RESUMO
Regulator of G protein signaling 1 (RGS1) is closely associated with the tumor immune microenvironment and is highly expressed in various tumors and immune cells. The specific effects of RGS1 in the dynamic progression from chronic gastritis to gastric cancer have not been reported, and the role of tumor-associated macrophages (TAMs) is also unclear. In the present study, RGS1 was identified as an upregulated gene in different pathological stages ranging from chronic gastritis to gastric cancer by using Gene Expression Omnibus (GEO) screening together with pancancer analysis of The Cancer Genome Atlas and clinical prognostic analysis. The results indicated that RGS1 is highly expressed in gastric cancer and has potential prognostic value. We confirmed through in vivo experiments that RGS1 inhibited the proliferation of gastric cancer cells and promoted apoptosis, which was further corroborated by in vitro experiments. Additionally, RGS1 influenced cell migration and invasion. In our subsequent investigation of RGS1, we discovered its role in the immune response. Through analyses of single-cell and GEO database data, we confirmed its involvement in immune cell regulation, specifically TAM activation. Subsequently, we conducted in vivo and in vitro experiments to confirm the involvement of RGS1 in polarizing M1 macrophages while indirectly regulating M2 macrophages through tumor cells. In conclusion, RGS1 could be a potential target for the transformation of chronic gastritis into gastric cancer and has a measurable impact on TAMs, which warrants further in-depth research.
Assuntos
Gastrite , Neoplasias Gástricas , Humanos , Macrófagos Associados a Tumor/metabolismo , Neoplasias Gástricas/patologia , Transdução de Sinais , Proteínas de Ligação ao GTP/metabolismo , Microambiente TumoralRESUMO
OBJECTIVES: Whether or not a gastric cancer (GC) patient exhibits lymph node metastasis (LNM) is critical to accurately guiding their treatment and prognostic evaluation, necessitating the ability to reliably predict preoperative LNM status. The present meta-analysis sought to examine the diagnostic value of computed tomography (CT)-based predictive models as a tool to gauge the preoperative LNM status of patients with GC. METHODS: Relevant articles were identified in the PubMed, Web of Science, and Wanfang databases. These studies were used to conduct pooled analyses examining sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) values, and area under the curve values were computed for summary receiver operating characteristic curves. RESULTS: The final meta-analysis incorporated data from 15 studies, all of which were conducted in China, enrolling 3,817 patients with GC (LNM+: 1790; LNM-: 2027). The developed CT-based predictive model exhibited respective pooled sensitivity, specificity, PLR, and NLR values of 84% (95% confidence interval [CI], 0.79-0.87), 81% (95% CI, 0.76-0.85), 4.39 (95% CI, 3.40-5.67), and 0.20 (95% CI, 0.16-0.26). The identified results were not associated with significant potential for publication bias ( P = 0.071). Similarly, CT-based analyses of LN status exhibited respective pooled sensitivity, specificity, PLR, and NLR values of 62% (95% CI, 0.53-0.70), 77% (95% CI, 0.72-0.81), 2.71 (95% CI, 2.20-3.33), and 0.49 (95% CI, 0.40-0.61), with no significant risk of publication bias ( P = 0.984). CONCLUSIONS: Overall, the present meta-analysis revealed that a CT-based predictive model may outperform CT-based analyses alone when assessing the preoperative LNM status of patients with GC, offering superior diagnostic utility.
