospective cohort studies with 3,791 unresectable or metastatic iCCA patients were enrolled in this study, including 1,120 who received ablation, arterially directed therapy (ADT), or external beam radiation therapy (EBRT) combined with ST. The meta-analysis showed that the LRT + ST group had a better OS (HR = 0.51; 95% CI =0.41-0.64; p value < 0.001), PFS (HR = 0.40, 95% CI = 0.22-0.71, p value = 0.002) and ORR (RR = 1.68; 95% CI = 1.17-2.42; p value = 0.005). Subgroup analysis showed that both ST combined with ADT (HR = 0.42, 95% CI = 0.31-0.56, p value < 0.001) and EBRT (HR = 0.67, 95% CI = 0.63-0.72, p value < 0.001) could improve OS. Neutropenia, thrombocytopenia, anemia, anorexia, and vomiting did not show significant differences between the groups (p value > 0.05). CONCLUSIONS: Compared with only ST, LRT + ST improved survival outcomes for unresectable and metastatic iCCA patients without increasing severe AEs, which can further provide a basis for guidelines.

Safety and Efficacy of CT-Guided Iodine-125 Brachytherapy for Portal Vein Tumor Thrombus in Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: Portal vein tumor thrombus (PVTT) seriously reduces the survival of patients with hepatocellular carcinoma (HCC). CT-guided iodine-125 (125I) brachytherapy has the advantage of a high local control rate and is minimally invasive. This study aims to evaluate the safety and efficacy of 125I brachytherapy for treating PVTT in HCC patients. MATERIALS AND METHODS: Thirty-eight patients diagnosed with HCC complicated with PVTT and treated with 125I brachytherapy for PVTT were included in this retrospective study. The local tumor control rate, local tumor progression-free survival, and overall survival (OS) were analyzed. Cox proportional hazards regression analysis was performed to identify predictors affecting survival. RESULTS: The local tumor control rate was 78.9% (30/38). The median local tumor progression-free survival was 11.6 (95% confidence interval [CI]: 6.7, 16.5) months, and the median overall survival was 14.5 (95% CI: 9.2, 19.7) months. Multivariate Cox analysis showed that age <60 years (hazard ratio [HR] = 0.362; 95% CI: 0.136, 0.965; p = 0.042), type I+II PVTT (HR = 0.065; 95% CI: 0.019, 0.228; p < 0.001), and tumor diameter <5 cm (HR = 0.250; 95% CI: 0.084, 0.748; p = 0.013) were significant predictors of OS. There were no serious adverse events related to 125I seed implantation during the follow-up period. CONCLUSION: CT-guided 125I brachytherapy is effective and safe for treating PVTT of HCC, with a high local control rate and no severe adverse events. Patients younger than 60 years old with type I+II PVTT and a tumor diameter less than 5 cm have a more favorable OS.

The association between blood heavy metals and gallstones: A cross-sectional study.

BACKGROUND AND AIMS: Exposure to heavy metals has been widely recognized as a risk factor for human health. However, there is limited information on the effects of blood heavy metals on gallstones. This study aims to investigate the relationship between blood heavy metals and gallstones using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: 7192 participants aged 20 years or older with complete information were included in the study. Serum concentrations of heavy metals were determined by inductively coupled plasma kinetic reaction cell mass spectrometry. Gallstones were presented by standard questionnaires. Logistic regression, nonlinear, subgroup, and sensitivity analyses were used to estimate the association between blood heavy metals and gallstones. RESULTS: Multivariate logistic regression showed that the highest quintile of blood selenium (Se) was associated with a higher risk of gallstones compared with the lowest quintile (OR = 1.66, 95% CI: 1.16-2.36), particularly in individuals who were under 65 years of age, females, non-Hispanic Whites, non-drinkers, obese, and had a college education or higher. There was no correlation between blood cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and gallstones in the total population. Restricted cubic spline curves showed that a negative correlation was observed between blood Cd (OR = 0.84, 95% CI: 0.710-1.00), Hg (OR = 0.87, 95% CI: 0.78-0.97) and gallstones when Cd < 0.302 µg/L and Hg < 3.160 µg/L. CONCLUSIONS: Blood Se was an independent risk factor for gallstones, particularly in individuals under 65 years old, females, non-Hispanic Whites, non-drinkers, obese, and had a college education or higher. Furthermore, blood Cd and Hg were associated with a reduced risk of gallstones within a certain range.

