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BACKGROUND AND AIMS: Early gastric cancers (EGCs) after Helicobacter pylori (H. pylori) eradication often appear as reddish depressed lesions (RDLs); the same features are also appeared in benign stomachs after eradication. We compared clinic-pathological and endoscopic features of benign and neoplastic RDLs after H. pylori eradication. METHODS: 228 neoplastic RDLs after H. pylori eradication were studied. All lesions were divided into neoplastic RDLs (differentiated carcinoma or adenoma, n=114) and benign RDLs (n=114) according to the histology. Clinical and pathological characteristics were compared in neoplastic and benign groups. Endoscopic diagnostic yields using the white light (WL) endoscopy, chromoendoscopy (CE) using indigo carmine dye and the magnifying endoscopy with narrow-band imaging (ME-NBI) were also evaluated in relation to the pathological diagnosis. RESULTS: Size of neoplastic RDLs was larger than that of benign RDLs (p<0.01). Sensitivity, specificity and accuracy for predicting pathological types of RDLs was 70.1%, 52.6% and 61.4% for the WL, 65.8%, 63.1% and 65.4% for the CE, while the ME-NBI scored better with the 88.6%, 88.6%, 99.1% and 93.9% of sensitivity, specificity and accuracy. The accuracy of the ME-NBI was 99.9% (113/114) in the benign RDLs and 89.4% (101/114) for the neoplastic RDLs. Undiagnosed neoplastic RDLs using the ME-NBI were associated with more differentiated tumors such as adenoma and well-differentiated adenocarcinoma (tub1) and the presence of an unclear demarcation line. CONCLUSIONS: ME-NBI is useful to diagnose RDLs after H. pylori eradiation, while some of neoplastic lesions are difficult to diagnose using the ME-NBI.
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Adenoma , Gastroscopía , Infecciones por Helicobacter , Helicobacter pylori , Imagen de Banda Estrecha , Valor Predictivo de las Pruebas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/microbiología , Infecciones por Helicobacter/patología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Persona de Mediana Edad , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/aislamiento & purificación , Masculino , Femenino , Anciano , Imagen de Banda Estrecha/métodos , Adenoma/patología , Adenoma/diagnóstico por imagen , Mucosa Gástrica/patología , Mucosa Gástrica/diagnóstico por imagen , Mucosa Gástrica/microbiología , Antibacterianos/uso terapéutico , Adulto , Resultado del Tratamiento , Biopsia , Detección Precoz del Cáncer/métodos , Estudios Retrospectivos , Carmin de ÍndigoRESUMEN
Objective In general, surface ulceration in gastric gastrointestinal stromal tumor (GIST) is considered a malignant feature; however, the mechanism underlying its formation has not been evaluated in detail. In this study, we analyzed the factors involved in ulceration using resected specimens of gastric GIST. Methods A total of 48 samples were retrospectively analyzed. We examined the association of surface ulceration of gastric GIST with the MIB-1 labeling index, mitotic number, tumor size, endoscopic ultrasound (EUS) findings and growth pattern on computed tomography (CT). Results The proportion of men was significantly higher in the ulceration group than in the non-ulceration group (p=0.04146), whereas age was not significantly different between the groups. Tumor was significantly larger in the ulceration group than in the non-ulceration group (p=0.0048). There was no correlation between tumor size and ulcer number. The MIB-1 index was not related to ulceration, nor were EUS findings. The number of mitotic cells tended to be higher in the ulceration group than in the non-ulceration group (p=0.05988). Intraluminal growth pattern was strongly associated with ulceration (p=0.00019). After a multivariate analysis, the growth pattern was the only factor associated with ulceration of gastric GIST. Conclusion Although formation of surface ulceration in gastric GIST was partially associated with the degree of malignancy, the growth pattern was the most important factor associated with ulceration in gastric GIST.
