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1.
Gastric Cancer ; 25(3): 481-489, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35067826

RESUMO

BACKGROUND: The numbers of Helicobacter pylori (HP)-infected individuals and deaths due to gastric cancer are decreasing in Japan. We aimed to determine whether the serological test for chronic gastritis (the ABC method) is still useful for gastric cancer risk stratification in the 2010s and to analyze risk factors for developing gastric cancer in Japan. METHODS: In this prospective study, we monitored 20773 individuals for the incidence of gastric cancer from 2010 to 2019. The relationships between blood sampling results, physical examination, and lifestyle in 2010 and the cumulative incidence of gastric cancer were analyzed. RESULTS: A total of 19343 participants who met the study criteria were analyzed. Overall, 0.08% of participants in group A (9/11717), 0.63% in group B (28/4452), 2.05% in group C (43/2098), 1.52% in group D (1/66), and 0.30% in group E (3/1010) developed gastric cancer. Cox hazard analysis showed that age ≥ 50 years; groups B, C, and D according to the ABC method; and current smoking habits were independent risk factors for gastric cancer. The hazard ratios (HRs) of the incidence of gastric cancer were 6.7 in group B and 21.7 in groups C and D, while the HRs of group E was 2.8, which was not significantly different from that of group A. The incidence of gastric cancer was not statistically significantly different between those with and without successful HP eradication in groups B, C, and D during follow-up. CONCLUSIONS: The ABC method was still useful for gastric cancer risk stratification in the 2010s.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Pepsinogênio A , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia
2.
Cancer Sci ; 112(7): 2855-2869, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33970549

RESUMO

Ten-eleven translocation 1 (TET1) is an essential methylcytosine dioxygenase of the DNA demethylation pathway. Despite its dysregulation being known to occur in human cancer, the role of TET1 remains poorly understood. In this study, we report that TET1 promotes cell growth in human liver cancer. The transcriptome analysis of 68 clinical liver samples revealed a subgroup of TET1-upregulated hepatocellular carcinoma (HCC), demonstrating hepatoblast-like gene expression signatures. We performed comprehensive cytosine methylation and hydroxymethylation (5-hmC) profiling and found that 5-hmC was aberrantly deposited preferentially in active enhancers. TET1 knockdown in hepatoma cell lines decreased hmC deposition with cell growth suppression. HMGA2 was highly expressed in a TET1high subgroup of HCC, associated with the hyperhydroxymethylation of its intronic region, marked as histone H3K4-monomethylated, where the H3K27-acetylated active enhancer chromatin state induced interactions with its promoter. Collectively, our findings point to a novel type of epigenetic dysregulation, methylcytosine dioxygenase TET1, which promotes cell proliferation via the ectopic enhancer of its oncogenic targets, HMGA2, in hepatoblast-like HCC.


Assuntos
Proteína HMGA2/genética , Neoplasias Hepáticas/genética , Oxigenases de Função Mista/genética , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Cromatina/genética , Citosina/metabolismo , Metilação de DNA , Dioxigenases/metabolismo , Epigênese Genética , Expressão Gênica , Técnicas de Silenciamento de Genes , Proteína HMGA2/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Oxigenases de Função Mista/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Regulação para Cima
3.
Dig Dis Sci ; 63(10): 2617-2625, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29956011

RESUMO

BACKGROUND: Sporadic nonampullary duodenal epithelial tumors (NADETs) are uncommon, and thus their clinicopathological features have not been fully assessed. AIMS: In this study, we have analyzed a series of early sporadic NADETs, focusing on various immunohistological features. METHODS: We conducted a multicenter retrospective analysis of 68 patients with endoscopically resected sporadic NADETs. Associations between immunohistological features and clinicopathological features were statistically analyzed. RESULTS: The 68 patients consisted of 46 men (68%) and 22 women (32%) with a mean age of 60.7 ± 12.2 years (range 37-85 years). The 68 tumors were composed of 39 adenomas (57%) and 29 early-stage adenocarcinomas (43%). Duodenal adenocarcinomas were larger in size than adenomas and had papillary architecture in their pathological diagnosis with statistical significance. Duodenal adenocarcinomas also demonstrated a significantly higher expression of gastric markers (MUC5AC and MUC6) and a higher MIB-1 index. Duodenal adenomas were contrastively apt to express intestinal markers (MUC2, CDX1 and CDX2). Of the 68 cases analyzed, there were only 3 tumors positive for p53 staining, all of which were adenocarcinoma. When 7 submucosal invasive cancers and 21 intramucosal cancers were compared, submucosal invasion was positively associated with expression of MUC5AC. Also, submucosal invasion showed strong association with double-positivity of MUC5AC and MUC6. CONCLUSIONS: Our results indicate that immunohistochemical evaluation is useful for predicting malignant potential of NADETs, especially focusing on the expression of gastrointestinal markers.


