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BACKGROUND AND AIMS: Identifying patients with steatotic liver disease who are at a high risk of developing HCC remains challenging. We present a deep learning (DL) model to predict HCC development using hematoxylin and eosin-stained whole-slide images of biopsy-proven steatotic liver disease. APPROACH AND RESULTS: We included 639 patients who did not develop HCC for ≥7 years after biopsy (non-HCC class) and 46 patients who developed HCC <7 years after biopsy (HCC class). Paired cases of the HCC and non-HCC classes matched by biopsy date and institution were used for training, and the remaining nonpaired cases were used for validation. The DL model was trained using deep convolutional neural networks with 28,000 image tiles cropped from whole-slide images of the paired cases, with an accuracy of 81.0% and an AUC of 0.80 for predicting HCC development. Validation using the nonpaired cases also demonstrated a good accuracy of 82.3% and an AUC of 0.84. These results were comparable to the predictive ability of logistic regression model using fibrosis stage. Notably, the DL model also detected the cases of HCC development in patients with mild fibrosis. The saliency maps generated by the DL model highlighted various pathological features associated with HCC development, including nuclear atypia, hepatocytes with a high nuclear-cytoplasmic ratio, immune cell infiltration, fibrosis, and a lack of large fat droplets. CONCLUSIONS: The ability of the DL model to capture subtle pathological features beyond fibrosis suggests its potential for identifying early signs of hepatocarcinogenesis in patients with steatotic liver disease.
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BACKGROUND & AIMS: PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 have been associated with an increased risk of liver-related events (LREs) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, we investigated the combined effects of these variants on LREs. METHODS: The longitudinal multicenter cohort study enrolled 1178 patients with biopsy-proven MASLD. We calculated the genetic risk of hepatic fibrosis and LRE according to the impact of these variants. RESULTS: Patients with genetic fibrosis scores of 2, 3, and 4 or 5 were at greater risk than patients with scores of 0 or 1, with odds ratios of 2.45 (95% CI, 1.27-4.74), 2.14 (95% CI, 1.17-3.94), and 2.54 (95% CI, 1.35-4.77), respectively. Multivariate analysis revealed that PNPLA3 and TM6SF2, but not HSD17B13, were associated significantly with LRE development. The hazard ratio of the genetic high-risk group for LRE was 1.91 (95% CI, 1.20-3.04). The higher risk of LRE development in the genetic high-risk group also was seen in patients with F ≥ 3 or Fibrosis-4 index > 2.67. The hazard ratios of the genetic high-risk group for LRE were greater in patients without obesity, without diabetes, and of younger age compared with patients with obesity, with diabetes, or of older age, respectively. CONCLUSIONS: This combination of MASLD-related genetic variants is useful for predicting LREs in Japanese patients with MASLD. The genetic risk according to these variants is useful for LRE risk assessment, especially in patients without metabolic risk factors or in younger patients in Japan.
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17-Hidroxiesteroide Desidrogenases , Lipase , Proteínas de Membrana , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Proteínas de Membrana/genética , Lipase/genética , Adulto , Estudos Longitudinais , 17-Hidroxiesteroide Desidrogenases/genética , Idoso , Predisposição Genética para Doença , Comorbidade , Japão/epidemiologia , Polimorfismo de Nucleotídeo Único , Fígado Gorduroso/genética , Fígado Gorduroso/complicações , Cirrose Hepática/genética , Cirrose Hepática/complicações , Aciltransferases , Fosfolipases A2 Independentes de CálcioRESUMO
BACKGROUND AND AIMS: The diagnostic performance of the Fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) is poor in patients with type 2 diabetes mellitus (T2DM). We determined the usefulness of the Enhanced Liver Fibrosis (ELF) test in patients with T2DM. METHODS: A total of 1228 patients with biopsy-proven NAFLD were enrolled. The diagnostic performance of the ELF test for predicting advanced fibrosis in participants with or without T2DM was evaluated in comparison with the FIB-4 index and NFS. RESULTS: Overall, the area under the curve of the ELF test for predicting advanced fibrosis was greater (0.828) than that of the FIB-4 index (0.727) and NFS (0.733). The diagnostic performance of the ELF test (area under the curve, 0.820) was also superior to that of the FIB-4 index (0.698) and NFS (0.700) in patients with T2DM. With the low cutoff values for each noninvasive test, the ELF test provided an acceptable false negative rate (cutoff value 9.8, 6.7%) in this population, unlike the FIB-4 index (1.30, 14.5%) and NFS (-1.455, 12.4%). After propensity score matching to avoid selection bias including age, sex, body mass index, and the prevalence of advanced fibrosis, the ELF test with a low cutoff value showed a high sensitivity (≥91.4%) and a high negative predictive value (≥96.8%), irrespective of the presence or absence of T2DM. CONCLUSIONS: The high diagnostic performance of the ELF test for predicting advanced fibrosis in individuals with or without T2DM could address an unmet medical need for accurate assessment of liver fibrosis in patients with diabetes and NAFLD.
