Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF.

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy with limited treatment options and a dismal prognosis. The tumor immune microenvironment (TIME) is crucial for iCCA progression, yet its comprehensive characterization remains incomplete. This study utilized mass cytometry by time of flight (CyTOF) to comprehensively analyze immune cell populations in fresh iCCA tumor samples and adjacent peritumor liver tissues. Notably, NK cell percentages significantly decreased in iCCA lesions compared to peritumor liver tissues. Conversely, an enrichment of immunosuppressive CD39+Foxp3+CD4+ regulatory T cells (CD39+T-regs) and exhausted-like CD8+T cells (with pronounced CD39 and PD-1 expression) within TIME was identified and confirmed by multiplex immunofluorescence staining in an independent patient cohort (n = 140). Crucially, tumor-infiltrating CD39+T-regs and CD39+PD-1+CD8+T cells emerged as independent prognostic indicators associated with an unfavorable prognosis in iCCA. These findings unveil the intricate immune landscape within iCCA, offering valuable insights for disease management and novel cancer immunotherapies.

Selection of endovascular treatment strategies and analysis of the efficacy of different locations and types of splenic artery aneurysms.

PURPOSE: To analyze the selection of endovascular treatment strategies and the efficacy of various locations and types of splenic artery aneurysms (SAAs). METHODS: Sixty-three cases of patients diagnosed with SAA from January 2016 to October 2021 were collected, and their clinical data and follow-up results were analyzed. RESULTS: Among the 63 patients, 55 had true SAAs, and 8 had false SAAs. The average diameter of the true SAAs was 2.0 ± 0.8 cm. There were 10 cases of intra-aneurysm embolization, 24 cases of intra-aneurysm and aneurysm-bearing artery embolization, 10 cases of bare stent-assisted coil embolization, and 11 cases of stent grafts. The false SAAs had an average diameter of 2.3 ± 1.1 cm. Aneurysm-bearing artery embolization was applied in 5 cases, and stent grafts were applied in 3 cases. The incidence of complications after embolization of the aneurysm-bearing artery was higher (P < 0.01). Postembolization syndrome occurred in 10 patients; 7 patients developed splenic infarction to varying degrees, 1 patient had mildly elevated blood amylase, and 1 patient developed splenic necrosis with abscess formation, all of which improved after active treatment. The average length of hospital stay was 5.5 ± 3.2 days. The average follow-up time was 17.2 ± 16.1 months, and the aneurysm cavity of all patients was completely thrombotic. CONCLUSION: Endovascular treatments of SAAs are safe and effective. For various locations and types of SAAs, adequate selection of treatment is necessary. Stent grafts are recommended for their safety, economy, practicality, and preservation of the physiological functions of the human body.

Upregulation of TTK expression is associated with poor prognosis and immune infiltration in endometrial cancer patients.

BACKGROUND: Threonine and tyrosine kinase (TTK) is associated with invasion and metastasis in various tumors. However, the prognostic importance of TTK and its correlation with immune infiltration in endometrial cancer (EC) remain unclear. METHODS: The expression profile of TTK was analyzed using data from The Cancer Genome Atlas (TCGA) and the Clinical Proteome Cancer Analysis Consortium (CPTAC). TTK protein and mRNA levels were verified in EC cell lines. Receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of TTK to distinguish between normal and EC tissues. K-M survival analysis was also conducted to evaluate the impact of TTK on survival outcomes. Protein‒protein interaction (PPI) networks associated with TTK were explored using the STRING database. Functional enrichment analysis was performed to elucidate the biological functions of TTK. TTK mRNA expression and immune infiltration correlations were examined using the Tumor Immune Estimation Resource (TIMER) and the Tumor-Immune System Interaction Database (TISIDB). RESULTS: TTK expression was significantly greater in EC tissues than in adjacent normal tissues. Higher TTK mRNA expression was associated with tumor metastasis and advanced TNM stage. The protein and mRNA expression of TTK was significantly greater in tumor cell lines than in normal endometrial cell lines. ROC curve analysis revealed high accuracy (94.862%), sensitivity (95.652%), and specificity (94.894%) of TTK in differentiating EC from normal tissues. K-M survival analysis demonstrated that patients with high TTK expression had worse overall survival (OS) and disease-free survival (DFS) rates. Correlation analysis revealed that TTK mRNA expression was correlated with B cells and neutrophils. CONCLUSION: TTK upregulation is significantly associated with poor survival outcomes and immune infiltration in patients with EC. TTK can serve as a potential biomarker for poor prognosis and a promising immunotherapy target in EC. Further investigation of the role of TTK in EC may provide valuable insights for therapeutic interventions and personalized treatment strategies.

