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1.
Clin Cancer Res ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526363

RESUMO

PURPOSE: Targeted therapy and immunotherapy are transforming the treatment approach for intrahepatic cholangiocarcinoma(ICC). However, little is known about the intertumor heterogeneity(ITH) of multifocal ICC and its impacts on patient response to these treatments. We aimed to characterize the immunogenomic and epigenomic heterogeneity of multifocal ICC to guide treatment decision making. EXPERIMENTAL DESIGN: We obtained 66 tumor samples from sixteen multifocal ICC patients and characterized the tumor and immune heterogeneity using whole-exome sequencing, bulk and single-cell RNA-sequencing, methylation-microarray and multiplex immunostaining. Patients were divided into high or low ITH groups according to the median ITH index. Two independent cohorts were used to validate findings. Responses to anti-PD-1 therapy were assessed. RESULTS: Multifocal ICC presented considerable intertumor genomic, transcriptional and epigenomic heterogeneity within a patient in high ITH group. The immune profile among multiple tumors within a patient was relatively less heterogeneous in high- or low-ITH group, and consistent responses of multiple tumors to anti-PD-1 immunotherapy were observed. Unsupervised clustering of immune markers identified one low and one high immune subtype, with higher immune cell infiltration, closer tumor-immune cell interactions and upregulated IFN-signature expression in high immune subtype. Determining expression levels of CD8B and ICOS facilitated this immune classification and prediction of patient prognosis. Finally, promoter DNA-methylation contributed to different immune profiles of two subtypes by regulating immune-gene expression. CONCLUSIONS: There is comprehensive heterogeneity in the genome, transcriptome and epigenome of multifocal ICC. Based on the less heterogeneous immune profile of ICC, we suggest an immune classification that stratifies patients' prognosis and may support personalized immunotherapy.

2.
Mol Cell ; 81(16): 3339-3355.e8, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34352206

RESUMO

Cancer cells selectively promote translation of specific oncogenic transcripts to facilitate cancer survival and progression, but the underlying mechanisms are poorly understood. Here, we find that N7-methylguanosine (m7G) tRNA modification and its methyltransferase complex components, METTL1 and WDR4, are significantly upregulated in intrahepatic cholangiocarcinoma (ICC) and associated with poor prognosis. We further reveal the critical role of METTL1/WDR4 in promoting ICC cell survival and progression using loss- and gain-of-function assays in vitro and in vivo. Mechanistically, m7G tRNA modification selectively regulates the translation of oncogenic transcripts, including cell-cycle and epidermal growth factor receptor (EGFR) pathway genes, in m7G-tRNA-decoded codon-frequency-dependent mechanisms. Moreover, using overexpression and knockout mouse models, we demonstrate the crucial oncogenic function of Mettl1-mediated m7G tRNA modification in promoting ICC tumorigenesis and progression in vivo. Our study uncovers the important physiological function and mechanism of METTL1-mediated m7G tRNA modification in the regulation of oncogenic mRNA translation and cancer progression.


Assuntos
Colangiocarcinoma/genética , Proteínas de Ligação ao GTP/genética , Metiltransferases/genética , Biossíntese de Proteínas , Animais , Carcinogênese/genética , Colangiocarcinoma/patologia , Progressão da Doença , Receptores ErbB/genética , Guanosina/análogos & derivados , Guanosina/genética , Humanos , Camundongos , Processamento Pós-Transcricional do RNA/genética , RNA Mensageiro/genética , RNA de Transferência/genética
5.
J Gastroenterol Hepatol ; 36(9): 2531-2539, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33948991

