ABSTRACT
Budd-Chiari syndrome (B-CS) is a rare and lethal condition characterized by hepatic venous outflow tract blockage. Gut microbiota has been linked to numerous hepatic disorders, but its significance in B-CS pathogenesis is uncertain. First, we performed a case-control study (Ncase = 140, Ncontrol = 63) to compare the fecal microbiota of B-CS and healthy individuals by metagenomics sequencing. B-CS patients' gut microbial composition and activity changed significantly, with a different metagenomic makeup, increased potentially pathogenic bacteria, including Prevotella, and disease-linked microbial function. Imbalanced cytokines in patients were demonstrated to be associated with gut dysbiosis, which led us to suspect that B-CS is associated with gut microbiota and immune dysregulation. Next, 16S ribosomal DNA sequencing on fecal microbiota transplantation (FMT) mice models examined the link between gut dysbiosis and B-CS. FMT models showed damaged liver tissues, posterior inferior vena cava, and increased Prevotella in the disturbed gut microbiota of FMT mice. Notably, B-CS-FMT impaired the morphological structure of colonic tissues and increased intestinal permeability. Furthermore, a significant increase of the same cytokines (IL-5, IL-6, IL-9, IL-10, IL-17A, IL-17F, and IL-13) and endotoxin levels in B-CS-FMT mice were observed. Our study suggested that gut microbial dysbiosis may cause B-CS through immunological dysregulation. IMPORTANCE: This study revealed that gut microbial dysbiosis may cause Budd-Chiari syndrome (B-CS). Gut dysbiosis enhanced intestinal permeability, and toxic metabolites and imbalanced cytokines activated the immune system. Consequently, the escalation of causative factors led to their concentration in the portal vein, thereby compromising both the liver parenchyma and outflow tract. Therefore, we proposed that gut microbial dysbiosis induced immune imbalance by chronic systemic inflammation, which contributed to the B-CS development. Furthermore, Prevotella may mediate inflammation development and immune imbalance, showing potential in B-CS pathogenesis.
ABSTRACT
Oxaliplatin is currently used for chemotherapy in patients with hepatocellular carcinoma, but its increasing tolerance to tumours over time limits its clinical application. Studies have shown that high PD-L1 expression promotes the polarization of M2 macrophages. The increased infiltration of M2 macrophages, including those in HCC, is positively correlated with poor prognosis in various solid tumours. We found that oxaliplatin promoted the expression of PD-L1 in liver cancer cells, which might be attributed partly to the tolerance of tumours to oxaliplatin. Therefore, in this study, we explored the antitumour effect of attenuated Salmonella carrying siRNA-PD-L1 combined with oxaliplatin via Western blotting, immunohistochemistry, immunofluorescence, and flow cytometry. The results revealed that attenuated Salmonella carrying siRNA-PD-L1 combined with oxaliplatin more significantly inhibited tumour growth in tumour-bearing mice, suppressed the expression of PD-L1 in tumour tissue, increased the apoptosis of tumour cells and the expression of the tumour-related protein cleaved-caspase3, and increased the infiltration of M1 macrophages and T lymphocytes in tumour tissues. Moreover, the combination therapy increased the activation of T cells and the number of T lymphocytes and NK cells in the spleens of the mice and improved the overall antitumour immune response in the mice. Our results confirmed that attenuated Salmonella harbouring siRNA-PD-L1 combined with oxaliplatin had a significant antitumour effect and did not increase the incidence of toxic side effects, providing a theoretical reference for addressing oxaliplatin tolerance in the treatment of hepatocellular carcinoma.
ABSTRACT
Immunotherapy shows great therapeutic potential for long-term protection against tumor relapse and metastasis. Innate immune sensors, such as cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), dissolve DNA and induce type I interferon. Through activation of the cGAS/STING pathway, chemotherapy drugs and reversine (REV) may provide synergetic anti-tumor effects. Here, we prepared drug-loaded cell membrane hybrid lipid nanovesicles (LEVs) (designated LEV@DOX@REV) by fusion of cell membranes, phospholipids, doxorubicin (DOX), and REV, to realize accurate delivery to tumors and chemo-immunotherapy. The cell membranes of LEVs confer "homing" abilities. DOX can induce immunogenic cell death as a result of its specific immunomodulatory effects, which promotes the maturation of immune cells and improves the microenvironment of the immune system. REV is proven to efficiently activate cGAS/STING signaling, thereby enhancing the immune system. The antitumor efficacy of LEV@DOX@REV was evaluated in a 4T1 subcutaneous tumor xenograft model, a distant metastatic tumor model, and a liver metastatic tumor model. LEV@DOX@REV facilitated the infiltration of cytotoxic T lymphocytes within tumors, increased the secretion of proinflammatory cytokines, and modified the tumor microenvironment. In conclusion, LEV@DOX@REV displayed favorable antitumor effects and extended the survival of tumor-bearing mice. We therefore successfully developed nanoparticles capable of enhancing immune activation that have potential therapeutic applications for cancer immunotherapy.