Computed Tomography-guided Percutaneous Lung Biopsy With Electromagnetic Navigation Compared With Conventional Approaches: An Open-label, Randomized Controlled Trial.

PURPOSE: The purpose of this study was to assess the efficiency and safety of computed tomography (CT)-guided percutaneous biopsy of lung lesions with electromagnetic (EM) navigation and compare them with those of conventional approaches. MATERIALS AND METHODS: Seventy-nine patients with lung or liver lesions who needed biopsies were enrolled in this trial. All patients were randomly assigned to the E group underwent CT-guided percutaneous biopsies with the EM navigation system or to the C group treated with conventional approaches. RESULTS: In total, 27 patients with lung lesions were assigned to the E group, and 20 patients were assigned to the C group. The diagnostic success rate was 92.6% and 95% in both groups, respectively (P>0.9999). The median number of needle repositions in the E group was less than that in the C group (2.0 vs. 2.5, P=0.03). The positioning success rate with 1 or 2 needle repositions for the E group was significantly higher than the C group (81.5% vs. 50%, P=0.03). The median accuracy of the puncture location in the E group was better than that in the C group (2.0 vs. 6.6 mm, P<0.0001). The total procedure time lengthened in the E group compared with the C group (30.5±1.6 vs. 18.3±1.7 min, P<0.0001), but the number of CT acquisitions was not significantly different (P=0.08). There was no significant difference in complication incidence between the 2 groups (P=0.44). CONCLUSION: The EM navigation system is an effective and safe auxiliary tool for CT-guided percutaneous lung biopsy, but lengthen the procedure time. TRIAL REGISTRATION: ChiCTR2100043361, registered February 9, 2021-retrospectively registered (http://www.medresman.org.cn/uc/project/projectedit.aspx?proj=7591).

The effects of irreversible electroporation triggering anti-tumor immunity and the value of its combination with immunotherapy.

Recently, interventional ablation techniques have gained prominence in tumor treatment guidelines and complement traditional approaches, such as surgery, chemotherapy, and radiotherapy. Conventional ablation techniques, such as microwave, radiofrequency, and cryoablation, have been used; however, they have certain limitations, including the risk of damaging surrounding normal tissues and the heat sink effect caused by tumor blood flow.1 Irreversible electroporation (IRE), an ablation technology independent of thermal energy, is a promising alternative.2 Clinical studies have demonstrated IRE's efficacy in treating tumors, such as pancreatic and liver tumors.3 Recent research has shown that IRE can elicit specific anti-tumor immune responses in the body.5 IRE also plays a crucial role in eliminating residual tumor cells postoperatively and preventing tumor recurrence.

Comparison of core needle biopsy and fine-needle aspiration methods in CT-guided percutaneous sampling of pancreatic tumors.

