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BACKGROUND & AIMS: Reported rates of delayed bleeding (DB) after endoscopic resection using direct oral anticoagulants (DOACs) are high and heterogeneous. This large-scale multicenter study analyzed cases of DB after colorectal endoscopic submucosal dissection related to various types of DOACs in Japan (the ABCD-J study) with those associated with warfarin. METHODS: We retrospectively reviewed 1019 lesions in patients treated with DOACs and 459 lesions in patients treated with warfarin among 34,455 endoscopic submucosal dissection cases from 47 Japanese institutions between 2012 and 2021. The DB rate (DBR) with each DOAC was compared with that with warfarin. Risk factors for DB in patients treated with DOACs or warfarin were also investigated. RESULTS: The mean tumor sizes in the DOAC and warfarin groups were 29.6 ± 14.0 and 30.3 ± 16.4 mm, respectively. In the DOAC group, the DBR with dabigatran (18.26%) was significantly higher than that with apixaban (10.08%, P = .029), edoxaban (7.73%, P = .001), and rivaroxaban (7.21%, P < .001). Only rivaroxaban showed a significantly lower DBR than warfarin (11.76%, P = .033). In the multivariate analysis, heparin bridging therapy (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.27-3.73, P = .005), rectal location (2.01, 1.28-3.16, P = .002), and procedure time ≥55 minutes (2.43, 1.49-3.95, P < .001) were significant risk factors for DB in the DOAC group. The DB risk in the DOAC group (OR, (95% CI)) was 2.13 (1.30-3.50) and 4.53 (2.52-8.15) for 1 and 2 significant risk factors, respectively. CONCLUSIONS: Dabigatran was associated with a higher DBR than other DOACs, and only rivaroxaban was associated with a significantly lower DBR than warfarin.
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Fibrilación Atrial , Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Humanos , Warfarina , Rivaroxabán/efectos adversos , Dabigatrán/efectos adversos , Japón , Resección Endoscópica de la Mucosa/efectos adversos , Estudios Retrospectivos , Hemorragia/inducido químicamente , Anticoagulantes , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/complicaciones , Administración Oral , Fibrilación Atrial/complicacionesRESUMEN
BACKGROUND AND AIMS: Evidence for endoscopic resection (ER) in elderly patients with early gastric cancer (EGC) is limited. We assessed its clinical outcomes and explored new indications and curability criteria. METHODS: We analyzed data from a Japanese multicenter, prospective cohort study. Patients aged ≥75 years with EGC treated with ER were included. We classified eCuraC-2 (corresponding to noncurative ER, defined in the Japanese gastric cancer treatment guidelines) into elderly-high (>10% estimated metastatic risk) and elderly-low (EL-L) (≤10% estimated metastatic risk). RESULTS: In total, 3371 patients with 3821 EGCs were included; endoscopic submucosal dissection was the prominent treatment choice. Among them, 3586 lesions met the guidelines' ER indications, and 235 did not. The proportions of en bloc and R0 resections and perforations were 98.9%, 94.4%, and 0.8%, respectively, in EGCs within the indications. In EGCs beyond the indications, they were 99.5%, 85.4%, and 5.9%, respectively, for lesions diagnosed as ≤3 cm and 96.0%, 64.0%, and 18.0%, respectively, for those >3 cm. Curative ER and EL-L were observed in 83.6% and 6.2% of lesions within the indications, respectively, and in 44.2% and 16.8% of lesions <3 cm beyond the indications, respectively. The 5-year cumulative gastric cancer death rates after curative ER and elderly-high were 0.3% (95% confidence interval [CI], 0.2-0.6) and 3.5% (95% CI, 2.0-5.7), respectively. After EL-L, the rate was 0.9% (95% CI, 0.2-3.5) even without subsequent treatment. CONCLUSIONS: The usefulness of endoscopic submucosal dissection for elderly EGC patients was confirmed by their clinical outcomes. Lesions of ≤3 cm and EL-L emerged as new ER indication and curability criteria, respectively. (Clinical trial registration number: UMIN000005871.).
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Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Anciano , Resección Endoscópica de la Mucosa/métodos , Masculino , Femenino , Estudios Prospectivos , Japón , Anciano de 80 o más Años , Gastroscopía/métodos , Estudios de Cohortes , Estadificación de Neoplasias , Guías de Práctica Clínica como Asunto , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Factores de Edad , Carga Tumoral , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Endoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate. METHODS: This is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study. DISCUSSION: This is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022.