CT-guided 125I brachytherapy for hepatocellular carcinoma in high-risk locations after transarterial chemoembolization combined with microwave ablation: a propensity score-matched study.

BACKGROUND: This study aimed to evaluate the safety and efficacy of 125I brachytherapy combined with transarterial chemoembolization (TACE) and microwave ablation (MWA) for unresectable hepatocellular carcinoma (HCC) in high-risk locations. PATIENTS AND METHODS: After 1:2 propensity score matching (PSM), this retrospectively study analyzed 49 patients who underwent TACE +MWA+125I brachytherapy (group A) and 98 patients who only received TACE +MWA (group B). The evaluated outcomes were progression-free survival (PFS), overall survival (OS), and treatment complications. Cox proportional hazards regression analysis survival was used to compare the two groups. RESULTS: The patients in group A showed a longer PFS than group B (7.9 vs. 3.3 months, P = 0.007). No significant differences were observed in median OS between the two groups (P = 0.928). The objective response rate (ORR), disease control rate of tumors in high-risk locations, and the ORR of intrahepatic tumors were 67.3%, 93.9%, and 51.0%, respectively, in group A, and 38.8%, 79.6% and 29.6%, respectively, in group B (P < 0.001, P = 0.025 and P = 0.011, respectively). TACE-MWA-125I (HR = 0.479, P < 0.001) was a significant favorable prognostic factor that affected PFS. The present of portal vein tumor thrombosis was an independent prognostic factor for PFS (HR = 1.625, P = 0.040). The Barcelona clinic liver cancer (BCLC) stage (BCLC C vs. B) was an independent factor affecting OS (HR = 1.941, P = 0.038). The incidence of complications was similar between the two groups, except that the incidence of abdominal pain was reduced in the group A (P = 0.007). CONCLUSIONS: TACE-MWA-125I resulted in longer PFS and better tumor control than did TACE-MWA in patients with unresectable hepatocellular carcinoma in high-risk locations.

The worthy role of hepatic arterial infusion chemotherapy in combination with anti-programmed cell death protein 1 monoclonal antibody immunotherapy in advanced hepatocellular carcinoma.

Systemic therapy remains the primary therapeutic approach for advanced hepatocellular carcinoma (HCC). Nonetheless, its efficacy in achieving control of intrahepatic lesions is constrained. Hepatic arterial infusion chemotherapy (HAIC) is a therapeutic approach that combines localized treatment with systemic antitumor effects, which aim is to effectively manage the progression of cancerous lesions within the liver, particularly in patients with portal vein tumor thrombosis (PVTT). Combining HAIC with anti-programmed cell death protein 1 (anti-PD-1) monoclonal antibody (mAb) immunotherapy is anticipated to emerge as a novel therapeutic approach aimed at augmenting the response inside the localized tumor site and achieving prolonged survival advantages. In order to assess the effectiveness, safety, and applicability of various therapeutic modalities and to address potential molecular mechanisms underlying the efficacy of HAIC-sensitizing immunotherapy, we reviewed the literature about the combination of HAIC with anti-PD-1 mAb therapies.

TIPS improves outcomes in patients with HCC and symptomatic portal hypertension: a multi-institution experience.