Aims: To compare the diagnostic efficacy and safety of CT-guided percutaneous core needle biopsy (CNB) and fine-needle aspiration (FNA) for pancreatic lesions. Methods and Material: A total of 176 patients with 176 pancreatic lesions who visited our hospital between January 2016 and March 2021 were retrospectively analyzed. They were divided into three groups: FNA group A (<1.5 cm between the lesion and great vessels necessitating FNA), FNA group B, and CNB (the latter two with ≥1.5 cm between the lesion and great vessels necessitating FNA). The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and postoperative. The statistical analysis was done using Statistical Package for the Social Sciences version 17.0. Results: One hundred and seventy six patient's specimens all met the requirements. There were no statistically significant differences in sensitivity, specificity, positive predictive value, negative predictive value, and accuracy between the CNB group and FNA group B, (P > 0.05). Thirteen samples submitted for genetic testing (5 in CNB group, 4 in each of the FNA groups A and B) all met the standards of next-generation sequencing gene detection. The main complications of these groups included abdominal pain, fever, and hyperamylasemia. Conclusions: CT-guided percutaneous FNA and CNB have similar diagnostic efficacy for pancreatic biopsy. Furthermore, FNA has a wide range of puncture indications and is very safe. Like CNB, the obtained tissue through FNA can be genetically tested to guide clinical treatment.

Interventional hydrogel microsphere vaccine as an immune amplifier for activated antitumour immunity after ablation therapy.

The response rate of pancreatic cancer to chemotherapy or immunotherapy pancreatic cancer is low. Although minimally invasive irreversible electroporation (IRE) ablation is a promising option for irresectable pancreatic cancers, the immunosuppressive tumour microenvironment that characterizes this tumour type enables tumour recurrence. Thus, strengthening endogenous adaptive antitumour immunity is critical for improving the outcome of ablation therapy and post-ablation immune therapy. Here we present a hydrogel microsphere vaccine that amplifies post-ablation anti-cancer immune response via releasing its cargo of FLT3L and CD40L at the relatively lower pH of the tumour bed. The vaccine facilitates migration of the tumour-resident type 1 conventional dendritic cells (cDC1) to the tumour-draining lymph nodes (TdLN), thus initiating the cDC1-mediated antigen cross-presentation cascade, resulting in enhanced endogenous CD8+ T cell response. We show in an orthotopic pancreatic cancer model in male mice that the hydrogel microsphere vaccine transforms the immunologically cold tumour microenvironment into hot in a safe and efficient manner, thus significantly increasing survival and inhibiting the growth of distant metastases.

Glomus mosseae improved the adaptability of alfalfa (Medicago sativa L.) to the coexistence of cadmium-polluted soils and elevated air temperature.

The coexistence of heavy metal-polluted soils and global warming poses serious threats to plants. Many studies indicate that arbuscular mycorrhizal fungi (AMF) can enhance the resistance of plants to adverse environments such as heavy metals and high temperature. However, few studies are carried out to explore the regulation of AMF on the adaptability of plants to the coexistence of heavy metals and elevated temperature (ET). Here, we investigated the regulation of Glomus mosseae on the adaptability of alfalfa (Medicago sativa L.) to the coexistence of cadmium (Cd)-polluted soils and ET. G. mosseae significantly enhanced total chlorophyll and carbon (C) content in the shoots by 15.6% and 3.0%, respectively, and Cd, nitrogen (N), and phosphorus (P) uptake by the roots by 63.3%, 28.9%, and 85.2%, respectively, under Cd + ET. G. mosseae significantly increased ascorbate peroxidase activity, peroxidase (POD) gene expression, and soluble proteins content in the shoots by 13.4%, 130.3%, and 33.8%, respectively, and significantly decreased ascorbic acid (AsA), phytochelatins (PCs), and malondialdehyde (MDA) contents by 7.4%, 23.2%, and 6.5%, respectively, under ET + Cd. Additionally, G. mosseae colonization led to significant increases in POD (13.0%) and catalase (46.5%) activities, Cu/Zn-superoxide dismutase gene expression (33.5%), and MDA (6.6%), glutathione (22.2%), AsA (10.3%), cysteine (101.0%), PCs (13.8%), soluble sugars (17.5%), and proteins (43.4%) contents in the roots and carotenoids (23.2%) under ET + Cd. Cadmium, C, N, G. mosseae colonization rate, and chlorophyll significantly influenced shoots defenses and Cd, C, N, P, G. mosseae colonization rate, and sulfur significantly affected root defenses. In conclusion, G. mosseae obviously improved the defense capacity of alfalfa under ET + Cd. The results could improve our understanding of the regulation of AMF on the adaptability of plants to the coexistence of heavy metals and global warming and phytoremediation of heavy metal-polluted sites under global warming scenarios.