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Tumores del Estroma Gastrointestinal , Neoplasias Gástricas , Masculino , Humanos , Tumores del Estroma Gastrointestinal/complicaciones , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Tumores del Estroma Gastrointestinal/patología , Estudios Retrospectivos , Úlcera/etiología , Úlcera/complicaciones , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/patología , Endosonografía/métodosRESUMEN
BACKGROUND AND AIM: The management of bleeding during endoscopic submucosal dissection (ESD) is critical and related to the procedure time. We collaborated on a new image enhancement algorithm with parameter optimization for clinical use being developed by FUJIFILM Co. and processed white light image data offline to evaluate the effectiveness of this technology. This study aims to evaluate the clinical usefulness of this technology. METHODS: Eighteen video scenes of bleeding points from five gastric ESDs were selected and processed by the new image enhancement algorithm. The time until a bleeding point was found, visibility of a bleeding point, and color abnormality of the submucosal layer were evaluated by ESD experts, ESD trainees, and endoscopy trainees. The color differences between the bleeding point and the surroundings in CIE-L*a*b* color space were calculated in the original and enhanced images. RESULTS: The time until a bleeding point was found in the enhanced videos was significantly shorter than that in the original videos (11.10 s vs 13.85 s) (P = 0.017). On a 5-point (-2 to +2) Likert scale of visibility, the enhanced image was slightly superior to the original (+0.45), and the appearance of the submucosa was comparable between images (+0.14). The color difference among the bleeding areas on the enhanced images was significantly larger than that on the original images (10.93 vs 8.36). CONCLUSION: This novel image enhancement algorithm emphasizes the color difference between a bleeding point and the surrounding area, which would help find bleeding points faster during ESD for the less experienced endoscopists.
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Refuerzo Biomédico , Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Endoscopía Gastrointestinal , Mucosa Gástrica/diagnóstico por imagen , Mucosa Gástrica/cirugía , Hemorragia , Humanos , Aumento de la Imagen , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/cirugía , Tecnología , Resultado del TratamientoRESUMEN
Gastric endoscopic submucosal dissection (ESD) is increasingly performed in patients receiving antithrombotic therapy. Second-look endoscopy (SLE) has been performed empirically in several clinical settings. We investigated whether SLE omission was associated with an increased risk of postESD bleeding in all patients, including those administered antithrombotic agents. Between July 2016 and June 2018, 229 patients were treated with a clinical pathway for gastric ESD that involved SLE on the day after ESD (SLE group). Between September 2018 and May 2020, 215 patients were treated using a clinical pathway that did not include SLE (nonSLE group). We retrospectively compared the incidence of postESD bleeding among the propensity score-matched cohorts and determined the risk factors for postESD bleeding using multivariate analysis. The propensity score-matched cohorts showed no significant differences in the incidence of postESD bleeding between the SLE (3.2%) and nonSLE (5.1%) groups. Multivariate analysis revealed that the presence of lesions in the lower gastric body (adjusted odds ratio [OR] 2.17, 95% confidence interval [CI] 1.06-4.35, P.03) was a significant risk factor for postESD bleeding during admission, whereas resected specimen size ≥ 40 mm (adjusted OR 3.21, 95% CI 1.19-8.19, P.02) and antiplatelet therapy (adjusted OR 4.16, 95% CI 1.47-11.80, P.007) were significant risk factors after discharge. Complete omission of SLE after gastric ESD does not increase postESD bleeding in clinical practice.
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RATIONALE: API2-MALT1 positive gastric mucosa-associated lymphoid tissue (MALT) lymphomas are considered to have favorable prognosis. We report a case of API2-MALT1 positive gastric MALT lymphoma, treated by endoscopic submucosal dissection (ESD). PATIENT CONCERNS: A 51-year-old man underwent esophagogastroduodenoscopy (EGD) for the annual health checkup examination. DIAGNOSES: The EGD showed a reddish depressed lesion with small reddish spots in the lower gastric body. There was no endoscopic atrophy in the entire stomach and Helicobacter pylori (H. pylori) serum test was negative. Infiltration of small lymphocytes was shown in the gastric tissues obtained by the endoscopic biopsy. The fluorescence in situ hybridization using the biopsy samples confirmed the presence of genetic translocation of API2-MALT1, suggesting that the lesion is API2-MALT1 positive MALT lymphoma. INTERVENTIONS: Since endoscopic ultrasound suggested that the lesion was localized within the lamina propria mucosae, we performed ESD to achieve the en bloc resection of the lesion. OUTCOMES: Conclusive diagnosis of gastric MALT lymphoma was made based on the resected specimen. Lateral and vertical margins were negative. No lymphoma cells were detected using endoscopic biopsy after 5 years. LESSONS: Our report suggests that ESD can be considered as alternative treatment for API2-MALT1 positive gastric MALT lymphoma if the lesion was localized within the gastric mucosa.