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Resección Endoscópica de la Mucosa , Tumores Neuroendocrinos , Neoplasias del Recto , Humanos , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Estudios Prospectivos , Estudios Retrospectivos , Ligadura , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Resección Endoscópica de la Mucosa/métodos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
BACKGROUND AND AIM: Convolutional neural network (CNN) systems that automatically detect abnormalities from small-bowel capsule endoscopy (SBCE) images are still experimental, and no studies have directly compared the clinical usefulness of different systems. We compared endoscopist readings using an existing and a novel CNN system in a real-world SBCE setting. METHODS: Thirty-six complete SBCE videos, including 43 abnormal lesions (18 mucosal breaks, 8 angioectasia, and 17 protruding lesions), were retrospectively prepared. Three reading processes were compared: (A) endoscopist readings without CNN screening, (B) endoscopist readings after an existing CNN screening, and (C) endoscopist readings after a novel CNN screening. RESULTS: The mean number of small-bowel images was 14 747 per patient. Among these images, existing and novel CNN systems automatically captured 24.3% and 9.4% of the images, respectively. In this process, both systems extracted all 43 abnormal lesions. Next, we focused on the clinical usefulness. The detection rates of abnormalities by trainee endoscopists were not significantly different across the three processes: A, 77%; B, 67%; and C, 79%. The mean reading time of the trainees was the shortest during process C (10.1 min per patient), followed by processes B (23.1 min per patient) and A (33.6 min per patient). The mean psychological stress score while reading videos (scale, 1-5) was the lowest in process C (1.8) but was not significantly different between processes B (2.8) and A (3.2). CONCLUSIONS: Our novel CNN system significantly reduced endoscopist reading time and psychological stress while maintaining the detectability of abnormalities. CNN performance directly affects clinical utility and should be carefully assessed.
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Endoscopía Capsular , Aprendizaje Profundo , Humanos , Endoscopía Capsular/métodos , Estudios Retrospectivos , Intestino Delgado/diagnóstico por imagen , Intestino Delgado/patología , Redes Neurales de la ComputaciónRESUMEN
INTRODUCTION: Colorectal cancer is a public health concern associated with high incidence rates. Sarcopenia is a known risk factor for postoperative complications, although an association between increased complications after colorectal endoscopic submucosal dissection (ESD) and sarcopenia remains undocumented. Herein, we aimed to explore the feasibility of colorectal ESD in patients with sarcopenia. METHODS: This retrospective study included 499 patients (69 with and 430 without sarcopenia). We evaluated the short- and long-term outcomes of colorectal ESD. RESULTS: There were no significant differences between the two groups regarding en bloc, R0, or curative resection rates. However, poor bowel preparation was significantly more common in the sarcopenia group. Moreover, patients with sarcopenia exhibited a significant increase in complications (37.7% vs. 10.5%). Multivariate analysis revealed that sarcopenia (odds ratio [OR]: 3.78, 95% confidence interval [Cl]: 1.85-7.73, p < 0.001), anticoagulation therapy (OR: 3.59, 95% Cl: 1.86-6.92, p < 0.001), procedure time (OR: 1.28, 95% Cl: 1.11-1.47, p < 0.001), and resection size (OR: 1.25, 95% Cl: 1.03-1.52, p = 0.02) were significantly correlated with the Common Terminology Criteria for Adverse Events (CTCAE) ≥ grade 2. The correlation between sarcopenia and CTCAE ≥ grade 2 was maintained after matching, resulting in more extended hospital stays in patients with sarcopenia. However, we detected no association between sarcopenia and overall survival and ESD-related death. CONCLUSION: Sarcopenia is a risk factor for complications in colorectal ESD, suggesting that colorectal ESD could be performed for patients with sarcopenia, although much caution should be taken.