ABSTRACT
BACKGROUND AND PURPOSE: The Neuroform Atlas stent and the LVIS Jr stent are intracranial microstent systems for the treatment of wide-neck intracranial aneurysms. Hence, this study aimed to compare the efficacy and safety of the Neuroform Atlas stent and the LVIS Jr stent for the treatment of unruptured intracranial aneurysms in parent arteries of <2 mm in diameter. MATERIALS AND METHODS: From March 2022 to April 2023, the clinical and imaging data of 135 patients with unruptured intracranial aneurysms treated with stent-assisted coiling using the Neuroform Atlas or LVIS Jr stent in parent arteries of <2 mm in diameter were retrospectively analyzed. Stent apposition was evaluated by high-resolution conebeam CT (HR-CBCT). Immediate aneurysm-embolization attenuation and occlusion at 6-month follow-up were evaluated using 2D DSA and the modified Raymond-Roy classification. Adverse events were recorded. Multivariate logistic regression analysis was undertaken to determine the independent factors affecting incomplete stent apposition. RESULTS: One hundred thirty-five patients (135 aneurysms) underwent stent-assisted coiling (66 Neuroform Atlas stents and 69 LVIS Jr stents). Intraoperative HR-CBCT showed that 1 Neuroform Atlas stent and 11 LVIS Jr stents had incomplete stent apposition at the aneurysm neck (P < .05). Perioperative complications occurred in 3 cases (2.22%). These comprised 2 cases of neurologic complications (1 case of distal intracranial vascular embolism and 1 case of cerebral parenchymal hemorrhage) and 1 case of severe postprocedural gastrointestinal hemorrhage. DSA follow-up showed 3 cases of aneurysm recurrence in the LVIS Jr group. Multivariate regression analysis showed that a stent angle of ≥75° (OR, 23.963; P = .005) or a parent artery diameter mismatch ratio of ≥1.25 (OR, 8.043; P = .037) were risk factors for incomplete stent apposition, especially for the LVIS Jr stent (OR, 20.297; P = .015). CONCLUSIONS: The Neuroform Atlas stent and LVIS Jr stent are efficacious in the treatment of unruptured intracranial aneurysms in parent arteries of <2 mm in diameter. Apposition of the LVIS Jr stent was worse than in the Neuroform Atlas stent at the neck of some aneurysms.
Subject(s)
Embolization, Therapeutic , Intracranial Aneurysm , Stents , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/therapy , Intracranial Aneurysm/surgery , Male , Female , Middle Aged , Retrospective Studies , Aged , Embolization, Therapeutic/instrumentation , Embolization, Therapeutic/methods , Adult , Treatment Outcome , Endovascular Procedures/instrumentation , Endovascular Procedures/methods , Cerebral Angiography , Cone-Beam Computed Tomography , Angiography, Digital SubtractionABSTRACT
OBJECTIVE: To study the predictive factors of false negatives in the diagnosis of biliary stricture (BS) by percutaneous transluminal clamp biopsy (PTCB). METHOD: From January 2016 to January 2021, 194 patients with a high suspicion of malignant tumors due to BS underwent PTCB during biliary drainage at our department. The final diagnosis was confirmed by postoperative pathology, other tissue or cell evidence, or medical imaging follow-up. Univariate and multivariate regression analyses were performed on the pathological results, summarizing the independent risk factors for false-negative value (FNV) to help further clinical diagnosis and treatment. RESULTS: Of the 194 cases, 176 and 18 cases were finally diagnosed as malignant and benign BS, respectively, compared to 144 and 50 cases by PTCB, including 32 false-negative cases. The sensitivity, specificity, false-positive value, and FNV of PTCB were 81.8%, 100%, 0%, and 18.2%, respectively. Multivariate analysis showed that non-cholangiocarcinoma BS was an independent risk factor for FNV of PTCB (odds ratio 7.5 (95% CI 1.74-32.6), p < 0.01). CONCLUSION: PTCB is an effective minimally invasive interventional technique for BS diagnosis. Non-cholangiocarcinoma BS is an independent risk factor for FNV. CRITICAL RELEVANCE STATEMENT: Identifying factors that are predictive of false-negative results by percutaneous transluminal clamp biopsy in the setting of biliary stricture may have a guiding effect on clinical practice. KEY POINTS: ⢠Factors predictive of false negatives in the diagnosis of biliary stricture etiology by PTCB may aid in the interpretation of results. ⢠Non-cholangiocarcinoma BS is an independent risk factor for FNV on PTCB. ⢠PTCB is an effective minimally invasive interventional technique for BS diagnosis.