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Linfoma de Células B de la Zona Marginal/genética , Neoplasias Gástricas/genética , Translocación Genética , Helicobacter pylori/genética , Humanos , Linfoma de Células B de la Zona Marginal/patología , Linfoma de Células B de la Zona Marginal/cirugía , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica , Neoplasias Gástricas/cirugíaRESUMEN
Background and study aims Endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADETs) has not been established. Probe-based confocal laser endomicroscopy (pCLE: Cellvizio) provides real-time endomicroscopic analysis. We developed and validated a new pCLE classification of SNADET based on abnormal findings. Patients and methods pCLE scanning of 20 SNADET lesions including 16 adenomas and four carcinomas was retrospectively evaluated to explore abnormal pCLE findings in relation to histological features. Diagnostic yield of pCLE findings was prospectively evaluated in an additional 20 SNADET lesions including 16 adenomas and four carcinomas. Results In a retrospective study, we identified four abnormal pCLE findings of SNADETs: (1) dark epithelium, (2) columnar cells irregularly extending to the lumen, (3) distorted crypt structure, and (4) fluorescein leakage. Dark epithelium distinguished neoplastic lesions (adenomas and carcinomas) from non-neoplastic duodenal mucosa with a sensitivity of 90â% and a specificity of 100â%. Distorted crypt structure distinguished carcinomas from adenomas and non-neoplastic duodenal mucosa with a sensitivity of 100% and a specificity of 94â%. In the prospective study, the sensitivity and the specificity of the dark epithelium for the diagnosis of neoplastic lesions (adenomasâ+âcarcinomas) was 75% and 100â%. Sensitivity and the specificity of the distorted crypt structure for discrimination of carcinoma from adenoma were 100â% and 94â%, respectively. Conclusions The pCLE findings correlated with the histopathology of the SNADETs. Dark epithelium and distorted crypt structure were informative pCLE findings to predict presence of neoplasia and cancer in the SNADET, respectively. UMIN-CTR UMIN000013857 TRIAL REGISTRATION: Single-Center, prospective observational trial UMIN000013857 at upload.umin.ac.jp.
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Aim: To investigate the associations between LINE1 methylation, an indicator for genome-wide hypomethylation, molecular and clinicopathological characteristics of gastric cancer (GC) patients. Patients & methods:LINE1 methylation statuses were examined in paired cancerous, non-neoplastic mucosa from 217 GC and gastric mucosa from separate group of 224 noncancer patients. CpG island methylator phenotype, TP53 and KRAS mutation, MLH1 methylation status and promoter hypermethylation of GC related and H. pylori-related genes were examined. Results: Lower LINE1 methylation was observed in primary GC compared with non-neoplastic gastric mucosa and associated with CpG island methylator phenotype, TP53 mutation, MLH1 methylation and promoter hypermethylation of GC related and H. pylori-related genes. Conclusion: Lower LINE1 methylation correlates specific molecular subtypes and promoter hypermethylation in GC.
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Metilación de ADN/genética , Elementos de Nucleótido Esparcido Largo/genética , Regiones Promotoras Genéticas/genética , Neoplasias Gástricas/genética , Anciano , Islas de CpG/genética , Femenino , Mucosa Gástrica/microbiología , Regulación Neoplásica de la Expresión Génica/genética , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Humanos , Masculino , Fenotipo , Neoplasias Gástricas/microbiologíaRESUMEN
Predicting Helicobacter pylori (Hp) status by endoscopic finding would be useful in recent clinical condition that the use of proton-pump inhibitors, anti-platelet, and anti-coagulant have become widespread. We aimed to elucidate the diagnostic accuracy of magnifying narrow-band imaging (M-NBI) endoscopy in distinguishing Hp status in patients with or without history of successful Hp eradication and compare this accuracy to the diagnostic accuracy of conventional white light (WL) endoscopy.Two hundred seven endoscopic examinations before and after Hp eradication were performed in prospective 163 patients. Endoscopic images by using the M-NBI and conventional WL were stored electronically and randomly allocated to 2 readers for evaluation. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were assessed by reference to Hp status assessed by conventional clinical test.Sensitivity, specificity, PPV, NPV, and accuracy for predicting Hp status for the conventional WL was 72.2%, 75.5%, 72.2%, 75.5%, and 73.9% for the first reader; 86.6%, 57.3%, 64.1%, 82.9%, and 71.0% for the second reader. On the other hand, sensitivity, specificity, PPV, NPV, and accuracy for predicting Hp status for the M-NBI was 96.9%, 93.6%, 93.1%, 97.1%, and 95.2% for the first reader; 92.8%, 93.6%, 92.8%, 93.6%, and 93.2% for the second reader, respectively. The diagnostic accuracy of M-NBI was significantly higher than that of WL (Pâ<â.0001 for both readers). Inter-observer agreement of M-NBI (kâ=â0.83) was also better than that of WL (kâ=â0.53).M-NBI was capable of distinguishing Hp status before and after eradication therapy.