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Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Estudios de Factibilidad , Complicaciones Posoperatorias , Sarcopenia , Humanos , Sarcopenia/epidemiología , Sarcopenia/complicaciones , Sarcopenia/etiología , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Masculino , Femenino , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/complicaciones , Anciano , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Resultado del Tratamiento , Persona de Mediana Edad , Anciano de 80 o más Años , Colonoscopía/efectos adversos , Colonoscopía/métodos , Colonoscopía/estadística & datos numéricos , Mucosa Intestinal/cirugía , Mucosa Intestinal/patologíaRESUMEN
INTRODUCTION: We investigated the factors associated with synchronous multiple early gastric cancers and determined their localization. METHODS: We analyzed 8,191 patients who underwent endoscopic submucosal dissection for early gastric cancers at 33 hospitals in Japan from November 2013 to October 2016. Background factors were compared between single-lesion (n = 7,221) and synchronous multi-lesion cases (n = 970) using univariate and multivariate analyses. We extracted cases with two synchronous lesions (n = 832) and evaluated their localization. RESULTS: Significant independent risk factors for synchronous multiple early gastric cancer were older age (≥75 years old) (odds ratio [OR] = 1.257), male sex (OR = 1.385), severe mucosal atrophy (OR = 1.400), tumor localization in the middle (OR = 1.362) or lower region (OR = 1.404), and submucosal invasion (OR = 1.528 [SM1], 1.488 [SM2]). Depressed macroscopic type (OR = 0.679) and pure undifferentiated histology OR = 0.334) were more common in single early gastric cancers. When one lesion was in the upper region, the other was more frequently located in the lesser curvature of the middle region. When one lesion was in the middle region, the other was more frequently located in the middle region or the lesser curvature of the lower region. When one lesion was in the lower region, the other was more frequently located in the lesser curvature of the middle region or the lower region. CONCLUSION: Factors associated with synchronous multiple early gastric cancer included older age, male sex, severe mucosal atrophy, tumor localization in the middle or lower region, and tumor submucosal invasion. Our findings provide useful information regarding specific areas that should be examined carefully when one lesion is detected.
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Resección Endoscópica de la Mucosa , Mucosa Gástrica , Gastroscopía , Neoplasias Primarias Múltiples , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/epidemiología , Masculino , Femenino , Anciano , Japón/epidemiología , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/cirugía , Neoplasias Primarias Múltiples/epidemiología , Persona de Mediana Edad , Resección Endoscópica de la Mucosa/métodos , Mucosa Gástrica/patología , Mucosa Gástrica/cirugía , Factores de Riesgo , Gastroscopía/métodos , Gastroscopía/estadística & datos numéricos , Estudios Retrospectivos , Anciano de 80 o más Años , Factores de Edad , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/estadística & datos numéricos , Invasividad Neoplásica , Atrofia , Factores SexualesRESUMEN
OBJECTIVES: Colonoscopy withdrawal times are associated with the adenoma detection rate (ADR). However, the relationship between ADR and cecal insertion time has been inadequately characterized. We aimed to evaluate endoscopist-related factors involved in the ADR, including the average individual colonoscopy insertion and withdrawal times. METHODS: This observational study used a colonoscopy database with pathology data from routine clinical practice in Japanese institutions. The odds ratios (OR) of endoscopist-related factors related to ADRs were examined using a generalized linear mixed model. RESULTS: Of the 186,293 colonoscopies performed during the study period, 47,705 colonoscopies by 189 endoscopists in four hospitals were analyzed for ADR. The overall ADR was 38.3% (95% confidence interval [CI] 37.8, 38.7). Compared to endoscopists with mean cecal insertion times of <5 min, the OR of ADR for those with mean cecal insertion times of 5-9, 10-14, and ≥15 min were 0.84 (95% CI 0.71, 0.99), 0.68 (95% CI 0.52, 0.90), and 0.45 (95% CI 0.25, 0.78), respectively. Compared to endoscopists with mean withdrawal times of <6 min, the OR of ADR for those with mean withdrawal times of 6-9, 10-14, and ≥15 min were 1.38 (95% CI 1.03, 1.85), 1.48 (95% CI 1.09, 2.02), and 1.68 (95% CI 1.04, 2.61), respectively. There were no significant differences in ADRs by endoscopist specialty, gender, or the total number of examinations performed. CONCLUSION: Individual mean colonoscopy insertion time was associated with ADR and might be considered as a colonoscopy quality indicator as well as withdrawal time.
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Adenoma , Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/diagnóstico , Colonoscopía , Adenoma/diagnóstico , Factores de Tiempo , Bases de Datos Factuales , Detección Precoz del CáncerRESUMEN
OBJECTIVES: This study investigated the incidence of lymph node metastasis and long-term outcomes in patients with T1 colorectal cancer where endoscopic submucosal dissection (ESD) resulted in noncurative treatment. It is focused on those with deep submucosal invasion, a factor considered a weak predictor of lymph node metastasis in the absence of other risk factors. METHODS: This nationwide, multicenter, prospective study conducted a post-hoc analysis of 141 patients with T1 colorectal cancer ≥20 mm where ESD of the lesion resulted in noncurative outcomes, characterized by poor differentiation, deep submucosal invasion (≥1000 µm), lymphovascular invasion, high-grade tumor budding, or positive vertical margins. Clinicopathologic features and patient prognoses focusing on lesion sites and additional surgery requirements were evaluated. Lymph node metastasis incidence in the low-risk T1 group, identified by deep submucosal invasion as the sole high-risk histological feature, was assessed. RESULTS: Lymph node metastasis occurred in 14% of patients undergoing additional surgery post-noncurative endoscopic submucosal dissection for T1 colorectal cancer. In the low-risk T1 group, in the absence of other risk factors, the frequency was 9.7%. The lymph node metastasis rates in patients with T1 colon and rectal cancers did not differ significantly (14% vs. 16%). Distant recurrence was observed in one patient (2.3%) in the ESD only group and in one (1.0%) in the additional surgery group, both of whom had had rectal cancer removed. CONCLUSION: The risk of lymph node metastasis or distant occurrence was not negligible, even in the low-risk T1 group. The findings suggest the need for considering additional surgery, particularly for rectal lesions (Clinical Trial Registration: UMIN000010136).