Assuntos
Adenocarcinoma , Adenoma , Neoplasias Duodenais , Endoscopia do Sistema Digestório/métodos , Proteínas de Homeodomínio/análise , Mucina-5AC/análise , Mucina-2/análise , Mucina-6/análise , Adenocarcinoma/epidemiologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenoma/metabolismo , Adenoma/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias Duodenais/epidemiologia , Neoplasias Duodenais/metabolismo , Neoplasias Duodenais/patologia , Neoplasias Duodenais/cirurgia , Duodeno/patologia , Duodeno/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Estatística como Assunto
4.
Gastric Cancer ; 20(1): 136-145, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26792292

RESUMO

BACKGROUND: Gastric cancer (GC) is highly influenced by aberrant methylation, and accumulation of aberrant methylation in gastric mucosae produces an epigenetic field for cancerization. Nevertheless, the individual driver genes involved in such field cancerization are still unclear. Here, we aimed to demonstrate that FAT4, a novel tumor suppressor identified by exome sequencing of GC, is methylation-silenced and that such methylation is involved in epigenetic field cancerization for GC. METHODS: A transcription start site was determined by the 5' rapid amplification of complementary DNA ends method. DNA methylation was analyzed by bisulfite sequencing with use of a next-generation sequencer or quantitative methylation-specific PCR. Gene expression was analyzed by quantitative reverse transcription PCR. RESULTS: A single transcription start site was identified for FAT4 in gastric epithelial cells, and a CpG island was located in the FAT4 promoter region. FAT4 was highly methylated in two of 13 GC cell lines and was not expressed in them. Removal of FAT4 methylation by a DNA demethylating agent (5-aza-2'-deoxycytidine) restored its expression in the two cell lines. In primary GC samples, FAT4 was methylated in 12 of 82 GCs (14.6 %). FAT4 methylation was associated with the presence of the CpG island methylator phenotype but not with prognosis, tumor invasion, lymph node metastasis, or histological types. In noncancerous gastric mucosae, high FAT4 methylation levels were associated with the presence of GC and Helicobacter pylori infection. CONCLUSIONS: FAT4 was methylation-silenced in GCs. Its methylation in gastric mucosae was associated with H. pylori infection and likely contributed to epigenetic field cancerization.


Assuntos
Biomarcadores Tumorais/genética , Caderinas/genética , Epigênese Genética/genética , Neoplasias Gastrointestinais/genética , Tumores do Estroma Gastrointestinal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/genética , Proteínas Supressoras de Tumor/genética , Idoso , Ilhas de CpG , Metilação de DNA , Mucosa Gástrica/metabolismo , Mucosa Gástrica/virologia , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Neoplasias Gastrointestinais/virologia , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/virologia , Inativação Gênica , Infecções por Helicobacter/virologia , Helicobacter pylori/isolamento & purificação , Humanos , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Regiões Promotoras Genéticas , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/virologia , Taxa de Sobrevida , Células Tumorais Cultivadas
5.
Int J Cancer ; 139(5): 1150-6, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27083518

RESUMO

We have previously reported that serum pepsinogen (PG) can quantify the level of gastric mucosal atrophy, and that H. pylori eradication reduces cancer development in subjects with mild atrophy identified by serum PG levels. The aim of this study was to elucidate the predictive ability of serum PG levels for the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) of primary cancer in association with H. pylori eradication. A retrospective chart review was performed, and 330 patients who underwent ER for initial early gastric cancer were enrolled. Presence or absence of H. pylori, serum PG levels, and endoscopic atrophy at ER were evaluated. H. pylori eradication was performed at the patient's request after ER. The incidence of MGC in these patients was analyzed. Of 330 patients, 47 developed MGC. Endoscopic extensive atrophy was observed more frequently in patients with MGC (p = 0.001). Although PG I or PG II alone did not significantly differ according to development of MGC, the proportion of PG I/II ≤ 3.0, which is one of the criteria of PG test-positive, was significantly higher in patients with MGC (83 vs. 69%, p = 0.04). H. pylori eradication after ER did not affect MGC development (p = 0.2). On multivariate analysis, serum PG I/II ratio ≤ 3.3 was significantly associated with the development of MGC (hazard ratio: 3.66, 95% confidence interval: 1.47-12.25, p = 0.004). The risk of MGC after ER could be quantitatively predicted by the PG I/II ratio regardless of H. pylori status.