Assuntos
Neoplasias Gástricas , Humanos , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X , Probabilidade , Linfonodos/diagnóstico por imagem , Linfonodos/patologiaRESUMO
BACKGROUND: Inflammation has been implicated in the pathology of schizophrenia and may cause neuronal cell death and dendrite loss. Neuroimaging studies have highlighted longitudinal brain structural changes in patients with schizophrenia, yet it is unclear whether this is related to inflammation. We aim to address this question, by relating brain structural changes with the transcriptional profile of inflammation markers in the early stage of schizophrenia. METHODS: Thirty-eight patients with first-episode schizophrenia and 51 healthy controls were included. High-resolution T1-weighted magnetic resonance imaging (MRI) and clinical assessments were performed at baseline and 2 ~ 6 months follow-up for all subjects. Changes in the brain structure were analyzed using surface-based morphological analysis and correlated with the expression of immune cells-related gene sets of interest reported by previous reviews. Transcriptional data were retrieved from the Allen Human Brain Atlas. Furthermore, we examined the brain structural changes and peripheral inflammation markers in association with behavioral symptoms and cognitive functioning in patients. RESULTS: Patients exhibited accelerated cortical thickness decrease in the left frontal cortices, less decrease or an increase in the superior parietal lobule and right lateral occipital lobe, and increased volume in the bilateral pallidum, compared with controls. Changes in cortical thickness correlated with the transcriptional level of monocyte across cortical regions in patients (r = 0.54, p < 0.01), but not in controls (r = - 0.05, p = 0.76). In addition, cortical thickness change in the left superior parietal lobule positively correlated with changes in digital span-backward test scores in patients. CONCLUSIONS: Patients with schizophrenia exhibit regional-specific cortical thickness changes in the prefrontal and parietooccipital cortices, which is related to their cognitive impairment. Inflammation may be an important factor contributing to cortical thinning in first-episode schizophrenia. Our findings suggest that the immunity-brain-behavior association may play a crucial role in the pathogenesis of schizophrenia.
Assuntos
Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Cognição , Córtex Cerebral/patologiaRESUMO
PURPOSE: To evaluate the safety and clinical efficacy of image-guided radiofrequency ablation (RFA) in patients exhibiting adrenal metastatic tumors (AMTs). METHODS: The PubMed, Web of Science, and Wanfang databases were searched for relevant studies published as of November 2022, and study results were pooled for subsequent analysis. The endpoints of this meta-analysis included primary and secondary technical success, local hemorrhage, pneumothorax, hypertensive crisis, local recurrence, and 1- and 3-year overall survival (OS) rates. RESULTS: This analysis incorporated 11 studies enrolling 351 patients that underwent RFA treatment for 373 AMTs. The pooled primary and secondary technical success, local hemorrhage, pneumothorax, hypertensive crisis, local recurrence, and 1- and 3-year OS rates in these patients were 84%, 91%, 4%, 6%, 7%, 19%, 82%, and 46%, respectively. The 1-year OS (I2 = 75.2%, p = 0.003) and 3-year OS (I2 = 81.4%, p = 0.001) endpoints were subject to significant heterogeneity. Subgroup analyses suggested that primary technical success rates were < 80% in patients with tumors exhibiting a mean diameter ≥ 4 cm. Guidance type and tumor size had no impact on a hypertensive crisis or local recurrence rates. CONCLUSIONS: These data indicate that image-guided RFA represents a safe and effective means of treating AMTs.
Assuntos
Neoplasias das Glândulas Suprarrenais , Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Pneumotórax , Ablação por Radiofrequência , Humanos , Ablação por Radiofrequência/métodos , Resultado do Tratamento , Neoplasias das Glândulas Suprarrenais/cirurgia , Taxa de Sobrevida , Ablação por Cateter/métodos , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/cirurgiaRESUMO
BACKGROUND: Cognitive impairment is the main factor in the poor prognosis of schizophrenia, but its mechanism remains unclear. The inferior parietal lobule (IPL) is related to various clinical symptoms and cognitive impairment in schizophrenia. We aimed to explore the relationship between IPL-related functions and cognitive impairment in schizophrenia. METHODS: 136 schizophrenia patients and 146 demographically matched healthy controls were enrolled for a cross-sectional study. High-spatial-resolution structural and resting-state functional images were acquired to demonstrate the alternations of brain structure and function. At the same time, the digit span and digit symbol coding tasks of the Chinese Wechsler Adult Intelligence Test Revised (WAIS-RC) were utilized in assessing the subjects' cognitive function. Patients were divided into cognitive impairment and normal cognitive groups according to their cognitive score and then compared whether there were differences between the three groups in fractional amplitude of low-frequency fluctuation (fALFF). In addition, we did a correlation analysis between cognitive function and the fALFF for the left IPL of patients and healthy controls. Based on the Allen Human Brain Atlas, we obtained genes expressed in the left IPL, which were then intersected with the transcriptome-wide association study results and differentially expressed genes in schizophrenia. RESULTS: Grouping of patients by the backward digit span task and the digit symbol coding task showed differences in fALFF values between healthy controls and cognitive impairment patients (P < 0.05). We found a negative correlation between the backward digit span task score and fALFF of the left IPL in healthy controls (r = - 0.388, P = 0.003), which was not seen in patients (r = 0.203, P = 0.020). In addition, none of the other analyses were statistically significant (P > 0.017). In addition, we found that diacylglycerol kinase ζ (DGKζ) is differentially expressed in the left IPL and associated with schizophrenia. CONCLUSION: Our study demonstrates that the left IPL plays a vital role in cognitive impairment in schizophrenia. DGKζ may act as an essential regulator in the left IPL of schizophrenia patients with cognitive impairment.