ABSTRACT
Hypoxia is a hallmark of solid tumors. Hypoxic cancer cells adjust their metabolic characteristics to regulate the production of cellular reactive oxygen species (ROS) and facilitate ROS-mediated metastasis. Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that regulates the transcription of fatty acid metabolism-related genes that have a key role in the survival and proliferation function of hypoxic cancer cells. In the present study, mRNA expression in HepG2 cells under chemically induced hypoxia was assessed. The protein expression levels of hypoxia-inducible factor 1α (HIF-1α) were measured using western blotting. Following treatment with the PPARγ agonist pioglitazone, cell viability was assessed using a Cell Counting Kit-8 assay, whilst cell proliferation and death were determined using 5-ethynyl-2'-deoxyuridine incorporation staining, and calcein-acetoxymethyl ester and propidium iodide staining, respectively. Cellular ROS production was assessed using dihydroethidium staining. Cobalt chloride was used to induce hypoxia in HepG2 cells, which was evaluated using HIF-1α expression. The results revealed that the mRNA expression of PPARγ, CD36, acetyl-co-enzyme A dehydrogenase (ACAD) medium chain (ACADM) and ACAD short-chain (ACADS) was downregulated in hypoxic HepG2 cells. The PPARγ agonist pioglitazone decreased the cell viability of hypoxic HepG2 cells by inhibiting cell proliferation and inducing cell death. Following treatment with the PPARγ agonist pioglitazone, hypoxic HepG2 cells produced excessive ROS. ROS-mediated cell death induced by the PPARγ agonist pioglitazone was rescued with the antioxidant N-acetyl-L-cysteine. The downregulated mRNA expression of PPARγ, CD36, ACADM and ACADS was not reverted by a PPARγ agonist in hypoxic HepG2 cells. By contrast, the PPARγ agonist suppressed the mRNA expression of BCL2, which was upregulated in hypoxic HepG2 cells. In summary, the PPARγ agonist stimulated excessive ROS production to inhibit cell proliferation and increase the death of hypoxic HepG2 cells by decreasing BCL2 mRNA expression, suggesting a negative association between PPARγ and BCL2 in the regulation of ROS production in hypoxic HepG2 cells.
ABSTRACT
The treatment of hepatocellular carcinoma (HCC) remains a major challenge in the medical field. Lenvatinib, a multi-target tyrosine kinase inhibitor, has demonstrated anti-HCC effects by targeting and inhibiting pathways such as vascular endothelial growth factor receptor 1-3 (VEGFR1-3). However, the therapeutic efficacy of Lenvatinib is subject to various influences, with the hypoxic microenvironment of the tumor being a pivotal factor. Consequently, altering the hypoxic milieu of the tumor emerges as a viable strategy to augment the efficacy of Lenvatinib. Hypoxia-inducible factor-1α (HIF-1α), synthesized by tumor cells in response to oxygen-deprived conditions, regulates the expression of resistance genes, promotes tumor angiogenesis and cell proliferation, enhances tumor cell invasion, and confers resistance to radiotherapy and chemotherapy. Thus, we constructed a self-designed siRNA targeting HIF-1α to suppress its expression and improve the efficacy of Lenvatinib in treating HCC. The therapeutic efficacy of siRNA-HIF-1α in combination with Lenvatinib on HCC were evaluated through in vivo and in vitro experiments. The results showed that the recombinant Salmonella delivering siRNA-HIF-1α in combination with Lenvatinib effectively inhibited tumor growth and prolonged the survival of tumor-bearing mice. This treatment approach reduced cell proliferation and angiogenesis in HCC tissues while promoting tumor cell apoptosis. Additionally, this combined therapy significantly increased the infiltration of T lymphocytes and M1 macrophages within the tumor microenvironment, as well as elevated the proportion of immune cells in the spleen, thereby potentiating the host's immune response against the tumor.
