Update on diagnosis and treatment of early signet-ring cell gastric carcinoma: A literature review.

Gastric signet-ring cell gastric carcinoma (GSRC) is an unfavorable subtype of gastric cancer (GC) that presents with greater invasiveness and poorer prognosis in advanced stage than other types of GC. However, GSRC in early stage is often considered an indicator of less lymph node metastasis and more satisfying clinical outcome compared to poorly differentiated GC. Therefore, the detection and diagnosis of GSRC at early stage undoubtedly play a crucial role in the management of GSRC patients. In recent years, technological advancement in endoscopy including narrow-band imaging and magnifying endoscopy has significantly improved the accuracy and sensitivity of the diagnosis under endoscopy for GSRC patients. Researches have confirmed that early stage GSRC that meets the expanded criteria of endoscopic resection showed comparable outcomes to surgery after receiving endoscopic submucosal dissection (ESD), indicating that ESD could be considered standard treatment for GSRC after thorough selection and evaluation. This article summarizes the current knowledge and updates pertaining to the endoscopic diagnosis and treatment of early stage signet-ring cell gastric carcinoma.

Utilizing artificial intelligence in endoscopy: a clinician's guide.

INTRODUCTION: Artificial intelligence (AI) that surpasses human ability in image recognition is expected to be applied in the field of gastrointestinal endoscopes. Accordingly, its research and development (R &D) is being actively conducted. With the development of endoscopic diagnosis, there is a shortage of specialists who can perform high-precision endoscopy. We will examine whether AI with excellent image recognition ability can overcome this problem. AREAS COVERED: Since 2016, papers on artificial intelligence using convolutional neural network (CNN in other word Deep Learning) have been published. CNN is generally capable of more accurate detection and classification than conventional machine learning. This is a review of papers using CNN in the gastrointestinal endoscopy area, along with the reasons why AI is required in clinical practice. We divided this review into four parts: stomach, esophagus, large intestine, and capsule endoscope (small intestine). EXPERT OPINION: Potential applications for the AI include colorectal polyp detection and differentiation, gastric and esophageal cancer detection, and lesion detection in capsule endoscopy. The accuracy of endoscopic diagnosis will increase if the AI and endoscopist perform the endoscopy together.

Histological and magnified endoscopic evaluation of villous atrophy in gastrointestinal graft-versus-host disease.

AIM:  To measure histological villous atrophy and to clarify the diagnostic accuracy of endoscopic villous atrophy in gastrointestinal graft-versus-host disease. METHODS:  Data for patients who underwent upper and/or lower endoscopic examinations after hematopoietic stem cell transplantation were retrospectively collected. In study 1, group A included 56 patients in whom GI-GVHD was histologically confirmed and group B included 60 patients in whom GI-GVHD was not histologically confirmed. Group C included 59 patients before HSCT. The lengths of villi and crypts in the duodenum and terminal ileum were histologically measured. In study 2, the diagnostic accuracies of villous atrophy of the duodenum and of the terminal ileum using magnifying endoscopy were evaluated. RESULTS:  In study 1, the lengths of villi and the villi/crypt (V/C) ratios of the duodenum and terminal ileum in group A were significantly smaller than those in the other groups (p < 0.05). V/C ratio was moderately correlated with clinical severity, histological grades, and endoscopic grades in the terminal ileum. In study 2, the diagnostic accuracies of magnified images for villous atrophy were 83.8% in the duodenum and 94.9% in the terminal ileum. CONCLUSION:  Magnifying endoscopy enables evaluation of villous atrophy and is useful for optical biopsy of GVHD.

The Diagnostic Performance for Colorectal Neoplasms Using Magnified Endoscopy Differs between Experts and Novice Endoscopists: A Post Hoc Analysis.

