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1.
Gastrointest Endosc ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964479

RESUMO

BACKGROUND AND AIMS: There is a high incidence of stricture after endoscopic submucosal dissection (ESD) for cervical esophageal cancer. We aimed to elucidate the risk factors for stricture and evaluate the efficacy of steroid injection for stricture prevention in the cervical esophagus. METHODS: We retrospectively analyzed 100 patients who underwent ESD for cervical esophageal cancer to: (1) identify the factors associated with stricture among patients who did not receive steroid injection; (2) compare the incidence of stricture between patients with and without steroid injection. RESULTS: Among 48 patients who did not receive steroid injection, there were significant differences in tumor size (P = .026), resection time (P = .028), and circumferential extent of the mucosal defect (P = .005) between patients with stricture (n = 5) and without stricture (n = 43). Compared with patients without steroid injection, patients with steroid injection had a significantly lower incidence of stricture when the post-ESD mucosal defect was < 3/4 and ≥ 1/2 (40% versus 8%, P = .039). As for the patients with a post-ESD mucosal defect of ≥ 3/4 (n = 13), local steroid injection was performed for all the patients, and 6 patients (46%) developed stricture. CONCLUSIONS: Patients who underwent ≥ 1/2 circumferential resection were at high risk of cervical esophageal stricture. Steroid injection had a stricture-prevention effect in patients with < 3/4 and ≥ 1/2 circumferential resection, but seemed to be insufficient in preventing stricture in patients with ≥ 3/4 circumferential resection.

2.
Dig Endosc ; 36(4): 421-427, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37553826

RESUMO

OBJECTIVES: Prediction of the risk of esophageal squamous cell carcinoma (SCC) by endoscopic findings without iodine staining, which is irritating to the esophagus, would be beneficial. In a previous retrospective study, we found that multiple foci of dilated vascular areas (MDV) of the esophageal mucosa, seen in narrow-band imaging (NBI)/blue laser imaging (BLI), are associated with iodine-unstained lesions and, thus, may be a predictor of esophageal SCC. This prospective study aimed to investigate the association between MDV and metachronous esophageal SCC. METHODS: Patients with a history of endoscopic resection for esophageal SCC were included in the study. First, evaluation of the MDV using NBI or BLI was conducted during the initial endoscopy. The patients were then monitored for metachronous esophageal SCC by endoscopic surveillance. The association between the number of MDV and incidence of metachronous esophageal SCC was investigated. RESULTS: From February 2018 to May 2019, 206 patients were enrolled and 201 patients were included in the analysis. Patients were followed up until October 2022. The median (interquartile range) endoscopic follow-up period was 1260 (1105-1348) days. The incidence of metachronous esophageal SCC at 2 years was 7.1% in patients with MDV ≤4 and 13.9% in patients with MDV ≥5 (P < 0.01). In the multivariate analysis, MDV was an independent predictor of metachronous esophageal SCC, with an odds ratio (95% confidence interval) of 2.37 (1.06-5.31). CONCLUSION: Multiple foci of dilated vascular area is a useful predictor for stratifying the risk of metachronous esophageal SCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Iodo , Humanos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/epidemiologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Estudos Prospectivos , Esofagoscopia/métodos
3.
Esophagus ; 21(1): 58-66, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38082187