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Endoscopía del Sistema Digestivo/estadística & datos numéricos , Gastritis/diagnóstico por imagen , Infecciones por Helicobacter/diagnóstico por imagen , Helicobacter pylori , Imagen de Banda Estrecha/estadística & datos numéricos , Magnificación Radiográfica/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Endoscopía del Sistema Digestivo/métodos , Femenino , Gastritis/tratamiento farmacológico , Gastritis/microbiología , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Humanos , Luz , Masculino , Persona de Mediana Edad , Imagen de Banda Estrecha/métodos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Magnificación Radiográfica/métodos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Genome-wide association study identified two functional SNPs associated with gastric cancer especially the diffuse type. The first was a polymorphism (rs2294008) in prostate stem cell antigen (PSCA), and the other was a polymorphism (rs4072037) in mucin 1 (MUC1). DNA methylation is associated with gastric cancer and Helicobacter pylori (H. pylori)-induced gastritis, while hypermethylation of promoter CpG island (CGI) is a common characteristic of enlarged-fold gastritis induced by H. pylori, a risk factor of diffuse-type gastric cancer. We evaluated the association between PSCA and MUC1 polymorphisms with H. pylori--related promoter CGI methylation in the nonneoplastic gastric mucosa. PSCA rs2294008 C/T and MUC1 rs4072037 A/G polymorphisms were genotyped in 410 cancer-free subjects in relation to promoter CGI methylation status of three candidate genes, of which the methylation status is associated with H. pylori infection (IGF2, MYOD1, and SLC16A12). Methylation levels of all three genes were significantly higher in subjects with PSCA rs2294008 T/T compared with the PSCA rs2294008 C/C (all P < 0.05). Such associations were more enhanced in H. pylori-positive subjects (all P < 0.01). The multivariate analysis demonstrated that PSCA C/T [OR, 2.37; 95% CI (confidence interval), 1.06-5.29; P = 0.035] and T/T genotypes (OR, 3.2; 95% CI, 1.41-7.25; P = 0.005) were significantly associated with methylation-high gastric mucosa as independent factors. MUC1 rs4072037 A/G polymorphism was not associated with methylation status of all three genes. PSCA C/T and T/T genotypes are associated with H. pylori-related promoter DNA methylation in the gastric mucosa.Impact: Our observations provided the evidence that PSCA polymorphism influence the susceptibility to gastric cancer through DNA methylation induction.
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Antígenos de Neoplasias/genética , Metilación de ADN/genética , Mucosa Gástrica/metabolismo , Infecciones por Helicobacter/genética , Helicobacter pylori/fisiología , Proteínas de Neoplasias/genética , Regiones Promotoras Genéticas/genética , Adulto , Anciano , Anciano de 80 o más Años , Transformación Celular Neoplásica/genética , Estudios de Cohortes , Islas de CpG , Femenino , Proteínas Ligadas a GPI/genética , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis/genética , Gastritis/microbiología , Gastritis/patología , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Infecciones por Helicobacter/patología , Humanos , Masculino , Persona de Mediana Edad , Mucina-1/genética , Polimorfismo de Nucleótido Simple , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologíaRESUMEN
Both genetic and epigenetic abnormalities play important roles in gastric cancer (GC) development. We investigated whether the molecular subtypes of gastric cancer by combining genetic and epigenetic anomalies define its clinicopathological features and prognosis. The CpG island methylator phenotype (CIMP), MLH1 methylation, TP53, and KRAS mutation statuses were characterized in 214 GCs in relation to their clinicopathological features and prognosis. The molecular subtypes based on CIMP and TP53 hot spot mutation status (R175, G245, R248, R273, and R282) best predicted prognosis of GC. These subtypes contained 120 CIMP-positive (CIMP+) TP53 hot spot mutation-negative (TP53 hot spot-) cases, 81 CIMP-negative (CIMP-) TP53 hot spot- cases, 8 CIMP+TP53 hot spot mutation-positive (TP53 hot spot+) cases, and 5 CIMP- TP53 hot spot+ cases. The CIMP-TP53 hot spot+ group presented the worst overall survival (OS) and progression-free survival (PFS), followed by the CIMP+TP53 hot spot+, CIMP-TP53 hot spot- and CIMP+TP53 hot spot- groups (both P < 0.0001). These subtypes also correlated well with several aggressive clinicopathological features in that order. The molecular subtypes were independent factors for predicting overall survival (hazard ratio = 1.66, 95% CI = 1.07-2.57, P = 0.006). The molecular subtypes combining the CIMP and TP53 hot spot mutation status provide distinct clinicopathological features and prognostic impacts in GC.