Effect of Glomus mosseae, cadmium, and elevated air temperature on main flavonoids and phenolic acids contents in alfalfa.

Global warming and heavy metal-contaminated soils co-occur in natural ecosystems. Flavonoids and phenolic acids in plants have significant antioxidant activity and free radical scavenging ability, which can quickly increase under adverse environments. Arbuscular mycorrhizal fungi (AMF) colonization can affect the synthesis of flavonoids and phenolic acids in host plants. This study focused on the main effect of Glomus mosseae, cadmium (Cd, 8 mg kg-1 dry soils), and elevated temperature (ET, + 3 °C) on main flavonoids and phenolic acids in 120-d Medicago sativa L. (alfalfa). Elevated temperature decreased G. mosseae colonization ratio by 49.5% under Cd exposure. Except for p-hydroxybenzoic acid, flavonoids and phenolic acids content in shoots increased (p < 0.05) under G. mosseae + Cd relative to Cd only. G. mosseae and Cd showed significant effects on rutin, quercetin, apigenin, liquiritigenin, gallic acid, p-hydroxybenzoic acid, p-coumaric acid, and ferulic acid, and G. mosseae colonization led to increases in these compounds by 41.7%, 35.4%, 32.2%, 267.8%, 84.7%, 33.5%, 102.8%, and 89.4%, respectively, under ET + Cd. Carbon, N, and Cd in alfalfa and G. mosseae colonization rate were significant factors on flavonoids and phenolic acids accumulation. Additionally, P content in shoots significantly influenced flavonoids content. G. mosseae inoculation significantly stimulated the synthesis of main flavonoids and phenolic acids in alfalfa shoots under ET + Cd, which was helpful to understand the regulation of AMF on non-enzyme antioxidant system of plants grown in heavy metal-contaminated soils under global change scenarios.

Covered stent treatment for arterial complications after pancreatic surgery: risk assessment for recurrence and peri-stent implantation management.

OBJECTIVES: To explore the risk factors for recurrence of arterial complications after pancreatectomy during the period of covered stent implantation and to provide some opinions on peri-stent implantation management. METHODS: Data on patients implanted with covered stents due to arterial complications after pancreatectomy between January 2017 and December 2021 were analyzed retrospectively. Technical success, clinical success, recurrence, and survival were evaluated to elucidate the practicability of covered stents. Wilson score, Random Forest, logistic regression, and Pearson's chi-square test with bootstrap aggregation were performed for determining the perioperative risk factors for recurrence. RESULTS: Among all fifty-five patients, success stent implantation (technical success) was achieved 100%. Patients who were hemodynamically stabilized without further treatment for artery complications in situ (clinical success) accounted for 89.1%. Based on statistical analysis, pre-stent implantation pancreatic fistula was identified as a robust recurrence-related risk factor for preoperative assessment (p = 0.02, OR = 4.5, 95% CI [1.2, 16.9]; pbootstrap = 0.02). Post-stent implantation pancreatic fistula (p = 0.01, OR 4.5, 95% CI [1.4, 14.6]; pbootstrap < 0.05) and SMA branches or GDA stumps (p = 0.02, OR 3.4, 95% CI [1.1, 10.3]) were relevant to recurrence. The survival rate during hospitalization was 87.3%. All survivors were free from recurrence during the subsequent follow-up. Vasospasm and stent occlusion were observed as short-term and long-term complications, respectively. CONCLUSION: A covered stent implantation is a feasible and effective treatment option for post-pancreatectomy arterial complications. Rigorous management of pancreatic fistula, timely detection of problems, sensible strategies during stent implantation, and reasonable anticoagulation therapy are necessary for a better prognosis. KEY POINTS: • A covered stent is feasible for various artery-related complications after pancreatectomy and has an ideal therapeutic effect. • Pancreatic fistula during the perioperative period of the covered stent is an independent risk factor for recurrent arterial complications and SMA branches or GDA stumps are prone to be recurrent offending arteries. • Rigorous management of pancreatic fistula, timely detection of problems, sensible strategies during stent implantation, and reasonable anticoagulation therapy are necessary for a better prognosis.