RESUMO

BACKGROUND AND AIM: The evidences for use of postoperative antibiotics (POA) in hepatocellular carcinoma (HCC) patients who underwent hepatectomy are controversial. We aimed to explore the relationship between POA and hepatectomy-related infection in a hepatitis B virus (HBV)-related HCC population. METHODS: We retrospectively collected 934 HCC patients who underwent hepatectomy for curative intent from three tertiary hospitals in China. The incidences of postoperative infection including surgical site infection and remote site infection were recorded and calculated. Univariable and multivariable logistic regression analyses were performed to explore related factors of postoperative infection and POA. And the relationship between infection rates with different durations of POA was investigated. RESULTS: The overall infection rate was 8.2% (77/934), including 6.5% (61/934) of surgical site infection and 2.0% (19/934) of remote site infection. Multivariable analysis revealed that the administration of POA was negatively related with the incidence of postoperative infection significantly (odds ratio = 0.50, 95% confidence interval = 0.30 to 0.83; P = 0.008). Albumin-bilirubin score, Barcelona Clinic Liver Cancer (BCLC) stage and extent of hepatectomy were independently related to the POA. And 3-day regimen seemed to be the shortest duration of POA to gain the lowest incidence of postoperative infection. CONCLUSIONS: Postoperative antibiotic is necessary for HBV-related HCC patients to prevent postoperative infection, especially for those with higher albumin-bilirubin score, at BCLC stage B-C, or who underwent major hepatectomy. For HBV-related HCC patients, postoperative second-generation cephalosporins, or ceftriaxone for 3 days after surgery might be proper.

6.
Eur Radiol ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33877387

RESUMO

OBJECTIVES: Pretreatment evaluation of tumor biology and microenvironment is important to predict prognosis and plan treatment. We aimed to develop nomograms based on gadoxetic acid-enhanced MRI to predict microvascular invasion (MVI), tumor differentiation, and immunoscore. METHODS: This retrospective study included 273 patients with HCC who underwent preoperative gadoxetic acid-enhanced MRI. Patients were assigned to two groups: training (N = 191) and validation (N = 82). Univariable and multivariable logistic regression analyses were performed to investigate clinical variables and MRI features' associations with MVI, tumor differentiation, and immunoscore. Nomograms were developed based on features associated with these three histopathological features in the training cohort, then validated, and evaluated. RESULTS: Predictors of MVI included tumor size, rim enhancement, capsule, percent decrease in T1 images (T1D%), standard deviation of apparent diffusion coefficient, and alanine aminotransferase levels, while capsule, peritumoral enhancement, mean relaxation time on the hepatobiliary phase (T1E), and alpha-fetoprotein levels predicted tumor differentiation. Predictors of immunoscore included the radiologic score constructed by tumor number, intratumoral vessel, margin, capsule, rim enhancement, T1D%, relaxation time on plain scan (T1P), and alpha-fetoprotein and alanine aminotransferase levels. Three nomograms achieved good concordance indexes in predicting MVI (0.754, 0.746), tumor differentiation (0.758, 0.699), and immunoscore (0.737, 0.726) in the training and validation cohorts, respectively. CONCLUSION: MRI-based nomograms effectively predict tumor behaviors in HCC and may assist clinicians in prognosis prediction and pretreatment decisions. KEY POINTS: • This study developed and validated three nomograms based on gadoxetic acid-enhanced MRI to predict MVI, tumor differentiation, and immunoscore in patients with HCC. • The pretreatment prediction of tumor microenvironment may be useful to guide accurate prognosis and planning of surgical and immunological therapies for individual patients with HCC.