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Epigénesis Genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Islas de CpG/genética , Metilación de ADN/genética , Femenino , Herpesvirus Humano 4/fisiología , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación/genética , Recurrencia Local de Neoplasia/patología , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias Gástricas/clasificación , Proteína p53 Supresora de Tumor/genéticaRESUMEN
DNA methylation of leukocyte DNA has been proposed to be a biomarker for cancer that can be used to target patients for appropriate clinical implementation. We investigated IGF2 DMR and LINE1 methylation in the leukocyte DNA and their association with clinicopathological features and prognosis of gastric cancer (GC) patients. Methylation status of IGF2 DMR and LINE1 in the leukocyte DNA was quantified using bisulfite pyrosequencing in 207 GC patients. Methylation of both IGF2 DMR and the LINE1 was significantly higher in the undifferentiated histologic type compared to the differentiated histologic type (both P = 0.0002). Hypermethylation of both the IGF2 DMR and the LINE1 was associated with more aggressive features of GC such as advanced stage (IGF2 DMR, P = 0.0002; LINE1, P < 0.0001), lymphatic invasion positive (IGF2 DMR, P = 0.004; LINE1, P = 0.002), venous invasion positive (IGF2 DMR, LINE1, both P = 0.03), lymph node metastasis positive (IGF2 DMR, P = 0.01; LINE1, P = 0.001), peritoneal dissemination positive (IGF2 DMR, P = 0.04; LINE1, P = 0.002), liver metastasis positive (IGF2 DMR, P = 0.008; LINE1, P = 0.001), and other distant metastasis positive (IGF2 DMR, P = 0.04). Our data suggest that high LINE1 and IGF2 DMR methylation status would be a phenomenon that is observed with the progression of GC, supporting their potential utility as a biomarker in GC patients.
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Metilación de ADN , Factor II del Crecimiento Similar a la Insulina/genética , Leucocitos/química , Elementos de Nucleótido Esparcido Largo , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Análisis de Secuencia de ADN , Neoplasias Gástricas/sangre , Neoplasias Gástricas/genéticaRESUMEN
BACKGROUND AND AIM: Early-stage gastric cancer (EGC) found after Helicobacter pylori (Hp) eradication often displays non-tumorous regenerative epithelium and/or maturated tumorous epithelium overlying the cancerous tissue, which may confuse endoscopic and histological diagnosis. Probe-based confocal laser endomicroscopy (pCLE) enables in vivo real-time optical biopsy. We compared the diagnostic yields for these EGC cases using conventional white light endoscopy (WL), magnifying endoscopy with narrow-band imaging (ME-NBI), pCLE, and endoscopic biopsy; we also compared the accuracy of the horizontal extent diagnosis between ME-NBI and pCLE. METHODS: This study enrolled 30 patients with 36 EGC lesions after successful Hp eradication. Diagnostic yields of WL, ME-NBI, pCLE, and endoscopic biopsy were prospectively compared. Four points of cancerous margins (oral, anal, anterior, and posterior sites) were also prospectively evaluated with M-NBI and pCLE to determine the horizontal extent of the EGC. RESULTS: Diagnostic yield was significantly higher with pCLE than with WL and endoscopic biopsy (97 vs 72%, 97 vs 72%, P = 0.0159, 0.0077, respectively), whereas it did not differ from ME-NBI (88.9%, P = 0.371). Height of non-tumorous regenerative epithelium or maturated atypical glands was 104.7 ± 34.2 µm in the pCLE-positive cases, whereas it was 188.3 ± 27.1 µm in a pCLE-negative case (P = 0.0004). Diagnostic accuracy of the horizontal margin of EGC was significantly higher with pCLE than with ME-NBI (92 vs 70%, P = 0.0159). CONCLUSION: pCLE may be helpful for the diagnosis of ambiguous ECG found after Hp eradication because it enables real-time scanning throughout the lesion and detection of subsurface microstructure.