BACKGROUND: Hepatocellular carcinoma (HCC) with symptomatic portal hypertension (SPH) has poor prognosis. A transjugular intrahepatic portosystemic shunt (TIPS) relieves SPH, but its application in HCC remains unclear. We evaluated TIPS efficacy in patients with HCC and SPH. METHODS: Pre- and post-TIPS Child-pugh(C-P) scores and stages in 123 HCC patients with SPH from three centers were compared. The impact of postoperative C-P stage indicators on overall survival (OS) was explored. RESULTS: Post-TIPS responses to SPH included complete response (CR) (92 [74.8%]), partial response (PR) (23 [18.7%]), and nonresponse (NR) (8 [6.5%]). The control (proportion of CR and PR) for SPH was 93.5%. Median C-P scores pre-TIPS and at one month post-TIPS were 8 (IQR 6-9) and 7 (IQR 6-8), respectively (P < 0.001). Forty-one (33.3%) patients had C-P downstaging; 73 (59.3%) had lowered C-P scores; and 73 (59.3%) received intrahepatic local therapy post-TIPS. The median OS was 10.7 (1.1-55.2) months. Among the five indicators of C-P stage, lower post-TIPS ascites grading [(0/1)/(2/3); P = 0.014, HR = 0.31 (95% CI: 0.12-0.79)] and bilirubin [< 34/ ≥ 34 µmol/L; P = 0.022, HR = 0.47 (95% CI: 0.23-0.82)] and prothrombin time prolongation < 6 s [< 6/ ≥ 6 s; P = 0.001, HR = 0.17 (95% CI: 0.06-0.47)] were independent protective indicators of OS. These three indicators were included in the nomogram model to predict survival probabilities. CONCLUSIONS: TIPS is safe and effective for HCC with SPH. This procedure can relieve the symptoms, enable subsequent antitumor therapy, and bring survival benefits, possibly through improved liver function by reducing C-P stage.

Retrograde venous coil embolization prior to transarterial chemoembolization in hepatocellular carcinoma with arterio-hepatic venous shunts.

PURPOSE This study explored the clinical efficacy of transcatheter retrograde shunt occlusion with coils to prevent pulmonary oil or particle embolization prior to transarterial chemoembolization (TACE) in patients with artero-hepatic venous shunts (AHVS) secondary to hepatocellular carcinoma (HCC). METHODS From July 2017 to January 2021, 6 patients with advanced, unresectable HCC were found to have an AHVS by hepatic arteriography at the time of attempted TACE. The AHVS was embolized ret rogradely with metal coils through a transfemoral or transjugular venous approach. After venous embolization and confirmation of the absence of the AHVS, TACE was performed using an emul sion of iodized oil and doxorubicin or drug-eluting beads. Follow-up computed tomography (CT) was performed within 1 month after the first TACE to evaluate the results and complications. RESULTS Hepatic angiography after venous embolization showed that AHVS had utterly disappeared in all patients during the operation. The immediate technical success of the retrograde venous embo lization was 100%. The AHVS had disappeared entirely during the follow-up period through triple-phase enhancement CT scanning. According to the modified response evaluation criteria in solid tumors, TACE in all 6 patients had a disease control response rate of 100% (6/6) with complete response in 2 patients and partial response in 4 patients. One patient died during the 6-month follow-up, and the other 5 were still alive. No complications related to pulmonary embolism occurred. CONCLUSION Retrograde venous coil embolization of AHVS via the draining hepatic vein appears to be a safe, feasible, and effective treatment to allow TACE treatment without pulmonary embolic events. This approach appears to provide better tumor control and effectively decreases the occurrence of pulmonary embolism.

Single-Centre Retrospective Study Using Propensity Score Matching Comparing Left Versus Right Internal Jugular Vein Access for Transjugular Intrahepatic Portosystemic Shunt (TIPS) Creation.