Assuntos
Biomarcadores Tumorais , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/etiologia , Pepsinogênio A/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Idoso , Atrofia , Feminino , Mucosa Gástrica/patologia , Gastroscópios , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/epidemiologia , Risco , Neoplasias Gástricas/cirurgia
6.
Gastric Cancer ; 19(3): 911-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26420267

RESUMO

BACKGROUND: A previous multicenter prospective randomized study from Japan showed that Helicobacter pylori eradication reduced the development of metachronous gastric cancer (MGC) after endoscopic resection for early gastric cancer. MGC risk, however, is not eliminated; yet few studies have evaluated its long-term incidence and risk factors. In this study, we investigated the incidence of and risk factors for MGC in patients who underwent endoscopic resection for early gastric cancer with successful H. pylori eradication. METHODS: A total of 594 patients who underwent endoscopic resection for early gastric cancer and successful H. pylori eradication at three institutions (National Cancer Center Hospital, University of Tokyo Hospital, and Wakayama Medical University Hospital) were analyzed retrospectively. Annual endoscopic surveillance was performed after initial endoscopic resection. MGC was defined as a gastric cancer newly detected at least 1 year after successful H. pylori eradication. RESULTS: Ninety-four MGCs were detected in 79 patients during the 4.5-year median follow-up period. Kaplan-Meier analysis showed the cumulative incidence of MGC 5 years after successful H. pylori eradication was 15.0 %; the incidence of MGC calculated by use of the person-year method was 29.9 cases per 1000 person-years. Multivariate analysis using the Cox proportional hazards model revealed that male sex, severe gastric mucosal atrophy, and multiple gastric cancers before successful H. pylori eradication were independent risk factors for MGC. Eleven percent of MGCs (10 of 94) were detected more than 5 years after successful H. pylori eradication. CONCLUSION: Surveillance endoscopy for MGC in patients who have undergone endoscopic resection for early gastric cancer should be performed even after successful H. pylori eradication.


Assuntos
Gastrectomia/efeitos adversos , Infecções por Helicobacter/complicações , Segunda Neoplasia Primária/epidemiologia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Endoscopia , Feminino , Seguimentos , Gastroscopia , Infecções por Helicobacter/virologia , Helicobacter pylori , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/cirurgia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
7.
Gastric Cancer ; 19(3): 894-901, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26362271

RESUMO

BACKGROUND: Watering eyes is a common late adverse event associated with S-1 chemotherapy; however, the frequency and predictive factors are not known. METHODS: This study included 304 consecutive gastric cancer patients treated with adjuvant S-1 monotherapy for 1 year at Shizuoka Cancer Center. We retrospectively evaluated the frequency of watering eyes, and explored other nonhematological adverse events during the first course of S-1 monotherapy which could become predictive factors for watering eyes. RESULTS: The severest grade of watering eyes during S-1 monotherapy was grade 2 in 41 patients (13.5 %) and grade 3 in 36 patients (11.8 %). The median time to onset of grade 2 and grade 3 watering eyes was 82 days (range 6-344 days) and 249 days (range 84-653 days), respectively, and the median cumulative S-1 dose at the onset of grade 2 and grade 3 watering eyes was 4174 mg/m(2) (range 491-16,095 mg/m(2)) and 10,243 mg/m(2) (range 4943-16,341 mg/m(2)), respectively. Multivariate analysis showed that anorexia (odds ratio 2.37, P = 0.008), oral mucositis (odds ratio 3.86, P = 0.0003), skin hyperpigmentation (odds ratio 3.84, P = 0.0001), and rash (odds ratio 3.76, P = 0.01) observed during the first course were significantly associated with watering eyes. CONCLUSION: The risk of watering eyes was higher in patients who also had anorexia, oral mucositis, skin hyperpigmentation, or rash during first course of S-1 monotherapy than in those without them.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Doenças do Aparelho Lacrimal/induzido quimicamente , Ácido Oxônico/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Lágrimas/metabolismo , Tegafur/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Doenças do Aparelho Lacrimal/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Lágrimas/efeitos dos fármacos
8.
Gastric Cancer ; 19(3): 1016-22, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26486508