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BACKGROUND: Endoscopic resection (ER) is a minimally invasive treatment for esophageal cancer that sometimes causes complications. To understand the real-world incidence and risk factors for these complications, a nationwide survey was conducted across Japan. METHODS: This retrospective multicenter study included patients who underwent ER for esophageal cancer from April 2017 to March 2018 (2017 complication analysis) and April 2021 to March 2022 (2021 complication analysis). The study assessed the complication rates and conducted risk factor analyses for endoscopic submucosal dissection (ESD) using data for these patients, with exclusions based on specific criteria to ensure data accuracy. RESULTS: In the 2021 complication analysis, there were two mortalities highly likely attributable (0.03%) to ER and one mortality possibly attributable (0.01%) to ER. Intraoperative perforation, delayed bleeding, and pneumonia occurred in 137 cases (1.8%), 44 cases (0.6%), and 130 cases (1.7%), respectively. In the multivariate analysis for complications after ESD, low ER volume of the facility was an independent risk factor for perforation, while lesion location in the cervical or upper thoracic esophagus was an independent factor for reduced risk of perforation. Age ≥ 80 years was a risk factor for pneumonia, while use of traction techniques was a factor for reduced risk of pneumonia. Lesions located in the middle thoracic esophagus had a lower risk of stricture, and the risk of stricture increased as the circumferential extent of the lesion increased. CONCLUSIONS: This large-scale study provided detailed insights into the complications associated with esophageal ER and identified significant risk factors.
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BACKGROUND & AIMS: We aimed to clarify the long-term outcomes of endoscopic resection (ER) for early gastric cancers (EGCs) based on pathological curability in a multicenter prospective cohort study. METHODS: We analyzed the long-term outcomes of 9054 patients with 10,021 EGCs undergoing ER between July 2010 and June 2012. Primary endpoint was the 5-year overall survival (OS). The hazard ratio for all-cause mortality was calculated using the Cox proportional hazards model. We also compared the 5-year OS with the expected one calculated for the surgically resected patients with EGC. If the lower limit of the 95% confidence interval (CI) of the 5-year OS exceeded the expected 5-year OS minus a margin of 5% (threshold 5-year OS), ER was considered to be effective. Pathological curability was categorized into en bloc resection, negative margins, and negative lymphovascular invasion: differentiated-type, pT1a, ulcer negative, ≤2 cm (Category A1); differentiated-type, pT1a, ulcer negative, >2 cm or ulcer positive, ≤3 cm (Category A2); undifferentiated-type, pT1a, ulcer negative, ≤2 cm (Category A3); differentiated-type, pT1b (SM1), ≤3 cm (Category B); or noncurative resections (Category C). RESULTS: Overall, the 5-year OS was 89.0% (95% CI, 88.3%-89.6%). In a multivariate analysis, no significant differences were observed when the hazard ratio of Categories A2, A3, and B were compared with that of A1. In all the pathological curability categories, the lower limit of the 95% CI for the 5-year OS exceeded the threshold 5-year OS. CONCLUSION: ER can be recommended as a standard treatment for patients with EGCs fulfilling Category A2, A3, and B, as well as A1 (UMIN Clinical Trial Registry, UMIN000005871).