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Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Alanina Transaminase , Aspartato Aminotransferases , Cirrose Hepática/patologia , Biópsia , Fígado/patologia , Índice de Gravidade de DoençaRESUMO
Insulin resistance in adipose tissue is thought to be a key contributor to the pathogenesis of various metabolic disorders including metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis (MASLD/MASH), but the mechanism underlying this contribution to MASLD/MASH has remained unknown. We previously showed that dysregulation of the PDK1-FoxO1 signaling axis in adipocytes plays a role in the development of MASLD/MASH by analysis of adipocyte-specific PDK1 knockout (A-PDK1KO) and adipocyte-specific PDK1/FoxO1 double-knockout (A-PDK1/FoxO1DKO) mice. We here focused on the role of the extracellular matrix protein thrombospondin-1 (TSP-1) as a secreted factor whose expression in adipose tissue is increased in A-PDK1KO mice and normalized in A-PDK1/FoxO1DKO mice. Genetic ablation of TSP-1 markedly ameliorated liver fibrosis in A-PDK1KO mice fed a high-fat diet. With regard to the potential mechanism of this effect, TSP-1 augmented the expression of fibrosis-related genes induced by TGF-ß in LX-2 human hepatic stellate cells. We also showed that TSP-1 expression and secretion were negatively regulated by insulin signaling via the PDK1-FoxO1 axis in cultured adipocytes. Our results thus indicate that TSP-1 plays a key role in the pathogenesis of liver fibrosis in MASH. Regulation of TSP-1 expression by PDK1-FoxO1 axis in adipocytes may provide a basis for targeted therapy of hepatic fibrosis in individuals with MASH.
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Células Estreladas do Fígado , Fator de Crescimento Transformador beta , Animais , Humanos , Camundongos , Adipócitos/metabolismo , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/patologia , Trombospondina 1/genética , Trombospondina 1/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
This study aimed to complement the results of the REACH-2 study by prospectively evaluating the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma (HCC) in a real-world setting. This was an open-label, nonrandomized, multicenter, prospective study conducted at 13 institutions in Japan (jRCTs031190236). The study included Child-Pugh Class A patients with advanced HCC who had received pretreatment with atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib. Ramucirumab was introduced as a second-line treatment after Atez/Bev or lenvatinib and as a third-line treatment after Atez/Bev and lenvatinib. Between May 2020 and July 2022, we enrolled 19 patients, including 17 who received ramucirumab. Additionally, seven patients received lenvatinib, another seven patients received Atez/Bev, and three patients received Atez/Bev followed by lenvatinib as prior treatment. The primary endpoint was a 6-month progression-free survival (PFS) rate, which was 14.3%. The median PFS and overall survival were 3.7 and 12.0 months, respectively. The most common grade ≥ 3 adverse events (AEs) were hypertension (23.5%), proteinuria (17.6%), and neutropenia (11.8%). The discontinuation rate due to AEs was 29.4%. Six patients progressed from Child-Pugh A to B after treatment with ramucirumab. Thirteen patients were eligible for post-ramucirumab treatment, including systemic therapy. Despite the limited number of patients, the efficacy of ramucirumab was comparable to that observed in the REACH-2 study when used after lenvatinib and Atez/Bev. However, the incidence of AEs was higher than that in the REACH-2 study.