RESUMO

BACKGROUND: Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is the standard gastric cancer screening method in Japan. Atrophic gastritis and enlarged gastric folds are considered the two major features of Helicobacter pylori-induced chronic gastritis, but the clinical meaning of evaluating them by UGI-XR has not been elucidated. METHODS: We analyzed healthy UGI-XR examinees without a history of gastrectomy, previous Helicobacter pylori eradication and usage of gastric acid suppressants. RESULTS AND CONCLUSIONS: Of the 6433 subjects, 1936 (30.1 %) had atrophic gastritis and 1253 (19.5 %) had enlarged gastric folds. During the 3-year prospective observational follow-up, gastric cancer developed in seven subjects, six of whom (85.7 %) had atrophic gastritis with H. pylori infection and five of whom (71.4 %) had enlarged gastric folds with H. pylori infection. The Kaplan-Meier method with log-rank testing revealed that both UGI-XR-based atrophic gastritis (p = 0.0011) and enlarged gastric folds (p = 0.0003) are significant predictors for future gastric cancer incidence.


Assuntos
Bário , Mucosa Gástrica/patologia , Gastrite Atrófica/diagnóstico por imagem , Radiografia Abdominal/métodos , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Mucosa Gástrica/diagnóstico por imagem , Gastrite Atrófica/complicações , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia , Raios X , Adulto Jovem
9.
Hepatol Res ; 46(7): 634-41, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26407147

RESUMO

AIM: The present study aimed to evaluate pathological features of hepatocellular carcinomas (HCC) appearing hypointense on the apparent diffusion coefficient (ADC) map, and to elucidate the association between the signal intensity on the ADC map and metastatic recurrences after hepatectomy. METHODS: In total, 52 consecutive patients with initial hypervascular HCC (solitary lesion ≤5 cm in diameter) without vascular invasion on imaging were examined by diffusion-weighted magnetic resonance imaging before hepatectomy. The signal intensities of HCC on the ADC map were visually compared with the surrounding liver and categorized as hypointense or non-hypointense. Intrahepatic metastatic recurrence was defined as more than three intrahepatic recurrences. RESULTS: The 52 HCC were evaluated as 26 hypointense and 26 non-hypointense tumors. No significant differences between the hypointense and non-hypointense groups were seen for age, sex, etiology, tumor size and tumor marker levels. However, in resected specimens, significant differences between the two groups were noted for histological grade and microscopic portal invasion. The percentages of poorly differentiated HCC and microscopic portal invasion in the hypointense group were significantly higher than those in the non-hypointense group. The cumulative 3-year metastatic recurrence rates of the hypointense and non-hypointense groups on the ADC map were 56% and 13% (P = 0.001), respectively. Multivariate analyses indicated that hypointensity on the ADC map was the only independent factor related to metastatic recurrence. CONCLUSION: Hypointense HCC on ADC mapping are characterized by poor histological differentiation and more frequent microscopic portal invasion, and are significantly associated with metastatic recurrences after hepatectomy.

10.
J Ultrasound Med ; 35(2): 359-71, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26782163

RESUMO

OBJECTIVES: An ultrasound contrast agent consisting of perfluorobutane microbubbles (Sonazoid; Daiichi Sankyo, Tokyo, Japan) accumulates in Kupffer cells, which thus enables Kupffer imaging. This study aimed to elucidate the association of defect patterns of hepatocellular carcinoma during the Kupffer phase of Sonazoid contrast-enhanced sonography with outcomes after radiofrequency ablation (RFA). METHODS: For this study, 226 patients with initial hypervascular hepatocellular carcinoma, who could be evaluated by contrast-enhanced sonography with Sonazoid before RFA, were analyzed. Patients were divided into 2 groups according to the tumor defect pattern during the Kupffer phase. The irregular-defect group was defined as patients with hepatocellular carcinoma that had a defect with an irregular margin, and the no-irregular-defect group was defined as patients with hepatocellular carcinoma that had either a defect with a smooth margin or no defect. Critical recurrence was defined as more than 3 intrahepatic recurrences, vascular invasion, dissemination, or metastasis. RESULTS: The irregular-defect and no-irregular-defect groups included 86 and 140 patients, respectively, and had cumulative 5-year critical recurrence rates of 49% and 17% (P < .01). Multivariate analysis indicated that the tumor diameter, lens culinaris agglutinin- reactive α-fetoprotein level, and defect pattern were independent factors related to critical recurrence. The cumulative 5-year overall survival rates for the irregular-defect and no-irregular-defect groups were 46% and 61% (P< .01). Multivariate analysis indicated that the Child-Pugh class, tumor diameter, lens culinaris agglutinin-reactive α-fetoprotein level, and defect pattern were independent factors related to survival. CONCLUSIONS: The defect pattern of hepatocellular carcinoma during the Kupffer phase of Sonazoid contrast-enhanced sonography is associated with critical recurrence and survival after RFA.