RESUMO

BACKGROUND: Esophageal endoscopic submucosal dissection (ESD) is technically challenging, especially for trainees, and requires a safe training system. This study aimed to identify predictors of technical difficulty facing trainees performing esophageal ESD to establish such system. METHODS: This was a single-center retrospective study of patients with esophageal cancer who underwent ESD performed by trainees between January 2010 and August 2022. Technical difficulties were defined as muscularis propria exposure and long procedure time (≥ 90 min). Factors associated with these technical difficulties were investigated. RESULTS: A total of 798 lesions in 721 patients were evaluated. Muscularis propria exposure occurred in 298 lesions (37.3%), including 10 perforations (1.3%). The procedure time was ≥ 90 min in 134 lesions (16.8%). In the multivariate analysis, tumor size ≥ 20 mm, tumors ≥ 1/2 of the circumference, and those close to previous treatment scars significantly increased the incidence of both difficulties, whereas tumors in the upper esophagus significantly decreased this incidence. Furthermore, female sex and tumors in the left wall were independent predictors of muscularis propria exposure, and elevated morphology was an independent predictor of long procedure time. Muscularis propria exposure and long procedure time occurred in more than half of the cases with three or more predictors of each difficulty. CONCLUSIONS: Large tumors and tumors close to previous treatment scars increase technical difficulties for trainees in esophageal ESD. Conversely, tumors in the upper esophagus reduce these difficulties. These results enable us to predict the difficulty level preoperatively and select appropriate cases in stepwise training.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Humanos , Feminino , Ressecção Endoscópica de Mucosa/métodos , Estudos Retrospectivos , Cicatriz/patologia , Neoplasias Esofágicas/patologia
4.
Gastrointest Endosc ; 98(2): 170-177, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36990127

RESUMO

BACKGROUND AND AIMS: Local triamcinolone (TA) injection is widely used to prevent stricture formation after endoscopic submucosal dissection (ESD). However, stricture develops in up to 45% of patients despite this prophylactic measure. We therefore conducted a single-center prospective study to identify predictors of stricture after esophageal ESD and local TA injection. METHODS: Patients who underwent esophageal ESD and local TA injection and who were comprehensively assessed for lesion- and ESD-related factors were included in the study. Multivariate analyses were conducted to identify the predictors of stricture. RESULTS: A total of 203 patients were included in the analysis. Multivariate analysis identified residual mucosal width ≤5 mm (odds ratio [OR], 29.0; P < .0001) or 6 to 10 mm (OR, 3.7; P = .04), history of chemoradiotherapy (OR, 5.1; P = .045), and tumor in the cervical or upper thoracic esophagus (OR, 3.8; P = .018) as independent predictors of stricture. Based on the ORs of the predictors, patients were stratified into 2 groups according to stricture risk: patients in the high-risk group (residual mucosal width ≤5 mm or 6-10 mm with another predictor) had a stricture rate of 52.5% (31 of 59 cases), and patients in the low-risk group (residual mucosal width ≥11 mm or 6-10 mm without other predictors) had a stricture rate of 6.3% (9 of 144 cases). CONCLUSIONS: We identified predictors of stricture after ESD and local TA injection. Local TA injection prevented stricture formation after ESD in low-risk patients but was not sufficient to prevent stricture in high-risk patients. Additional interventions should thus be considered in high-risk patients. (University Hospital Medical Network Clinical Trials Registry number: UMIN 000028894.).


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Estenose Esofágica , Humanos , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Constrição Patológica/etiologia , Estudos Prospectivos , Estenose Esofágica/epidemiologia , Estenose Esofágica/etiologia , Estenose Esofágica/prevenção & controle , Neoplasias Esofágicas/patologia , Triancinolona/uso terapêutico
5.
BMC Gastroenterol ; 23(1): 326, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37740192

