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The reinvigoration of anti-tumor T cells in response to immune checkpoint blockade (ICB) therapy is well established. Whether and how ICB therapy manipulates antibody-mediated immune response in cancer environments, however, remains elusive. Using tandem mass spectrometric analysis of modification of immunoglobulin G (IgG) from hepatoma tissues, we identified a role of ICB therapy in catalyzing IgG sialylation in the Fc region. Effector T cells triggered sialylation of IgG via an interferon (IFN)-γ-ST6Gal-I-dependent pathway. DC-SIGN+ macrophages represented the main target cells of sialylated IgG. Upon interacting with sialylated IgG, DC-SIGN stimulated Raf-1-elicited elevation of ATF3, which inactivated cGAS-STING pathway and eliminated subsequent type-I-IFN-triggered antitumorigenic immunity. Although enhanced IgG sialylation in tumors predicted improved therapeutic outcomes for patients receiving ICB therapy, impeding IgG sialylation augmented antitumorigenic T cell immunity after ICB therapy. Thus, targeting antibody-based negative feedback action of ICB therapy has potential for improving efficacy of cancer immunotherapies.
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Carcinoma Hepatocelular , Interferon Tipo I , Neoplasias Hepáticas , Humanos , Imunoglobulina G , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Imunoterapia/métodosRESUMO
Whether and how tumor intrinsic signature determines macrophage-elicited metastasis remain elusive. Here, we show, in detailed studies of data regarding 7,477 patients of 20 types of human cancers, that only 13.8% ± 2.6%/27.9% ± 3.03% of patients with high macrophage infiltration index exhibit early recurrence/vascular invasion. In parallel, although macrophages enhance the motility of various hepatoma cells, their enhancement intensity is significantly heterogeneous. We identify that the expression of malignant Dicer, a ribonuclease that cleaves miRNA precursors into mature miRNAs, determines macrophage-elicited metastasis. Mechanistically, the downregulation of Dicer in cancer cells leads to defects in miRNome targeting NF-κB signaling, which in turn enhances the ability of cancer cells to respond to macrophage-related inflammatory signals and ultimately promotes metastasis. Importantly, transporting miR-26b-5p, the most potential miRNA targeting NF-κB signaling in hepatocellular carcinoma, can effectively reverse macrophage-elicited metastasis of hepatoma in vivo. Our results provide insights into the crosstalk between Dicer-elicited miRNome and cancer immune microenvironments and suggest that strategies to remodel malignant cell miRNome may overcome pro-tumorigenic activities of inflammatory cells.
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Carcinoma Hepatocelular , MicroRNAs , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Carcinoma Hepatocelular/patologia , Transdução de Sinais/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , Macrófagos/metabolismo , Linhagem Celular Tumoral , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Melanocytic nevi (MN) can be classified into three subtypes according to the depth of the nests of nevus cells which is important for management. High-frequency ultrasound (HF-US) can clearly reveal the lesion size, contour, depth, and internal structures. However, the HF-US studies of MN according to subtypes are limited. We aimed to describe the HF-US features of MN and explore its value in accurate classification. MATERIALS AND METHODS: This retrospective study was conducted from January 2018 to November 2019. Eighty-five patients with MN were included and examined by 50 and 20 MHz HF-US. The HF-US features were recorded including morphological flatness, depth, shape, boundary, internal echogenicity, hyperechoic spots, lateral acoustic shadow, posterior echoic patterns, mushroom signs, and straw-hat signs. Each image was evaluated by two physicians independently, and the consistency was tested. RESULTS: Eleven lesions could not be detected by HF-US. The rest 74 lesions underwent ultrasonic analysis. MN appeared as strip-shaped or oval, hypoechoic areas localized in the epidermis and dermis under ultrasonography. A strong consistency between HF-US and dermoscopy of determining the lesion depth was achieved (κ = 0.935, p < 0.001). The hyperechoic spots were found in 57.6% intradermal nevi. The mushroom signs were seen in 34.8% intradermal nevi, and the straw-hat signs were seen in all the compound nevi. CONCLUSION: MN can be correctly classified using HF-US, and it had a strong correlation with dermoscopic and clinical classification. HF-US could further reveal the internal morphological features of MN, which may support more precise classification and management.