Assuntos
Disfunção Cognitiva , Esquizofrenia , Adulto , Humanos , Disfunção Cognitiva/complicações , Estudos Transversais , Diacilglicerol Quinase , Lobo Parietal , Esquizofrenia/complicaçõesRESUMO
BACKGROUND: Recently, a new type of pulmonary nodule positioning needle has been adopted clinically. We aimed to evaluate the efficacy and safety of a new type of localization needles compared with coils for the simultaneous localization of multiple pulmonary nodules guided by computed tomography (CT) prior to video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: From January 2021 to March 2022, 87 pulmonary nodules from 40 patients were localized using the new localization needle. From January 2020 to December 2020, 68 pulmonary nodules in 31 patients were localized using coils. The relative outcomes were compared. RESULTS: The success rate of pulmonary nodule localization in the needle group was 97.7% while that in the coil group was 98.5%. In the needle group, the time needed to locate the first nodule was significantly shorter than in the coil group (10.9 min vs. 17.2 min, P = 0.001). Moreover, the time needed per patient was also significantly shorter for the needle group compared with the coil group (23.7 min vs. 30 min, P = 0.017). The incidence of pneumothorax in the needle group was 25.0% vs. 12.9% in the coil group (P = 0.204). The rate of pulmonary hemorrhage in the needle group was 40.0% vs. 32.3% in the coil group (P = 0.502). The success rate of VATS wedge resection was 100% in both groups. CONCLUSION: Both disposable pulmonary nodule localization needles and coils are safe and effective for CT-guided localization of multiple pulmonary nodules of the same stage prior to VATS. However, the use of needles is time-saving compared with the use of coils. The coil localization may exhibit better safety than needle localization.
Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Nódulos Pulmonares Múltiplos/cirurgia , Agulhas , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/métodos , Pulmão/cirurgiaRESUMO
As a non-invasive detection method and an advanced imaging method, magnetic resonance imaging (MRI) has been widely used in the research of schizophrenia. Although a large number of neuroimaging studies have confirmed that MRI can display abnormal brain phenotypes in patients with schizophrenia, no valid uniform standard has been established for its clinical application. On the basis of previous evidence, we argue that MRI is an important tool throughout the whole clinical course of schizophrenia. The purpose of this commentary is to systematically describe the role of MRI in schizophrenia and to provide references for its clinical application.
