Although erosions and ulcerations are the most common small-bowel abnormalities found on wireless capsule endoscopy (WCE), a computer-aided detection method has not been established. We aimed to ...develop an artificial intelligence system with deep learning to automatically detect erosions and ulcerations in WCE images.
We trained a deep convolutional neural network (CNN) system based on a Single Shot Multibox Detector, using 5360 WCE images of erosions and ulcerations. We assessed its performance by calculating the area under the receiver operating characteristic curve and its sensitivity, specificity, and accuracy using an independent test set of 10,440 small-bowel images including 440 images of erosions and ulcerations.
The trained CNN required 233 seconds to evaluate 10,440 test images. The area under the curve for the detection of erosions and ulcerations was 0.958 (95% confidence interval CI, 0.947-0.968). The sensitivity, specificity, and accuracy of the CNN were 88.2% (95% CI, 84.8%-91.0%), 90.9% (95% CI, 90.3%-91.4%), and 90.8% (95% CI, 90.2%-91.3%), respectively, at a cut-off value of 0.481 for the probability score.
We developed and validated a new system based on CNN to automatically detect erosions and ulcerations in WCE images. This may be a crucial step in the development of daily-use diagnostic software for WCE images to help reduce oversights and the burden on physicians.
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MicroRNAs (miRNAs) are a class of small non-coding RNAs that, in general, negatively regulate gene expression. They have been identified in various tumor types, showing that different sets of miRNAs ...are usually deregulated in different cancers. Some miRNA genes harboring CpG islands undergo methylation-mediated silencing, a characteristic of many tumor suppressor genes. To identify such miRNAs in hepatocellular carcinoma (HCC), we first examined the methylation status of 43 loci containing CpG islands around 39 mature miRNA genes in a panel of HCC cell lines and non-cancerous liver tissues as controls. Among 11 miRNA genes frequently methylated in HCC cell lines but not in non-cancerous liver tissues, three miRNA genes, i.e. miR-124, miR-203 and miR-375, were selected as silenced miRNAs through CpG-island methylation by comparing methylation and expression status and evaluating restored expression after treatment with 5-aza-2′-deoxycytidine. In primary tumors of HCC with paired non-tumorous liver tissues, only miR-124 and miR-203 showed frequent tumor-specific methylation, and their expression status was inversely correlated with methylation status. Ectopic expression of miR-124 or miR-203 in HCC cells lacking their expression inhibited cell growth, with direct downregulation of possible targets, cyclin-dependent kinase 6 (CDK6), vimentin (VIM), SET and MYND domain containing 3 (SMYD3) and IQ motif containing GTPase activating protein 1 (IQGAP1) or ATP-binding cassette, subfamily E, member 1 (ABCE1), respectively. Our results suggest that miR-124 and miR-203 are novel tumor-suppressive miRNAs for HCC epigenetically silenced and activating multiple targets during hepatocarcinogenesis.
Background and Aim
Although small‐bowel angioectasia is reported as the most common cause of bleeding in patients and frequently diagnosed by capsule endoscopy (CE) in patients with obscure ...gastrointestinal bleeding, a computer‐aided detection method has not been established. We developed an artificial intelligence system with deep learning that can automatically detect small‐bowel angioectasia in CE images.
Methods
We trained a deep convolutional neural network (CNN) system based on Single Shot Multibox Detector using 2237 CE images of angioectasia. We assessed its diagnostic accuracy by calculating the area under the receiver operating characteristic curve (ROC‐AUC), sensitivity, specificity, positive predictive value, and negative predictive value using an independent test set of 10 488 small‐bowel images, including 488 images of small‐bowel angioectasia.
Results
The AUC to detect angioectasia was 0.998. Sensitivity, specificity, positive predictive value, and negative predictive value of CNN were 98.8%, 98.4%, 75.4%, and 99.9%, respectively, at a cut‐off value of 0.36 for the probability score.
Conclusions
We developed and validated a new system based on CNN to automatically detect angioectasia in CE images. This may be well applicable to daily clinical practice to reduce the burden of physicians as well as to reduce oversight.