Subject(s)
Carcinoma, Hepatocellular , Hypoxia-Inducible Factor 1, alpha Subunit , Liver Neoplasms , Phenylurea Compounds , Quinolines , RNA, Small Interfering , RNAi Therapeutics , Salmonella , Animals , Mice , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/therapy , Cell Line, Tumor , Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Liver Neoplasms/drug therapy , Liver Neoplasms/therapy , Phenylurea Compounds/therapeutic use , Quinolines/therapeutic use , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/therapeutic use , Tumor Microenvironment , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Combined Modality Therapy , RNAi Therapeutics/methodsABSTRACT
Transarterial chemoembolization (TACE) is a first-line treatment for intermediate to advanced-stage liver cancer, with drug-eluting microspheres commonly used as embolic agents. However, currently available drug-eluting microspheres suffer from low drug-loading capacity and limited drug options. In this work, we developed polydopamine-modified polyvinyl alcohol dual-drug-loaded microspheres encapsulating celecoxib and cisplatin (referred to as PCDMS). Physicochemical characterization revealed that the surface of the microspheres displayed increased roughness after polydopamine modification, and celecoxib and cisplatin were successfully loaded onto the microsphere surface. In vitro cell experiments demonstrated that the PCDMS significantly inhibited the proliferation and migration of highly metastatic human liver cancer cells (MHCC-97H) and human liver cancer cells (SMMC-7721). Furthermore, the dual-loaded microspheres exhibited remarkable tumor growth inhibition and reshaped the tumor microenvironment in both subcutaneous H22 liver cancer model in Balb/c mice and intrahepatic VX2 tumor model in New Zealand rabbits, demonstrating a synergistic antitumor effect where 1 + 1>2. This work provides a potential therapeutic approach for the treatment of refractory liver cancer and holds significant translational potential.
ABSTRACT
Our objective was to assess the safety and efficacy of 3 tubes with or without covered esophageal stent placement for the management of gastro-mediastinal or gastro-pleural fistula. We retrospectively assessed the clinical data of 31 consecutive patients with gastro-mediastinal or gastro-pleural fistula treated by using a noninvasive treatment from February 2013 to July 2022. Patients received 3 tubes (jejunal feeding tube, gastrointestinal drainage tube and abscess drainage tube) with or without esophageal-covered stent placement. All patients received continue abscess drainage and nutritional support after procedure. The tubes and/or esophageal-covered stents were removed after fistula healing. All patients received 3 tubes placement and 11 patients with luminal narrowing received esophageal covered stent placement. Technically success was found in all patients, with no procedure-related death, esophageal rupture or massive hemorrhage. Abscess cavity disappeared in 22 patients, with a clinical success rate of 71.0%. All patients received esophageal stent placement were cured and stents were removed, for a median duration of 1.6 months (interquartile ranges [IQR] 1.4, 3.7). Three patients showed clinical improved, with markedly decreased abscess cavity and markedly shrunk fistula. The median survival was 30.8 months. The 1-, 3-, 5-year survival rates were 71.1%, 46.1% and 39.5%, respectively. A noninvasive treatment of 3 tubes with or without covered esophageal stent placement is safe and effective for gastro-mediastinal or gastro-pleural fistula after esophagogastrectomy.