Assuntos
Esquizofrenia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Esquizofrenia/diagnóstico por imagemRESUMO
PURPOSE: To assess the efficacy and safety of transarterial chemoembolization (TACE) and portal vein radioactive seed insertion (RSI) combination in hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). MATERIAL AND METHODS: The relevant databases were searched from the earliest to January 2021. The endpoints included treatment response, treatment side effects, and overall survival (OS). RESULTS: Nine studies were included in this meta-analysis. The pooled total response (TR, p = 0.55) and disease control (DC, p = 0.13) rates for HCC were similar between the two treatment groups. The pooled TR (p = 0.0004) and DC (p < 0.0001) rates for PVTT were both significantly higher in the TACE with portal vein RSI group than in the TACE without portal vein RSI group. The pooled HR for OS was significantly better in the TACE with portal vein RSI group than in the TACE without portal vein RSI group (p < 0.00001). The pooled rates of fever (p = 0.97), vomiting (p = 0.64), and myelosuppression (p = 0.65) were similar between the two groups. CONCLUSION: Compared to traditional TACE, TACE combined with portal vein RSI can effectively prolong the patients' OS and decrease PVTT disease progression.
Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Trombose , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Veia Porta , Estudos Retrospectivos , Trombose/patologia , Resultado do TratamentoRESUMO
PURPOSE: To assess the effectiveness of I-125 seeds (IS) insertion with transcatheter arterial chemoembolization (TACE) in treating patients with advanced hepatocellular carcinoma (HCC). MATERIAL AND METHODS: An extensive search was conducted for relevant randomized controlled trials (RCTs) from the establishment date of each database to November 2020. RESULTS: A total of nine RCTs were included in this study. Our analysis showed no significant changes in the pooled Δalpha-fetoprotein values (p = .06), incident rates of myelosuppression (p = .46), vomit occurrence (p = .27), and abnormal liver function (p = .42) between the two treatment groups. However, the complete response (p < .00001), total response (p < .00001), and disease control (p < .00001) rates were significantly higher in patients who underwent TACE with IS insertion, as opposed to patients who received TACE alone. Furthermore, patients who underwent TACE with IS insertion experienced markedly longer pooled overall survival (OS) time (p < .0001), with better OS rates at the six-month (p = .0002), one-year (p < .0001), and three-year (p = .0003) follow-ups than patients who received TACE alone. CONCLUSION: TACE with IS insertion can significantly improve clinical response and prolong the survival of advanced HCC patients.
Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Terapia Combinada , Humanos , Radioisótopos do Iodo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
PURPOSE: To compare the clinical effectiveness between transarterial embolization (TAE) with staged hepatectomy (SH) and emergency hepatectomy (EH) for ruptured hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Pubmed, Embase, and Cochrane Library databases were screened for eligible publications from the inception of the databases till February 2021. RESULTS: This meta-analysis included seven studies comprising 162 patients who underwent TAE with SH and 266 patients who underwent EH. The pooled intraoperative blood loss was less in the TAE with SH cohort, as compared to the EH cohort without significant difference (p = .20). The pooled blood transfer rate (p<.00001), blood transfer volume (p = .002), and 30-day patient death (p = .04) were all markedly reduced in the TAE with SH cohort versus the EH cohort. No significant differences in surgery duration (p = .27), hospital stay period (p = .81), complication rate (p = 0.92), disease-free survival (DFS) (p = .79), and overall survival (OS) (p = 0.28) were found between the two groups. CONCLUSIONS: Compared with EH for ruptured HCC, TAE with SH could effectively decrease intraoperative blood loss and 30-day mortality. However, the long-term DFS and OS might not be beneficial to preoperative TAE.
Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Perda Sanguínea Cirúrgica , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Ruptura Espontânea/complicações , Ruptura Espontânea/cirurgia , Resultado do TratamentoRESUMO
Multimodal neuroimaging features provide opportunities for accurate classification and personalized treatment options in the psychiatric domain. This study aimed to investigate whether brain features predict responses to the overall treatment of schizophrenia at the end of the first or a single hospitalization. Structural and functional magnetic resonance imaging (MRI) data from two independent samples (N = 85 and 63, separately) of schizophrenia patients at baseline were included. After treatment, patients were classified as responders and non-responders. Radiomics features of gray matter morphology and functional connectivity were extracted using Least Absolute Shrinkage and Selection Operator. Support vector machine was used to explore the predictive performance. Prediction models were based on structural features (cortical thickness, surface area, gray matter regional volume, mean curvature, metric distortion, and sulcal depth), functional features (functional connectivity), and combined features. There were 12 features after dimensionality reduction. The structural features involved the right precuneus, cuneus, and inferior parietal lobule. The functional features predominately included inter-hemispheric connectivity. We observed a prediction accuracy of 80.38% (sensitivity: 87.28%; specificity 82.47%) for the model using functional features, and 69.68% (sensitivity: 83.96%; specificity: 72.41%) for the one using structural features. Our model combining both structural and functional features achieved a higher accuracy of 85.03%, with 92.04% responder and 80.23% non-responders to the overall treatment to be correctly predicted. These results highlight the power of structural and functional MRI-derived radiomics features to predict early response to treatment in schizophrenia. Prediction models of the very early treatment response in schizophrenia could augment effective therapeutic strategies.