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Melanoma , Nevo Pigmentado , Neoplasias Cutâneas , Dermoscopia/métodos , Humanos , Melanoma/patologia , Nevo Pigmentado/patologia , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , UltrassonografiaRESUMO
Low back pain is common after lumbar spine surgery and the injury from extensive detachment of paraspinal muscles during the surgery may play a vital role. Previously, we prepared a bovine acellular tendon fiber (ATF) material through lyophilization and proved that it could retain its original fibrillar structure and mechanical properties. The objective of this study is to evaluate the effectiveness of this new fiber material used for attachment structure reconstruction of paraspinal muscle. Defect of spinous process, interspinous and supraspinous ligament was established on lumbar spine in rabbit and rat and ATF linear material was implanted to reconstruct the attachment structure. Ultrasound showed the cross-sectional area of the paraspinal muscle in ATF group was larger than that of control group in rats. MRI showed the irregular shape and high signal changes in control group, but regular shape and uniform signal in the ATF group in rabbit. For Electromyogram, the frequency of evoked potential in control group was lower than ATF group and normal rats. HE and Masson staining showed good tissue healing, and immunohistochemical results showed the immune rejection of ATF is significantly lower than that of suture. Reconstruction of the attachment structure of paraspinous muscles with ATF linear material could maintain the morphology, volume and function of paraspinal muscle. ATF material has the potential to be used to manufacture personalized ligaments and other tissue engineering scaffolds. Graphical abstract.
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Músculos , Projetos de Pesquisa , Animais , Bovinos , Coelhos , Ratos , Ligamentos , Vértebras Lombares , TendõesRESUMO
BACKGROUND: The role of nucleos(t)ide analogs (NAs) therapy in intermediate and advanced hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unclear. AIMS: The aim was to evaluate the effect of NAs therapy on survival of intermediate- and advanced-stage HBV-related HCC patients initially treated with chemoembolization. METHODS: A total of 1016 Barcelona Clinic Liver Cancer (BCLC) stage B/C HBV-related HCC patients initially treated with chemoembolization were included. Propensity score matching (PSM) was performed to decrease heterogeneity between the antiviral and non-antiviral groups. Kaplan-Meier and Cox regression analysis were performed to evaluate the effects of NAs therapy on overall survival (OS). RESULTS: Antiviral group (n = 394) significantly prolonged OS compared with non-antiviral group (n = 622) (p = 0.003). NAs therapy (p < 0.001) along with tumor size (p = 0.002), tumor number (p = 0.001), gross vascular invasion (p < 0.001), metastasis (p < 0.001), α-fetoprotein (p < 0.001), Child-Pugh score (p = 0.008), aspartate aminotransferase (p < 0.001), and HBV DNA (p = 0.018) were identified as independent prognostic factors for OS. After PSM processing, deducting the influence of subsequent treatments for HCC, NAs therapy was still identified as an independent protective factor (p = 0.009) for OS in patients who survived ≥ 7 months, regardless of BCLC stage B or C HCC. CONCLUSION: NAs therapy prolongs OS in intermediate- and advanced-stage HBV-related HCC patients initially treated with chemoembolization. After PSM processing, patients who survived ≥ 7 months still benefited from NAs therapy.
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Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/virologia , Quimioembolização Terapêutica , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/virologia , Nucleosídeos/análogos & derivados , Biomarcadores Tumorais/sangue , Terapia Combinada , Feminino , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nucleosídeos/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Background: Hepatic caudate lobectomy is considered to be a technically difficult surgery because of the unique anatomy and deep location of the hepatic caudate lobe. Here, we assessed the technical feasibility and safety of robotic partial caudate lobectomy using the da Vinci® Surgical System and compared it with traditional open/laparoscopic surgery.Material and methods: Six patients diagnosed with liver cancer (primary liver cancer, 5; metastasis of breast cancer, 1) who underwent caudate lobectomy were prospectively enrolled. Two patients underwent robotic surgery, one underwent laparoscopic surgery, and three underwent traditional/open surgery. Surgical procedure, recovery, and characteristics of robotic surgery were noted and compared with other approaches.Results: All surgeries were successfully completed, and no serious postsurgical complications were observed. In the robotic group, the time taken to complete the surgery and the estimated intraoperative bleeding were 150 and 90 min and 50 and 100 ml in patient 1 and patient 2, respectively. The patients were able to tolerate fluid diet on the following postsurgical day. These two patients had no postsurgical complications and were discharged from the hospital on days 5 and 6 after recovery, respectively. Pathologically, the margins of specimens obtained from these two patients were tumor-free (R0 resection). Tumor size in the traditional/open group was larger than that in the robotic and laparoscopic groups. Blood loss in the laparoscopic case was 50 ml and was less than that in the traditional/open surgery cases (300, 2100, and 1500 ml).Conclusions: Robot-assisted partial hepatic caudate lobectomy is a technically feasible surgery. Our study illustrated an advantage of robotic hepatic caudate lobectomy over laparoscopic or traditional/open surgery and suggested that da Vinci® minimally invasive hepatectomy is applicable in even more technically challenging anatomic locations.