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Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular , Neoplasias Hepáticas , Ramucirumab , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Japão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quinolinas/uso terapêutico , Quinolinas/efeitos adversos , Intervalo Livre de Progressão , Idoso de 80 Anos ou mais , Adulto , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/administração & dosagem , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Bevacizumab/uso terapêutico , Bevacizumab/efeitos adversos , Bevacizumab/administração & dosagem , População do Leste AsiáticoRESUMO
BACKGROUND AND AIMS: This study aimed to determine the safety and efficacy of atezolizumab + bevacizumab therapy in hepatocellular carcinoma patients receiving anti-platelet agents or anticoagulants. METHODS: Patients were divided into those using (IM out) and those not using (IM in) anti-platelet agents or anticoagulants, who violated the exclusion criteria of the IMbrave150 trial, and were retrospectively examined. RESULTS: The study included 185 patients (IM in: 157; IM out: 28). For first-line treatment, progression-free survival was 184 days for IM in and 266 days for IM out (p = .136). Overall survival was 603 days for IM in and not reached for IM out (p = .265), with no significant between-group difference. Similarly, there were no significant between-group differences in progression-free survival or overall survival for later-line treatment. Haemorrhagic adverse events of ≥grade 3 were observed in 11 IM in patients and 3 IM out patients. No significant factors associated with haemorrhagic adverse events of ≥grade 3 were identified in the multivariate analysis including IM out classification, whose p value was .547. Regarding thrombotic/embolic adverse events in the IM out group, one case of exacerbation of portal vein thrombosis was observed. No deaths were directly attributable to bleeding events or exacerbations of thrombosis. CONCLUSION: Atezolizumab + bevacizumab therapy shows similar safety and efficacy in patients receiving and those not receiving anti-platelet agents or anticoagulants; therefore, it can be considered for patients with hepatocellular carcinoma receiving anti-platelet agents or anticoagulants.
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Anticorpos Monoclonais Humanizados , Anticoagulantes , Bevacizumab , Carcinoma Hepatocelular , Neoplasias Hepáticas , Inibidores da Agregação Plaquetária , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Bevacizumab/uso terapêutico , Bevacizumab/efeitos adversos , Bevacizumab/administração & dosagem , Masculino , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Progressão , Hemorragia/induzido quimicamente , AdultoRESUMO
INTRODUCTION: Esophagogastroduodenoscopy (EGD) is the most important tool to detect gastric cancer (GC). In this study, we developed a computer-aided system (CADe) to detect gastric cancer (GC) with white light imaging (WLI) and linked color imaging (LCI) modes and aimed to compare the performance of CADe with that of endoscopists. METHODS: The system was developed based on the deep learning framework from 9021 images in 385 patients between 2017 and 2020. A total of 116 LCI and WLI videos from 110 patients between 2017 and 2023 were used to evaluate per-case sensitivity and per-frame specificity. RESULTS: The per-case sensitivity and per-frame specificity of CADe with a confidence level of 0.5 in detecting GC were 78.6% and 93.4% for WLI and 94.0% and 93.3% for LCI, respectively (P < 0.001). The per-case sensitivities of nonexpert endoscopists for WLI and LCI were 45.8% and 80.4%, whereas those of expert endoscopists were 66.7% and 90.6%, respectively. Regarding detectability between CADe and endoscopists, the per-case sensitivities for WLI and LCI were 78.6% and 94.0% in CADe, respectively, which were significantly higher than those for LCI in experts (90.6%, P = 0.004) and those for WLI and LCI in nonexperts (45.8% and 80.4%, respectively, P < 0.0001); however, no significant difference for WLI was observed between CADe and experts (P = 0.134). CONCLUSIONS: Our CADe system showed a significantly better sensitivity in detecting GC when used in LCI compared with WLI mode. Moreover, the sensitivity of CADe using LCI is significantly higher than those of expert endoscopists using LCI.