RESUMO

BACKGROUND: Autophagy plays an important role in carcinogenesis and tumor progression in many cancers, including gastric cancer. Cytotoxin-associated gene A (CagA) is a well-known virulent factor in Helicobacter pylori (H. pylori) infection that plays a critical role in gastric inflammation and gastric cancer development. However, its role in autophagy during these processes remains unclear. Therefore, we aimed to clarify the role of CagA in autophagy in CagA-related inflammation. METHODS: We evaluated the autophagic index of AGS cells infected with wild-type cagA-positive H. pylori (Hp-WT) and cagA-knockout H. pylori (Hp-ΔcagA) and rat gastric mucosal (RGM1) cells transfected with CagA genes. To identify the mechanisms underlying the down regulation of autophagy in AGS cells infected with H. pylori, we evaluated protein and mRNA expression levels of autophagy core proteins using western blotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR). To determine whether autophagy induced the expression of the pro-inflammatory mediator, cyclooxygenase-2 (COX-2), we evaluated COX-2 expression in AGS cells treated with an autophagy inducer and inhibitor and infected with H. pylori. In addition, we evaluated whether COX-2 protein expression in AGS cells influenced beclin-1 (BECN1) expression with si-RNA transfection when infected with H. pylori. RESULTS: Autophagic flux assay using chloroquine showed that autophagy in AGS cells was significantly suppressed after H. pylori infection. The autophagic index of AGS cells infected with Hp-WT was decreased significantly when compared with that in AGS cells infected with Hp-ΔcagA. The autophagic index of RGM1 cells transfected with CagA was lower, suggesting that CagA inhibits autophagy. In addition, BECN1 expression levels in AGS cells infected with Hp-WT were reduced compared to those in AGS cells infected with Hp-ΔcagA. Furthermore, COX-2 expression in AGS cells infected with H. pylori was controlled in an autophagy-dependent manner. When AGS cells were transfected with small interfering RNA specific for BECN1 and infected with Hp-WT and Hp-ΔcagA, COX-2 was upregulated significantly in cells infected with Hp-ΔcagA. CONCLUSIONS: In conclusion, the H. pylori CagA protein negatively regulated autophagy by downregulating BECN1. CagA-induced autophagy inhibition may be a causative factor in promoting pro-inflammatory mediator production in human gastric epithelial cells.


Assuntos
Helicobacter pylori , Neoplasias Gástricas , Humanos , Animais , Ratos , Neoplasias Gástricas/genética , Ciclo-Oxigenase 2/genética , Autofagia/genética , Citotoxinas , Mediadores da Inflamação
6.
BMC Gastroenterol ; 23(1): 184, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37231330

RESUMO

BACKGROUND: Several pre-clinical studies have reported the usefulness of artificial intelligence (AI) systems in the diagnosis of esophageal squamous cell carcinoma (ESCC). We conducted this study to evaluate the usefulness of an AI system for real-time diagnosis of ESCC in a clinical setting. METHODS: This study followed a single-center prospective single-arm non-inferiority design. Patients at high risk for ESCC were recruited and real-time diagnosis by the AI system was compared with that of endoscopists for lesions suspected to be ESCC. The primary outcomes were the diagnostic accuracy of the AI system and endoscopists. The secondary outcomes were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and adverse events. RESULTS: A total of 237 lesions were evaluated. The accuracy, sensitivity, and specificity of the AI system were 80.6%, 68.2%, and 83.4%, respectively. The accuracy, sensitivity, and specificity of endoscopists were 85.7%, 61.4%, and 91.2%, respectively. The difference between the accuracy of the AI system and that of the endoscopists was - 5.1%, and the lower limit of the 90% confidence interval was less than the non-inferiority margin. CONCLUSIONS: The non-inferiority of the AI system in comparison with endoscopists in the real-time diagnosis of ESCC in a clinical setting was not proven. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs052200015, 18/05/2020).


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Inteligência Artificial , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/patologia , Esofagoscopia , Estudos Prospectivos
7.
J Gastroenterol Hepatol ; 38(6): 948-954, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36797208