Assuntos
Esquizofrenia , Encéfalo , Humanos , Imageamento por Ressonância Magnética , Neuroimagem , Estudos Retrospectivos , Máquina de Vetores de SuporteRESUMO
PURPOSE: To evaluate the relative clinical efficacy associated with the unilateral and bilateral insertion of a stent with a radioactive strand (RS) for the treatment of inoperable hilar cholangiocarcinoma (HCCA) patients. METHODS: From January 2017 to June 2020, consecutive patients diagnosed with inoperable HCCA underwent either unilateral or bilateral stent with RS insertion in our hospital. Outcomes compared between these groups included rates of technical success, clinical success, stent-related complications, stent patency and overall survival (OS). RESULTS: Unilateral and bilateral stent with RS insertion procedures were performed in 36 and 30 patients over the study period, respectively, with 100% technical and clinical success rates in both groups. No instances of procedure-related complications were reported. Cholangitis was observed in 7 (19.4%) and 6 (20%) patients in unilateral and bilateral groups (p= .955), respectively, while these groups exhibited respective cholecystitis in 2 (5.5%) and 1 (3.3%) cases, respectively (p=.662), and stent restenosis in 9 (25%) and 7 (23.3%) cases, respectively (p=.661). The median duration of stent patency in the unilateral and bilateral groups was comparable at 208 and 222 d, respectively (p=.889). All patients died over the course of follow-up, with similar median OS rates in the unilateral and bilateral groups of 250 and 246 d, respectively (p=.483). CONCLUSIONS: These data indicated that similar inoperable HCCA patient clinical outcomes are achieved following stent with RS insertion regardless of whether it is conducted via a unilateral or bilateral approach.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Colestase , Tumor de Klatskin , Colangiocarcinoma/complicações , Colangiocarcinoma/radioterapia , Colangiocarcinoma/cirurgia , Colestase/etiologia , Humanos , Tumor de Klatskin/complicações , Tumor de Klatskin/cirurgia , Cuidados Paliativos/métodos , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do TratamentoRESUMO
PURPOSE: To assess the safety and clinical effectiveness of computed tomography (CT)-guided cryoablation for functional adrenal aldosteronoma. MATERIAL AND METHODS: From June 2012 to December 2018, 11 patients with functional adrenal aldosteronoma underwent CT-guided cryoablation in our center. Data comprising complete ablation rate, clinical success rate, procedure-related complications and long-term outcome were collected and analyzed. RESULTS: A total of 11 aldosteronoma in 11 patients were treated. Complete ablation was achieved in all patients after a single ablation session. No procedure-related complications occurred. Clinical success rate was 100%. Mean aldosterone levels, and systolic and diastolic pressure decreased from 858.6 ± 93.2 pmol/L, 156.4 ± 7.8 mmHg and 90.0 ± 10.5 mmHg prior to treatment, respectively, to 321.8 ± 41.2 pmol/L (p < .001), 129.1 ± 9.4 mmHg (p < .001) and 76.4 ± 5.5 mmHg (p = .005) after treatment, respectively. Mean renin and potassium improved from 0.2 ± 0.1 µg/L/h and 2.9 ± 0.2 mmol/L before treatment, respectively to 4.6 ± 0.4 µg/L/h (p < .001) and 4.2 ± 0.2 mmol/L (p < .001) following treatment, respectively. No tumor or clinical symptom recurrence occurred during the follow-up. CONCLUSIONS: CT-guided cryoablation is a safe and effective method for the treatment of functional adrenal aldosteronoma.