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BACKGROUND AND AIM: Prophylactic closure with the over-the-scope clip (OTSC) after endoscopic submucosal dissection (ESD) of superficial non-ampullary duodenal epithelial tumors (SNADETs) has been reported to reduce postoperative adverse events (AEs). However, there are few evidences regarding AEs-associated factors and long-term outcomes of OTSCs. METHODS: From January 2011 to December 2020, 139 consecutive patients with SNADETs who underwent ESD followed by OTSC closure in five institutions were extracted in this retrospective study. The primary endpoint was the rate of postoperative AEs after prophylactic OTSC closure. The secondary endpoints were the complete closure rate, residual rate, and long-term AEs associated with residual OTSCs. RESULTS: The rate of complete closure of the mucosal defect was 97.3% (142) in 146 SNADETs, which were completely resected by ESD. Postoperative AEs, including delayed bleeding, delayed perforation, and localized peritonitis, occurred in 6.2%, 3.4%, and 2.1% of patients, respectively; however, all of the cases improved without surgical treatment. In the multivariate logistic regression analysis, the use of two or more OTSCs was a significant independent risk factor for postoperative AEs (odds ratio, 2.94; 95% confidence interval, 1.02-8.46; P = 0.046). The residual OTSC rate was 46.4% at 1 year postoperatively, and long-term AEs included duodenal erosions and ulcers associated with residual OTSCs. CONCLUSIONS: Prophylactic closure with OTSCs after duodenal ESD can provide acceptable short-and long-term outcomes for preventing postoperative AEs. However, multiple OTSCs were the independent risk factors of postoperative AEs due to the gaps between and near the OTSCs.
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Neoplasias Duodenais , Ressecção Endoscópica de Mucosa , Humanos , Ressecção Endoscópica de Mucosa/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Duodenais/cirurgia , Neoplasias Duodenais/patologia , Instrumentos CirúrgicosRESUMO
BACKGROUND AND AIM: There are no previous studies in which computer-aided diagnosis (CAD) diagnosed colorectal cancer (CRC) subtypes correctly. In this study, we developed an original CAD for the diagnosis of CRC subtypes. METHODS: Pretraining for the CAD based on ResNet was performed using ImageNet and five open histopathological pretraining image datasets (HiPreD) containing 3 million images. In addition, sparse attention was introduced to improve the CAD compared to other attention networks. One thousand and seventy-two histopathological images from 29 early CRC cases at Kyoto Prefectural University of Medicine from 2019 to 2022 were collected (857 images for training and validation, 215 images for test). All images were annotated by a qualified histopathologist for segmentation of normal mucosa, adenoma, pure well-differentiated adenocarcinoma (PWDA), and moderately/poorly differentiated adenocarcinoma (MPDA). Diagnostic ability including dice sufficient coefficient (DSC) and diagnostic accuracy were evaluated. RESULTS: Our original CAD, named Colon-seg, with the pretraining of both HiPreD and ImageNET showed a better DSC (88.4%) compared to CAD without both pretraining (76.8%). Regarding the attentional mechanism, Colon-seg with sparse attention showed a better DSC (88.4%) compared to other attentional mechanisms (dual: 79.7%, ECA: 80.7%, shuffle: 84.7%, SK: 86.9%). In addition, the DSC of Colon-seg (88.4%) was better than other types of CADs (TransUNet: 84.7%, MultiResUnet: 86.1%, Unet++: 86.7%). The diagnostic accuracy of Colon-seg for each histopathological type was 94.3% for adenoma, 91.8% for PWDA, and 92.8% for MPDA. CONCLUSION: A deep learning-based CAD for CRC subtype differentiation was developed with pretraining and fine-tuning of abundant histopathological images.
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BACKGROUND AND OBJECTIVE: Several endoscopic resection methods have been developed as less invasive treatments for superficial non-ampullary duodenal epithelial tumours. This study aimed to compare outcomes of conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours, including resection depth and rate of the muscularis mucosa contained under the lesion. METHODS: This single-centre retrospective cohort study conducted from January 2009 to December 2021 enrolled patients who underwent conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours and investigated their clinicopathological outcomes using propensity score matching. RESULTS: Of the 285 superficial non-ampullary duodenal epithelial tumours, 98 conventional endoscopic mucosal resections and 187 underwater endoscopic mucosal resections were included. After propensity score matching, 64 conventional endoscopic mucosal resections and 64 underwater endoscopic mucosal resections were analysed. The R0 resection rate was significantly higher in underwater endoscopic mucosal resection cases than in conventional endoscopic mucosal resection cases (70.3% vs. 50.0%; P = 0.030). In the multivariate analysis, a lesion diameter > 10 mm (odds ratio 7.246; P = 0.001), being in the 1st-50th treatment period (odds ratio 3.405; P = 0.008), and undergoing conventional endoscopic mucosal resection (odds ratio 3.617; P = 0.016) were associated with RX/R1 resection. Furthermore, in underwater endoscopic mucosal resection cases, the R0 rate was significantly higher for lesions diameter ≤10 mm than >10 mm, and was significantly higher in the 51st-treatment period than in the 1st-50th period. Conventional endoscopic mucosal resection and underwater endoscopic mucosal resection cases showed no significant difference in resection depth and muscularis mucosa containing rate. CONCLUSIONS: Underwater endoscopic mucosal resection may be more acceptable than conventional endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours ≤ 10 mm. A steep early learning curve may be acquired for underwater endoscopic mucosal resection. Large multicentre prospective studies need to be conducted to confirm the effectiveness of underwater endoscopic mucosal resection.