Balloon-occluded retrograde transvenous obliteration with lauromacrogol sclerosant foam for gastric varices.

Objectives: To evaluate the safety and efficacy of balloon-occluded retrograde transvenous obliteration (BRTO) using lauromacrogol sclerosant foam for gastric varices (GVs) with gastrorenal venous shunts. Methods: Data of GV patients treated with BRTO using lauromacrogol sclerosant foam in 2016-2020 were retrospectively analyzed along with procedural success rate, complications, and follow-up efficacy. Results: A total of 31 patients were treated with BRTO. The sclerosant foam was prepared by mixing iodinated oil, lauromacrogol, and air at a 1:2:3 ratio. The BRTO procedure was successfully completed in 93.5% of patients. One patient was allergic to the lauromacrogol injection. A mild postoperative fever occurred in three patients. One patient experienced grand mal seizures after the procedure. There was no significant difference in the median Child-Turcotte-Pugh scores before versus after BRTO. Complete GV resolution was observed in 93.1% of patients. One patient underwent endoscopic treatment for the development of high-risk esophageal varices. Another patient underwent transjugular intrahepatic portosystemic shunt placement for the aggravation of ascites. Conclusions: Lauromacrogol sclerosant foam is safe and effective in patients undergoing BRTO for GV.

Effect of arbuscular mycorrhizal fungi (Glomus mosseae) and elevated air temperature on Cd migration in the rhizosphere soil of alfalfa.

Cadmium (Cd) migration in the rhizosphere soil is easily affected by plants and microorganisms. Global warming significantly affects plant growth, and arbuscular mycorrhizal fungi (AMF) can chelate heavy metals by mycelium, cell wall components, and mycelial secretion. Here, we investigated the regulation of Glomus mosseae on Cd migration in the rhizosphere soil of alfalfa under elevated temperature (ET, + 3 °C). Elevated temperature significantly decreased G. mosseae colonization rate in the roots by 49.5% under Cd exposure. Under ET + G. mosseae + Cd relative to ET + Cd, the contents of free amino acids, total and easily extractable glomalin-related soil protein (GRSP), and root Cd increased significantly; however, the changes in DTPA-Cd in the rhizosphere soil and Cd in the shoots were insignificant. In addition, G. mosseae colonization enhanced the bioconcentration factor of Cd in the roots and the total removal rate of Cd in the rhizosphere soil by 63.4% and 16.3%, respectively, under ET + Cd. However, the changes in the expression of iron-regulated transport 1 (IRT1) and natural resistance-associated macrophage protein 1 genes were insignificant under ET + G. mosseae + Cd relative to ET + Cd. In summary, temperature and G. mosseae significantly affected Cd fate in the rhizosphere soil, and IRT1 gene and rhizosphere soil pH, N, and C/N ratio were significant factors influencing Cd migration. Additionally, G. mosseae improved the remediation efficiency of Cd-contaminated soils by alfalfa under ET. The results will help us understand the regulation of AMF on the phytoremediation of heavy metal-contaminated soils under global warming scenarios.

Novel irreversible electroporation ablation (Nano-knife) versus radiofrequency ablation for the treatment of solid liver tumors: a comparative, randomized, multicenter clinical study.