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Hepatectomia/métodos , Hepatectomia/normas , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Guias de Prática Clínica como Assunto , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/normas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Herbal materials derived from Juniperus communis (JCo) possess anticancer activity. In this study, we evaluated the efficacy of a JCo berry extract in suppressing glioblastoma growth. METHODS: The effects of JCo extract on the viability of normal and glioma cell lines was analyzed using a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The synergistic therapeutic effect of JCo extract and temozolomide (TMZ) on glioma cells was examined by MTT analysis. Flow cytometry analysis, the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) test, and western blotting were performed to identify the apoptotic pathway. To determine the in vivo efficacy of the JCo extract, rats were injected with 5 × 104 rat glioma RG2 cells in the back skin and brain hemisphere and then received a subcutaneous injection in the back skin that contained either JCo extract or vehicle. Finally, blood and histologic examinations were performed to evaluate JCo toxicity. RESULTS: The IC50 values of JCo extract were 57-69 µg/mL and 49-67 µg/mL in the glioblastoma cell lines after 24 and 48 h, respectively. However, in non-tumor cell lines, the respective IC50 values of JCo extract were 76-105 µg/mL and 77-108 µg/mL. The JCo extract had a stronger cytotoxicity and a larger range of IC50 values in glioma than in normal cells as compared to those effects caused by temozolomide (TMZ). In addition, the results of flow cytometry analysis, TUNEL test, and western blotting revealed that the JCo extract induced glioma cell cycle arrest through intrinsic and extrinsic apoptotic pathways. In the in vivo studies, a significant reduction of tumor size in JCo-treated rats, as measured by animal MRI, demonstrated that the JCo extract effectively inhibited glioma cell growth and successfully penetrated the blood-brain barrier. The immunohistochemical (IHC) staining detected positive signals of PCNA, VEGFR-1, and VEGFR -2 in 44.49%, 5.88%, and 5.85% of JCo-treated glioma cells, respectively. However, positive signals of PCNA, VEGFR-1, and VEGFR-2 were detected in 73.08%, 9.67%, and 11.70% of vehicle-treated glioma cells, respectively. The IHC examination of PCNA and VEGFR-1 and -2 indicated that JCo extract significantly decreased the degree of neovascularization. However, no significant differences in serum levels of blood cell count and hepatic enzymes, renal function index, and the histologic appearance of vital organs were detected between the JCo and vehicle-treated rats. CONCLUSION: The JCo extract penetrated the blood-brain barrier and significantly induced glioma cell apoptosis by reducing neovascularization via suppression of the PI3K/AKT/mTOR pathway. Furthermore, JCo extract was less cytotoxic to non-neoplastic vital organs than TMZ.