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Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Humanos , Estudios Prospectivos , Resultado del Tratamiento , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Úlcera , Estudios Retrospectivos , Mucosa Gástrica/patologíaRESUMEN
BACKGROUND AND AIMS: Data are lacking regarding post-endoscopic submucosal dissection (ESD) bleeding in patients with early gastric cancer (EGC) who take antiplatelet agents (APAs), particularly in those taking thienopyridine and cilostazol. We aimed to clarify the association between the status of APA medication and post-ESD bleeding risk. METHODS: This study is a secondary analysis using data from a recently conducted nationwide multicenter study in Japan. We retrospectively reviewed patients treated with APAs or on no antithrombotic therapy recruited from 33 institutions who underwent ESD for EGC between November 2013 and October 2016. The primary outcome of this study was the relationship between the rate of post-ESD bleeding and the status of each APA medication. RESULTS: A total of 9736 patients were included in the analysis. Among 665 aspirin users, the continuation group was significantly associated with post-ESD bleeding (odds ratio [OR], 2.79; 95% confidence interval [CI], 1.77-4.37). Among 227 thienopyridine users, the aspirin or cilostazol replacement group was not significantly associated with post-ESD bleeding (OR, 1.85; 95% CI, .72-4.78). Among 158 cilostazol users, there was no significant association with post-ESD bleeding, irrespective of medication status. The rate of post-ESD bleeding was approximately 10% to 20% irrespective of the status of APA administration among dual-antiplatelet therapy users. No patients experienced thromboembolic events in this study. CONCLUSIONS: Replacement of thienopyridine with aspirin or cilostazol may be acceptable for minimizing both the risk of post-ESD bleeding and thromboembolism in patients with EGC. In patients on cilostazol monotherapy undergoing ESD, continuation of therapy may be acceptable.
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Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Tromboembolia , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Neoplasias Gástricas/etiología , Resección Endoscópica de la Mucosa/efectos adversos , Estudios Retrospectivos , Cilostazol/uso terapéutico , Hemorragia Posoperatoria/epidemiología , Hemorragia Posoperatoria/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Factores de Riesgo , Gastroscopía/efectos adversos , Aspirina/uso terapéutico , Tromboembolia/etiología , Tromboembolia/prevención & control , Tienopiridinas/uso terapéutico , Mucosa Gástrica/cirugíaRESUMEN
BACKGROUND: Gastric adenocarcinoma of fundic-gland type (GA-FG) is a gastric malignancy with little relation to Helicobacter pylori. Clinical characteristics of GA-FG have been established, but molecular mechanisms leading to tumorigenesis have not yet been elucidated. METHODS: We subjected three GA-FG tumors-normal mucosa pairs to microarray analysis. Network analysis was performed for the top 30 up-regulated gene transcripts, followed by immunohistochemical staining to confirm the gene expression analysis results. AGS and NUGC4 cells were transfected with the gene-encoding NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) to evaluate transcriptional changes in its target genes. RESULTS: Comprehensive gene expression analysis identified 1410 up-regulated and 1395 down-regulated gene probes with ≥ two-fold difference in expression. Among the top 30 up-regulated genes in GA-FG, we identified transcription factor NKX2-1/TTF-1, a master regulator of lung/thyroid differentiation, together with surfactant protein B (SFTPB), SFTPC, and secretoglobin family 3A member 2(SCGB3A2), which are regulated by NKX2-1/TTF-1. Immunohistochemical analysis of 16 GA-FG specimens demonstrated significantly higher NKX2-1/TTF-1 and SFTPB levels, as compared to that in adjacent normal mucosa (P < 0.05), while SCGB3A2 levels did not differ (P = 0.341). Transduction of NKX2-1/TTF-1 into AGS and NUGC4 cells induced transactivation of SFTPB and SFTPC, indicating that NKX2-1/TTF-1 can function as normally in gastric cells as it can in the lung cells. CONCLUSIONS: Our first transcriptome analysis of GA-FG indicates significant expression of NKX2-1/TTF1 in GA-FG. Immunohistochemistry and cell biology show ectopic expression and normal transactivation ability of NKX2-1/TTF-1, suggesting that it plays an essential role in GA-FG development.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Factor Nuclear Tiroideo 1/genética , Genes Homeobox , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Adenocarcinoma/genética , Adenocarcinoma/patología , Perfilación de la Expresión GénicaRESUMEN
BACKGROUND AND AIM: The incidence of early-onset colorectal neoplasms has been increasing in both Western and Eastern countries. However, the risks and preventive factors for these neoplasms in Eastern countries remain unclear. METHODS: The data of 5580 patients who underwent colonoscopy between 2016 and 2021 were retrospectively evaluated. The primary outcome was advanced colorectal neoplasm (ACRN), defined as advanced adenomas (adenoma ≥10 mm, or with high-grade dysplasia or villous component) or adenocarcinoma. The clinical factors associated with ACRNs were determined for each age category (≤50 and >50 years), and the differences between the two categories were assessed. Odds ratios adjusted for age and sex were calculated. RESULTS: Among 1001 patients (age ≤50 years), ACRN was found in 94 (9.4%). In this younger category, male sex (adjusted odds ratio [aOR]:2.34, 95% confidence interval [CI]:1.51-3.63) and a family history of colorectal cancer (aOR:2.14, 95% CI:1.17-3.89) were significantly associated with higher odds of developing ACRNs. ACRNs were detected in 726 (15.9%) of 4579 patients (age >50 years). In the older age category, smoking (aOR:1.32, 95% CI:1.08-1.63) was significantly associated with a higher risk of ACRNs. Exercise of >3.5 metabolic equivalent of task (METs) (aOR,0.80; 95% CI:0.67-0.96) was significantly associated with a lower risk of ACRNs. CONCLUSION: The development of early-onset ACRNs was primarily associated with congenital factors, whereas that of late-onset ACRNs was associated with acquired ones. Colonoscopy is recommended for young male patients, particularly for those with a family history of colorectal cancer.