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Carcinoma , Neoplasias Duodenais , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Resultado do Tratamento , Endoscopia , Neoplasias Duodenais/patologiaRESUMO
INTRODUCTION: Scissor-type knives are spreading as safe devises in endoscopic submucosal dissection (ESD). We evaluated the efficacy of two kinds of scissor-type knives (Clutch Cutter: CC, Fujifilm Co. and SB Knife Jr2: SB, SB-KAWASUMI Laboratories. Inc.) in colorectal ESD. METHODS: This single-center retrospective study analyzed 178 ESD cases treated with CC from January 2020 to August 2021 and 91 cases with SB from September 2021 to December 2023. The two groups were compared through propensity score matching. Therapeutic results, such as ESD procedure time, en bloc resection rate, perioperative bleeding frequency, and complications, were analyzed in each group. Risk factors for long ESD procedure time (≥ 90 min) were also examined. RESULTS: After matching, 87 cases in each group were analyzed. There was no significant difference in the ESD procedure time (min, median [interquartile range]) between the CC and SB groups (54.0 [36.0-72.0] vs. 53.0 [39.0-72.0], p = 0.99). Additionally, there were no differences in the en bloc resection (100% vs. 100%, p = 1.00), perioperative perforation (1.1% vs. 1.1%, p = 1.00), or delayed bleeding (1.1% vs. 0.0%, p = 1.00). There was a significant difference in perioperative bleeding frequency (mean ± standard deviation: 1.8 ± 2.6 vs. 3.0 ± 3.5, p < 0.01). The significant risk factors (odds ratio [95% confidence interval]) for long ESD procedure time in patients treated with CC or SB were antiplatelet (7.51 [1.82-31.00]), large lesion size (1.08 [1.05-1.12]), severe fibrosis (24.30 [7.60-77.90]), and perioperative bleeding frequency (1.34 [1.14-1.56]). CONCLUSIONS: CC and SB in colorectal ESD enabled high en bloc resection and low complication rates. CC showed significantly less perioperative bleeding than SB.
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BACKGROUND AND AIMS: This retrospective study aimed to compare the short- and long-term outcomes of endoscopic submucosal dissection and laparoscopic and endoscopic cooperative surgery in patients with superficial non-ampullary duodenal epithelial tumors. PATIENTS AND METHODS: We investigated consecutive patients with SNADETs > 10 mm in size who underwent ESD (ESD group) or LECS (LECS group) between January 2015 and March 2021. The data was used to analyze the clinical course, management, survival status, and recurrence between the two groups. RESULTS: A total of 113 patients (100 and 13 in the ESD and LECS groups, respectively) were investigated. The rates of en bloc resection and curative resection were 100% vs. 100% and 93.0% vs. 77.0% in the ESD and LECS groups, respectively, with no significant difference. The ESD group had shorter resection and suturing times than the LECS group, but there were no significant difference after propensity score matching. There were also no differences in the rates of postoperative adverse event (7.0% vs. 23.1%; P = 0.161). The 3-year overall survival (OS) rate was high in both the ESD and LECS groups (97.6% vs. 100%; P = 0.334). One patient in the ESD group experienced recurrence due to liver metastasis; however, no deaths related to SNADETs were observed. CONCLUSION: ESD and LECS are both acceptable treatments for SNADETs in terms of a high OS rate and a low long-term recurrence rate, thereby achieving a comparable high rate of curative resection. Further studies are necessary to compare the outcomes of ESD and LECS for SNADETs once both techniques are developed further.