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Apoptose/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Juniperus/química , Extratos Vegetais/farmacologia , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Caspase 3/química , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Dacarbazina/análogos & derivados , Dacarbazina/farmacologia , Dacarbazina/uso terapêutico , Sinergismo Farmacológico , Feminino , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Humanos , Juniperus/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Antígeno Nuclear de Célula em Proliferação/metabolismo , Temozolomida , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Cancer immunotherapy restores or enhances the effector function of T cells in the tumor microenvironment, but the efficacy of immunotherapy has been hindered by therapeutic resistance. Here, we identify the proto-oncogene serine/threonine protein kinase PIM2 as a novel negative feedback regulator of IFNγ-elicited tumor inflammation, thus endowing cancer cells with aggressive features. Mechanistically, IL1ß derived from IFNγ-polarized tumor macrophages triggered PIM2 expression in cancer cells via the p38 MAPK/Erk and NF-κB signaling pathways. PIM2+ cancer cells generated by proinflammatory macrophages acquired the capability to survive, metastasize, and resist T-cell cytotoxicity and immunotherapy. A therapeutic strategy combining immune checkpoint blockade (ICB) with IL1ß blockade or PIM2 kinase inhibition in vivo effectively and successfully elicited tumor regression. These results provide insight into the regulatory and functional features of PIM2+ tumors and suggest that strategies to influence the functional activities of inflammatory cells or PIM2 kinase may improve the efficacy of immunotherapy. SIGNIFICANCE: Cross-talk between T cells and macrophages regulates cancer cell PIM2 expression to promote cancer aggressiveness, revealing translational approaches to improve response to ICB in hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Hepáticas/terapia , Macrófagos/metabolismo , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas/metabolismo , Serina , Treonina , Microambiente Tumoral , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Background: Numerous studies have attempted to apply artificial intelligence (AI) in the dermatological field, mainly on the classification and segmentation of various dermatoses. However, researches under real clinical settings are scarce. Objectives: This study was aimed to construct a novel framework based on deep learning trained by a dataset that represented the real clinical environment in a tertiary class hospital in China, for better adaptation of the AI application in clinical practice among Asian patients. Methods: Our dataset was composed of 13,603 dermatologist-labeled dermoscopic images, containing 14 categories of diseases, namely lichen planus (LP), rosacea (Rosa), viral warts (VW), acne vulgaris (AV), keloid and hypertrophic scar (KAHS), eczema and dermatitis (EAD), dermatofibroma (DF), seborrheic dermatitis (SD), seborrheic keratosis (SK), melanocytic nevus (MN), hemangioma (Hem), psoriasis (Pso), port wine stain (PWS), and basal cell carcinoma (BCC). In this study, we applied Google's EfficientNet-b4 with pre-trained weights on ImageNet as the backbone of our CNN architecture. The final fully-connected classification layer was replaced with 14 output neurons. We added seven auxiliary classifiers to each of the intermediate layer groups. The modified model was retrained with our dataset and implemented using Pytorch. We constructed saliency maps to visualize our network's attention area of input images for its prediction. To explore the visual characteristics of different clinical classes, we also examined the internal image features learned by the proposed framework using t-SNE (t-distributed Stochastic Neighbor Embedding). Results: Test results showed that the proposed framework achieved a high level of classification performance with an overall accuracy of 0.948, a sensitivity of 0.934 and a specificity of 0.950. We also compared the performance of our algorithm with three most widely used CNN models which showed our model outperformed existing models with the highest area under curve (AUC) of 0.985. We further compared this model with 280 board-certificated dermatologists, and results showed a comparable performance level in an 8-class diagnostic task. Conclusions: The proposed framework retrained by the dataset that represented the real clinical environment in our department could accurately classify most common dermatoses that we encountered during outpatient practice including infectious and inflammatory dermatoses, benign and malignant cutaneous tumors.
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AIM: The prediction model of postoperative survival for single large and huge hepatocellular carcinoma (SLH-HCC, diameter > 5.0 cm) without portal vein tumour thrombus has not been well established. This study aimed to develop novel nomograms to predict postoperative recurrence and survival of these patients. METHODS: Data from 2469 patients with SLH-HCC who underwent curative resection from January 2005 to December 2015 in China were retrospectively collected. Specifically, nomograms of recurrence-free survival (RFS) and overall survival (OS) using data from a training cohort were developed with the Cox regression model (n = 1012). The modes were verified in an internal validation cohort (n = 338) and an external cohort comprising four tertiary institutions (n = 1119). RESULTS: The nomograms of RFS and OS based on tumour clinicopathologic features (diameter, differentiation, microvascular invasion, α-fetoprotein), operative factors (preoperative transcatheter arterial chemoembolisation therapy, scope of liver resection and intraoperative blood transfusion), underlying liver function (albumin-bilirubin grade) and systemic inflammatory or immune status (neutrophil-to-lymphocyte ratio) achieved high C-indexes of 0.85 (95% confidence interval [CI], 0.79-0.91) and 0.86 (95% CI, 0.79-0.93) in the training cohort, respectively, which were significantly higher than those of the five conventional HCC staging systems (0.62-0.73 for RFS, 0.63-0.75 for OS). The nomograms were validated in the internal cohort (0.83 for RFS, 0.84 for OS) and external cohort (0.87 for RFS, 0.88 for OS) and had well-fitted calibration curves. Our nomograms accurately stratified patients with SLH-HCC into low-, intermediate- and high-risk groups of postsurgical recurrence and mortality. CONCLUSIONS: The two nomograms achieved optimal prediction for postsurgical recurrence and OS for patients with SLH-HCC after curative resection.