PURPOSE: To compare the safety and efficacy of left versus right internal jugular vein access for portal vein puncture during transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with a small liver and short vertical puncture distance. MATERIALS AND METHODS: The vertical distance from the hepatic vein orifice to the puncture point of the portal vein was measured by CT and DSA. A distance ≤ 30 mm is defined as a short vertical puncture distance. After 1:1 propensity score matching (PSM), 29 patients of left internal jugular vein-TIPS (LIJ-TIPS) and 29 patients of right internal jugular vein-TIPS (RIJ-TIPS) were included. The number of needle punctures, fluoroscopy time, and radiation dose during the puncture process were statistically analyzed. RESULTS: There was no significant difference in the average vertical puncture distances on CT or DSA between LIJ-TIPS and RIJ-TIPS (19.10 ± 0.60 mm vs. 19.30 ± 0.60 mm, P = 0.840; 22.02 ± 0.69 mm vs. 22.23 ± 0.64 mm, P = 0.822, respectively). The average number of needle punctures, fluoroscopy time, and radiation dose in LIJ-TIPS were significantly lower than those in RIJ-TIPS (2.07 ± 0.20 vs. 4.10 ± 0.24, P < 0.001; 78.45 ± 12.80 s vs. 201.16 ± 23.71 s, P < 0.001; 31.55 ± 7.04 mGy vs. 136.69 ± 16.38 mGy, P < 0.001, respectively). Within three punctures, the technical success rate in LIJ-TIPS was significantly higher than that in RIJ-TIPS (86.2 vs. 27.6%, P < 0.001). The incidence of hemoperitoneum in LIJ-TIPS was significantly lower than that in RIJ-TIPS (0% vs. 13.8%, P = 0.038). CONCLUSION: The left internal jugular vein could be used as primary access for TIPS creation in patients with a small liver and short vertical puncture distance.

Effect of transjugular intrahepatic portosystemic shunt on transarterial chemoembolization for hepatocellular carcinoma: a systematic review and meta-analysis.

PURPOSE: Hepatocellular carcinoma (HCC) usually occurs accompanied by portal hypertension. Transcatheter arterial chemoembolization (TACE) is recommended as an effective treatment in HCC. Recent studies had conflicting results regarding the effectiveness and safety of TACE for HCC in patients with transjugular intrahepatic portosystemic shunt (TIPS). This meta-analysis aimed to evaluate the influence of TIPS on the effectiveness and safety of TACE for patients with HCC. METHODS: A comprehensive search of studies among PubMed, Web of Science and Cochrane Library was conducted, from the earliest publishing date to January 27th, 2020. Statistical analyses were all performed using the Stata 13.0 software. I2 index statistic was used to assess heterogeneity. RESULTS: Six studies with a total of 536 patients with HCC were included in the analysis. The pooled response rate was 51% (95% CI: 25% to 77%) with a significant heterogeneity (I2=93.3%, p < 0.001). The TACE + TIPS group had an inferior response rate than the non-TIPS group, but the difference had no statistical significance (p = 0.171) and heterogeneity was low (I2=0.00%, p = 0.490). Pooled hepatic failure rate was 8.8% (95% CI: 5.2% to 12.4%) with low heterogeneity (I2=0.0%, p = 0.747). But the pooled hepatic failure rate increased to 12.7% (95% CI: 5.7% to 19.7%) with low heterogeneity (I2=11.5%, p = 0.323) if the patients who received TIPS after TACE were excluded. CONCLUSION: TIPS does not influence the effectiveness of TACE, but attention should be paid to the risk of hepatic failure.

Transcriptome sequencing-based personalized analysis of hepatocellular carcinoma patients with portal vein tumor thrombus.