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Resección Endoscópica de la Mucosa/métodos , Gastroscopía/métodos , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/aislamiento & purificación , Lesiones Precancerosas/patología , Neoplasias Gástricas/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Estudios de Cohortes , Detección Precoz del Cáncer/métodos , Femenino , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/patología , Hospitales Universitarios , Humanos , Inmunohistoquímica , Masculino , Microscopía Confocal/métodos , Persona de Mediana Edad , Imagen de Banda Estrecha , Lesiones Precancerosas/diagnóstico por imagen , Lesiones Precancerosas/cirugía , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/etiología , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugíaRESUMEN
BACKGROUND AND AIM: Fusobacterium enrichment has been associated with colorectal cancer development. Ulcerative colitis (UC) associated tumorigenesis is characterized as high degree of methylation accumulation through continuous colonic inflammation. The aim of this study was to investigate a potential link between Fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in UC. METHODS: In the candidate analysis, inflamed colonic mucosa from 86 UC patients were characterized the methylation status of colorectal a panel of cancer related 24 genes. In the genome-wide analysis, an Infinium HumanMethylation450 BeadChip array was utilized to characterize the methylation status of >450,000 CpG sites for fourteen UC patients. Results were correlated with Fusobacterium status. RESULTS: UC with Fusobacterium enrichment (FB-high) was characterized as high degree of type C (for cancer-specific) methylation compared to other (FB-low/neg) samples (P<0.01). Genes hypermethylated in FB-high samples included well-known type C genes in colorectal cancer, such as MINT2 and 31, P16 and NEUROG1. Multivariate analysis demonstrated that the FB high status held an increased likelihood for methylation high as an independent factor (odds ratio: 16.18, 95% confidence interval: 1.94-135.2, P=0.01). Genome-wide methylation analysis demonstrated a unique methylome signature of FB-high cases irrespective of promoter, outside promoter, CpG and non-CpG sites. Group of promoter CpG sites that were exclusively hypermethylated in FB-high cases significantly codified the genes related to the catalytic activity (P=0.039). CONCLUSION: Our findings suggest that Fusobacterium accelerates DNA methylation in specific groups of genes in the inflammatory colonic mucosa in UC.
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BACKGROUND/AIM: In the colorectum, lymphoid follicles hyperplasia (LH) is sometimes observed as small, round, yellowish-white nodules. The novel image-enhanced endoscopy system named blue laser imaging (BLI) provides enhanced the contrast of surface vessels using lasers for light illumination. We investigated the endoscopic features of LH observed by using BLI endoscopy and its association with chronic bowel symptoms. PATIENTS/METHODS: 300 participants undergoing colonoscopy for various indications were enrolled. Entire colorectum was observed by using BLI-bright mode with non-magnification view. LH was defined as well demarcated white nodules. Elevated LH with erythema was distinguished as LH severe. RESULTS: LHs were observed more clearly by using BLI-bright mode compared to conventional white light colonoscopy and were also histologically confirmed as intense infiltration of lymphocytes or plasmacytes. LH was observed in 134 subjects (44.6%) and 67 (22.3%) were LH severe. LH was associated younger age (Odds ratio (OR) = 1.05, 95%Confidence Interval (95%CI) = 1.03-1.07, P<0.0001) and chronic bowel symptoms including constipation, hard stools, diarrhea and loose stools (all LH: OR = 4.03, 95%CI = 2.36-6.89, P<0.0001, LH severe: OR = 5.31, 95%CI = 2.64-10.71, P<0.0001). LH severe was closely associated with both constipation associated symptoms (OR = 3.94, 95%CI = 1.79-8.66, P = 0.0007) and diarrhea associated symptoms (OR = 5.22, 95%CI = 2.09-13.05, P = 0.0004). In particular, LH severe in the ascending colon was strongly associated with bowel symptoms (P<0.0001). CONCLUSION: LH, visualized by using BLI endoscopy was associated with bowel symptom, raising the possibility of pathogenic role of this endoscopic finding in the functional lower gastrointestinal disorders.