RESUMO

BACKGROUND AND AIM: Cold snare polypectomy is commonly performed to remove small colorectal polyps. Accidental resection of carcinomas during this procedure has been reported. Herein, we aimed to clarify the clinicopathological features and clinical course of colorectal carcinomas resected by cold snare polypectomy. METHODS: This multicenter retrospective cohort study was conducted at 10 Japanese healthcare centers. Of the colorectal lesions resected by cold snare polypectomy between April 2016 and March 2020, lesions pathologically diagnosed as carcinoma were reviewed. Centralized histology (based on the Vienna classification) and endoscopic reviews were performed. The study endpoints were endoscopic features and clinical outcomes of cold snare polypectomy-resected colorectal carcinomas (Vienna category ≥4.2). RESULTS: We reviewed 74 of the 70 693 lesions resected by cold snare polypectomy. After a central pathological review, 68 lesions were diagnosed as carcinomas. The Japan Narrow-band imaging Expert Team (JNET) classification type 2B, lesion size ≥6 mm, and multinodular morphology were the significant endoscopic predictors of carcinoma resected by cold snare polypectomy. No adverse events related to the procedure occurred. Sixty-three lesions were diagnosed as carcinomas within the mucosal layer, and 34 were curative resections. Of the five carcinoma lesions with submucosal invasion, additional surgery revealed remnant cancer tissues in one lesion. No local or metastatic recurrence was observed during follow-up. CONCLUSIONS: Although most of the carcinomas resected by cold snare polypectomy were within the mucosal layer, few lesions invading the submucosa were identified. Careful pre-procedural endoscopic evaluation, especially focusing on the JNET classification and multinodular morphology, is recommended.


Assuntos
Carcinoma , Pólipos do Colo , Neoplasias Colorretais , Humanos , Pólipos do Colo/patologia , Colonoscopia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Colorretais/patologia , Progressão da Doença , Estudos Multicêntricos como Assunto
8.
Surg Endosc ; 37(4): 3018-3028, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36536083

RESUMO

BACKGROUND: Although the combination of conventional endoscopy (CE) and endoscopic ultrasonography (EUS) is useful for predicting the depth of early gastric cancer (EGC), the diagnostic value of EUS for submucosal (SM) invasive cancer has not been fully investigated. METHODS: We conducted a multicenter prospective study from May 2017 to January 2021 to evaluate the validity of a diagnostic strategy combining CE and EUS and to clarify the additional value of EUS for EGC suspected of SM invasion. In each case, the diagnosis was first made using CE, followed by EUS, and finally confirmed using a combination algorithm. RESULTS: A total of 180 patients with EGC were enrolled from 10 institutions, of which 175 were analyzed. The histopathological depths were M, SM1, SM2, and ≥ MP in 72, 16, 64, and 23 lesions, respectively. Treatment included 92 endoscopic submucosal dissection cases and 83 surgical cases. The overall diagnostic accuracy classified by M-SM1 or SM2-MP was 58.3% for CE, 75.7% for EUS, and 78.9% for the combination of CE and EUS; the latter two were significantly higher than that of CE alone (P < 0.001). The CE, EUS, and combination accuracy rates in 108 differentiated-type lesions were 51.9%, 77.4%, and 79.6%, respectively; the latter two were significantly higher than CE alone (P < 0.001). A significant additive effect of EUS was observed in CE-SM2 low-confidence lesions but not in CE-M-SM1 lesions or in CE-SM2 high-confidence lesions. Among the nine CE findings, irregular surface, submucosal tumor-like elevation, and non-extension signs were significant independent markers of pSM2-MP. Poorly delineated EUS lesions were misdiagnosed. CONCLUSIONS: EUS provides additional value for differentiated-type and CE-SM2 low-confidence EGCs in diagnosing invasion depth. CLINICAL REGISTRATION NUMBER: UMIN000025862.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Endossonografia , Estudos Prospectivos , Mucosa Gástrica/cirurgia , Estadiamento de Neoplasias , Invasividade Neoplásica/patologia , Estudos Retrospectivos
9.
Digestion ; 103(5): 347-356, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35709705