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Ressecção Endoscópica de Mucosa , Laparoscopia , Neoplasias Epiteliais e Glandulares , Humanos , Estudos Retrospectivos , Ressecção Endoscópica de Mucosa/métodos , Resultado do Tratamento , Laparoscopia/métodosRESUMO
Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) show excessive peristalsis, and antispasmodic agents may be useful therapeutic agents. There are few reports on the use of Kampo medicines for the treatment of IBS-D. Shakuyakukanzoto (SKT) is a Kampo medicine that is effective against abdominal pain. We examined the relationship between SKT and intestinal peristalsis in an animal model and a prospective study. In the animal model, SKT and its components were administered from the serosal side of the colon and colonic peristalsis was evaluated using intraluminal pressure and spatiotemporal mapping before and after the administration of SKT and its components. In this clinical trial, we used abdominal ultrasonography (US) to obtain long-axis images of the sigmoid colon of 11 patients. The frequency of intestinal peristalsis was measured using US in five patients with SKT and six patients without medication after the ingestion of a test meal. The primary outcome was the frequency of peristalsis. The Clinical Trial Registry Website (Trial No. UMIN-CTR; UMIN000051547). In the animal model, peony did not suppress peristalsis frequency, but SKT (p = 0.005) and glycyrrhiza (p = 0.001) significantly suppressed peristalsis frequency compared with saline and peony. Among the glycyrrhiza components, glycycoumarin and isoliquiritigenin suppressed the peristalsis frequency compared to dimethyl sulfoxide (control) (p = 0.001, 0.01, respectively). In a clinical trial, peristalsis was significantly suppressed after oral administration in patients taking SKT (p = 0.03). Administration of SKT was found to inhibit colonic peristalsis, with glycicumarin and isoliquiritigenin being particularly relevant among its components.
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Chalconas , Síndrome do Intestino Irritável , Humanos , Animais , Peristaltismo , Estudos Prospectivos , Modelos Animais , DiarreiaRESUMO
Conventional clip closure of mucosal defects after duodenal endoscopic submucosal dissection decreases the incidence of delayed adverse events, but may result in incomplete closure, depending on size or location. This study aimed to assess the effectiveness of the underwater clip closure method for complete duodenal defect closure without the difficulties associated with conventional closure methods. We investigated 19 patients with 20 lesions who underwent endoscopic submucosal dissection of the duodenum and subsequent mucosal defect closure in underwater conditions at our facility between February 2021 and January 2022. The success rate of the underwater clip closure method was defined as the complete endoscopic closure of the mucosal defect; a success rate of 100% was achieved. The median resected specimen size was 34.3 mm, the median procedure time for mucosal defect closure was 14 min, and the median number of clips used per patient was 12. No delayed adverse events were observed. The underwater clip closure method is a feasible option for complete closure of mucosal defects, regardless of the size or location of a duodenal endoscopic submucosal dissection.
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Ressecção Endoscópica de Mucosa , Humanos , Ressecção Endoscópica de Mucosa/métodos , Duodeno/cirurgia , Técnicas de Fechamento de Ferimentos , Mucosa Intestinal/cirurgia , Instrumentos Cirúrgicos , Resultado do Tratamento , Estudos RetrospectivosRESUMO
After endoscopic treatment for esophageal cancer, a 65-year-old male underwent surveillance esophagogastroduodenoscopy. A 12-mm discolored flat lesion was noted on the greater curvature of the middle gastric body. Magnifying endoscopy with blue laser imaging demonstrated an irregular papillary surface. Biopsy revealed atypical cells with mucus and irregularly distributed nuclei. The lesion was diagnosed as a gastric-type neoplasm with low atypia. Thereafter, endoscopic submucosal dissection (ESD) was conducted and specimen was sent for biopsy. The ESD specimen suggested a signet-ring cell carcinoma with MUC5AC-positive phenotype and adenocarcinoma of the fundic gland type, with MUC6 positivity and pepsinogen I positivity in the shallow and deeper layers, respectively. Moreover, the cervical region of fundic glands demonstrated a transformation zone of the signet-ring cell carcinoma into an adenocarcinoma of the fundic gland type. Herein, we report this rare case along with a literature review.