7.
BMC Med ; 19(1): 80, 2021 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-33775248

RESUMO

BACKGROUND: Targeted therapy and immunotherapy put forward higher demands for accurate lung cancer classification, as well as benign versus malignant disease discrimination. Digital whole slide images (WSIs) witnessed the transition from traditional histopathology to computational approaches, arousing a hype of deep learning methods for histopathological analysis. We aimed at exploring the potential of deep learning models in the identification of lung cancer subtypes and cancer mimics from WSIs. METHODS: We initially obtained 741 WSIs from the First Affiliated Hospital of Sun Yat-sen University (SYSUFH) for the deep learning model development, optimization, and verification. Additional 318 WSIs from SYSUFH, 212 from Shenzhen People's Hospital, and 422 from The Cancer Genome Atlas were further collected for multi-centre verification. EfficientNet-B5- and ResNet-50-based deep learning methods were developed and compared using the metrics of recall, precision, F1-score, and areas under the curve (AUCs). A threshold-based tumour-first aggregation approach was proposed and implemented for the label inferencing of WSIs with complex tissue components. Four pathologists of different levels from SYSUFH reviewed all the testing slides blindly, and the diagnosing results were used for quantitative comparisons with the best performing deep learning model. RESULTS: We developed the first deep learning-based six-type classifier for histopathological WSI classification of lung adenocarcinoma, lung squamous cell carcinoma, small cell lung carcinoma, pulmonary tuberculosis, organizing pneumonia, and normal lung. The EfficientNet-B5-based model outperformed ResNet-50 and was selected as the backbone in the classifier. Tested on 1067 slides from four cohorts of different medical centres, AUCs of 0.970, 0.918, 0.963, and 0.978 were achieved, respectively. The classifier achieved high consistence to the ground truth and attending pathologists with high intraclass correlation coefficients over 0.873. CONCLUSIONS: Multi-cohort testing demonstrated our six-type classifier achieved consistent and comparable performance to experienced pathologists and gained advantages over other existing computational methods. The visualization of prediction heatmap improved the model interpretability intuitively. The classifier with the threshold-based tumour-first label inferencing method exhibited excellent accuracy and feasibility in classifying lung cancers and confused nonneoplastic tissues, indicating that deep learning can resolve complex multi-class tissue classification that conforms to real-world histopathological scenarios.

8.
Ann Surg Oncol ; 28(11): 6747-6757, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33751300

RESUMO

BACKGROUND: The aim of this work is to explore the impact of the number of sampling sites (NuSS) and sampling location on microvascular invasion (MVI) detection rate and long-term survival of hepatocellular carcinoma (HCC), and determine the minimum NuSS for sufficient MVI detection. PATIENTS AND METHODS: From January 2008 to March 2017, 1144 HCC patients who underwent hepatectomy were retrospectively enrolled. Associations between NuSS and MVI positive rates and overall survival were investigated. NuSS thresholds were determined by Chow test and confirmed prospectively in 305 patients from April 2017 to February 2019. In the prospective cohort, the distribution of MVI in different sampling locations and its prognostic effect was evaluated. RESULTS: MVI positive rates increased as NuSS increased, steadily reaching a plateau when NuSS reached a threshold. A threshold of four, six, eight, and eight sampling sites within paracancerous parenchyma ≤ 1 cm from tumor was required for detecting MVI in solitary tumors measuring 1.0-3.0, 3.1-4.9, and ≥ 5.0 cm and multiple tumors. Patients with adequate NuSS achieved longer survival than those with inadequate NuSS [hazard ratio (HR) = 0.75, P = 0.043]. For all MVI-positive patients, MVI could be detected positive in paracancerous parenchyma ≤ 1 cm from tumor. Patients with MVI positive in paracancerous parenchyma > 1 cm had higher recurrence risk than those with MVI positive only in parenchyma ≤ 1 cm (HR = 6.05, P < 0.001). CONCLUSIONS: Adequate NuSS is associated with higher MVI detection rate and better survival of HCC patients. We recommend four, six, eight, and eight as the cut-points for evaluating MVI sampling quality and patients' prognostic stratification in the subgroups of solitary tumors measuring 1.0-3.0 cm, 3.1-4.9 cm and ≥ 5.0 cm and multiple tumors, respectively.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Microvasos , Invasividade Neoplásica , Recidiva Local de Neoplasia/cirurgia , Estudos Prospectivos , Estudos Retrospectivos
9.
Lancet Digit Health ; 3(4): e250-e259, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33766289