Assuntos
Criocirurgia , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
PURPOSE: To explore the clinical efficacy and long-term outcomes of accessory hepatic vein (AHV) recanalization as a means of treating hepatic vein (HV)-type Budd-Chiari syndrome (BCS). METHODS: Between January 2011 and December 2018, a total of 46 symptomatic HV-type BCS patients were treated by AHV recanalization in our hospital. The technical and clinical success of this treatment, as well as associated long-term patient prognosis was assessed herein. RESULTS: The AHV recanalization approach was technically successful in 100% of patients, without any instances of complications associated with the operation. This procedure was 95.7% (44/46) clinically successful and resultant. AHV re-obstruction occurred in 12 patients. The cumulative primary one-, two-, and five-year patency rates were 77.3%, 71.7%, and 71.7%, respectively. The secondary cumulative one-, two-, and five-year patency rates were 97.7, 87.1, and 87.1%, respectively. The five-year patency rates did not differ significantly between patients treated with balloons and stents (p = .674). Based on Cox-regression analysis, younger age was an independent predictor of re-obstruction (p = .005). The cumulative one-, two-, and five-year survival rates were 97.7, 92.2, and 92.2%, respectively. CONCLUSIONS: AHV recanalization is a safe and effective treatment for HV-type BCS.
Assuntos
Síndrome de Budd-Chiari , Síndrome de Budd-Chiari/terapia , Veias Hepáticas , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Veia Cava InferiorRESUMO
PURPOSE: This study aimed to assess clinical efficacy and long-term patient outcomes in individuals with malignant hilar biliary obstruction (MHBO) that had been treated via insertion of a stent with a radioactive seed strand (RSS). MATERIAL AND METHODS: A total of 84 MHBO patients were treated via either normal stent insertion (n = 48) or stent with RSS insertion (n = 36) from January 2015 to December 2018. RESULTS: The technical success rates of normal stent insertion and stent with RSS insertion were 93.8% (45/48) and 97.2% (35/36), respectively (p = .632), with clinical success rates of 93.3% (42/45) and 100% (35/35), respectively (p = .252). In these two patient groups, 11 and seven patients, respectively, suffered from stent dysfunction (p = .637). In the normal and RSS groups, median stent patency was 165 and 225 days, respectively (p < .001). All patients in the present study died due to tumor progression, with median survival times of 188 and 250 days in the normal and RSS stent groups, respectively (p < .001). CONCLUSION: Relative to normal stent insertion, combined stent with RSS insertion can effectively prolong both stent patency and patient survival in patients with MHBO.
Assuntos
Neoplasias dos Ductos Biliares , Braquiterapia , Colestase , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/radioterapia , Braquiterapia/efeitos adversos , Humanos , Estudos Retrospectivos , Stents , Resultado do TratamentoRESUMO
Given the poor prognosis of unresectable advanced gastric cancer (GC), novel therapeutic strategies are needed. The mitogen-activated protein kinase (MAPK) signaling cascade, the most frequently activated pathway in GC, plays an important role in tumorigenesis and metastasis. The MAPK/extracellular signal-regulated kinase (ERK) pathway is an attractive therapeutic target for GC. In this study, trametinib, a mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor, reduced the p-ERK level and significantly increased signal transducer and activator of transcription 3 (STAT3) phosphorylation in GC cells, resulting in reduced sensitivity to trametinib. Physapubescin B (PB), a steroidal compound extracted from the plant Physalis pubescens L., inhibited the proliferation and induced the apoptosis of GC cells by suppressing STAT3 phosphorylation. The combination of PB and trametinib suppressed the STAT3 phosphorylation induced by trametinib, and synergistically suppressed gastric tumor growth in vitro and in vivo. Together, these results indicate that inhibition of both MEK and STAT3 may be effective for patients with MAPK/ERK pathway-addicted GC.