BACKGROUND: The mechanism of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) has been widely studied, and numerous diagnostic and prognostic biomarkers for HCC with PVTT have been identified. We aimed to evaluate the extent to which these biomarkers may aid the personalized precision therapy of HCC with PVTT. METHODS: Matched tissue specimens [primary HCC tumor (PT), adjacent normal (N) liver, and PVTT tissues] were acquired from 3 Chinese HCC patients who underwent surgery at Sun Yat-sen University Cancer Centre between 2019 and 2020. Ribonucleic acid (RNA) sequencing was performed on the 9 tissue samples. GFOLD (generalized fold change) algorithm was used to analyze the differently expressed genes (DEGs) between the PVTT, PT, and normal tissues from each patient. Genes with a P<0.01 and a |GFOLD value| >1 were identified as having significantly different expression. RESULTS: In total, 3,543, 32,472, and 12,901 tumorigenesis-associated genes, and 2,919, 17,679, and 14,825 metastasis-associated genes, were detected in Patient 1 (P1), Patient 2 (P2), and Patient 3 (P3), respectively. We analyzed the expression levels of genes associated with hypoxia, macrophage recruitment and cancer stem cells (CSCs). The results showed that hypoxia and CSCs may have contributed to tumorigenesis but not to metastasis in P1. We also found the hypoxia microenvironment played an important role in tumorigenesis and metastasis in P2, and CSCs may have contributed to metastasis. Additionally, we found that CSCs played critical roles in metastasis but not in tumorigenesis in P3. The results also showed that the long non-coding RNA (lncRNA) Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) was greatly overexpressed in the PTs and PVTT in all 3 patients, and Heart and Neural Crest Derivatives Expressed 2-antisense RNA 1 (HAND2-AS1) was downregulated in PVTT compared with PTs in all 3 patients. Thus, MALAT1 and HAND2-AS1 may be robust biomarkers for metastasis in HCC patients with PVTT. CONCLUSIONS: Tumor-associated macrophages (TAMs)-targeted immunotherapy is a promising therapy for HCC patients with PVTT. LncRNAs MALAT1, and HAND2-AS1 may be promising targets for HCC therapy.

Resection vs. ablation for lesions characterized as resectable-ablative within the colorectal liver oligometastases criteria: a propensity score matching from retrospective study.

BACKGROUND: There has been no prospective or retrospective studies reporting the comparison outcome between surgery and ablation for resectable-ablative (lesions could be treated by resection or complete ablation) colorectal liver oligometastases (CLOM). The purpose of this study was to compare the efficacy and prognostic difference in patients who underwent R0 resection vs. complete ablation within the resectable-ablative CLOM criteria. METHODS: From January 2008 to May 2018, a total of 2,367 patients diagnosed with colorectal liver metastases were included in this observational study. The metastasis was characterized by only limited to liver with number ≤5, size ≤5 cm, and resectable-ablative (lesions could be treated by resection or complete ablation). The evaluated indications, including liver progression-free survival (LPFS), overall survival (OS), survival rates, pattern and number of recurrences, and complications, were compared by using propensity score matching (PSM). The Kaplan-Meier curves were generated, and a log-rank test was performed. The Cox regression model was used for univariate and multivariate analyses to identify predictors of outcomes. RESULTS: A total of 421 consecutive patients were eligible for this study, with 250 and 171 undergoing R0 resection and complete ablation, respectively. PSM identified 145 patients from each group. The 1-, 3-, 5- and 8-year OS rates in the resection group and the ablation group were 95.8% vs. 95.0%, 69.8% vs. 60.1%, 53.6% vs. 42.5%, and 45.1% vs. 32.9% (p = 0.075), respectively. The median LPFS in the resection group was significantly longer than that in the ablation group (35 months vs. 15 months, p = 0.011). No statistical difference was found in LPFS between the two groups when comparing ≤3 cm liver metastases. For liver metastasis >3 cm, the median LPFS in the resection group and ablation group was 11 months and 5 months, respectively (p = 0.001). In terms of high risk of clinical risk score (CRS), the resection group showed longer LPFS than the ablation group (median 18 months vs. 10 months, p = 0.043). CONCLUSION: For patients within the CLOM criteria suggesting that liver metastases were resectable as well as ablative, resection could result in longer liver recurrence-free survival than ablation in cases with size >3 cm or high risk of CRS. But for ≤3 cm liver metastases, their treatment efficacies were comparable.

Clinical efficacy and prognostic factors of CT-guided 125I brachytherapy for the palliative treatment of retroperitoneal metastatic lymph nodes.