RESUMO

BACKGROUND: Strategies for integrating artificial intelligence (AI) into thyroid nodule management require additional development and testing. We developed a deep-learning AI model (ThyNet) to differentiate between malignant tumours and benign thyroid nodules and aimed to investigate how ThyNet could help radiologists improve diagnostic performance and avoid unnecessary fine needle aspiration. METHODS: ThyNet was developed and trained on 18 049 images of 8339 patients (training set) from two hospitals (the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, and Sun Yat-sen University Cancer Center, Guangzhou, China) and tested on 4305 images of 2775 patients (total test set) from seven hospitals (the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; the Guangzhou Army General Hospital, Guangzhou, China; the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; the First Affiliated Hospital of Sun Yat-sen University; Sun Yat-sen University Cancer Center; and the First Affiliated Hospital of Guangxi Medical University, Nanning, China) in three stages. All nodules in the training and total test set were pathologically confirmed. The diagnostic performance of ThyNet was first compared with 12 radiologists (test set A); a ThyNet-assisted strategy, in which ThyNet assisted diagnoses made by radiologists, was developed to improve diagnostic performance of radiologists using images (test set B); the ThyNet assisted strategy was then tested in a real-world clinical setting (using images and videos; test set C). In a simulated scenario, the number of unnecessary fine needle aspirations avoided by ThyNet-assisted strategy was calculated. FINDINGS: The area under the receiver operating characteristic curve (AUROC) for accurate diagnosis of ThyNet (0·922 [95% CI 0·910-0·934]) was significantly higher than that of the radiologists (0·839 [0·834-0·844]; p<0·0001). Furthermore, ThyNet-assisted strategy improved the pooled AUROC of the radiologists from 0·837 (0·832-0·842) when diagnosing without ThyNet to 0·875 (0·871-0·880; p<0·0001) with ThyNet for reviewing images, and from 0·862 (0·851-0·872) to 0·873 (0·863-0·883; p<0·0001) in the clinical test, which used images and videos. In the simulated scenario, the number of fine needle aspirations decreased from 61·9% to 35·2% using the ThyNet-assisted strategy, while missed malignancy decreased from 18·9% to 17·0%. INTERPRETATION: The ThyNet-assisted strategy can significantly improve the diagnostic performance of radiologists and help reduce unnecessary fine needle aspirations for thyroid nodules. FUNDING: National Natural Science Foundation of China and Guangzhou Science and Technology Project.


Assuntos
Inteligência Artificial , Tomada de Decisões Assistida por Computador , Aprendizado Profundo , Diagnóstico por Computador/métodos , Nódulo da Glândula Tireoide/diagnóstico , Área Sob a Curva , China/epidemiologia , Humanos , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e Especificidade
10.
Hepatology ; 74(3): 1339-1356, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33638162

RESUMO

BACKGROUND AND AIMS: The dynamic N6-methyladenosine (m6 A) mRNA modification is essential for acute stress response and cancer progression. Sublethal heat stress from insufficient radiofrequency ablation (IRFA) has been confirmed to promote HCC progression; however, whether m6 A machinery is involved in IRFA-induced HCC recurrence remains open for study. APPROACH AND RESULTS: Using an IRFA HCC orthotopic mouse model, we detected a higher level of m6 A reader YTH N6-methyladenosine RNA binding protein 1-3 (YTHDF1) in the sublethal-heat-exposed transitional zone close to the ablation center than that in the farther area. In addition, we validated the increased m6 A modification and elevated YTHDF1 protein level in sublethal-heat-treated HCC cell lines, HCC patient-derived xenograft (PDX) mouse model, and patients' HCC tissues. Functionally, gain-of-function/loss-of-function assays showed that YTHDF1 promotes HCC cell viability and metastasis. Knockdown of YTHDF1 drastically restrains the tumor metastasis evoked by sublethal heat treatment in tail vein injection lung metastasis and orthotopic HCC mouse models. Mechanistically, we found that sublethal heat treatment increases epidermal factor growth receptor (EGFR) m6 A modification in the vicinity of the 5' untranslated region and promotes its binding with YTHDF1, which enhances the translation of EGFR mRNA. The sublethal-heat-induced up-regulation of EGFR level was further confirmed in the IRFA HCC PDX mouse model and patients' tissues. Combination of YTHDF1 silencing and EGFR inhibition suppressed the malignancies of HCC cells synergically. CONCLUSIONS: The m6 A-YTHDF1-EGFR axis promotes HCC progression after IRFA, supporting the rationale for targeting m6 A machinery combined with EGFR inhibitors to suppress HCC metastasis after RFA.