INTRODUCTION: Magnified endoscopy is difficult for novice endoscopists because it requires both knowledge and skill of endoscopic diagnosis. The aim of this study was to examine the diagnostic performance of novice endoscopists on determining the invasive depth of colorectal neoplasms and compare it with that of experts. METHODS: The present study was conducted as a post hoc analysis. Thirty expert and 30 novice endoscopists who use magnifying endoscopy (narrow-band imaging [NBI] and pit pattern analysis) were recruited for the online survey. Novice endoscopist was defined as one who has <5 years of experience in magnifying endoscopy. Three outcomes were assessed: (a) diagnostic accuracy of both novice and expert endoscopists in determining the depth of invasion; (b) additional diagnostic accuracy of novice endoscopists in determining the depth of invasion with magnifying NBI or pit pattern compared with nonmagnifying white light imaging (WLI); (c) difference in confidence on diagnosis among each modality between novice and expert endoscopists. RESULTS: The area under the curve (AUC) of expert endoscopists was significantly higher than that of novice endoscopists. The AUC of the pit pattern was significantly higher than that of WLI regardless of lesion characteristics as determined by novice endoscopists. The proportion of answers with high confidence was significantly higher with expert endoscopists than with novice endoscopists. CONCLUSIONS: Aside from learning basic diagnosis of colorectal neoplasms, magnifying endoscopy may have substantial clinical benefit for novice endoscopists.

Magnified Endoscopic Findings of Multiple White Flat Lesions: A New Subtype of Gastric Hyperplastic Polyps in the Stomach.

BACKGROUND/AIMS: While the occurrence of multiple whitish flat elevated lesions (MWFL) was first reported in 2007, no studies on MWFL have been published to date. The present retrospective observational study aimed to clarify the endoscopic findings and clinicopathological features of MWFL. METHODS: Subjects were consecutive patients who underwent upper gastrointestinal endoscopy as part of routine screening between April 2014 and March 2015. The conventional white-light, non-magnifying and magnifying narrow-band images were reviewed. Clinical features were compared between patients with and without MWFL. RESULTS: The conventional endoscopic findings of MWFL include multiple whitish, flat, and slightly elevated lesions of various sizes, mainly located in the gastric body and fundus. Narrow-band imaging enhanced the contrast of MWFL and background mucosa, and magnifying narrow-band imaging depicted a uniformly long, narrow, and elliptical marginal crypt epithelium with an unclear microvascular pattern. Histopathological findings revealed hyperplastic changes of the foveolar epithelium, and parietal cell protrusions and oxyntic gland dilatations were observed in the fundic glands, without any intestinal metaplasia. The rate of acid-reducing drug use was significantly higher in patients with MWFL than in those without (100% [13/13] vs. 53.7% [88/164], p<0.001). CONCLUSION: The present study indicated a relationship between the presence and endoscopic features of MWFL and history of acidreducing drug use.

Magnified Endoscopic Findings of Multiple White Flat Lesions: A New Subtype of Gastric Hyperplastic Polyps in the Stomach

BACKGROUND/AIMS:: While the occurrence of multiple whitish flat elevated lesions (MWFL) was first reported in 2007, no studies on MWFL have been published to date. The present retrospective observational study aimed to clarify the endoscopic findings and clinicopathological features of MWFL. METHODS:: Subjects were consecutive patients who underwent upper gastrointestinal endoscopy as part of routine screening between April 2014 and March 2015. The conventional white-light, non-magnifying and magnifying narrow-band images were reviewed. Clinical features were compared between patients with and without MWFL. RESULTS:: The conventional endoscopic findings of MWFL include multiple whitish, flat, and slightly elevated lesions of various sizes, mainly located in the gastric body and fundus. Narrow-band imaging enhanced the contrast of MWFL and background mucosa, and magnifying narrow-band imaging depicted a uniformly long, narrow, and elliptical marginal crypt epithelium with an unclear microvascular pattern. Histopathological findings revealed hyperplastic changes of the foveolar epithelium, and parietal cell protrusions and oxyntic gland dilatations were observed in the fundic glands, without any intestinal metaplasia. The rate of acid-reducing drug use was significantly higher in patients with MWFL than in those without (100% [13/13] vs. 53.7% [88/164], p < 0.001). CONCLUSIONS:: The present study indicated a relationship between the presence and endoscopic features of MWFL and history of acidreducing drug use.