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Adenocarcinoma , Carcinoma de Células em Anel de Sinete , Neoplasias Gástricas , Humanos , Masculino , Carcinoma de Células em Anel de Sinete/patologia , Carcinoma de Células em Anel de Sinete/diagnóstico por imagem , Carcinoma de Células em Anel de Sinete/cirurgia , Idoso , Adenocarcinoma/patologia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Fundo Gástrico/patologia , Fundo Gástrico/diagnóstico por imagemRESUMO
INTRODUCTION: The efficacy of texture and color enhancement imaging (TXI) in the novel light-emitting diode endoscopic system for polyp detection has not been examined. We aimed to evaluate the noninferiority of the additional 30-second (Add-30-s) observation of the right-sided colon (cecum/ascending colon) with TXI compared with narrow band imaging (NBI) for detecting missed polyps. METHODS: We enrolled 381 patients ≥40 years old who underwent colonoscopy from September 2021 to June 2022 in 3 institutions and randomly assigned them to either the TXI or NBI groups. The right-sided colon was first observed with white light imaging in both groups. Second, after reinsertion from hepatic flexure to the cecum, the right-sided colon was observed with Add-30-s observation of either TXI or NBI. The primary endpoint was to examine the noninferiority of TXI to NBI using the mean number of adenomas and sessile serrated lesions per patient. The secondary ones were to examine adenoma detection rate, adenoma and sessile serrated lesions detection rates, and polyp detection rates in both groups. RESULTS: The TXI and NBI groups consisted of 177 and 181 patients, respectively, and the noninferiorities of the mean number of adenomas and sessile serrated lesions per patients in the second observation were significant (TXI 0.29 [51/177] vs NBI 0.30 [54/181], P < 0.01). The change in adenoma detection rate, adenoma and sessile serrated lesions detection rate, and polyp detection rate for the right-sided colon between the TXI and NBI groups were not different (10.2%/10.5% [ P = 0.81], 13.0%/12.7% [ P = 0.71], and 15.3%/13.8% [ P = 0.71]), respectively. DISCUSSION: Regarding Add-30-s observation of the right-sided colon, TXI was noninferior to NBI.
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BACKGROUND & AIMS: PNPLA3 rs738409 has been associated with an increased risk of liver-related events in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the epidemiology of NAFLD and the impact of PNPLA3 on prognosis in Japan. METHODS: A longitudinal multicentre cohort study, the JAGUAR study, includes 1550 patients with biopsy-proven NAFLD in Japan. We performed genetic testing and evaluated outcomes from this cohort. Liver-related events were defined as hepatocellular carcinoma (HCC) and decompensated liver cirrhosis events. RESULTS: During follow-up (median [range], 7.1 [1.0-24.0] years), 80 patients developed HCC, 104 developed liver-related events, and 59 died of any cause. The 5-year rate of liver-related events for each single-nucleotide polymorphism was 0.5% for CC, 3.8% for CG, and 5.8% for GG. Liver-related deaths were the most common (n = 28); only three deaths were due to cardiovascular disease. Multivariate analysis identified carriage of PNPLA3 CG/GG (hazard ratio [HR] 16.04, p = .006) and FIB-4 index >2.67 (HR 10.70, p < .01) as predictors of liver-related event development. No HCC or liver-related death was found among patients with PNPLA3 CC. There was a significantly increased risk of HCC, liver-related events, and mortality for CG/GG versus CC, but no difference between the CG and GG genotypes. CONCLUSIONS: In Japanese individuals, the main cause of death from NAFLD is liver-related death. The greater risk of liver-related events incurred by PNPLA3 G allele was shown in Japan. Risk stratification for NAFLD in Japan is best accomplished by integrating PNPLA3 with the FIB-4 index.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/genética , Estudos de Coortes , População do Leste Asiático , Predisposição Genética para Doença , Genótipo , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Polimorfismo de Nucleotídeo Único , Prognóstico , Japão/epidemiologia , Seguimentos , Medição de Risco , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Cirrose Hepática/genéticaRESUMO
BACKGROUND AND AIM: The aim of this study was to develop a novel noninvasive test using an artificial intelligence/neural network system (called HCC-Scope) to diagnose early-stage hepatocellular carcinoma (HCC) on the background of nonalcoholic steatohepatitis (NASH). METHODS: In total, 175 patients with histologically proven nonalcoholic fatty liver disease and 55 patients with NASH-HCC were enrolled for training and validation studies. Of the 55 patients with NASH-HCC, 27 (49.1%) had very early-stage HCC, and six (10.9%) had early-stage HCC based on the Barcelona Clinic Liver Cancer staging system. Diagnosis with HCC-Scope was performed based on 12 items: age, sex, height, weight, AST level, ALT level, gamma-glutamyl transferase level, cholesterol level, triglyceride level, platelet count, diabetes status, and IgM-free apoptosis inhibitor of macrophage level. The FMVWG2U47 hardware (Fujitsu Co. Ltd, Tokyo, Japan) and the originally developed software were used. RESULTS: HCC-Scope had sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100% for the differential diagnosis between non-HCC and HCC in a training study with gray zone analysis. It was also excellent in the validation study (95.0% sensitivity, 100% specificity, 100% PPV, and 97.1% NPV with gray zone analysis and 95.2% sensitivity, 100% specificity, 100% PPV, and 97.1% NPV without gray zone analysis). HCC-Scope had a significantly higher sensitivity (85.3%) and specificity (85.1%) than alpha-fetoprotein (AFP) level, AFP-L3 level, des-gamma-carboxy prothrombin (DCP) level, and the gender-age-AFP-L3-AFP-DCP (GALAD) score. CONCLUSIONS: HCC-Scope can accurately differentially diagnose between non-HCC NASH and NASH-HCC, including very early-stage NASH-HCC.