Asymmetric Pd‐catalyzed Tsuji‐Trost‐type allylation is an important catalytic reaction toward chiral natural and unnatural product syntheses. We successfully modified a desalt‐type reaction using ...allyl ester or halide to a dehydrative one using allylic alcohol via the establishment of two redox‐mediated donor acceptor bifunctional catalyst systems. These systems were cationic CpRu‐Cl‐Napy‐PyCOOH and cationic CpRu‐Naph‐diPIM‐dioxo‐iPr/p‐TsOH and were designed on the basis of the soft ruthenium and hard Brønsted acid combined catalyst concept. The complementary use of the two chiral catalysts for dehydrative asymmetric allylation expands the application scope facilitating the utilization of both aliphatic and aromatic allylic alcohols with various nucleophiles in the substrate. In this account, the design, synthesis, and application of these catalysts were reported.
Two RDACat catalysts, CpRu‐2‐pyridinecarboxylic acid and CpRu‐bisamidine/p‐TsOH, catalyze the dehydrative allylation of various types of nucleophiles including carbon, nitrogen, and oxygen with allylic alcohol. Complementary use of these catalysts constructs the expanded range of chiral allylic compounds.
Background and Aims The Japan NBI Expert Team (JNET) was established in 2011 and has proposed a universal narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors. The aim ...of this study was to evaluate the clinical usefulness of the JNET classification for colorectal lesions. Methods We analyzed 2933 colorectal lesions, which were diagnosed by NBI magnifying observation before endoscopic treatment or surgery. The colorectal lesions consisted of 136 hyperplastic polyps/sessile serrated polyps (HPs/SSPs), 1926 low-grade dysplasia (LGD), 571 high-grade dysplasia (HGD), 87 superficial submucosal invasive (SM-s) carcinomas, and 213 deep submucosal invasive (SM-d) carcinomas. We evaluated the relationship between the JNET classification and the histologic findings of these lesions. Results The sensitivity, specificity, positive and negative predictive values, and accuracy of Type 1 lesions for the diagnosis of HP/SSP were, respectively, 87.5%, 99.9%, 97.5%, 99.4%, and 99.3%; of Type 2A lesions for the diagnosis of LGD were 74.3%, 92.7%, 98.3%, 38.7%, and 77.1%; of Type 2B lesions for the diagnosis of HGD/SM-s carcinoma were 61.9%, 82.8%, 50.9%, 88.2%, and 78.1%; for Type 3 lesions for the diagnosis of SM-d carcinoma were 55.4%, 99.8%, 95.2%, 96.6%, and 96.6%, respectively. Conclusions Type 1, 2A, and 3 of the JNET classification were very reliable indicators for HP/SSP, LGD, and SM-d carcinoma, respectively. However, the specificity and positive predictive value of Type 2B were relatively lower than those of others. Therefore, an additional examination such as pit pattern diagnosis using chromoagents is necessary for accurate diagnosis of Type 2B lesions.
Cancer development is a multistep process involving genetic and cellular alterations, and recent advances in next-generation sequencing have elucidated mutation landscapes of premalignant lesions as ...well as early- and late-stage tumors. In this issue of Journal of Gastroenterology, Kim and colleagues contributed to the better understanding of genetic events in putative precursors of hepatocellular carcinoma (HCC). Precancerous tissues are divided into canonical and non-canonical types, which share common driver mutations with cancerous lesions or not, and potential gatekeeper gene(s) for clonal selection play a critical role in driving precursors to cancers not only in HCC, but also in esophageal, gastric, colorectal, and pancreatic cancers.