Application of novel magnified single balloon enteroscopy for a patient with Cronkhite-Canada syndrome.

We present a case of Cronkhite-Canada syndrome (CCS) in which the entire intestine was observed using a prototype of magnifying single-balloon enteroscope (SIF Y-0007, Olympus). CCS is a rare, non-familial gastrointestinal polyposis with ectodermal abnormalities. To our knowledge, this is the first report showing magnified intestinal lesions of CCS. A 73-year-old female visited our hospital with complaints of diarrhea and dysgeusia. The blood test showed mild anemia and hypoalbuminemia. The esophagogastroduodenoscopy and colonoscopy revealed diffuse and reddened sessile to semi-pedunculated polyps, resulting in the diagnosis of CCS. In addition to the findings of conventional balloon-assisted enteroscopy or capsule endoscopy, magnifying observation revealed tiny granular structures, non-uniformity of the villus, irregular caliber of the loop-like capillaries, scattered white spots in the villous tip, and patchy redness of the villus. Histologically, the scattered white spots and patchy redness of the villus reflect lymphangiectasia and bleeding to interstitium, respectively.

Endoscopic imaging modalities for diagnosing invasion depth of superficial esophageal squamous cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Diagnosis of cancer invasion depth is crucial for selecting the optimal treatment strategy in patients with gastrointestinal cancers. We conducted a meta-analysis to determine the utilities of different endoscopic modalities for diagnosing invasion depth of esophageal squamous cell carcinoma (SCC). METHODS: We conducted a comprehensive search of MEDLINE, Cochrane Central, and Ichushi databases to identify studies evaluating the use of endoscopic modalities for diagnosing invasion depth of superficial esophageal SCC. We excluded case reports, review articles, and studies in which the total number of patients or lesions was <10. RESULTS: Fourteen studies fulfilled our criteria. Summary receiver operating characteristic curves showed that magnified endoscopy (ME) and endoscopic ultrasonography (EUS) performed better than non-ME. ME was associated with high sensitivity and a very low (0.08) negative likelihood ratio (NLR), while EUS had high specificity and a very high (17.6) positive likelihood ratio (PLR) for the diagnosis of epithelial or lamina propria cancers. NLR <0.1 provided strong evidence to rule out disease, and PLR >10 provided strong evidence of a positive diagnosis. CONCLUSIONS: EUS and ME perform better than non-ME for diagnosing invasion depth in SCC. ME has a low NLR and is a reliable modality for confirming deep invasion of cancer, while EUS has a high PLR and can reliably confirm that the cancer is limited to the surface. Effective use of these two modalities should be considered in patients with SCC. TRIAL REGISTRATION: PROSPERO (International Prospective Register of Systematic Reviews); number 42015024462 .

Overexpression of CD55 from Barrett's esophagus is associated with esophageal adenocarcinoma risk.

BACKGROUND AND AIM: Although several molecular biomarkers for esophageal adenocarcinoma (EAC) have been shown to be useful disease indicators, none has been established as a reliable indicator for risk of EAC or have progressed to routine use. The aim was to identify biomarkers of high risk for EAC in patients with Barrett's esophagus (BE). METHODS: Following endoscopic observation by magnified endoscopy with narrow band imaging (ME-NBI), brushing was followed by obtaining biopsy samples from columnar-lined esophagus (CLE) and from EAC lesions of EAC patients, and from age- and sex-matched non-EAC controls with BE. Total RNA was extracted for microarray analysis using Affymetrix GeneChip Human Genome U133 plus 2.0 Array. Real-time-PCR analysis of identified candidate genes was used to confirm the results. RESULTS: Overall, 9 EAC patients and 50 patients with BE were studied. Seventy-nine candidate genes were identified by microarray analysis based on a proportional hazards model (P < 0.005). Six genes exhibited significantly differential expressions in both BE and cancer lesions of the EAC group compared to BE of the controls. In the brushing samples, median CD55 relative expression levels in cancer lesions were highest and decreased in BE of EAC group and BE of the controls, in that order (P < 0.001). CONCLUSION: Over expression of CD55 in brushing samples taken from BE may be associated with the risk of EAC.