11.
Cancer Lett ; 503: 1-10, 2021 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-33444692

RESUMO

Ablative treatment evokes antitumor immunity, but knowledge on the emerging irreversible electroporation (IRE)-induced immunity in hepatocellular carcinoma (HCC) is limited. To investigate the immune effects induced by IRE and its role in preventing post-ablation HCC progression, a C57BL/6J mouse model bearing subcutaneous H22 hepatoma was employed. IRE treatment significantly suppresses HCC growth, and treated mice are tumor-free after secondary tumor injection and show increased splenic interferon-gamma (IFN-γ)+CD8+ T cells. Additionally, more CD8+ T and dendritic cells, but not CD4+ T, B or NK cells, infiltrate into peri-ablation zones after IRE at day 7. Depletion of CD8+ T cells induces local tumor regrowth and distant metastasis after IRE. Vaccination using IRE-processed H22 lysates prevents tumorigenesis in mice, suggesting a protective immune response. IRE also alleviates immunosuppression by reducing local and splenic Treg and PD-1+ T cells. Regarding mechanism, IRE induces cell necrosis and significant release of danger-associated molecular patterns including ATP, high mobility group box 1 and calreticulin that are pivotal to CD8+ T cell immunity. Together, IRE is a promising approach to evoke CD8+ T cell immunity, which help prevent post-ablation HCC progression.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Carcinoma Hepatocelular/terapia , Interferon gama/metabolismo , Neoplasias Hepáticas/terapia , Ablação por Radiofrequência/métodos , Animais , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Progressão da Doença , Eletroporação , Células Hep G2 , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos C57BL , Baço/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Int J Cancer ; 148(5): 1106-1114, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32930403

RESUMO

Reasons behind the rapid increase of thyroid cancer (TC) in China are uncertain. We assessed the burden of TC and the role of access to screening and salt iodization. We analyzed two national databases in China: Hospital Quality Monitoring System (HQMS) and China Reinsurance Company (CRC) database. HQMS covered 1037 (44.3%) Class 3 hospitals and 76 263 617 Class 3 hospital inpatients in 2013 to 2017 and CRC covered 93 123 018 clients in 2000 to 2016. The proportion of TC inpatients among inpatients in HQMS and TC incidence in critical illness insurance buyers were used to evaluate the association with screening and iodine status. Between 2013 and 2017, the proportion of TC patients in HQMS with urban employee medical insurance and good access to screening increased sharply while there was little change among those with the other two forms of medical insurance. Across provinces, the proportion of TC inpatients in HQMS was positively correlated with per capita disposable income but not with median urinary iodine. Similar findings were observed in the CRC database. In 2017, approximately 1000 individuals were overdiagnosed with TC daily. We conservatively forecast that 5.1 million healthy individuals would become TC patients unnecessarily between 2019 and 2030. Our findings suggested the epidemic of TC in China was substantially underestimated. It was associated with screening but not with salt iodization.

13.
Cell Mol Immunol ; 18(4): 1005-1015, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32879468

RESUMO

The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer types. Although a role for cancer cell invasion programs has been well characterized, whether and how liver-intrinsic factors drive metastatic spread is incompletely understood. Here, we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase (CCRK) signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive microenvironment. Using an inducible liver-specific transgenic model, we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer (CRC) metastasis to the liver, which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells (PMN-MDSCs) and lacking natural killer T (NKT) cells. Depletion of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7% (metastatic tumor weights) in the melanoma and CRC models, respectively. Mechanistically, CCRK activated nuclear factor-kappa B (NF-κB) signaling to increase the PMN-MDSC-trafficking chemokine C-X-C motif ligand 1 (CXCL1), which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic mice. Accordingly, CRC liver metastasis patients exhibited hyperactivation of hepatic CCRK/NF-κB/CXCL1 signaling, which was associated with accumulation of PMN-MDSCs and paucity of NKT cells compared to healthy liver transplantation donors. In summary, this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic immunosurveillance. Our findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention.