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Adenoma , Neoplasias Colorrectales , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estudios Retrospectivos , Colonoscopía/efectos adversos , Adenoma/patología , Neoplasias Colorrectales/patologíaRESUMEN
INTRODUCTION: Colonic diverticular bleeding is the major cause of lower gastrointestinal bleeding. Hypertension is a major risk factor for diverticular rebleeding. Direct evidence of an association between actual 24-h blood pressure (BP) and rebleeding is lacking. Therefore, we analyzed the association between 24-h BP and diverticular rebleeding. METHODS: We performed a prospective observational cohort trial involving hospitalized patients with colonic diverticular bleeding. We performed 24-h BP measurements (ambulatory BP monitoring [ABPM]) in the patients. The primary outcome was diverticular rebleeding. We evaluated the 24-h BP difference and the morning and pre-awaking BP surge between rebleeding and non-rebleeding patients. Morning BP surge was defined as early-morning systolic BP minus the lowest night systolic BP >45 mm Hg (highest quartile of morning BP surge). The pre-awaking BP surge was defined as the difference between morning BP and pre-awaking BP. RESULTS: Of 47 patients, 17 were excluded, leaving 30 who underwent ABPM. Of the 30 patients, 4 (13.33%) had rebleeding. The mean 24-h systolic and diastolic BP were 125.05 and 76.19 mm Hg in rebleeding patients and 129.98 and 81.77 mm Hg in non-rebleeding patients, respectively. Systolic BP at 5:00 (difference -23.53 mm Hg, p = 0.031) and 11:30 (difference -31.48 mm Hg, p = 0.006) was significantly lower in rebleeding patients than in non-rebleeding patients. Diastolic BP at 2:30 (difference -17.75 mm Hg, p = 0.023) and 5:00 (difference -16.12 mm Hg, p = 0.043) was significantly lower in rebleeding patients than in non-rebleeding patients. A morning surge was observed in one rebleeding patient and no non-rebleeding patients. The pre-awaking surge was significantly higher in rebleeding patients (28.44 mm Hg) than in non-rebleeding patients (9.30 mm Hg) (p = 0.015). CONCLUSION: Lower BP in the early-morning and a higher pre-awaking surge were risk factors for diverticular rebleeding. A 24-h ABPM can identify these BP findings and reduce the risk of rebleeding by enabling interventions in patients with diverticular bleeding.
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Enfermedades Diverticulares , Hipertensión , Humanos , Presión Sanguínea/fisiología , Estudios Prospectivos , Ritmo Circadiano , Hipertensión/complicacionesRESUMEN
INTRODUCTION: Submucosal invasion is a core hallmark of early gastric cancer (EGC) with poor prognosis. However, the molecular mechanism of the progression from intramucosal gastric cancer (IMGC) to early submucosal-invasive gastric cancer (SMGC) is not fully understood. The objective of this study was to identify genes and pathways involved in the submucosal invasion in EGC using comprehensive gene expression analysis. METHODS: Gene expression profiling was performed for eight cases of IMGC and eight cases of early SMGC with submucosal invasion ≥500 µm. To validate the findings of gene expression analysis and to examine the gene expression pattern in tissues, immunohistochemical (IHC) staining was performed for 50 cases of IMGC and SMGC each. RESULTS: Gene expression analysis demonstrated that the expression levels of small intestine-specific genes were significantly decreased in SMGC. Among them, defensin alpha 5 (DEFA5) was the most downregulated gene in SMGC, which was further validated in SMGC tissues by IHC staining. Gene set enrichment analysis showed a strong association between SMGC, the JAK-STAT signaling pathway, and the upregulation of STAT3-activating cytokines. The expression of phosphorylated STAT3 was significant in the nucleus of tumor cells in SMGC tissues but not in areas expressing DEFA5. CONCLUSION: The results of this study strongly suggest that the downregulation of DEFA5 and the activation of STAT3 play a significant role in the submucosal invasion of EGC.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Mucosa Gástrica/patología , Gastrectomía/métodos , Perfilación de la Expresión Génica , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Estudios Retrospectivos , Factor de Transcripción STAT3/genéticaRESUMEN