Subject(s)
Esophageal Fistula , Gastric Fistula , Pleural Diseases , Humans , Abscess/therapy , Retrospective Studies , Treatment Outcome , Stomach , Pleural Diseases/etiology , Pleural Diseases/surgery , Stents , Esophageal Fistula/etiology , Esophageal Fistula/surgeryABSTRACT
Most patients with benign esophageal stenosis require multiple or even continuous balloon dilation treatments to achieve symptom relief. In this study, eighteen rabbits were used to establish an esophageal benign stenosis model and were divided into a control group (n = 6), a balloon group (n = 6) and a PTX-coated balloon group (n = 6) to evaluate the feasibility and effectiveness of paclitaxel (PTX)-coated balloons for the rabbit esophageal benign stenosis model. The weight and esophageal diameter were recorded every 2 weeks until 8 weeks post-surgery. Hematoxylin-eosin staining, Masson's trichrome staining and immunohistochemical staining were performed for pathological analysis. Four weeks post-operation, there was a significant difference in weight between the control group and the balloon group (p = 0.01) and between the control group and the PTX balloon group (p = 0.01). There was a significant difference in the esophageal diameter between the balloon group and the PTX balloon group at 8 weeks post-operation (p = 0.02). Four weeks post-operation, the degree of inflammatory cell infiltration in the PTX balloon group was significantly lower than that in the control group (p = 0.002) and balloon group (p = 0.001). The degree of collagen deposition in the PTX balloon group was significantly lower than that in the control group (p = 0.002) and balloon group (p = 0.03). Eight weeks post-operation, the percentage of cells positive for TGF-ß (p < 0.001), the degree of inflammatory cell infiltration (p = 0.02) and the degree of collagen deposition (p = 0.02) in the PTX balloon group were significantly lower than those in the balloon group. Therefore, PTX-coated balloons may alleviate the local inflammatory response and collagen deposition when used during dilation treatment of benign esophageal stenosis.
Subject(s)
Esophageal Stenosis , Paclitaxel , Animals , Humans , Rabbits , Paclitaxel/pharmacology , Esophageal Stenosis/therapy , Constriction, Pathologic , Collagen , Catheters , Treatment OutcomeABSTRACT
As a promising drug delivery system, the temperature-sensitive liquid embolic agent (TempSLE) has yet to be reported in animal experiments in treating gastric cancer. We observed and compared computed tomography (CT) imaging changes, tumor volume, HE staining, and immunohistochemistry after transcatheter arterial chemoembolization (TACE) treatment in rabbit VX2 gastric cancer models to clarify the effectiveness of TempSLE loaded with oxaliplatin (TempSLE/Oxa) in treating gastric cancer. One milliliter TempSLE can be loaded with 20 mg oxaliplatin. The accumulative drug release rate at 30 min was 38.76%, and after 24 h, it reached more than 90%. CT examination 1 week after TACE revealed that the TempSLE/Oxa group presents unenhanced hypodense necrotic foci, the iodinated oil loaded with oxaliplatin (Ioil/Oxa) group presents shrinking tumors but still visible speckled foci of enhancement, and the normal saline (NS) group presents heterogeneous enhancement with larger tumors than before. In the postoperative autopsy of TACE, the tumor volumes of TempSLE/Oxa, Ioil/Oxa, and NS groups were 0.15 ± 0.06 cm3, 0.37 ± 0.11 cm3, and 1.19 ± 0.16 cm3, respectively, all of which were statistically different. The positive vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) expression percentages in the TempSLE/Oxa, Ioil/Oxa, and NS groups were statistically different and lowest in the TempSLE/Oxa group. In conclusion, the TempSLE can load a high dose of oxaliplatin to meet the demand of clinical applications. TempSLE/Oxa could effectively inhibit tumor cell proliferation and angiogenesis. This study provides experimental evidence for the further clinical application of the TempSLE/Oxa.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Stomach Neoplasms , Animals , Rabbits , Oxaliplatin , Liver Neoplasms/therapy , Chemoembolization, Therapeutic/methods , Stomach Neoplasms/drug therapy , Temperature , Vascular Endothelial Growth Factor AABSTRACT