RESUMO

INTRODUCTION: Magnifying endoscopy with narrow-band imaging (M-NBI) is useful for determining lateral demarcation of early gastric cancers; however, this is sometimes difficult. Features related to an unclear lateral demarcation remain unknown. We evaluated the clinical and histopathological features of early gastric cancers with unclear lateral demarcation on M-NBI. METHODS: This single-center, retrospective, cohort study analyzed early gastric cancer treated by endoscopic submucosal dissection between January 2013 and August 2015. We evaluated the clinicopathological and immunohistochemical features using anti-p53, anti-Ki-67, anti-MUC5AC, anti-MUC6, anti-MUC2, and anti-CD10 antibody staining. We compared the lateral demarcation between the demarcation clear (DC) and the demarcation unclear (DU) lesions by using M-NBI. RESULTS: A total of 224 differentiated adenocarcinomas (DU group: 18 lesions; DC group: 206 lesions) were analyzed. A history of successful Helicobacter pylori eradication was significantly more frequent in the DU group (p = 0.001). We examined the tissues of 72 lesions (DU group: 18 lesions, DC group: 54 lesions [randomly selected]) immunohistochemically. The nonneoplastic superficial epithelium was observed more frequently in the DU group as compared to in the DC group (p = 0.006). Additionally, compared to the DC group, the DU group showed a significantly higher expression of the gastric phenotype markers (p = 0.023) and had lower p53 scores (p < 0.001) and Ki-67 labeling indexes (p = 0.029). Multivariate analysis revealed the nonneoplastic superficial epithelium and a low p53 score as the significant independent variables associated with an unclear lateral demarcation on M-NBI. CONCLUSIONS: The nonneoplastic superficial epithelium and a low p53 score were associated with difficulties in determining the lateral demarcation in early gastric cancers on M-NBI.


Assuntos
Helicobacter pylori , Neoplasias Gástricas , Estudos de Coortes , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Gastroscopia/métodos , Humanos , Imagem de Banda Estreita/métodos , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
10.
Dig Endosc ; 34(3): 569-578, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34297872

RESUMO

OBJECTIVES: Data on the long-term outcomes of endoscopic submucosal dissection (ESD) performed in elderly patients with early colorectal cancer (CRC) are limited. We analyzed the prognosis of elderly CRC patients, not only from the viewpoint of treatment curability but also from the patients' baseline physical condition assessed by several indexes. METHODS: A retrospective analysis of 729 patients aged ≥75 years who underwent ESD for Tis/T1 CRC in 16 institutions was conducted. The patients were classified into three groups based on curability: curative ESD (Group A, n = 582), non-curative ESD with additional surgery (Group B, n = 60), and non-curative ESD without additional surgery (Group C, n = 87). Overall survival (OS) was compared among the groups, and factors associated with reduced OS were investigated. RESULTS: The median follow-up periods in Groups A, B, and C were 41, 49, and 46 months, respectively (P = 0.62), during which 92 patients died. Two patients (0.3%) in Group A, none (0%) in Group B, and three (3.4%) in Group C died of CRC. Three-year OS rates in Groups A, B, and C were 93.9%, 96.1%, and 90.1%, respectively, without a significant difference (P = 0.07). Multivariate analysis indicated low (<96.3) geriatric nutritional risk index (GNRI) as the sole independent predictor for reduced OS (hazard ratio 3.37; 95% confidence interval 2.18-5.22; P < 0.0001). CONCLUSIONS: Low GNRI, but not the curability attained by ESD, was independently associated with reduced OS in patients with early CRC aged ≥75 years.


Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Idoso , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/efeitos adversos , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Resultado do Tratamento
11.
J Gastroenterol Hepatol ; 36(8): 2239-2246, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33694189