Endoscopic features of submucosal deeply invasive colorectal cancer with NBI characteristics : S Saito et al. Endoscopic images of early colorectal cancer.

In this review, we discuss the features of conventional endoscopy, magnified endoscopy involving image enhanced endoscopy and endoscopic ultrasonography (EUS) using illustrations for submucosal deeply invasive colorectal cancer (SM-Ca). First, the typical features of SM-Ca were observed, including fold convergence, stiffness, depression (ulceration) and elevated lesions in depressed areas. Magnified endoscopic findings using NBI showed dilated, irregularly shaped micro-capillary vessels. In addition, VI and VN pits were clearly visible using crystal violet staining. In contrast, using EUS, at the third layer we found a layer that was thin compared to the surrounding normal mucosa, which suggested the existence of SM-Ca.

Endocytoscopic narrow-band imaging efficiency for evaluation of inflammatory activity in ulcerative colitis.

AIM: To assess the efficacy of endocytoscopic narrow-band imaging (EC-NBI) for evaluating the severity of inflammation in ulcerative colitis (UC). METHODS: This retrospective study was conducted at a single tertiary care referral center. We included UC patients who underwent colonoscopy with endocytoscopy from July 2010 to December 2013. EC-NBI was performed, and the images were evaluated by assessing visibility, increased vascularization, and the increased calibers of capillaries and were classified as Obscure, Visible or Dilated. Obscure was indicative of inactive disease, while Visible and Dilated were indicative of acute inflammation. This study received Institutional Review Board approval. The primary outcome measures included the diagnostic ability of EC-NBI to distinguish between active and inactive UC on the basis of histological activity. The conventional endoscopic images were classified according to the Mayo endoscopic score. A score of 0 or 1 indicated inactive disease, whereas a score of 2 indicated active disease. RESULTS: Fifty-two patients were enrolled. There was a strong correlation between the EC-NBI findings and the histological assessment (r=0.871, P<0.01). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EC-NBI for diagnosing acute inflammation were 84.0%, 100%, 87.1%, 100%, and 92.3%, respectively, while those for the Mayo endoscopic score were 100%, 40.7%, 100%, 61.0%, and 69.2%, respectively. Compared with conventional endoscopy, EC-NBI was superior in diagnostic specificity, negative predictive value, and accuracy (P<0.001, P=0.001 and P=0.047, respectively). CONCLUSION: The EC-NBI finding of capillaries in the rectal mucosa was strongly correlated with histological inflammation and aided in the differential diagnosis between active and inactive UC.

Utility of magnifying endoscopy with narrow band imaging in determining the invasion depth of superficial pharyngeal cancer.

BACKGROUND: Magnifying endoscopy with narrow band imaging (ME-NBI) is useful to diagnose invasion depth of superficial esophageal cancer. The purpose of this study was to evaluate the utility of ME-NBI of superficial pharyngeal cancer. METHODS: Between April 2008 and June 2012, 146 lesions in 104 patients who underwent ME-NBI and en bloc resection were retrospectively analyzed. Based on magnifying endoscopic classification, proposed by the Japan Esophageal Society, microvasculature type was classified into B1, B2, and B3. RESULTS: B1 alone, B2, and B3 were observed in 128, 14, and 4 lesions, respectively. The frequency of subepithelial cancer were 20.3% (26 of 128), 78.6% (11 of 14), and 100% (4 of 4), respectively (p < .05). Mean invasion distance were 650 µm, 720.0 µm, and 2256.5 µm. Positive and negative predictive value for diagnosing subepithelial cancer based on the presence of B2 or B3 was 83.3% (15 of 18) and 79.7% (102 of 128). CONCLUSION: ME-NBI is useful to determining invasion depth of superficial pharyngeal cancer.