Poor clinical efficacy associated with postoperative hepatocellular carcinoma (HCC) often results from recurrence and metastasis. Hence, research has focused on establishing an effective multimodal therapy. However, complex combinations of active ingredients require multiple functions in therapeutic systems. Herein, a portable nanofiber patch composing germanium phosphorus (GeP) and anlotinib (AL) was designed to form a versatile platform for molecularly targeted photothermal-immune checkpoint blockade (ICB) trimodal combination therapy. The patches possess hydrophilic, satisfactory mechanical, and excellent photothermal conversion properties. Moreover, they achieve a penetrating and sustained drug release. The near-infrared light-assisted GeP-induced temperature increase regulates AL release, downregulating the expression of vascular-related factor receptors, triggering immunogenic cell death of tumor cells, and inducing dendritic cell maturation. Simultaneously, ICB therapy (programmed cell death ligand 1, PD-L1) was introduced to improve treatment outcomes. Notably, this trimodal combination therapy significantly inhibits vascular hypergrowth, enhances effector T-cell infiltration, and sensitizes the PD-L1 antibody response, boosting immunotherapy to suppress residual HCC recurrence and metastasis. Further validation of the genome sequencing results revealed cell pathways related primarily to regulatory immune effects. This study demonstrates the use of an effective and practical nanofiber patch to improve multimodal therapy of postoperative HCC, with high clinical translation value.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Nanofibers , Humans , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , B7-H1 Antigen , Nanofibers/therapeutic use , Combined Modality Therapy , Immunotherapy/methods , Tumor MicroenvironmentABSTRACT
Background & aims: This multicenter retrospective study evaluated the efficacy and safety of transarterial chemoembolization (TACE) combined with donafenib and a programmed death-1 (PD-1) inhibitor (TACE+DP) and TACE combined with donafenib (TACE+D) for unresectable hepatocellular carcinoma (uHCC). Methods: The clinical data of 388 patients with uHCC who received TACE+DP or TACE+D as first-line treatment at six Chinese academic centers from July 2021 to July 2022 were collected and analyzed retrospectively. Patients in the TACE+DP group received an intravenous administration of a PD-1 inhibitor every three weeks and oral donafenib (0.2 g) twice daily until intolerable toxicity or disease progression. Patients in the TACE+D group received the same dose of donafenib for 3-5 days after TACE. Overall survival (OS) and progression-free survival (PFS)were analyzed by Kaplan-Meier method and log-rank test. The tumor response was compared between the two groups according to modified RECIST criteria. Adverse events were also analyzed between the two groups. Results: The TACE+D group included 157 patients and the TACE+DP group included 166 patients. Patients in the TACE+DP group had a longer median OS (18.1 vs. 13.2 months, P<0.001) and longer median PFS (10.6 vs. 7.9 months, P<0.001) than those in the TACE+D group. Patients in the TACE+DP group achieved a greater objective response rate (ORR; 50.6% vs. 41.4%, P=0.019) and greater disease control rate (DCR) (89.2% vs. 82.8%, P=0.010) than those in the TACE+D group. No significant differences were found in the incidence or severity of adverse events between the TACE+DP and TACE+D groups (any grade: 92.9% vs. 94.6%, P=0.270; grade 3 or 4: 33.8% vs. 37.3%, P=0.253). Conclusion: With favorable safety and tolerability, TACE combined with donafenib and PD-1 inhibitors significantly improved PFS, OS, and ORR compared to TACE combined with donafenib.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , Retrospective Studies , Programmed Cell Death 1 Receptor , Chemoembolization, Therapeutic/adverse effectsABSTRACT
BACKGROUND: Our objective was to assess the efficacy and safety of initial hepatic arterial infusion of chemotherapy combined with transarterial chemoembolisation using camrelizumab-eluting Callisphere beads (camrelizumab-DEB-TACE) for treating unresectable hepatocellular carcinoma (HCC). METHODS: Enrolment included patients with unresectable HCC who underwent camrelizumab-DEB-TACE treatment from September 2021 to February 2023. The assessment included the examination of tumour response, overall survival (OS), progression-free survival (PFS), and the monitoring of adverse events (AEs). RESULTS: Twenty-one patients were included in the study. The objective response rates (ORR) and disease control rates (DCR) were 55.0% and 90.0% at 1 month and 57.9% and 78.9% at 3 months, respectively. The median PFS and OS were 7.4 and 15.5 months months, respectively. Among the 21 patients, 4 underwent more than 2 procedures of camrelizumab-DEB-TACE, with a mean of 1.9 ± 1.1 procedures (range: 1-4) per patient. No severe complications or treatment-related mortalities were observed. In addition, no patient developed severe AEs related to camrelizumab, such as reactive cutaneous capillary endothelial proliferation, immune-related pneumonia, or immune-related myocarditis. Nineteen patients experienced at least one type of AEs related to DEB-TACE, with abdominal pain (n = 16, 76.2%) being the most prevalent AE. CONCLUSION: Camrelizumab-DEB-TACE demonstrated effectiveness and safety as a treatment for unresectable HCC, with no occurrence of severe camrelizumab-related AEs.