BACKGROUND: Due to the unique anatomical location of retroperitoneal metastatic lymph nodes, current treatment options are limited. This study was designed to explore the clinical efficacy and prognostic factors of CT-guided 125I brachytherapy for the treatment of retroperitoneal metastatic lymph nodes. METHODS: We retrospectively evaluated 92 patients received 125I brachytherapy for retroperitoneal metastatic lymph nodes. A layered Cox proportional hazards model was established to filter out the independent factors affecting local tumor progression-free survival (LTPFS). RESULTS: The median LTPFS was 8 months. Metastatic lymph node with uniform density (p-0.009), clear boundaries (p-0.011), regular morphology (P < 0.001), and < 3 organs at risk of metastasis (p-0.020) were associated with better LTPFS. Necrotic lymph nodes (p < 0.001), fusion (p-0.003), and invasion of vessels visible on images (p < 0.001) were associated with poor LTPFS. Puncture path through abdominal wall or paravertebral approach were also associated with better LTPFS than a hepatic approach (P < 0.05). A maximum diameter ≤ 3 cm (P-0.031) or 3-5 cm (P-0.018) were also associated with significantly better LTPFS than a maximum diameter ≥ 5 cm. The Cox proportional hazards model suggested that lymph nodes invaded the large vessels visible on images, maximum diameter and puncture path were independent risk factors for LTPFS. CONCLUSION: CT-guided 125I brachytherapy is an optional palliative treatment modality for retroperitoneal metastatic lymph nodes, which can provide high local control without severe complications. Better preoperative planning, intraoperative implementation, better choice of puncture path, and selection of appropriate tumor size are important factors that can improve the clinical efficacy of 125I brachytherapy for retroperitoneal metastatic lymph nodes.

Feasibility and clinical value of TIPS combined with subsequent antitumor treatment in HCC patients with refractory ascites.

BACKGROUND: Currently, hepatocellular carcinoma (HCC) patients with refractory ascites (RA) have a very poor prognosis, and there are no effective treatments recommended by the guidelines. A treatment strategy that utilizes a transjugular intrahepatic portosystemic shunt (TIPS) combined with subsequent antitumor treatment is explored in this study for its feasibility and clinical value. METHODS: One month after TIPS, the ascites grade and Child-Pugh scores and stages were reassessed to compare changes in the preoperative indicators. RESULTS: A total of 68 patients from 3 centers were enrolled. After TIPS, the following results were obtained: a complete response (CR), partial response (PR), or absent RA response (AR) of 38 [55.9%], 21 [30.9%], and 9 [13.2%], respectively. The control of RA was 86.8%. The median Child-Pugh scores prior to TIPS and one month after TIPS were 8 (IQR 7-9) and 7 (IQR 6-8), respectively. The down, unchanged, and elevated Child-Pugh stages were 26 [38.2%], 36 [53.0%], and 6 [8.8%], respectively. The postoperative Child-Pugh scores were significantly lower than the preoperative (p < 0.001). 92.6% (63/61) of the patients received subsequent anti-tumor treatment opportunities. The median overall survival (OS) was 8.7 (range, 0.4-49.6) months. The lower postoperative Child-Pugh stage(p = 0.001), downward change of the Child-Pugh stage(p = 0.027), and downward change of the Child-Pugh score (p = 0.002) were independent protected prognostic factors for OS. CONCLUSION: As a minimally invasive method, TIPS can effectively control ascites and improve Child-Pugh scores and stages. TIPS combined with subsequent anti-tumor therapy is a feasible and effective management for HCC patients with RA.

Whole-course management of interventional treatment in liver cancer patients with portal hypertension.

Primary liver cancer often occurs in patients with hepatitis and cirrhosis. Some patients have portal hypertension due to cirrhosis, and present with varying degrees of collateral circulation, splenomegaly and hypersplenism, ascites, and liver dysfunction. It often interferes with the treatment of tumors and affects the disease prognosis. There are internationally recognized guidelines for interventional treatment of liver cancer and portal hypertension which will not be repeated in this paper. This paper focuses on how to treat portal hypertension and intervene with tumors in the treatment of liver cancer to optimize the management of patients with liver cancer and portal hypertension. We propose that the Interventional Management Mode of Liver Cancer with Portal Hypertension can improve the treatment of liver cancer patients with portal hypertension.