Macrophages are an essential component of antitumor activity; however, the role of tumor‐associated macrophages (TAMs) in colorectal cancer (CRC) remains controversial. Here, we elucidated the role ...of TAMs in CRC progression, especially at the early stage. We assessed the TAM number, phenotype, and distribution in 53 patients with colorectal neoplasia, including intramucosal neoplasia, submucosal invasive colorectal cancer (SM‐CRC), and advanced cancer, using double immunofluorescence for CD68 and CD163. Next, we focused on the invasive front in SM‐CRC and association between TAMs and clinicopathological features including lymph node metastasis, which were evaluated in 87 SM‐CRC clinical specimens. The number of M2 macrophages increased with tumor progression and dynamic changes were observed with respect to the number and phenotype of TAMs at the invasive front, especially at the stage of submucosal invasion. A high M2 macrophage count at the invasive front was correlated with lymphovascular invasion, low histological differentiation, and lymph node metastasis; a low M1 macrophage count at the invasive front was correlated with lymph node metastasis. Furthermore, receiver operating characteristic curve analysis revealed that the M2/M1 ratio was a better predictor of the risk of lymph node metastasis than the pan‐, M1, or M2 macrophage counts at the invasive front. These results suggested that TAMs at the invasive front might play a role in CRC progression, especially at the early stages. Therefore, evaluating the TAM phenotype, number, and distribution may be a potential predictor of metastasis, including lymph node metastasis, and TAMs may be a potential CRC therapeutic target.
We identified dynamic changes in the number and phenotype of tumor‐associated macrophages (TAMs) at the invasive front in colorectal cancer (CRC), especially at the stage of submucosal invasion. Furthermore, TAMs at the invasive front may play a role in CRC progression, especially in early stage CRC, ie, M1 macrophages at the invasive front may inhibit CRC progression, while M2 macrophages may promote CRC progression via EMT. Therefore, a marker comprising the phenotype, number, and distribution of TAMs may serve as a potential predictor of metastasis, including lymph node metastasis, and TAMs may be a potential therapeutic target in CRC.
Abstract
α-Alkylation of a β-keto ester is a frequently used reaction for carbon–carbon bond formation. However, extension to a stereoselective reaction remains a significant challenge, because the ...product easily racemizes under acidic or basic conditions. Here, we report a hybrid system consisting of Pd and Ru complexes that catalyzes the asymmetric dehydrative condensation between cinnamyl-type allylic alcohols and β-keto esters. α-Non-substituted β-keto ester can be allylated to afford an α-mono-substituted product with high regio-, diastereo-, and enantioselectivity. No epimerization occurs owing to the nearly neutral conditions, which is achieved by a rapid proton transfer from Pd-enolate formation to Ru π-allyl complex formation. Four diastereomers can be synthesized on demand by changing the stereochemistry of the Pd or Ru complex. Eight stereoisomers with three adjacent stereogenic centers can be synthesized by employing diastereoselective reduction of the ketone in the products. The formal synthesis of (+)-pancratistatin demonstrates the utility of the reaction.
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.
Background
We aimed to clarify the long-term outcomes of patients with T1 colorectal carcinoma (CRC) after endoscopic resection (ER) and surgical resection.
Methods
We examined T1 CRC patients ...treated during 1992–2008 and who had ≥5 years of follow-up. Patients who did not meet the curative criteria after ER according to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines were defined as “non-endoscopically curable” and classified into three groups: ER alone (Group A: 121 patients), additional surgery after ER (Group B: 238 patients), and surgical resection alone (Group C: 342 patients). Long-term outcomes and predictors of recurrence were analyzed.
Results
Of the 882 patients with T1 CRC, 701 were non-endoscopically curable. Among these patients, recurrence and 5-year overall survival (OS) rates were 0.6 and 91.1%, respectively. In Groups A, B, and C, recurrence rates were 5.0, 5.5, and 3.8%, OS rates were 79.3, 92.4, and 91.5% (
p
< 0.01), and 5-year disease-free survival (DFS) rates were 98.1, 97.9, and 98.5%, respectively. Thirty-two patients experienced local recurrence or distant/lymph node metastasis (Group A: 6; Group B: 13; Group C: 13) and 14 patients died of primary CRC (Group A: 3; Group B: 7; Group C: 4). Age ≥65 years, protruded gross type, positive lymphatic invasion, and high budding grade were significant predictors of recurrence in non-endoscopically curable patients.
Conclusions
Our findings supported the JSCCR criteria for endoscopically curable T1 CRC. ER for T1 CRC did not worsen the clinical outcomes of patients who required additional surgical resection.