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Pilot Projects , Retrospective Studies , Doxorubicin , Chemoembolization, Therapeutic/methods , Treatment OutcomeABSTRACT
Hepatic stellate cell is one of the major nonparenchymal cell types in liver. It has been proved the hepatic stellate cells are activated upon liver injury and produce excessive extracellular matrix to induce liver fibrosis. Single-cell RNA sequencing has been introduced to identify the subpopulations and function of hepatic stellate cells for its remarkable resolution of representation of single-cell transcriptome. According to the re-analysis of single-cell RNA sequencing data and pseudotime trajectory inference, we have found the C-type lectins including Colec10 and Colec11 are not produced by hepatocytes but predominantly produced by hepatic stellate cells, especially quiescent ones in the mice livers. In addition, the expression of Colec10 is decreased in the fibrotic livers of CCl4-challenged mice. COLEC10 is also mainly expressed in the hepatic stellate cells of human livers and the expression of COLEC10 is decreased with the progression of liver fibrosis. The bulk RNA sequencing data of the lentivirus transfected LX-2 cells indicates the function of COLEC10 is associated with inflammation, angiogenesis and extracellular matrix alteration. Surprisingly, the in vitro overexpression of COLEC10 in LX-2 cells promotes the mRNA expression of extracellular matrix components including COL1A1, COL1A2 and COL3A1 and the extracellular matrix degradation enzyme MMP2. To further investigate the role of COLEC10 in the pathogenesis of liver fibrosis, the serum concentration of COLEC10 in patients with chronic liver disease and healthy donors is measured. The serum concentration of COLEC10 is elevated in the patients with chronic liver disease compared to the healthy donors and positively correlated with serum concentration of the D-dimer but not the most of liver function markers. Altogether, we conclude that the C-type lectin COLEC10 is predominantly produced by the hepatic stellate cells and involved in the pathogenesis of liver fibrosis.
Subject(s)
Hepatic Stellate Cells , Liver Diseases , Humans , Mice , Animals , Hepatic Stellate Cells/metabolism , Lectins, C-Type/genetics , Lectins, C-Type/metabolism , Liver Cirrhosis/pathology , Liver/metabolism , Liver Diseases/metabolism , Collectins/metabolismABSTRACT
Surgical resection of esophageal cancer may result in benign anastomotic strictures, which are usually treated by balloon dilatation. Here we reported the long-term outcomes of large balloon dilatation for benign anastomotic strictures secondary to esophagectomy for esophageal cancer. From February 2011 to December 2016, 27 esophageal cancer patients underwent large balloon dilatation for benign strictures following surgical resection. Clinical success rate, number of dilatation sessions, complication rate, and mortality rate were evaluated. A total of 27 patients developed a benign stricture at the esophagectomy site. A total of 50 dilatation sessions of large balloon were performed, with a mean of 1.8 sessions per patients (range 1.0-5.0). Only 1 perforation was observed (2.0% per dilatation session), and required no surgery. No procedure-related deaths were recorded. Large balloon dilation was technically successful in the remained 26 patients (96.3%). Dysphagia score and stricture index decreased significantly (P < .0001). Proximal diameter of stricture, stricture diameter and length decreased significantly. Patients were followed up for 36.3 ± 7.1 months, and 14 patients survived without dysphagia. The survival rates were 95.0%, 69.1%, 34.5% for 1, 5, and 9 years, respectively. The median survival was 96.0 months. Large balloon dilatation can be a safe and feasible treatment for benign anastomic strictures following surgical resection of esophageal cancer, with a low perforation rate. However, further study compared with small balloon dilatation is warranted.