Irreversible electroporation (IRE) is a soft tissue ablation technique that uses short electrical fields which induce the death of target cells. To evaluate the safety and efficacy of an IRE-based device compared to regular radiofrequency ablation (RFA) of solid liver tumors, in this multicenter, randomized, parallel-arm, non-inferiority study, 152 patients with malignant liver tumors were randomized into IRE (n = 78) and RFA (n = 74) groups. The primary endpoint was the success rate of tumor ablation; the secondary endpoints included the tumor ablation time, complications, tumor recurrence rates and treatment-related adverse events (TRAE). The success rate of tumor ablation using IRE was 94.9% and was non-inferior to the RFA group (96.0%) (P = 0.761). For the secondary endpoints, the average ablation time was 34.29 ± 30.38 min for the IRE group, which was significantly longer than for the RFA group (19.91 ± 16.08 min) (P < 0.001). The incidences of postoperative complications after 1 week (P = 1.000), 1 month (P = 0.610) and 3 months (P = 0.490) were not significantly different between the 2 groups. The recurrence rates of liver tumor at 1, 3 and 6 months after ablation were 0 (0.0%), 10 (13.9%) and 10 (13.3%) in the IRE group and 2.9%, 7.3% and 19.7% in the RFA control group (all P > 0.05), respectively. For safety assessments, 51 patients experienced 191 AEs (65.4%) in the IRE group, which was not different from the RFA group (73.0%, 54/184) (P = 0.646). In 7 IRE patients, 8 TRAEs (7.9%) occurred, the most common being edema of the limbs (mild grade) and fever (severe grade), while no TRAEs occurred in the RFA group. This study proved that the excellent safety and efficacy of IRE was non-inferior to the regular radiofrequency device in ablation performance for the treatment of solid liver tumors. Clinical trial registration: Chinese Clinical Trial Registry: ChiCTR1800017516.

Tumor-infiltrating OX40+ lymphocytes is an independent positive prognostic factor for patients with pancreatic ductal adenocarcinoma

Purpose: OX40 signaling pathway occupies a vital place in anti-tumor immunity; however, the role of tumor-infiltrating OX40+ lymphocytes in pancreatic ductal adenocarcinoma (PDAC) remains to be identified.MethodsA total of 325 sequential PDAC patients who received curative tumor resection between January 2014 and December 2016 were enrolled. Tissues of these patients were immunohistochemically assessed for tumor infiltration of CD4+ T cells, CD8+ cytotoxic T cells (CTLs), and OX40+ lymphocytes. The frequency of OX40+ tumor-infiltrating lymphocytes (TILs) was then analyzed to various clinicopathological features, densities of tumor infiltration of CD4+ T cells and CTLs, and survival analysis was conducted using Kaplan–Meier (KM) curves. The risk scores of associated markers were calculated by the Cox proportional-hazards model.ResultsOur results showed that higher OX40+ lymphocytes infiltration was significantly correlated with superior median overall survival (OS) (25.8 vs 13.4 months, P < 0.001). Additionally, using univariate and multivariate Cox proportional hazards analyses, this study revealed that together with tumor differentiation, tumor size, serum CA199 levels, serum CA125 levels, and the infiltration of intratumoral CD8+ T cells. The abundance of OX40+ lymphocytes within the tumor was continued to be an independent predictor for OS (P = 0.023, HR = 0.713, 95% CI: 0.532–0.954).ConclusionsThis study demonstrated that intratumoral infiltration by a high number of OX40+ lymphocytes is a novel biomarker for favorable prognosis in resected PDAC patients, which implies that OX40-agonist-based immunotherapy might be a potential target in PDAC patients. (AU)

Integrated single-cell RNA-seq analysis identifies immune heterogeneity associated with KRAS/TP53 mutation status and tumor-sideness in colorectal cancers.