Assuntos
Técnicas de Ablação , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Meios de Contraste , Fluorocarbonos , Células de Kupffer/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Microbolhas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Resultado do Tratamento
11.
J Ultrasound Med ; 35(7): 1383-91, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27208196

RESUMO

OBJECTIVES: The role of contrast-enhanced sonography in the diagnosis of recurrent hepatocellular carcinoma is still unclear. This study aimed to clarify the usefulness and limitations of contrast-enhanced sonography with a perfluorobutane microbubble contrast agent (Sonazoid; Daiichi-Sankyo, Tokyo, Japan) after contrast-enhanced computed tomography (CT) for diagnosis of recurrent hepatocellular carcinoma and to establish its optimal use. METHODS: A total of 514 patients, who were suspected to have recurrent hepatocellular carcinoma on contrast-enhanced CT, underwent contrast-enhanced sonography. Of 514 suspicious lesions, 484 were diagnosed as recurrent hepatocellular carcinomas, including 142 recurrent hepatocellular carcinomas measuring 1 cm or smaller in diameter. The largest lesion was evaluated in each patient. A final diagnosis of recurrent hepatocellular carcinoma after contrast-enhanced CT was reached on the basis of the typical hallmarks of hepatocellular carcinoma on any of the other contrast imaging modalities or by resected tissue or tumor enlargement during follow-up. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of contrast-enhanced CT were 68%, 93%, 99%, 15%, and 70%, respectively, and the values of contrast-enhanced sonography were 91%, 100%, 100%, 31%, and 91%, excluding 60 unassessable lesions on contrast-enhanced sonography. The diagnostic rate for recurrent hepatocellular carcinoma on contrast-enhanced sonography for lesions with an atypical enhancement pattern on contrast-enhanced CT was 71%. On multivariate analysis of factors contributing to the unassessability of contrast-enhanced sonography, lesion size, location, and abdominal wall thickness were independent factors. CONCLUSIONS: Although the assessability of contrast-enhanced sonography depends on lesion size, location, and abdominal wall thickness, contrast-enhanced sonography after contrast-enhanced CT is useful for confirmative diagnosis of small recurrent hepatocellular carcinoma with an atypical enhancement pattern on contrast-enhanced CT, even for lesions measuring 1 cm or smaller in diameter.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Fluorocarbonos , Aumento da Imagem/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Microbolhas , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
12.
Dig Endosc ; 28(1): 42-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26295791

RESUMO

BACKGROUND AND AIM: Esophageal varices are usually treated with endoscopic injection sclerotherapy (EIS) or endoscopic band ligation (EBL). However, frequent recurrences of varices after those procedures have been problematic. Argon plasma coagulation (APC) after EIS may be effective for preventing varix recurrence and, in recent years, we have routinely carried out APC after EIS. The aim of the present study was to verify the effectiveness of APC for preventing recurrence of varices after EIS. METHODS: A case-control study was carried out using a historical control cohort in a single center. The varix recurrence rate in 62 patients (34 men and 28 women, median age; 69 years) who underwent APC after EIS for hemorrhagic or risky esophageal varices (APC group) was compared with that of control patients who did not undergo APC after EIS (control group). Age-, sex-, and liver function-matched two control subjects were selected for one case subject (control group). Recurrence of varices was defined as rupture of varices or reappearance of risky varices. RESULTS: The 1-year and 2-year recurrence rates of the APC group were 9.7% and 11.3%, respectively. In contrast, the rates of the control group were 29.0% and 34.7%, respectively. Kaplan-Meier curves showed a significantly lower recurrence rate in the APC group (P = 0.013, log-rank test). No APC-related severe adverse events were observed. CONCLUSION: APC after EIS was safe and could significantly prevent recurrence of esophageal varices. Therefore, the addition of APC should be routinely carried out after EIS.