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Colon/diagnóstico por imagen , Colonoscopía , Enfermedades Intestinales/diagnóstico por imagen , Rayos Láser , Enfermedades Linfáticas/diagnóstico por imagen , Recto/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Enfermedad Crónica , Colon/patología , Estreñimiento , Diarrea , Femenino , Humanos , Hiperplasia , Linfocitos/citología , Masculino , Persona de Mediana Edad , Imagen de Banda Estrecha , Oportunidad Relativa , Células Plasmáticas/citología , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Gastric cancer develops after successful H. pylori eradication in patients with severe atrophic gastritis. We classified atrophic and non-atrophic mucosa of gastric body using magnifying NBI endoscopy in patients after successful H. pylori eradication. MATERIALS AND METHODS: One hundred and twenty-five patients after successful H. pylori eradication (median period after eradication: 36 months) were enrolled. Magnifying NBI patterns in the uninvolved gastric body were divided into the following: restored-small, round pits, accompanied with honeycomb-like subepithelial capillary networks; atrophic-well-demarcated oval or tubulovillous pits with clearly visible coiled or wavy vessels. The subjects were also classified into the three types: Grade 0-restored pattern is shown in all or almost the entire area of gastric body; Grade 1-mixture of restored and atrophic pattern, there is a considerable portion of the atrophic area in the lesser curvature; Grade 2-atrophic pattern is shown in all or almost the entire area of the gastric body. RESULTS: Sensitivity and specificity for atrophic type for detection of histological intestinal metaplasia were 95.9 and 98.3%, respectively. No association was observed between the prevalence of Grades 0, 1 and 2 and duration after eradication, while grades 1 and 2 were significantly frequent in gastric cancer patients diagnosed both before (27/35: 77%) and after (23/31: 74%) eradication, compared to the cancer-free subjects (15/59: 25%) (P < 0.001). The grades 1 and 2 were also common in patients who underwent H. pylori eradication for gastric ulcer. CONCLUSIONS: Magnifying the NBI pattern well correlates with pathological status of gastric mucosa after H. pylori eradication and may predict gastric cancer occurrence.
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Erradicación de la Enfermedad , Mucosa Gástrica/diagnóstico por imagen , Infecciones por Helicobacter/diagnóstico por imagen , Helicobacter pylori , Imagen de Banda Estrecha/métodos , Neoplasias Gástricas/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Erradicación de la Enfermedad/tendencias , Femenino , Mucosa Gástrica/microbiología , Infecciones por Helicobacter/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Imagen de Banda Estrecha/tendencias , Estudios Prospectivos , Factores de Riesgo , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/microbiologíaRESUMEN
Neoadjuvant chemotherapy may improve outcomes for patients with locally advanced gastric cancer (GC). To explore useful predictive factors for the response of advanced GC to neoadjuvant chemotherapy, tumor responses were assessed using computed tomography (CT) with histological based criteria. A total of 78 patients with advanced GC undergoing neoadjuvant chemotherapy were included. CT-based response assessment was performed following 2 courses of treatment. Histological evaluation of resected specimens was also performed according to the Japanese classification of gastric carcinoma. Grade 1b, 2 and 3 (viable tumor cells remaining in <2/3 of the tumorous area) were defined as histological responders. The results were associated with overall survival (OS) and progression-free survival (PFS). The majority of the cases underwent tegafur/gimeracil/oteracil based preoperative chemotherapy as the first line of treatment (n=76, 96%). A total of 25 (32%) and 29 (37%) cases were considered to be CT and histological responders, respectively. CT-based evaluation was not associated with OS or PFS, while histological evaluation was significantly associated with OS and PFS. Histological based evaluation was not associated with CT and GI X-ray or endoscopy-based evaluation of primary lesions. Multivariate survival analysis using Cox's regression model demonstrated that histological non-response was an independent prognostic factor for predicting worse OS. Histological-based evaluation of primary lesions was independently associated with prognosis in patients with GC who underwent neoadjuvant chemotherapy.
RESUMEN
BACKGROUND/AIM: Telomere shortening in leukocytes has been thought to be associated with reduced immune response capacity and increased chromosome instability. Several studies indicate that telomere length in the peripheral blood leukocyte DNA can predict clinical outcome of several cancers. We evaluated the potential association between telomere shortening in the leukocyte DNA and clinicopathological features and prognosis of gastric cancer (GC) in Japanese patients. MATERIALS AND METHODS: Telomere length in leukocyte DNA was measured using quantitative real-time polymerase chain reaction (PCR) in 207 GC patients. The association between telomere length and clinicopathological features and prognosis was evaluated. RESULTS: These short-telomere group was significantly associated with advanced stage (p=0.015), worse overall survival (OS) and progression-free survival (PFS) (p=0.046 and 0.026, respectively). The same group was also weakly associated with overall and peritoneal recurrences (p=0.052 and 0.059, respectively). CONCLUSION: Telomere shortening in leukocyte DNA is associated with advanced stage and poor prognosis of GC, which may reflect their reduced immune response capacity or increased chromosome instability.