14.
Transl Oncol ; 14(1): 100866, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33074127

RESUMO

OBJECTIVES: To develop a radiomics algorithm, improving the performance of detecting recurrence, based on posttreatment CT images within one month and at suspicious time during follow-up. MATERIALS AND METHODS: A total of 114 patients with 228 images were randomly split (7:3) into training and validation cohort. Radiomics algorithm was trained using machine learning, based on difference-in-difference (DD) features extracted from tumor and liver regions of interest on posttreatment CTs within one month after resection or ablation and when suspected recurrent lesion was observed but cannot be confirmed as HCC during follow-up. The performance was evaluated by area under the receiver operating characteristic curve (AUC) and was compared among radiomics algorithm, change of alpha-fetoprotein (AFP) and combined model of both. Five-folded cross validation (CV) was used to present the training error. RESULTS: A radiomics algorithm was established by 34 DD features selected by random forest and multivariable logistic models and showed a better AUC than that of change of AFP (0.89 [95% CI: 0.78, 1.00] vs 0.63 [95% CI: 0.42, 0.84], P = .04) and similar with the combined model in detecting recurrence in the validation set. Five-folded CV error in the validation cohort was 21% for the algorithm and 26% for the changes of AFP. CONCLUSIONS: The algorithm integrated radiomic features of posttreatment CT showed superior performance to that of conventional AFP and may act as a potential marker in the early detecting recurrence of HCC.

15.
Eur Radiol ; 31(4): 2368-2376, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33033863

RESUMO

OBJECTIVES: To investigate and compare radiomics and clinical information for preoperative prediction of futile resection in intrahepatic cholangiocarcinoma (ICC). METHODS: A total of 203 ICC patients from two centers were included and randomly allocated with a ratio of 7:3 into the training cohort and the validation cohort. Clinical characteristics and radiomics features were selected using random forest algorithm and logistic models to construct a clinical model and a radiomics model, respectively. A combined logistic model that incorporated the developed radiomics signature and clinical risk factors was then built. The performance of these models was evaluated and compared by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). RESULTS: The radiomics model showed a higher AUC than the clinical model in the validation cohort (AUC: 0.804 (95% CI: 0.697, 0.912) vs. 0.590 (95% CI: 0.415, 0.765), p = 0.043) for predicting futile resection in ICC. The radiomics model reached a sensitivity of 0.846 (95% CI: 0.546, 0.981) and a specificity of 0.771 (95% CI: 0.627, 0.880) in the validation cohort. Moreover, the radiomics model had comparable AUCs with the combined model in training and validation cohorts. CONCLUSIONS: We presented an internally validated radiomics model for the prediction of futile resection in ICC patients. Compared with clinical information, radiomics using CT images had greater potential for predicting futile resection accurately before surgery. KEY POINTS: • Radiomics model using CT images could predict futile resection in intrahepatic cholangiocarcinoma preoperatively. • Radiomics model using CT images was superior to clinical information for predicting futile resection accurately before surgery.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias Hepáticas , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Humanos , Tomografia Computadorizada por Raios X
16.
Front Endocrinol (Lausanne) ; 11: 575799, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329384

RESUMO

Background: A better understanding of the current characteristics of clinical trials on thyroid cancer (TC) is important to improve trial designs and identify neglected areas of research. However, there is a lack of a thorough understanding of the clinical studies on TC. Therefore, this study aimed to present a comprehensive overview of clinical trials on TC based on the ClinicalTrials.gov database and evaluate their publication status. Methods: We searched for TC-related clinical studies registered in the ClinicalTrials.gov database before December 2018 by using the keyword "thyroid cancer" and assessed the characteristics of the included trials. We searched the publication status of primary completed studies in PubMed and Google Scholar. Results: A total of 450 studies were identified for analysis, including 333 (74.0%) interventional studies and 117 (26.0%) observational studies. Interventional studies about TC were commonly non-randomized (67.6%), single-arm (55.6%), single-center (76.3%), and early-phase (60.0%) trials. The major category for which studies were performed was for target drug-related therapy (53.6%). In addition, 57.0% of the primary completed interventional studies were published. The published studies were more commonly primary completed studies after 2010 and used randomization and were less commonly designed as single-arm studies and were conducted in the USA/Canada, compared to non-published studies (P < 0.05 for all). The median time from primary completion to publication was 46.5 months, and the time decreased to 36.5 months after 2010. Studies conducted in the USA/Canada [odds ratio (OR) = 9.43, P = 0.020] and multi-center studies (OR = 6.55, P = 0.021) significantly increased the potential of publication in high-impact journals. Conclusions: High-quality, randomized phase 3 trials regarding TC are still insufficient. Therefore, more efforts are needed to improve the treatment of poor prognostic TC and timely publication.