BACKGROUND: Advances in endoscopic imaging technology have led to an increase in detection of superficial pharyngeal squamous carcinoma. Endoscopic submucosal dissection (ESD) has been reported to be effective for the treatment of these lesions, however there is still insufficient evidence on the long-term results of pharyngeal ESD. METHODS: This is a single-center retrospective study of all cases of superficial pharyngeal cancer that underwent ESD as primary treatment between January 2010 and May 2022. A total of 83 lesions in 63 patients were analyzed. RESULTS: The en bloc resection rate was 100%, and R0 resection rate was 59.0%, with an adverse event rate of 6.0%. During a mean observation period of 1134 days, there were 0 cases of disease-specific metastasis or death. However, the 5-year cumulative incidence of metachronous head and neck cancer after resection was 27.1% and the 5-year overall survival and 10-year overall survival after pharyngeal ESD were 87.0% and 69.6%, respectively. Of the 34 cases with non-R0 resection, local recurrence occurred in 8.8%. Location of lesion (p = 0.011), disparity between demarcation of the lesion with NBI and iodine staining (p = 0.026), and non-effective laryngeal elevation (p = 0.080) were risk factors for non-R0 resection. CONCLUSION: Pharyngeal ESD is effective and safe. Further studies are needed to improve and standardize indications and strategies for pharyngeal ESD.
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Resección Endoscópica de la Mucosa , Neoplasias Faríngeas , Humanos , Estudios Retrospectivos , Resección Endoscópica de la Mucosa/métodos , Pronóstico , Endoscopía/efectos adversos , Resultado del Tratamiento , Neoplasias Faríngeas/cirugía , Neoplasias Faríngeas/patología , Factores de Riesgo , Recurrencia Local de Neoplasia/patologíaRESUMEN
BACKGROUND: Postoperative stricture and refractory stricture are severe adverse events which occur after expansive esophageal endoscopic submucosal dissection (ESD). The aim of this study was to assess the efficacy of steroid injection, polyglycolic acid (PGA) shielding, and of additional steroid injection thereafter for the prevention of refractory esophageal stricture. METHODS: This is a retrospective cohort study of 816 consecutive cases of esophageal ESD performed between 2002 and 2021 at the University of Tokyo Hospital. After 2013, all patients with a diagnosis of superficial esophageal carcinoma covering over 1/2 the esophageal circumference underwent preventive treatment immediately after ESD with either "PGA shielding", "steroid injection", or "steroid injection + PGA shielding". Additional steroid injection was performed for high-risk patients after 2019. RESULTS: The risk of refractory stricture was especially high in the cervical esophagus (OR 24.77, p = 0.002) and after total circumferential resection (OR 894.04, p < 0.001). "Steroid injection + PGA shielding" was the only method significantly effective in preventing stricture occurrence (OR 0.36; 95% CI 0.15-0.83, p = 0.012). This method also decreased the risk of refractory stricture (OR 0.38; 95% CI 0.10-1.28, p = 0.096), but additional steroid injection was the only significantly effective method for prevention of refractory stricture (OR 0.42; 95% CI 0.14-0.98, p = 0.029). CONCLUSION: Combining steroid injection and PGA shielding is effective for preventing post-ESD stricture and refractory stricture. Additional steroid injection is a viable option for patients at high-risk for refractory stricture.