Subject(s)
Deglutition Disorders , Esophageal Neoplasms , Humans , Constriction, Pathologic , Dilatation , Esophageal Neoplasms/surgery , AircraftABSTRACT
BACKGROUND: Airway fistula is a rare but threatening complication associated with high rates of morbidity and mortality. We report the experience of Amplatzer device application in airway fistulae that failed to be cured with a covered self-expandable metallic stent (SEMS). MATERIALS AND METHODS: Patients who failed occlusion with a covered self-expandable metallic stent and received Amplatzer device placement from Jan 2015 to Jan 2020 were retrospectively enrolled. A total of 14 patients aged 42 to 66 years (55.14 ± 7.87) were enrolled in this study. The primary diseases, types of fistula, types of stents, duration, size of fistula, and follow-up were recorded. RESULTS: All 14 patients with airway fistula failed to be occluded with a covered metallic stent and received Amplatzer device placement. Among the 14 patients, 6 had BPF, 3 had TEF and 5 had GBF. The average stent time was 141.93 ± 65.83 days. The sizes of the fistulae ranged from 3 to 6 mm. After Amplatzer device placement, the KPS score improved from 62.14 ± 4.26 to 75.71 ± 5.13 (P < 0.05). No procedure-related complications occurred. During the 1-month, 3-month and 6-month follow-ups, all the Amplatzer devices were partially surrounded with granulation. Only 1 patient with BPF failed with Amplatzer device occlusion due to the recurrence of lung cancer. CONCLUSION: In conclusion, the application of the Amplatzer device is a safe and effective option in the treatment of airway fistula that failed to be occluded with SEMSs.
Subject(s)
Fistula , Self Expandable Metallic Stents , Humans , Retrospective Studies , Treatment Outcome , StentsABSTRACT
Purpose: To evaluate the clinical results of nasal feeding nutritional tube (NFNT)-loaded iodine-125 (125I) seeds in intra-luminal brachytherapy (ILBT) for esophageal carcinoma (EC) patients with a 3/4 dysphagia score. Material and methods: From January 2019 to January 2020, 26 patients (female/male: 17/9, mean age: 75.3 years, dysphagia score 3/4: 6/20, mean Karnofsky score: 58.4) with EC underwent NFNT-loaded 125I seed placement for both nutrition and brachytherapy. Technical and clinical success, D90 (radiation dose received by 90% of tumor volume) and organ at risk (OAR) dose, complications, dysphagia-free time (DFT), and overall survival (OS) time were documented. Local tumor diameter, Karnofsky score, dysphagia score, and quality of life (QoL) were compared before and 6 weeks after tube placement. Results: Technical and clinical success rates were 100% and 76.9%, respectively. The D90 and OAR doses were 39.7 Gy and 2.3 Gy, respectively. Eight cases (30.8%) experienced mild complications, but no seed loss, fistula, and massive bleeding were observed. Median DFT and OS were 3.1 months and 13.7 months, respectively. Tumor diameter and dysphagia score significantly decreased (p < 0.05), Karnofsky score significantly improved (p < 0.05), and QoL scores related to physical function, physical functioning, general health, vitality, and emotional functioning improved (p < 0.05). Conclusions: NFNT-loaded 125I brachytherapy for ILBT is technically a safe and effective strategy for EC patients with low Karnofsky scores, and can be a bridging therapy for advanced anti-cancer treatment.
ABSTRACT
BACKGROUND: We aimed to evaluate the safety and efficacy of intraluminal iodine-125 seed strand brachytherapy and percutaneous nephrostomy in patients with ureteral carcinoma. METHODS: From January 2014 to January 2023, 48 patients with ureteral cancer not suitable for surgical resection were enrolled. Iodine-125 seed strand was inserted in 26 patients under c-arm CT and fluoroscopic guidance (Group A), and 22 patients underwent percutaneous nephrostomy without seed strand (Group B). The clinical outcomes (technical success rate, tumor sizes, hydronephrosis Girignon grade, complications, objective response rate (ORR), disease control rate (DCR), and survival time) were evaluated and compared. RESULTS: A total of 53 seed strands were successfully inserted and replaced in Group A, with a technical success rate of 100%. No procedure-related death or severe complications occurred in both group. Migration of seed strand or drainage tube was the most common complication. The Girignon grade of hydronephrosis was significantly improved 1, 3 and 6 months after procedure in both groups. DCR in Group A were 96.2%, 80.0%, and 70.0% at 1-, 3-, and 6-month follow up, respectively. At 1 and 6 months later, ORR in Group A were significantly higher than those in Group B (p < 0.05). The median overall survival were 30.0 months in Group A and 16.1 months in Group B, respectively (p = 0.04). The median progression-free survival were 11.1 months in Group A and 6.9 months in Group B, respectively (p = 0.09). CONCLUSION: Intraluminal Iodine-125 seed strand brachytherapy and percutaneous nephrostomy is safe and effective in patients with ureteral carcinoma, with higher ORR and median overall survival than patients underwent percutaneous nephrostomy without seed strand.