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Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Nomogramas , Adolescente , Adulto , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos de Validação como Assunto , Adulto JovemRESUMO
BACKGROUND: The importance of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) in hepatocellular carcinoma (HCC) has been studied extensively in Japan, where hepatitis C virus is the predominant aetiology of HCC. The clinical profiles of HCC regarding the state of AFP and DCP in a hepatitis B virus epidemic area have not been comprehensively investigated, and the value of these tumour markers in evaluating the response to treatment and the detection of recurrence has yet to be determined. PATIENTS AND METHODS: A total of 4792 patients treated in our centre were continuously analysed regarding accessible AFP and DCP data pre- and posttreatment. Baseline characteristics were summarized, and comparisons of progression-free survival (PFS) and overall survival (OS) rates were made independently. The prognostic significance of each factor was tested with the Cox proportional hazards model. Patients who had AFP and DCP data pretreatment, pre- and posttreatment, and those who were continuously monitored more than twice were analysed separately. RESULTS: A total of 2600 patients (53.4%) were positive for AFP and DCP; 362 (7.6%) and 1211 (25.3%) patients were AFP- or DCP-positive, respectively, and 619 patients (12.9%) were negative for both AFP and DCP. Patients in the AFP single-positive or double-negative groups had the best OS (P<0.001). Patients with less than 50% responses in AFP and DCP after treatments suffered from worse prognostic survival (P<0.001). In the multivariate analysis, elevated AFP and DCP were identified as independent prognostic factors of PFS and OS. In addition, different tumour markers were related to different clinical and pathological traits. CONCLUSION: The present study comprehensively explored the clinical value of classical tumour markers for HCC using the "point-to-line" method. Positivity of pretreatment AFP and DCP or less than 50% treatment response rates exhibited more aggressive HCC, resulting in poor PFS and OS in HCC patients.
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BACKGROUND: The effects of overweightness and weight loss on the development and prognosis of hepatocellular carcinoma (HCC) remain unclear. In this study, we aimed to evaluate the impact of overweightness and weight loss on the survival of patients with intermediate/advanced HCC receiving chemoembolization as initial treatment. METHODS: We examined 1,170 patients who underwent chemoembolization as initial treatment for Barcelona-Clínic Liver Cancer stages B and C HCC at Sun Yat-sen University Cancer Center (Guangzhou, China) between December 2009 and May 2015. A baseline body mass index (BMI) of ≥23 kg/m2 was defined as overweight, and body-weight loss of ≥5.0% from baseline was defined as critical weight loss (CWL). Cox regression analysis was used to determine the association between overweightness or CWL and overall survival (OS). RESULTS: The median survival time was 16.8 (95% confidence interval, 13.9-19.7) months and 11.1 (95% confidence interval, 10.0-12.2) months in the overweight and non-overweight groups (log-rank test, P < 0.001), respectively. Cox multivariate analysis identified overweightness as an independent protective prognostic factor for OS (P < 0.001). Subgroup stratification analysis revealed a significant association between overweightness and survival among patients receiving further treatment (P = 0.005), but not in those not receiving further treatment (P = 0.683). Multivariate analysis showed that both overweightness and CWL were independent prognostic factors for OS among patients receiving further treatment. CONCLUSION: Among patients with intermediate- or advanced-stage HCC initially treated with chemoembolization, overweightness was associated with longer OS. Furthermore, CWL was an independent adverse prognostic factor for OS in patients receiving additional treatment.