Assuntos
Ensaios Clínicos como Assunto/estatística & dados numéricos , Editoração/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Neoplasias da Glândula Tireoide/terapia , Bases de Dados Factuais , Humanos , Neoplasias da Glândula Tireoide/diagnóstico
17.
Front Med (Lausanne) ; 7: 368, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32984358

RESUMO

Due to the unsatisfactory robustness of current predictive biomarkers in many cases, application of immunotherapy in advanced cancers with limited treatment options, such as stage IV intrahepatic cholangiocarcinoma (ICC), was quite common. Hence, strategies to enhance the therapeutic effect of immunotherapy or to extend the scope of potential beneficial patients were urgently needed. Combination of radiotherapy and anti-programmed death receptor-1 (PD-1) immunotherapy was a promising one, since they were found to have a synergistic anti-tumor effect in animal models and a couple of patients. We here present a 68-years-old male with chemotherapy-intolerable stage IV ICC, whose primary tumor had low PD-L1 expression level, scarce CD8+ cells in tumor microenvironment, high microsatellite instability (MSI), and high tumor mutation burden (TMB). These biomarkers showed a conflicting prediction of the treatment response and clinical benefit of anti-PD-1 immunotherapy. Combination therapy of anti-PD-1 immunotherapy and radiotherapy was adopted as first-line treatment for the patient. After six cycles of immunotherapy, shrinkage of the primary liver tumor and metastatic lymph nodes happened, alongside with new lung metastasis, which indicated a mixed response. Radiotherapy was then administered to both the liver and lung lesions, accompanied with continued immunotherapy. The combined therapy eventually led to a complete response for both the primary tumor and all metastases without treatment-related adverse effects. The patient has survived for 26 months after the combined therapy and remains tumor-free currently. This case demonstrates the high inconsistency between immunotherapy response biomarkers and the synergetic anti-tumor effect of immunotherapy and radiotherapy in ICC.

18.
J Clin Endocrinol Metab ; 105(12)2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32880390

RESUMO

BACKGROUND: Systemic corticosteroids are now recommended in many treatment guidelines, although supporting evidence is limited to 1 randomized controlled clinical trial (RECOVERY). OBJECTIVE: To identify whether corticosteroids were beneficial to COVID-19 patients. METHODS: A total of 1514 severe and 249 critical hospitalized COVID-19 patients from 2 medical centers in Wuhan, China. Multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (inverse-probability-of-treatment-weighting [IPTW] and propensity score matching [PSM]) were used to estimate the association of corticosteroid use with risk of in-hospital mortality in severe and critical cases. RESULTS: Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to the non-corticosteroid group, systemic corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality in either severe cases (HR = 1.77; 95% CI, 1.08-2.89; P = 0.023), or critical cases (HR = 2.07; 95% CI, 1.08-3.98; P = 0.028). Findings were similar in time-varying Cox analysis. For patients with severe COVID-19 at admission, corticosteroid use was not associated with improved or harmful outcome in either PSM or IPTW analysis. For critical COVID-19 patients at admission, results were consistent with multivariable Cox model analysis. CONCLUSION: Corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality for severe or critical cases in Wuhan. Absence of the beneficial effect in our study in contrast to that observed in the RECOVERY clinical trial may be due to biases in observational data, in particular prescription by indication bias, differences in clinical characteristics of patients, choice of corticosteroid used, timing of initiation of treatment, and duration of treatment.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/mortalidade , Corticosteroides/uso terapêutico , Idoso , COVID-19 , Infecções por Coronavirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , SARS-CoV-2 , Taxa de Sobrevida
19.
BMJ ; 369: m2195, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522737