Asunto(s)
ADN de Neoplasias/genética , Leucocitos/patología , Neoplasias Hepáticas/secundario , Neoplasias Peritoneales/secundario , Neoplasias Gástricas/patología , Telómero/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Femenino , Humanos , Neoplasias Hepáticas/genética , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias Peritoneales/genética , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Neoplasias Gástricas/genética , Tasa de Supervivencia , Acortamiento del TelómeroRESUMEN
BACKGROUND: Chemotherapy may improve outcomes in gastric cancer (GC), especially for the patients with advanced stage. To explore useful predictive factor for GC performing chemotherapy, we compared the tumor responses assessed using computed tomography (CT) with endoscopy based criteria. METHODS: 192 GC patients performing chemotherapy were retrospectively studied. CT based response assessment was performed after 2 courses of treatment. Endoscopic evaluation according to The Japanese classification of gastric carcinoma was also performed at same period. Data were correlated with overall survival (OS) and progression-free survival (PFS). RESULTS: Majority of the cases (n = 178, 93%) received S-1 based chemotherapy as the first line treatment. 55 (29%) and 91 (47%) cases were considered to be CT and endoscopic responders. Endoscopic responder was more clearly associated with better OS and PFS compared to CT based responder by the log-rank test (P<0.0001 vs. 0.01 and P<0.0001 vs. 0.008, respectively). The association was more striking among patients performing neoadjuvant chemotherapy (P<0.0001 vs. 0.15 and P<0.0001 vs. 0.1, respectively). Multivariate survival analysis using Cox's regression model revealed that endoscopic non-responder was the independent predictive factor, being more strongly associated with worse OS when compared to CT non-responder (hazard ratio: 4.60 vs. 1.77, 95% confidence interval: 2.83-7.49 vs.1.08-2.89, P<0.0001 vs. 0.02). More advanced T, N stage and cases who had peritoneal dissemination were significantly associated with endoscopic non-responder (all P values <0.01). CONCLUSION: Endoscopy based evaluation of primary lesions are clearly associated with prognosis in patients with GC who perform chemotherapy.
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Gastroscopía/métodos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/mortalidad , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
Chromoendoscopy, narrow-band imaging (NBI), and confocal laser endomicroscopy (CLE) have been introduced in ulcerative colitis (UC)-associated neoplasia surveillance. We aimed to determine the ability of CLE to differentiate among UC-associated neoplasia (differentiated type or undifferentiated type), sporadic adenoma, and circumscribed regenerative lesions. Of 665 patients with UC, we carried out probe-based CLE (pCLE) on 12 patients with suspected UC-associated neoplasia in addition to magnifying chromoendoscopy with crystal violet and NBI. We compared pCLE findings with pathological diagnoses. pCLE could differentiate UC-associated differentiated cancer from other pathologies such as solitary adenoma and non-neoplastic circumscribed regenerative lesions on the basis of back-to-back orientation of crypts (P = 0.048), and UC-associated undifferentiated cancer from other pathologies on the basis of dark trabecular architecture (P = 0.015). Sensitivity, specificity, and accuracy of combination of back-to-back orientation of crypts and dark trabecular architecture for carcinoma or dysplasia were 100%, 83%, and 92%, respectively. In vivo microscopic observation with pCLE was helpful to evaluate the suspected UC-associated neoplasia.
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Adenoma/diagnóstico , Colitis Ulcerosa/diagnóstico por imagen , Colitis Ulcerosa/patología , Neoplasias del Colon/diagnóstico , Microscopía Confocal , Adulto , Anciano , Estudios de Cohortes , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
A new anhydroribotrisaccharide monomer, A2B3LR (1), was synthesized and ROP was carried out to elucidate the polymerizability and to obtain oligosaccharide-branched polysaccharides with defined structures. The new trisaccharide monomer was found to be polymerized readily with BF(3) . OEt(2) as a catalyst at -40 degrees C to give a lactose-branched polymer. Copolymerization with ADBR gave the corresponding copolymers in good yields. After removal of protective benzyl groups, D-lactose-branched ribofuranans with free hydroxyl groups were obtained in good yields. The structure of polymers was analyzed by (1)H, 13C, and two-dimensional NMR measurements, suggesting that D-lactose-branched ribofuranans had (1 --> 5)-alpha stereoregularity.