Background: The main objective of this study was to analyze the effects of KRAS/TP53 mutation status and tumor sideness on the immune microenvironment of colorectal cancer using integrated scRNA-seq data. Methods: A total of 78 scRNA-seq datasets, comprising 42 treatment-naive colorectal tumors, 13 tumor adjacent tissues and 23 normal mucosa tissues were included. Standardized Seurat procedures were applied to identify cellular components with canonical cell marks. The batch-effect was assessed and corrected using harmony algorithm. The scMetabolism algorithm was used for single-cell metabolic analysis. The results and clinical significance were further validated using immunofluorescent-staining and TCGA-COAD datasets. Immune-infiltration scores of bulk-RNA-seq data were estimated using ssGSEA. The presto-wilcoxauc algorithm was used to identify differentially enriched genes or pathways across different subgroups. Two-sided p-value less than 0.05 was considered statistically significant. Results: We refined the landscape of functional immune cell subtypes, especially T cells and myeloid cells, across normal mucosa, tumor adjacent and tumor tissue. The existence and function of two states of exhausted CD8+ T (Tex) subtypes in colorectal cancer, and FOLR2+ LYVE1+ macrophages indicating unfavorable prognosis in colorectal cancer were identified and validated. The diverse tumor mutation status reshaped the immune cell function and immune checkpoint ligands/receptors (ICLs/ICRs) expression pattern. Importantly, the KRAS/TP53 dual mutations significantly reduced the major energy metabolic functions in immune cells, and promoted the cell-to-cell communications towards immunosuppression in colorectal cancers. The results revealed LAG3, CD24-SIGLEC10 and HBEGF-CD9 pathways as potential therapeutic targets for dual mutant colorectal cancers. Conclusions: We revealed that the immune microenvironment underwent a gradual remodeling with an enrichment of immunosuppressive myeloid cells from normal mucosa to tumor regions in colorectal cancers. Moreover, we revealed the metabolic heterogeneity of tumor-infiltrating immune cells and suggested that the KRAS/TP53 dual mutation may impair antitumor immunity by reducing T and myeloid cell energy metabolism and reshaping cellular interactions toward immunosuppression.

Evaluation of D-TACE combined with endovascular brachytherapy for HCC with MPVTT.

Background: Hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT) may be able to have TACE through stent implantation into the portal vein with thrombosis to recover portal blood flow. Purpose: The goal of this study was to compare clinical results of conventional transcatheter arterial chemoembolization (C-TACE) and doxorubicin-eluting bead transcatheter arterial chemoembolization (D-TACE) combined with endovascular brachytherapy in HCC patients with MPVTT. Methods: This study was a retrospective controlled study with follow-up dates spanning from Mar 2015 to Feb 2020. Patients with both HCC and MPVTT were divided into two groups. Portal vein stents with iodine-125 seed strands were implanted first; then, C-TACE or D-TACE was administered to all patients. Objective response rates were assessed. Results: A total of 26 patients were enrolled, with 13 in each group. During follow-up, the portal stent patency times were 112.3 ± 98.2 days in the C-TACE group and 101.7 ± 90.4 days in the D-TACE group. The time to disease progression was 42 days in the C-TACE group and 120 days in the D-TACE group (p=0.03). The overall survival time from the first intervention procedure was 216 days in the C-TACE group and 239 days in the D-TACE group (p=0.047). The D-TACE group was superior to the C-TACE group in terms of progression-free survival (PFS) and overall survival (OS) times. Conclusion: Endovascular implantation of brachytherapy combined with TACE is safe and effective in HCC patients with MPVTT. This combination therapy may be helpful for survival benefits to patients with stage BCLC-C HCC.

Percutaneous Ablation of Hepatic Tumors at the Hepatocaval Confluence Using Irreversible Electroporation: A Preliminary Study.

BACKGROUND: Tumors at the hepatocaval confluence are difficult to treat, either surgically or ablatively. METHODS: A retrospective longitudinal study on patients ineligible for thermal ablation who underwent computed tomography-guided IRE for hepatic tumors at the hepatocaval confluence was conducted. Factors analyzed included patient and tumor characteristics, IRE procedure details, treatment-related complications, and prognosis. RESULTS: Between 2017 and 2021, 21 patients at our institute received percutaneous IRE. Of the 38 lesions, 21 were at the hepatocaval confluence. Complete ablation was achieved in all cases. Local and distant recurrence was observed in 4.8% (1/21) and 42.6% (9/21) of the ablated tumors, respectively. All postcava remained perfused at follow-up, except for 1 (4.8%) hepatic vein near the lesion found to be temporarily occluded and restored within 1 month. The ratio of the maximum diameter of ablation area at 1, 3, and 6 months post procedure compared to that immediately after IRE was 0.68 (0.50-0.84), 0.49 (0.27-0.61), and 0.38 (0.25-0.59), respectively. Progression-free survival of the patients with recurrence was 121 (range, 25-566) days. Four (19.0%) patients died at the end of follow-up with median overall survival of 451.5 (range, 25-716) days. CONCLUSIONS: IRE could be a safe and effective treatment for hepatic tumors at the hepatocaval confluence. This article provides valuable prognostic data; further clinical research is needed for better prognosis.