Assuntos
Coagulação com Plasma de Argônio/métodos , Endoscopia Gastrointestinal/métodos , Varizes Esofágicas e Gástricas/prevenção & controle , Hemorragia Gastrointestinal/prevenção & controle , Soluções Esclerosantes/efeitos adversos , Escleroterapia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Varizes Esofágicas e Gástricas/complicações , Feminino , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/etiologia , Humanos , Incidência , Injeções , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Soluções Esclerosantes/administração & dosagem , Escleroterapia/métodos , Resultado do Tratamento
13.
Dig Endosc ; 28(4): 434-442, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26623565

RESUMO

OBJECTIVES: The preventive effect of Helicobacter pylori (HP) eradication on metachronous gastric cancer development after endoscopic resection remains controversial. The aim of this study was to identify specific endoscopic features that correlated with the risk of metachronous gastric cancer development after endoscopic submucosal dissection (ESD) using both endoscopic findings before ESD and changes of findings after HP eradication. METHODS: This retrospective study investigated 122 consecutive patients who underwent ESD for early gastric cancer and successful HP eradication after ESD. Endoscopic findings linked with HP before ESD and changes after HP eradication were evaluated according to the development of metachronous cancer. RESULTS: Most patients showed severe atrophy and intestinal metaplasia (IM) before ESD (97% and 83%, respectively). Improvement of spotty redness, improvement of diffuse redness, emergence of patchy redness, and emergence of map-like redness were frequent findings after HP eradication (52%, 50%, 54%, and 32%, respectively). Kaplan-Meier curves indicated that patients without IM before ESD never developed metachronous cancer, while patients with emergence of map-like redness after HP eradication were significantly more likely to develop metachronous cancer (log-rank test, p = 0.031 and p < 0.001, respectively). Multivariate analysis indicated that emergence of map-like redness after HP eradication was the only predictive factor for development of metachronous cancer (hazard ratio, 3.61; 95% confidence interval, 1.41-9.21; p = 0.007). CONCLUSIONS: Absence of IM before ESD and emergence of map-like redness after HP eradication were useful endoscopic findings in the negative and positive prediction of metachronous gastric cancer developing after ESD.

14.
Dig Endosc ; 28(1): 3-15, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26234303

RESUMO

In response to the rapid and wide acceptance and use of endoscopic treatments for early gastric cancer, the Japan Gastroenterological Endoscopy Society (JGES), in collaboration with the Japanese Gastric Cancer Association (JGCA), has produced 'Guidelines for ESD and EMR for Early Gastric Cancer', as a set of basic guidelines in accordance with the principles of evidence-based medicine. These Guidelines cover the present state of knowledge and are divided into the following seven categories: Indications, Preoperative diagnosis, Techniques, Evaluation of curability, Complications, Long-term postoperative surveillance, and Histology. Twenty-three statements were finally accepted as guidelines, and the majority of these were obtained from descriptive studies with lower evidence levels. A number of statements had to be created by consensus (the lowest evidence level), as evidence levels remain low for many specific areas in this field.


Assuntos
Dissecação/métodos , Detecção Precoce de Câncer/normas , Endoscopia Gastrointestinal/normas , Gastroenterologia , Neoplasias Gástricas/cirurgia , Dissecação/normas , Humanos , Japão , Neoplasias Gástricas/diagnóstico
15.
Gut ; 64(3): 388-96, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25379950

RESUMO

BACKGROUND: Epigenetic alterations accumulate in normal-appearing tissues of patients with cancer, producing an epigenetic field defect. Cross-sectional studies show that the degree of the defect may be associated with risk in some types of cancer, especially cancers associated with chronic inflammation. OBJECTIVE: To demonstrate, by a multicentre prospective cohort study, that the risk of metachronous gastric cancer after endoscopic resection (ER) can be predicted by assessment of the epigenetic field defect using methylation levels. DESIGN: Patients with early gastric cancer, aged 40-80 years, who planned to have, or had undergone, ER, were enrolled at least 6 months after Helicobacter pylori infection discontinued. Methylation levels of three preselected genes (miR-124a-3, EMX1 and NKX6-1) were measured by quantitative methylation-specific PCR. Patients were followed up annually by endoscopy, and the primary endpoint was defined as detection of a metachronous gastric cancer. Authentic metachronous gastric cancers were defined as cancers excluding those detected within 1 year after the enrolment. RESULTS: Among 826 patients enrolled, 782 patients had at least one follow-up, with a median follow-up of 2.97 years. Authentic metachronous gastric cancers developed in 66 patients: 29, 16 and 21 patients at 1-2, 2-3 and ≥3 years after the enrolment, respectively. The highest quartile of the miR-124a-3 methylation level had a significant univariate HR (95% CI) (2.17 (1.07 to 4.41); p=0.032) and a multivariate-adjusted HR (2.30 (1.03 to 5.10); p=0.042) of developing authentic metachronous gastric cancers. Similar trends were seen for EMX1 and NKX6-1. CONCLUSIONS: Assessment of the degree of an epigenetic field defect is a promising cancer risk marker that takes account of life history.