Assuntos
Antineoplásicos/uso terapêutico , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Fator de Transcrição STAT3/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Vitanolídeos/uso terapêutico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos Nus , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Piridonas/farmacologia , Pirimidinonas/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Vitanolídeos/farmacologiaRESUMO
OBJECTIVES: To assess the relative diagnostic utility of low- and standard-dose computed tomography (CT)-guided lung biopsy. METHODS: In this single-center, single-blind, prospective, randomized controlled trial, patients were enrolled between November 2016 and June 2017. Enrolled study participants were randomly selected to undergo either low- or standard-dose CT-guided lung biopsy. Diagnostic accuracy was the primary study endpoint, whereas technical success, radiation dose, and associated complications were secondary study endpoints. RESULTS: In total, 280 patients underwent study enrollment and randomization, with 271 (low-dose group, 135; standard-dose group, 136) receiving the assigned interventions. Both groups had a 100% technical success rate for CT-guided lung biopsy, and complication rates were similar between groups (p > 0.05). The mean dose-length product (36.0 ± 14.1 mGy cm vs. 361.8 ± 108.0 mGy cm, p < 0.001) and effective dose (0.5 ± 0.2 mSv vs. 5.1 ± 1.5 mSv, p < 0.001) were significantly reduced in the low-dose group participants. Sensitivity, specificity, and overall diagnostic accuracy rates in the low-dose group were 91.8%, 100%, and 94.6%, respectively, whereas in the standard-dose group, the corresponding values were 89.6%, 100%, and 92.4%, respectively. These results indicated that diagnostic performance did not differ significantly between the 2 groups. Using univariate and multivariate analyses, we found larger lesion size (p = 0.038) and procedure-related pneumothorax (p = 0.033) to both be independent predictors of diagnostic failure. CONCLUSIONS: Our results demonstrate that low-dose CT-guided lung biopsy can yield comparable diagnostic accuracy to standard-dose CT guidance, while significantly reducing the radiation dose delivered to patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02971176 KEY POINTS: ⢠Low-dose CT-guided lung biopsy is a safe and simple method for diagnosis of lung lesions. ⢠Low-dose CT-guided lung biopsy can yield comparable diagnostic accuracy to standard-dose CT guidance. ⢠Low-dose CT-guided lung biopsy can achieve a 90% reduction in radiation exposure when compared with standard-dose CT guidance.
Assuntos
Biópsia Guiada por Imagem/métodos , Neoplasias Pulmonares/diagnóstico , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Doses de Radiação , Exposição à Radiação , Método Simples-CegoRESUMO
PURPOSE: The purpose of this study was to assess the diagnostic yield of computed tomography (CT)-guided core needle biopsy (CNB) for initial transbronchial biopsy (TBB)-based nondiagnostic lung lesions. METHODS: From January 2014 to December 2017, 101 consecutive patients with initial TBB-based nondiagnostic lung lesions underwent CT-guided CNB. All procedures were performed with an 18G core needle by a chest radiologist with more than 5 years of experience. The CT-guided CNB was performed within 30 days after the initial TBB. In total, 90 and 11 central and peripheral lung lesions were observed, respectively. The mean ± SD diameter of these lesions was 58.8 ± 21.8 mm. The diagnostic yield of CT-guided CNB was assessed. RESULTS: Computed tomography-guided CNB provided a definite diagnosis for 63 (62.4%) of the 101 lesions. The 63 CNB-based lesion diagnoses included malignant (n = 57) and specific benign (n = 6) lesions. The remaining 38 CNB-based nondiagnostic lesions included nonspecific benign (n = 35) and suspected malignant (n = 3) lesions. The 38 CNB-based nondiagnostic lesions were confirmed by surgery (n = 5), repeat CNB (n = 5), or CT follow-up (n = 28). The mean ± SD follow-up was 9.9 ± 7.3 months. Based on the final diagnosis, 67 lesions were malignant and 34 lesions were benign. The sensitivity, specificity, and accuracy of CT-guided CNB were 89.6% (60/67), 100% (34/34), and 93.1% (94/101), respectively. CONCLUSIONS: Computed tomography-guided CNB is a useful diagnostic modality for accurate diagnosis of lung lesions with inconclusive pathologic results after initial TBB.
Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Radiografia Intervencionista/métodos , Tomografia Computadorizada por Raios X/métodos , Feminino , Humanos , Biópsia Guiada por Imagem , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
PURPOSE: This study aimed to compare the feasibility, safety, diagnostic accuracy, and radiation dose between computed tomography (CT) fluoroscopy (CTF)-guided and conventional CT (CCT)-guided lung biopsy. METHODS: Relevant articles up until February 2020 were identified within the PubMed, Embase, and Cochrane Library databases. Diagnostic accuracy rate, pneumothorax, and pneumothorax requiring chest tube served as primary end points, with technical success, hemoptysis, operative time, and radiation dose serving as secondary end points. Pooled odds ratios (ORs) were calculated for the dichotomous variables. Pooled estimates of the mean difference (MD) were measured for the continuous variables. RESULTS: This meta-analysis included 9 studies. Seven studies were retrospective, and 2 studies were randomized controlled trials. A total of 6998 patients underwent either CTF-guided (n = 3858) or CCT-guided (n = 3154) lung biopsy. The diagnostic accuracy rate was significantly higher in the CTF group compared with the CCT group (OR, 0.32; P < 0.00001). No significant differences were detected between the CTF and CCT groups in terms of incidence rates of pneumothorax (OR, 0.95; P = 0.84), rates of pneumothorax requiring chest tube insertion (OR, 0.95; P = 0.84), technical success rates (OR, 0.41; P = 0.15), incidence rates of hemoptysis (OR, 1.19; P = 0.61), operative time (MD, -4.38; P = 0.24), and radiation dose (MD, 158.60; P = 0.42). A publication bias was found for the end points of pneumothorax requiring chest tube insertion and operative time. CONCLUSIONS: Compared with CCT-guided lung biopsy, CTF-guided lung biopsy could yield a higher diagnostic accuracy with similar safety and radiation exposure.
Assuntos
Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Ensaios Clínicos como Assunto , Fluoroscopia/efeitos adversos , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Pulmão/patologia , Doses de Radiação , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/efeitos adversosRESUMO
PURPOSE: This study was designed to evaluate the diagnostic accuracy of computed tomography (CT)-guided biopsy for small lung nodules (SLNs) (≤20 mm) and to assess related complication rates. METHODS: We reviewed the Pubmed, Embase, and Cochrane Library databases to identify all relevant studies published as of April 2020. Random effects modeling were then used to evaluate pooled data pertaining to technical success rates, diagnostic accuracy, pneumothorax rates, and rates of hemoptysis. The meta-analysis was conducted using Stata v12.0. RESULTS: In total, we identified 25 relevant studies for incorporation into this meta-analysis, incorporating 2922 total CT-guided lung biopsy. Pooled technical success rates, diagnostic accuracy, pneumothorax rates, and hemoptysis rates were 94% (95% confidential interval [CI], 0.91-0.98), 90% (95% CI, 0.88-0.93), 19% (95% CI:, 0.15-0.24), and 12% (95% CI, 0.08-0.15), respectively. We observed significant heterogeneity among these studies for all 4 of these parameters (I = 90.0%, 82.7%, 88.6%, and 88.4%, respectively). When we conducted a meta-regression analysis, we did not identify any variables that influenced diagnostic accuracy or technical success, pneumothorax, or hemoptysis rates. Publication bias risk analyses suggested that there was relatively little risk of publication bias pertaining to pneumothorax rates (P = 0.400) or hemoptysis rates (P = 0.377). In contrast, we detected a high risk of publication bias pertaining to reported technical success rates (P = 0.007) and diagnostic accuracy (P = 0.000). CONCLUSIONS: A CT-guided biopsy can be safely and effectively used to diagnose SLNs.