Tumor-infiltrating OX40+ lymphocytes is an independent positive prognostic factor for patients with pancreatic ductal adenocarcinoma.

PURPOSE: OX40 signaling pathway occupies a vital place in anti-tumor immunity; however, the role of tumor-infiltrating OX40+ lymphocytes in pancreatic ductal adenocarcinoma (PDAC) remains to be identified. METHODS: A total of 325 sequential PDAC patients who received curative tumor resection between January 2014 and December 2016 were enrolled. Tissues of these patients were immunohistochemically assessed for tumor infiltration of CD4+ T cells, CD8+ cytotoxic T cells (CTLs), and OX40+ lymphocytes. The frequency of OX40+ tumor-infiltrating lymphocytes (TILs) was then analyzed to various clinicopathological features, densities of tumor infiltration of CD4+ T cells and CTLs, and survival analysis was conducted using Kaplan-Meier (KM) curves. The risk scores of associated markers were calculated by the Cox proportional-hazards model. RESULTS: Our results showed that higher OX40+ lymphocytes infiltration was significantly correlated with superior median overall survival (OS) (25.8 vs 13.4 months, P < 0.001). Additionally, using univariate and multivariate Cox proportional hazards analyses, this study revealed that together with tumor differentiation, tumor size, serum CA199 levels, serum CA125 levels, and the infiltration of intratumoral CD8+ T cells. The abundance of OX40+ lymphocytes within the tumor was continued to be an independent predictor for OS (P = 0.023, HR = 0.713, 95% CI: 0.532-0.954). CONCLUSIONS: This study demonstrated that intratumoral infiltration by a high number of OX40+ lymphocytes is a novel biomarker for favorable prognosis in resected PDAC patients, which implies that OX40-agonist-based immunotherapy might be a potential target in PDAC patients.

The clinical applicability of percutaneous splenic vein stent implantation for pancreatic portal hypertension.

BACKGROUND: Pancreatic portal hypertension (PPH) is a type of extrahepatic portal hypertension. We compared the clinical efficacy of different treatment methods for PPH caused by splenic vein stenosis in chronic pancreatitis. METHODS: This article retrospectively analyzed the PPH cases that were caused by splenic vein stenosis after chronic pancreatitis. Patients were divided into three groups according to the different treatments: splenic vein stent implantation (stent group), splenectomy, and only medications (conservative group). The treatment effects from each group were compared. RESULTS: A total of 33 patients were retrospectively analyzed in this study (9, 12, and 12 patients in each group respectively). All the procedures were successful in the stent and splenectomy groups. During the follow-up, no patient had gastrointestinal bleeding recurrence in the stent and splenectomy groups. However, in the conservative group, the incidence of portal hypertensive gastropathy and upper gastrointestinal bleeding were 50% and 25%. In the stent group, all the varicose veins at the base of the stomach had shrunk by varying degrees, and the red color signs regressed. The stent patency rate was 100%. No major complication occurred. The average platelet count at 1, 3, 6-months postoperatively were all significantly higher than the preoperative value (P < 0.05). The average postoperative hospital stay duration was significantly shorter than that of the splenectomy group (3.1 ± 1.4 days vs. 16.1 ± 8.1 days; P < 0.05). In the splenectomy group, postoperative fever occurred in 4 patients. Postoperative infection occurred in 2 patients (one with abdominal cavity infection and the other with incision infection). Delayed abdominal bleeding occurred in one patient. Portal vein thrombosis occurred in 2 patients during follow up. CONCLUSION: Percutaneous splenic vein stent implantation for PPH treatment reduces the risk of gastrointestinal bleeding with minimal invasive. It has a high safety and reliable efficacy and is worthy of further clinical promotion.