Assuntos
Metilação de DNA , Epigênese Genética , Segunda Neoplasia Primária/etiologia , Neoplasias Gástricas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Marcadores Genéticos/genética , Proteínas de Homeodomínio/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Segunda Neoplasia Primária/genética , Reação em Cadeia da Polimerase , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/genética , Fatores de Transcrição/genética
16.
J Hepatol ; 63(6): 1352-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26212030

RESUMO

BACKGROUND & AIMS: Serological markers of hepatocellular carcinoma (HCC) indicate its invasiveness. We aimed to investigate whether the prognostic impact of surgical resection (SR) and radiofrequency thermal ablation (RFA) on patients with single nodular HCC ⩽5cm were different regarding positive conditions of the following three HCC markers: alpha-fetoprotein (AFP); lens culinaris agglutinin-reactive fraction of AFP; and des-γ-carboxy prothrombin. METHODS: This study reviewed 296 patients with single nodular HCC ⩽5cm with Child-Pugh grade A between 2001 and 2011 (SR, n=136; RFA, n=160). Based on positive conditions of previous HCC markers (defined as non-positive, single-positive, double-positive, and triple-positive), overall survival (OS) and prognostic factors were analyzed. RESULTS: Five-year OS rates of SR and RFA among all patients were 70.1% and 69.8%, respectively (p=0.14). However, when stratified by the positive conditions of three HCC markers, their rates of non-, single-, double-, and triple-positive patients were 60.6%, 78.2%, 54.2%, and 75.9% in the SR group, whereas rates were 83.3%, 75.7%, 62.2%, and 47.6% in the RFA group (p values between SR and RFA of each tumor marker condition were 0.45, 0.10, 0.77, and <0.01, respectively). Multivariate analyses showed that RFA itself became an independent prognostic factor in the triple-positive group, with an odds ratio of 1.78 (95% confidence interval, 1.16-2.72). CONCLUSIONS: Positive conditions of three HCC markers differently influenced survival rates of those who underwent SR and RFA when treating single nodular HCC ⩽5cm. RFA itself became an independent prognostic risk when all three HCC markers were positive. Preoperative evaluation of multiple HCC markers might become an index for selecting treatment modalities.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Idoso , Biomarcadores/sangue , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Lectinas de Plantas , Prognóstico , Precursores de Proteínas/sangue , Protrombina , alfa-Fetoproteínas/metabolismo
17.
BMC Gastroenterol ; 15: 132, 2015 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-26467439

RESUMO

BACKGROUND: Both double-balloon enteroscopy (DBE) and video capsule endoscopy (VCE) have similar diagnostic yields for patients with overt obscure gastrointestinal bleeding (OGIB). However, the choice of initial modality is still controversial. The aim of this study was to show the clinical outcome of the strategy of initial VCE, followed by DBE. METHODS: Eighty-nine consecutive overt OGIB patients who had undergone VCE as the initial examination were analyzed. The interpreters of VCE evaluated the necessity of performing DBE, and the antegrade or retrograde route was chosen, depending on the transit time of the capsule. RESULTS: Thirty-seven patients (42 %) underwent DBE depending on the findings of VCE. Of these, bleeding sites in the small bowel were identified in 29 patients with the initially selected route (21 antegrade and 8 retrograde). The remaining 8 later underwent DBE by the other route, but 7 had no bleeding lesion, which was confirmed by second-look VCE. One remaining patient had a jejunal varix found by VCE, but DBE from either side could not reach the lesion. The sensitivity and negative predictive value of VCE were 100 %, both for the presence of small bowel lesions and the requirement of hemostasis in the small bowel; this indicated that VCE never misses relevant findings in the small bowel, and that negative VCE findings correspond to the lack of necessity for further examination. CONCLUSIONS: VCE as the initial examination can efficiently identify overt OGIB patients who require DBE. The strategy of initial VCE for overt OGIB appears to be reasonable.