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BACKGROUND: Single port laparoscopic hepatectomy has been applied in some surgeries. We aimed to describe our experience with single port laparoscopic left lateral sectionectomy (SPLS) and to compare the safety and feasibility of this technique with those of conventional multi-port laparoscopic left lateral sectionectomy (MPLS) in the treatment of hepatocellular carcinoma (HCC). METHODS: A total of 72 consecutive patients who underwent SPLS (n = 33) and MPLS (n = 39) for HCC were enrolled. The peri-operative parameters of safety and feasibility, as well as the short-term oncological outcomes were compared. RESULTS: The length of postoperative hospital stay (LOS) was significantly shorter in the SPLS group than in the MPLS group (4.12 vs. 4.59 days, P = 0.043). No significant difference between the two groups was found in the operation time (104.58 vs. 95.69 min in the SPLS group and MPLS group respectively, P = 0.353) or the amount of blood loss (62.73 vs. 68.46 ml, P = 0.595). The 1-year recurrence-free survival rate was 77.9% in the SPLS group and 70.7% in the MPLS group (P = 0.82). Subgroup analysis showed that for patients without cirrhosis, the LOS was shorter in the SPLS group than in the MPLS group (P = 0.033), while for patients with cirrhosis, the LOS was not significantly different between the two groups (P = 0.201), although it was shorter in the SPLS group. CONCLUSIONS: SPLS was a feasible and safe surgical approach for the treatment of HCC on left lateral section.
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Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Tempo de Internação , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-IdadeRESUMO
Background: Both stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) are effective local treatments for hepatocellular carcinoma (HCC), but whether RFA is superior to SBRT is still controversial. Therefore, we performed a meta-analysis to compare the treatment outcomes of SBRT with RFA as curable or bridge intention. Methods: We searched online databases for studies that compared treatment outcomes for SBRT and RFA. Eligibility criteria included evaluation of local control, overall survival (OS), transplant rate, and post-transplant pathological necrosis. Results: As no randomized clinical trials met the criteria, 10 retrospective studies with a total of 2,732 patients were included. Two studies were in favor of SBRT in local control, two studies preferred RFA in OS, and others reported comparable outcomes for both. SBRT demonstrated significantly higher 1- and 3-year local control than RFA [odds ratio (OR) 0.42, 95% CI 0.24-0.74, P = 0.003; and OR 0.54, 95% CI 0.37-0.80, P = 0.002, respectively]. However, SBRT reported significantly shorter 1- and 2-year OS (OR 1.52, 95% CI 1.21-1.90, P = 0.0003; and OR 1.66, 95% CI 1.38-2.01, P < 0.00001, respectively). As bridge treatment, no significant difference was shown in transplant rate and post-transplant pathological necrosis rate (OR 0.57, 95% CI 0.32-1.03, P = 0.060; and OR 0.49, 95% CI 0.13-1.82, P = 0.290, respectively). Conclusions: This study demonstrates SBRT is able to complete a better local control for HCC than RFA, though the OS is inferior to RFA because of tumor burden or liver profiles of the enrolled studies. Well-designed, randomized, multicenter trials will be required to further investigate the conclusion.
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BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem and a primary cause of cancer-related death worldwide. Although great advances have achieved recently by large-scale high-throughput analysis, the precise molecular mechanism underlying HCC progression remains to be clearly elucidated. We investigated the relationship between Tescalcin (TESC), a candidate oncogene, and clinicopathological features of HCC patients and explored the role of TECS in HCC development. METHODS: To identify new genes involved in HCC development, we analyzed The Cancer Genome Atlas liver cancer database, and TESC was selected for further investigation. HCC tissue microarray analysis for TESC and its association with clinicopathological features were performed to investigate its clinical significance. TESC was knocked down by using short-hairpin RNAs. Cell proliferation was analyzed by WST-1 assay and cell counting. Cell apoptosis was tested by fluorescence-activated cell sorting. A subcutaneous xenograft tumor model in nude mice was established to determine the in vivo function of TESC. Affymetrix microarray was used to identify its molecular mechanism. RESULTS: TESC was significantly increased in HCC tissues compared with the adjacent normal liver tissues. High expression of TESC was detected in 61 of 172 HCC patients by tissue microarray. Large tumor (> 5 cm) and elevated total bilirubin were associated with high TESC expression (both P < 0.050). In multivariate analysis, TESC was identified as an independent prognostic factor for short overall survival of HCC patients. TESC knockdown impaired HCC cell growth in vitro and in vivo. TESC knockdown significantly increased cell apoptosis in HCC cell lines. Furthermore, Affymetrix microarray analysis revealed that TESC knockdown inhibited tumor proliferation-related pathways while activated cell death-related pathways. CONCLUSION: TESC was identified as an independent prognostic factor for short overall survival of HCC patients, and was critical for HCC cell proliferation and survival.