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Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Estenosis Esofágica , Humanos , Estenosis Esofágica/etiología , Estenosis Esofágica/prevención & control , Constricción Patológica/etiología , Estudios Retrospectivos , Neoplasias Esofágicas/patología , Esteroides , Ácido Poliglicólico/uso terapéutico , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodosRESUMEN
OBJECTIVES: To examine whether reasonable detection rate of endoscopically diagnosed lesions as adenoma ("endoscopic" adenoma detection rate [ADR]) could be calculated with a database generated from colonoscopy reports and whether it could be used as a surrogate colonoscopy quality indicator of "pathological" ADR. METHODS: A lesion-by-lesion database of colonoscopies performed between 2010 and 2020 at eight Japanese endoscopy centers and corresponding pathology database were integrated. Differences in numbers of detected polyps, "endoscopic" and "pathological" adenomas, and what these differences could be attributed to were examined. Polyp detection rate (PDR), "endoscopic" and "pathological" ADRs, and correlation coefficients between "pathological" ADR and PDR or "endoscopic" ADR by each endoscopist were calculated. RESULTS: Overall, 129,065 colonoscopy reports were analyzed. Among a total of 146,854 polyps, more "endoscopic" adenomas (n = 117,359) were observed than "pathological" adenomas (n = 70,076), primarily because adenomas were not resected on site, rather than because of a misdiagnosis. In all patients analyzed, PDR, "endoscopic" and "pathological" ADRs were 56.4% (95% confidence interval [CI] 56.2-56.7), 48.0% (95% CI 47.7-48.3), and 32.7% (95% CI 32.5-33.0), respectively. "Endoscopic" and "pathological" ADRs from each endoscopist showed a high correlation in hospitals where adenomas were usually resected at the time of examination. CONCLUSIONS: By appropriately describing endoscopically diagnosed lesions as "adenomas" in endoscopy reports, "endoscopic" ADR might be used as a surrogate colonoscopy quality indicator of "pathological" ADR (UMIN000040690).
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Adenoma , Pólipos del Colon , Neoplasias Colorrectales , Pólipos , Humanos , Indicadores de Calidad de la Atención de Salud , Colonoscopía/efectos adversos , Adenoma/diagnóstico , Adenoma/etiología , Errores Diagnósticos , Detección Precoz del Cáncer , Pólipos del Colon/patología , Neoplasias Colorrectales/patologíaRESUMEN
OBJECTIVES: We previously demonstrated that a favorable long-term prognosis indicated that endoscopic submucosal dissection (ESD) could be the standard treatment for large colorectal epithelial neoplasms, but the usefulness of ESD for local residual or recurrent tumors with submucosal fibrosis has not been fully demonstrated. The aim of the present study was to assess the usefulness of ESD for local residual or recurrent colorectal tumors. METHODS: We conducted a nationwide multicenter prospective study to evaluate the outcomes of ESD for colorectal tumors. In this post hoc analysis, a total of 54 local residual or recurrent colorectal tumors in 54 patients were included, and we analyzed the short-term and long-term outcomes of ESD for these lesions. RESULTS: The median size of the lesions was 16.0 (interquartile range [IQR] 11-25) mm. ESD was completed in 53 cases (98.1%) with a median procedure time of 65.0 min, but it was discontinued in one case because of submucosal cancer invasion. En bloc resection was achieved in 52 cases (96.3%), whereas R0 resection was achieved in 45 cases (83.3%). Intraoperative perforation was observed in four cases (7.4%) and delayed perforation in one (1.9%), but all cases could be managed conservatively. Delayed bleeding was not observed. There were no significant differences in short-term outcomes between the rectal and colonic lesions. There was no recurrence of the tumor during the median follow-up period of 60 (IQR 50-64) months. CONCLUSION: An analysis of our multicenter prospective study suggests that ESD is an effective salvage management for local residual or recurrent colorectal lesions.
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BACKGROUND AND AIMS: Accurate risk stratification for gastric cancer is required for optimal endoscopic surveillance in patients with chronic gastritis. We aimed to develop a machine learning (ML) model that incorporates endoscopic and histologic findings for an individualized prediction of gastric cancer incidence. METHODS: We retrospectively evaluated 1099 patients with chronic gastritis who underwent EGD and biopsy sampling of the gastric mucosa. Patients were randomly divided into training and test sets (4:1). We constructed a conventional Cox proportional hazard model and 3 ML models. Baseline characteristics, endoscopic atrophy, and Operative Link on Gastritis-Intestinal Metaplasia Assessment (OLGIM)/Operative Link on Gastritis Assessment (OLGA) stage at initial EGD were comprehensively assessed. Model performance was evaluated using Harrel's c-index. RESULTS: During a mean follow-up of 5.63 years, 94 patients (8.55%) developed gastric cancer. The gradient-boosting decision tree (GBDT) model achieved the best performance (c-index from the test set, .84) and showed high discriminative ability in stratifying the test set into 3 risk categories (P < .001). Age, OLGIM/OLGA stage, endoscopic atrophy, and history of malignant tumors other than gastric cancer were important predictors of gastric cancer incidence in the GBDT model. Furthermore, the proposed GBDT model enabled the generation of a personalized cumulative incidence prediction curve for each patient. CONCLUSIONS: We developed a novel ML model that incorporates endoscopic and histologic findings at initial EGD for personalized risk prediction of gastric cancer. This model may lead to the development of effective and personalized follow-up strategies after initial EGD.