Assuntos
Endoscopia por Cápsula/estatística & dados numéricos , Enteroscopia de Duplo Balão/estatística & dados numéricos , Hemorragia Gastrointestinal/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoscopia por Cápsula/métodos , Enteroscopia de Duplo Balão/métodos , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Intestino Delgado , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Cirurgia de Second-Look , Sensibilidade e Especificidade
18.
Hepatol Res ; 45(1): 75-87, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24533527

RESUMO

AIM: It has been reported that the apparent diffusion coefficient (ADC) value of hepatocellular carcinomas (HCC) on diffusion-weighted magnetic resonance imaging (MRI) is associated with their histological grade. The present study aimed to evaluate whether the signal intensity of small hypervascular HCC on the ADC map is related to the treatment outcome of radiofrequency ablation (RFA). METHODS: Between February 2008 and August 2012, 136 consecutive patients with initial small hypervascular HCC (≤3 tumors and ≤3 cm in diameter) were examined by diffusion-weighted MRI before RFA. The signal intensities of HCC on the ADC map were visually compared with the surrounding liver and categorized as hypointense and non-hypointense. Critical recurrence was defined as more than three intrahepatic recurrences, recurrence with vascular invasion, seeding, dissemination and/or extrahepatic metastasis. RESULTS: The median follow up was 619 days. The cumulative 2-year recurrence rates of the hypointense and non-hypointense on the ADC map groups were 79% and 50% (P < 0.001), respectively, with cumulative 2-year local recurrence rates of 18% and 7% (P = 0.014) and cumulative 2-year critical recurrence rates of 38% and 13% (P = 0.005), respectively. The cumulative 3-year survival rates were 60% and 82% (P = 0.007), respectively. On multivariate analysis, hypointensity on the ADC map was the strongest independent factor related to recurrence and survival after RFA. CONCLUSION: The signal intensity of HCC on the ADC map was strongly associated with outcome after RFA. These results suggest that treatment strategy should be determined carefully even for small HCC when they appear hypointense on the ADC map.

19.
Dig Endosc ; 27(4): 435-449, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25677012

RESUMO

Recently, the need for sedation in gastrointestinal endoscopy has been increasing. However, the National Health Insurance Drug Price list in Japan does not include any drug specifically used for the sedation. Although benzodiazepines are the main medication, their use in cases of gastrointestinal endoscopy has not been approved. This has led the Japan Gastrointestinal Endoscopy Society to develop the first set of guidelines for sedation in gastrointestinal endoscopy on the basis of evidence-based medicine in collaboration with the Japanese Society for Anesthesiologists. The present guidelines comprise 14 statements, five of which were judged to be valid on the highest evidence level and three on the second highest level. The guidelines are not intended to strongly recommend the use of sedation for gastrointestinal endoscopy, but rather to indicate the policy as to the choice of appropriate procedures when such sedation is deemed necessary. In clinical practice, the final decision as to the use of sedation should be made by physicians considering patient willingness and physical condition.


Assuntos
Anestesia Geral/normas , Sedação Consciente/normas , Sedação Profunda/normas , Endoscopia Gastrointestinal/normas , Hipnóticos e Sedativos/farmacologia , Guias de Prática Clínica como Assunto , Analgésicos Opioides/farmacocinética , Anestesia Geral/métodos , Anestésicos/farmacologia , Sedação Consciente/métodos , Sedação Profunda/métodos , Humanos , Japão
20.
Dig Endosc ; 27(4): 417-434, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25652022

RESUMO

Colorectal endoscopic submucosal dissection (ESD) has become common in recent years. Suitable lesions for endoscopic treatment include not only early colorectal carcinomas but also many types of precarcinomatous adenomas. It is important to establish practical guidelines in which the preoperative diagnosis of colorectal neoplasia and the selection of endoscopic treatment procedures are properly outlined, and to ensure that the actual endoscopic treatment is useful and safe in general hospitals when carried out in accordance with the guidelines. In cooperation with the Japanese Society for Cancer of the Colon and Rectum, the Japanese Society of Coloproctology, and the Japanese Society of Gastroenterology, the Japan Gastroenterological Endoscopy Society has recently compiled a set of colorectal ESD/endoscopic mucosal resection (EMR) guidelines using evidence-based methods. The guidelines focus on the diagnostic and therapeutic strategies and caveat before, during, and after ESD/EMR and, in this regard, exclude the specific procedures, types and proper use of instruments, devices, and drugs. Although eight areas, ranging from indication to pathology, were originally planned for inclusion in these guidelines, evidence was scarce in each area. Therefore, grades of recommendation were determined largely through expert consensus in these areas.


Assuntos
Adenoma/cirurgia , Carcinoma/cirurgia , Neoplasias Colorretais/cirurgia , Dissecação/normas , Endoscopia Gastrointestinal/normas , Guias de Prática Clínica como Assunto , Adenoma/diagnóstico , Carcinoma/diagnóstico , Neoplasias Colorretais/patologia , Endoscopia Gastrointestinal/efeitos adversos , Endoscopia Gastrointestinal/métodos , Humanos , Mucosa Intestinal , Japão , Seleção de Pacientes , Assistência Perioperatória/normas
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