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AIM: There are few reports on the prognosis of liver-related events in Japanese patients with nonalcoholic fatty liver disease (NAFLD). We undertook an observational study to compare the prognosis between fibrotic and nonfibrotic groups in Japanese NAFLD patients. METHODS: Prognosis in 393 NAFLD patients who underwent liver biopsy between April 2013 and April 2015 at multiple centers were investigated. The time to onset of liver-related events, cardiovascular events, development of extrahepatic cancers, and death were compared between the pathologically fibrotic nonalcoholic steatohepatitis (NASH) group and nonalcoholic fatty liver (NAFL) + nonfibrotic NASH group. A similar analysis was carried out based on the fibrotic classification diagnosed using four noninvasive fibrosis prediction models. RESULTS: The mean age and body mass index at the time of liver biopsy was 55.7 years old and 28.04 kg/m2 , respectively The cumulative incidence of liver-related events at 1080 days after liver biopsy was 5.79% in the pathologically fibrotic NASH group and 0% in the NAFL + nonfibrotic NASH group, with a significant difference (p = 0.0334). The cumulative incidence of liver-related events was significantly higher in the positive group for the prediction model than in the negative group in all four models (all p values were <0.0001). There was no significant difference between the pathologically fibrotic NASH group and NAFL + nonfibrotic NASH group in terms of cumulative incidence of cardiovascular events, development of extrahepatic cancers, and death. CONCLUSIONS: The incidence of liver-related events was significantly higher in the fibrotic NASH group than that of the NAFL + nonfibrotic NASH group in Japanese NAFLD patients.
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AIM: The enhanced liver fibrosis (ELF) test is a noninvasive method for diagnosing hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). This multicenter cohort study aimed to evaluate the accuracy of the ELF test and compare it with other noninvasive tests in Japan. METHODS: We analyzed 371 Japanese patients with biopsy-proven NAFLD. We constructed area under the receiver operator characteristic curves (AUROC) to determine the diagnostic accuracies of the ELF test, the Mac-2-binding protein glycosylation isomer (M2BPGi), the Fibrosis-4 (FIB-4) index, and combinations of these indices. RESULTS: In patients with F0/F1/F2/F3/F4 fibrosis, the median values of the ELF test were 8.98/9.56/10.39/10.92/11.41, respectively. The AUROCs of the ELF test for patients with F0 versus F1-4, F0-1 versus F2-4, F0-2 versus F3-4, and F0-3 versus F4 fibrosis were 0.825/0.817/0.802/0.812, respectively. The AUROCs of the ELF test were greater than those of the FIB-4 index and M2BPGi at each fibrosis stage. Respective low and high cut-off values yielded sensitivities and specificities for predicting advanced fibrosis (≥F3) of 91.1% and 50.8%, and 38.5% and 92.8%, respectively. For F3 or F4 fibrosis, the combined values from the ELF test and FIB-4 index showed a sensitivity of 98.5%, and the combined values from the ELF test and M2BPGi assay showed a specificity of 97.5%. CONCLUSIONS: In Japan, the ELF test predicts NAFLD-related fibrosis from its early stages. The diagnostic ability of the ELF test was not inferior to that of other indices, and the combined values of ELF plus other indices were more accurate.