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Proteínas de Ligação ao Cálcio/genética , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Animais , Apoptose , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Proliferação de Células , Feminino , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , PrognósticoRESUMO
BACKGROUND: Excessive intraoperative hemorrhage is a critical factor of poor prognoses after hepatectomy. Low central venous pressure during parenchymal transection is recognized to effectively reduce intraoperative hemorrhage in open procedures. However, the role of controlled low central venous pressure in laparoscopic hepatectomy is still controversial. METHODS: In the present randomized clinical trial, we set up a standard boundary of low central venous pressure according to our Pilot Study, then enrolled patients scheduled for elective laparoscopic hepatectomy and allocated them randomly to a group undergoing central venous pressure reduction by anesthesiologic interventions or a control group. The primary efficacy endpoint was total intraoperative blood loss and perioperative adverse events. Analyses were performed following the intention-to-treat principle, and patients and surgeons were blinded (ClinicalTrials.gov, Number: NCT03422913). RESULTS: Between January 2017 and October 2018, 146 out of 469 patients were randomized and eligible for inclusion in the final analyses. Based on the retrospective training cohort, we set a central venous pressure of 5 cm H2O as a cutoff value (standard low central venous pressure). Compared with patients in the control group, those in the controlled low central venous pressure group had a significantly lower central venous pressure during resection (4.83 ± 3.41 cm H2O vs 9.26 ± 3.38 cm H2O; P < .001) and significantly reduced total intraoperative blood loss (188.00 ± 162.00 mL vs 346.00 ± 336.00 mL; P < .001). The perioperative adverse events were comparable in both study groups (P = .313). CONCLUSION: The safety and efficacy of controlled low central venous pressure were demonstrated in complex laparoscopic hepatectomy for the first time by our study, and this technique is recommended to be applied routinely in laparoscopic hepatectomy.
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Perda Sanguínea Cirúrgica/prevenção & controle , Pressão Venosa Central , Hepatectomia , Laparoscopia , Vasoconstritores/uso terapêutico , Adulto , Aspartato Aminotransferases/sangue , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Método Duplo-Cego , Procedimentos Cirúrgicos Eletivos , Feminino , Hemoglobinas/análise , Hemorragia/prevenção & controle , Humanos , Cuidados Intraoperatórios , Complicações Intraoperatórias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Posicionamento do PacienteRESUMO
Skin toxicity, especially hand-foot syndrome (HFS), is one of the most common sorafenib-induced adverse events (AEs) in hepatocellular carcinoma (HCC) patients, leading to treatment interruption and failure. Mucocutaneous inflammation may cause HFS; therefore, we investigated whether celecoxib can alleviate HFS, improve patients' quality of life and increase survival when administered in conjunction with active therapy. Our randomized, open-label study prospectively enrolled 116 advanced HCC patients receiving sorafenib as targeted therapy from July 2015 to July 2016. All patients were randomly assigned (1:1) via a computer-generated sequence to receive sorafenib with or without celecoxib. Sorafenib-related AEs were recorded, Survival was compared between the two groups. Compared to the Sorafenib group, the SoraCele group had lower incidence rates of ≥ grade 2 and grade 3 HFS (63.8% vs 29.3%, P < 0.001; 19.0% vs 3.4%, P = 0.008, respectively), hair loss, rash and abdominal pain. Kaplan-Meier analysis revealed a lower risk of ≥ grade 2 HFS (HR, 0.384; P = 0.002) and a lower dose reduction/interruption rate (46.6% to 15.5%, P < 0.001) in the SoraCele group. Cox proportional hazards regression analysis demonstrated that celecoxib was the only independent predictive factor of developing ≥ grade 2 HFS (HR, 0.414; P = 0.004). Longer progression-free survival (PFS) was also observed in the SoraCele group (P = 0.039), although overall survival was not prolonged (P = 0.305). These results suggest that sorafenib + Celecoxib administration alleviated sorafenib-related skin toxicity. Longer PFS was achieved in clinical practice, although overall survival was not prolonged (ClinicalTrials.gov: NCT02961998).