RESUMO

BACKGROUND AND AIM: The morphological diagnosis of microvessels on the surface of superficial esophageal squamous cell carcinomas using magnifying endoscopy with narrow-band imaging is widely used in clinical practice. Nevertheless, inconsistency, even among experts, remains a problem. We constructed a convolutional neural network-based computer-aided diagnosis system to classify the microvessels of superficial esophageal squamous cell carcinomas and evaluated its diagnostic performance. METHODS: In this retrospective study, a cropped magnifying endoscopy with narrow-band images from superficial esophageal squamous cell carcinoma lesions was used as the dataset. All images were assessed by three experts, and classified into three classes, Type B1, B2, and B3, based on the Japan Esophagus Society classification. The dataset was divided into training and validation datasets. A convolutional neural network model (ResNeXt-101) was trained and tuned with the training dataset. To evaluate diagnostic accuracy, the validation dataset was assessed by the computer-aided diagnosis system and eight endoscopists. RESULTS: In total, 1777 and 747 cropped images (total, 393 lesions) were included in the training and validation datasets, respectively. The diagnosis system took 20.3 s to evaluate the 747 images in the validation dataset. The microvessel classification accuracy of the computer-aided diagnosis system was 84.2%, which was higher than the average of the eight endoscopists (77.8%, P < 0.001). The area under the receiver operating characteristic curves for diagnosing Type B1, B2, and B3 vessels were 0.969, 0.948, and 0.973, respectively. CONCLUSIONS: The computer-aided diagnosis system showed remarkable performance in the classification of microvessels on superficial esophageal squamous cell carcinomas.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias Esofágicas/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Esofagoscopia , Humanos , Microvasos/diagnóstico por imagem , Redes Neurais de Computação , Estudos Retrospectivos
12.
Cancer Sci ; 110(8): 2396-2407, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148360

RESUMO

The tumor microenvironment offers favorable conditions for tumor progression, and activated fibroblasts, known as cancer-associated fibroblasts, play a pivotal role. TP53-deficient cancer cells are known to induce strong fibroblast activation. We aimed to elucidate the oncogenic role of exosomes derived from TP53-deficient colon cancer cells in fibroblast proliferation and tumor growth. Cancer cell-derived exosomes (CDEs) were isolated from the conditioned media of cancer cells using a sequential ultracentrifugation method. The effects of exosomes on tumor growth were evaluated using human cell lines (TP53-WT colon cancer, HCT116; TP53-mutant colon cancer, HT29; and fibroblasts, CCD-18Co and WI-38) and an immune-deficient nude mouse xenograft model. HCT116 (HCT116sh p53 ) cells deficient in TP53 accelerated cocultured fibroblast proliferation compared to TP53-WT HCT116 (HCT116sh control ) cells in vitro. Exosomes from HCT116sh p53 cells suppressed TP53 expression of fibroblasts and promoted their proliferation. Xenografts of HCT116sh p53 cells grew significantly faster than those of HCT116sh control cells in the presence of co-injected fibroblasts, but this difference was diminished by CDE inhibition. Microarray analysis identified upregulation of several microRNAs (miR-1249-5p, miR-6737-5p, and miR-6819-5p) in TP53-deficient CDEs, which were functionally proven to suppress TP53 expression in fibroblasts. Exosomes derived from TP53-mutant HT29 cells also suppressed TP53 expression in fibroblasts and accelerated their growth. The proliferative effect of HT29 on cocultured fibroblasts was diminished by inhibition of these miRNAs in fibroblasts. Our results suggest that CDEs play a pivotal role in tumor progression by fibroblast modification. Cancer cell-derived exosomes might, therefore, represent a novel therapeutic target in colon cancer.


Assuntos
Neoplasias do Colo/genética , Exossomos/genética , MicroRNAs/genética , Proteína Supressora de Tumor p53/genética , Animais , Fibroblastos Associados a Câncer/patologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias do Colo/patologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Células HT29 , Xenoenxertos/patologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/genética , Microambiente Tumoral/genética , Regulação para Cima/genética
14.
BMC Cancer ; 19(1): 195, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30832605