RESUMO

OBJECTIVE: To examine the protective effects of appropriate personal protective equipment for frontline healthcare professionals who provided care for patients with coronavirus disease 2019 (covid-19). DESIGN: Cross sectional study. SETTING: Four hospitals in Wuhan, China. PARTICIPANTS: 420 healthcare professionals (116 doctors and 304 nurses) who were deployed to Wuhan by two affiliated hospitals of Sun Yat-sen University and Nanfang Hospital of Southern Medical University for 6-8 weeks from 24 January to 7 April 2020. These study participants were provided with appropriate personal protective equipment to deliver healthcare to patients admitted to hospital with covid-19 and were involved in aerosol generating procedures. 77 healthcare professionals with no exposure history to covid-19 and 80 patients who had recovered from covid-19 were recruited to verify the accuracy of antibody testing. MAIN OUTCOME MEASURES: Covid-19 related symptoms (fever, cough, and dyspnoea) and evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, defined as a positive test for virus specific nucleic acids in nasopharyngeal swabs, or a positive test for IgM or IgG antibodies in the serum samples. RESULTS: The average age of study participants was 35.8 years and 68.1% (286/420) were women. These study participants worked 4-6 hour shifts for an average of 5.4 days a week; they worked an average of 16.2 hours each week in intensive care units. All 420 study participants had direct contact with patients with covid-19 and performed at least one aerosol generating procedure. During the deployment period in Wuhan, none of the study participants reported covid-19 related symptoms. When the participants returned home, they all tested negative for SARS-CoV-2 specific nucleic acids and IgM or IgG antibodies (95% confidence interval 0.0 to 0.7%). CONCLUSION: Before a safe and effective vaccine becomes available, healthcare professionals remain susceptible to covid-19. Despite being at high risk of exposure, study participants were appropriately protected and did not contract infection or develop protective immunity against SARS-CoV-2. Healthcare systems must give priority to the procurement and distribution of personal protective equipment, and provide adequate training to healthcare professionals in its use.


Assuntos
Infecções por Coronavirus/prevenção & controle , Pessoal de Saúde , Controle de Infecções/instrumentação , Pandemias/prevenção & controle , Equipamento de Proteção Individual/provisão & distribuição , Pneumonia Viral/prevenção & controle , Adulto , Betacoronavirus , COVID-19 , China , Infecções por Coronavirus/diagnóstico , Estudos Transversais , Feminino , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/prevenção & controle , Pneumonia Viral/diagnóstico , SARS-CoV-2
20.
Artigo em Inglês | MEDLINE | ID: mdl-32503812

RESUMO

INTRODUCTION: With intense deficiency of medical resources during COVID-19 pandemic, risk stratification is of strategic importance. Blood glucose level is an important risk factor for the prognosis of infection and critically ill patients. We aimed to investigate the prognostic value of blood glucose level in patients with COVID-19. RESEARCH DESIGN AND METHODS: We collected clinical and survival information of 2041 consecutive hospitalized patients with COVID-19 from two medical centers in Wuhan. Patients without available blood glucose level were excluded. We performed multivariable Cox regression to calculate HRs of blood glucose-associated indexes for the risk of progression to critical cases/mortality among non-critical cases, as well as in-hospital mortality in critical cases. Sensitivity analysis were conducted in patient without diabetes. RESULTS: Elevation of admission blood glucose level was an independent risk factor for progression to critical cases/death among non-critical cases (HR=1.30, 95% CI 1.03 to 1.63, p=0.026). Elevation of initial blood glucose level of critical diagnosis was an independent risk factor for in-hospital mortality in critical cases (HR=1.84, 95% CI 1.14 to 2.98, p=0.013). Higher median glucose level during hospital stay or after critical diagnosis (≥6.1 mmol/L) was independently associated with increased risks of progression to critical cases/death among non-critical cases, as well as in-hospital mortality in critical cases. Above results were consistent in the sensitivity analysis in patients without diabetes. CONCLUSIONS: Elevation of blood glucose level predicted worse outcomes in hospitalized patients with COVID-19. Our findings may provide a simple and practical way to risk stratify COVID-19 inpatients for hierarchical management, particularly where medical resources are in severe shortage during the pandemic.


Assuntos
Betacoronavirus , Glicemia/análise , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Hospitalização , Hiperglicemia/diagnóstico , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Idoso , COVID-19 , Infecções por Coronavirus/virologia , Estado Terminal , Progressão da Doença , Feminino , Seguimentos , Mortalidade Hospitalar , Humanos , Pacientes Internados , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Resultado do Tratamento
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