RESUMO
OBJECTIVE: To compare the biomechanical stability of different fixation methods for anterior ring injury of unstable pelvic fractures, and to provide reference for clinical treatment. METHODS: An unstable pelvic fracture model (Tile C) with one side of the sacroiliac joint dislocation and the pubic rami fracture was constructed via three-dimensional finite element analysis. Five different fixation methods were used in the front, and the rear was fixed with sacroiliac screws. The von Mises stress and strain distributions of different combinations of fixation methods were analyzed under mimicking standing conditions. RESULTS: After being loaded with 500 N vertically, the maximum stress in the anterior fracture was 3.56 MPa in anterior pelvic external fixation (AEF) group, the total displacement and the vertical displacement of the Y axis at the sacroiliac joint and the fracture were not more than 1.5 mm. The maximum stress at fixation, the front of the fracture and sacroiliac joints in the anterior pelvic subcutaneous approach(APA) group and AEF, was significantly higher than anterior modified Stoppa approach(ASA) group, anterior pelvic Ilioinguinal approach (AIA) group, and canulated screw fixation(CSF) group. The total displacement and the vertical displacement of the Y axis at the sacroiliac joint and the fracture in APA group and AEF group were also greater than the other three groups. CONCLUSIONS: Anterior ring injury of unstable pelvic fractures can be significantly improved after the fixation of the implants in the five combined methods. However, overall biomechanical properties of ASA, AIA and CSF group are superior to APA and AEF group.
Assuntos
Fraturas Ósseas , Ossos Pélvicos , Parafusos Ósseos , Análise de Elementos Finitos , Fixação Interna de Fraturas , HumanosRESUMO
OBJECTIVE: Transarterial chemoembolization (TACE) is recommended to treat intermediate/advanced stage of hepatocellular carcinoma (HCC). However, the overall survival among initially TACE-treated patients varies significantly. The clinical characterization of long-term survival following TACE remains uncertain. We sought to identify clinical parameters and treatment requirements for long-term survival among patients with hepatitis B-related HCC who were initially treated with TACE. MATERIALS AND METHODS: The included patients with HCC were admitted to our cancer center between December 2009 and May 2015. Patients who survived for >3 years were compared with those who died within 3 years. The clinical and laboratory findings that were associated with the survival were also analyzed. RESULTS: One in six (17.9%) patients with HCC in this cohort survived for > 3 years after TACE. Body mass index (BMI) ≥ 23kg/m2 , aspartate aminotransferase levels ≤ 40 U/L, an activated partial thromboplastin time ≤ 34 seconds, α-fetoprotein (AFP) levels ≤ 25 ng/mL, antiviral therapy, tumor size ≤ 8 cm, solitary nodule, and the absence of vascular invasion were independently favorably associated with a 3-year survival. An absence of vascular invasion was the only independent factor associated with 3-year survival in patients who received resection and/or ablation after TACE. CONCLUSION: In this cohort, a 3-year survival was associated with BMI, antivirus treatment, tumor status, hepatic function, and AFP level. Distant metastasis did not negatively impact the long-term survival among patients with hepatitis B-related HCC initially treated with TACE. Vascular invasion was the single impediment to long-term survival in patients who received add-on resection and/or ablation after TACE.
Assuntos
Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Hepatite B/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Tomada de Decisão Clínica , Terapia Combinada , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Pesquisas sobre Atenção à Saúde , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Resultado do TratamentoRESUMO
Carpesium abrotanoides L. (CA) is widely used as a medicinal plant in Asia. The biological activities of the extract from the roots of Carpesium abrotanoides L. (PCA) and its major components were analyzed in this study. PCA was separated and identified with mass spectrometry. Furthermore, we sought to elucidate the anticancer activity of PCA and its mechanisms. PCA exerted its anti-breast cancer activity through inhibiting the expression of glycolysis-related genes, such as glucose transporter 1, lactate dehydrogenase A, and hexokinase 2. Moreover, PCA downregulated the expression of pyruvate kinase M2 and altered its cellular translocation. We also demonstrated PCA is an inhibitor of the PKM2/hypoxia-inducible factor-1α axis, indicating that PCA is potentially useful as an anti-breast cancer agent. PRACTICAL APPLICATION: In this study, the extract from roots of Carpesium abrotanoides Linn. (PCA) was shown to have a noticeable anticancer effect against breast cancer in vitro, and PCA exerts the anticancer activity by regulating glucose metabolism and PKM2 expression. These findings indicate that PCA is a promising agent with practical applications in the development of functional food containing Carpesium abrotanoides L. root extracts.