RESUMO

BACKGROUND: Chemoradiotherapy effectively treats superficial esophageal cancer and is optimal to preserve organs. However, late toxicity, particularly in cardiac diseases, obstructs clinical outcomes. We revealed the risk factors for cardiac event development post-chemoradiotherapy. METHODS: Data from 80 patients who were diagnosed with submucosal invasive esophageal cancer without metastasis (confirmed using multiple modalities) and who underwent chemoradiotherapy between 2006 and 2014 were analyzed. Patients were 11% (9/80) female, and the median age and follow-up were 66.5 y and 73 mo, respectively. We calculated the individual radiation dose to the heart and analyzed relationships between the cardiac event occurrence rate and each clinical factor. RESULTS: The 5-y overall and recurrence-free survival rates were 74.6 and 62.4%, respectively. Among the total number of deaths, 34.6% was caused by esophageal cancer. During the follow-up, 13 patients developed severe cardiac events (ischemic heart diseases, n = 7; pericardial effusion, n = 3, atrial fibrillation, n = 1; and sudden death, n = 2). The significant risk factor for cardiac events post-chemoradiotherapy was the level of the heart's exposure to radiation, with higher exposure associated with greater occurrence. History of smoking, obesity, comorbidity, and history of cardiac disease were unrelated to cardiac event occurrence post-chemoradiotherapy. CONCLUSIONS: Chemoradiotherapy is a favorable intervention for superficial esophageal cancer. Reducing the radiation dose to the heart likely contributes to preventing cardiac toxicity post-chemoradiotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fibrilação Atrial/epidemiologia , Quimiorradioterapia , Morte Súbita Cardíaca/epidemiologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Isquemia Miocárdica/epidemiologia , Derrame Pericárdico/epidemiologia , Exposição à Radiação/estatística & dados numéricos , Lesões por Radiação/epidemiologia , Idoso , Cardiotoxicidade , Cisplatino/administração & dosagem , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/mortalidade , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Órgãos em Risco , Doses de Radiação , Estudos Retrospectivos , Fatores de Risco
17.
J Gastroenterol Hepatol ; 33(11): 1853-1863, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29767452

RESUMO

BACKGROUND AND AIM: Colorectal laterally spreading tumors (LSTs) are morphologically subdivided into granular (LST-G) and nongranular (LST-NG) categories. We aimed to elucidate the differences in oncogenic characteristics between the two types. METHODS: Laterally spreading tumors resected by endoscopic submucosal dissection and surgery from March 2009 to May 2017 were examined for p53 positivity, Ki-67 labeling index (LI), microvessel density, degree of fibrosis, intensities of inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT), and expression of acid mucins. We compared these factors between adenomas, noninvasive cancers, and invasive cancers, both LST-G and LST-NG. RESULTS: Ninety-three LST-G (53 adenomas [LST-GA] and 40 cancers [LST-GC]) and 55 LST-NG (24 adenomas [LST-NGA] and 31 cancers [LST-NGC]) were evaluated. Although p53 positivity was lower in LST-GA than in LST-NGA (P < 0.001), there was no difference between LST-GC and LST-NGC. Ki-67 LI was higher in LST-NGA than in LST-GA (P < 0.001) and higher in LST-NGC than in LST-GC of noninvasive cancers (P < 0.001). Microvessel density and degree of fibrosis were higher in LST-NGA than in LST-GA (P < 0.001), and intensities of iNOS and NT were also higher in LST-NGA than in LST-GA (P < 0.001). Expression of acid mucins was lower in LST-NGA than in LST-GA (P < 0.001). Although there were significant differences in p53 positivity, Ki-67 LI, microvessel density, degree of fibrosis, intensities of iNOS and NT, and expression of acid mucins between LST-GA and LST-NGA, these factors were only slightly different between LST-GC and LST-NGC of invasive cancers. CONCLUSIONS: Unlike LST-GA, LST-NGA possessed phenotypic features similar to cancer.


Assuntos
Adenoma/genética , Adenoma/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fenótipo , Adenoma/irrigação sanguínea , Adenoma/metabolismo , Carcinogênese/patologia , Estudos de Coortes , Neoplasias Colorretais/irrigação sanguínea , Neoplasias Colorretais/metabolismo , Fibrose , Humanos , Mucosa Intestinal/patologia , Antígeno Ki-67 , Microvasos/patologia , Mucinas/metabolismo , Invasividade Neoplásica , Óxido Nítrico Sintase Tipo II/metabolismo , Estudos Retrospectivos , Proteína Supressora de Tumor p53 , Tirosina/análogos & derivados , Tirosina/metabolismo
18.
Surg Endosc ; 32(12): 5031-5036, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30259162

RESUMO

BACKGROUND: Despite improvements in therapeutic strategy and instrumentation in colorectal endoscopic submucosal dissection (ESD), adverse events sometimes occur. Further advancements in available techniques are required to improve procedural success rates and safety. We developed a novel method for ESD in saline, referred to as "underwater" ESD (UESD). UESD involves using a bipolar needle knife and aims to enable complete resection while minimizing thermal damage to the muscle layer. In this study, we evaluated the safety and efficacy of this new technique. METHODS: This was a retrospective study using data from two referral centers and included 40 lesions diagnosed as colorectal epithelial neoplasia (> 20 mm in diameter or with severe fibrosis) and treated with UESD between December 2015 and March 2017. The main outcome measures were technical success rate, incidence of adverse events, and feasibility of histologic evaluation of the resected specimens. RESULTS: All 40 lesions, including those with submucosal fibrosis, underwent successful en bloc resection using the UESD technique. No procedural adverse events including perforation, delayed bleeding, and electrocoagulation syndrome were observed, and all patients had an uneventful clinical course associated with UESD. In all cases, UESD provided a resected specimen adequate for histological evaluation, without unwarranted burn effect to the tissues. CONCLUSIONS: Our UESD technique was safe and effective for complete resection of colorectal epithelial neoplasia.


Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Complicações Intraoperatórias , Neoplasias Epiteliais e Glandulares , Irrigação Terapêutica/métodos , Idoso , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/instrumentação , Ressecção Endoscópica de Mucosa/métodos , Feminino , Humanos , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/prevenção & controle , Japão , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Solução Salina/uso terapêutico , Instrumentos Cirúrgicos
20.
BMC Cancer ; 17(1): 152, 2017 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-28228152

RESUMO

BACKGROUND: Cardiac metastasis from colorectal cancer is rare. There is little evidence supporting the effectiveness of chemotherapy, and standard therapy for metastatic cardiac tumors has not been established. CASE PRESENTATION: A 76-year-old woman presented with a right ventricle tumor that was detected incidentally on screening cardiac ultrasonography. The initial computed tomography (CT) scan showed the cardiac tumor, which was approximately 40 mm in size, and multiple pulmonary nodules. Serum levels of tumor markers CEA and CA19-9 were elevated aberrantly. The suspected primary tumor, a well-differentiated adenocarcinoma of the transverse colon with wild-type KRAS was found by colonoscopy, and treatment with 5-fluorouracil, leucovorin, and oxaliplatin (modified FOLFOX6) plus panitumumab was initiated. After 4 courses of the therapy, a CT scan showed that the cardiac tumor size had markedly decreased and the pulmonary nodules had diminished. The serum levels of CEA and CA19-9 were also markedly decreased. After 12 courses of chemotherapy during 10 months of treatment, the patient continued to show a partial response, and she remained asymptomatic with continuation of the treatment through 15 courses. CONCLUSION: To the best of our knowledge, this is the first report of the efficacy of combination therapy using cytotoxic and molecular targeted agents against cardiac metastasis from colon cancer.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/patologia , Neoplasias Cardíacas/tratamento farmacológico , Neoplasias Cardíacas/secundário , Idoso , Feminino , Fluoruracila/uso terapêutico , Neoplasias Cardíacas/diagnóstico por imagem , Humanos , Leucovorina/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Panitumumabe , Tomografia Computadorizada por Raios X
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