A case of gastric mucosa-associated lymphoid tissue lymphoma in which magnified endoscopy with narrow band imaging was useful in the diagnosis.

Recently, we reported a case of gastric mucosa-associated lymphoid tissue (MALT) lymphoma presenting with unique vascular features. In the report, we defined the tree-like appearance (TLA) on the images of abnormal blood vessels which resembled branches from the trunk of a tree in the shiny mucosa, in which the glandular structure was lost. The 67-year-old female was diagnosed with gastric MALT lymphoma. The patient received eradication therapy for H. pylori. Conventional endoscopy revealed multiple ill-delineated brownish depressions in the stomach and cobblestone-like mucosa was observed at the greater curvature to the posterior wall of the upper gastric body 7 mo after successful eradication. Unsuccessful treatment of gastric MALT lymphoma was suspected on conventional endoscopy. Conventional endoscopic observations found focal depressions and cobblestone-like appearance, and these lesions were subsequently observed using magnified endoscopy combined with narrow band imaging to identify abnormal vessels presenting with a TLA within the lesions. Ten biopsies were taken from the area where abnormal vessels were present within these lesions. Ten biopsies were also taken from the lesions without abnormal vessels as a control. A total of 20 biopsy samples were evaluated to determine whether the diagnosis of MALT lymphoma could be obtained histologically from each sample. A positive diagnosis was obtained in 8/10 TLA (+) sites and in 2/10 TLA(-) sites. Target biopsies of the site with abnormal blood vessels can potentially improve diagnostic accuracy of gastric MALT lymphoma.

Diagnosis of boundary in early gastric cancer.

Endoscopic submucosal dissection (ESD) is an advanced therapeutic endoscopic technique, which allowsresection of larger superficial tumors in the esophagus, stomach, and colon. Precise diagnosis of the boundary between tumor and the non-tumorous surrounding portion is especially important before starting ESD, because too much resection can potentially take more time and can induce a higher complication rate, while too little resection can result in a non-curative resection. The boundary diagnosis is often difficult for early gastric cancer, mainly because of the underlying condition of chronic gastritis. Due to recent developments in endoscopy, including magnified endoscopy and narrow band endoscopy, the boundary diagnosis is becoming easy and more accurate.We have also applied magnified endoscopy combined with narrow band imaging to fresh specimens immediately after resection using thetiling method and XY stage.

Diagnostic utility of narrow-band imaging endoscopy for pharyngeal superficial carcinoma.

AIM: To investigate the endoscopic features of pharyngeal superficial carcinoma and evaluate the utility of narrow-band imaging (NBI) for this disease. METHODS: In the present prospective study, 335 patients underwent conventional white light (CWL) endoscopy and non-magnified/magnified NBI endoscopy, followed by an endoscopic biopsy, for 445 superficial lesions in the oropharynx and hypopharynx. The macroscopic appearance of superficial lesions was categorized as either elevated (< 5 mm in height), flat, or depressed (not ulcerous). Superficial carcinoma (SC) was defined as a superficial lesion showing high-grade dysplasia or squamous cell carcinoma on histology. The color, delineation, and macroscopic appearances of the lesions were evaluated by CWL endoscopy. The ratio of the brownish area/intervascular brownish epithelium (IBE), as well as microvascular proliferation, dilation, and irregularities, was determined by non-magnified/magnified NBI endoscopy. An experienced pathologist who was unaware of the endoscopic findings made the histological diagnoses. By comparing endoscopic findings with histology, we determined the endoscopic features of SC and evaluated the diagnostic utility of NBI. RESULTS: The 445 lesions were divided histologically into two groups: a non-SC group, including non-neoplasia and low-grade dysplasia cases, and an SC group. Of the 445 lesions examined, 333 were classified as non-SC and 112 were classified as SC. There were no significant differences in age, gender, or the location of the lesions between the patients in the two groups. The mean diameter of the SC lesions was significantly greater than that of non-SC lesions (11.0 ± 7.6 mm vs 4.6 ± 3.6 mm, respectively, P < 0.001). Comparisons of CWL endoscopy findings for SC and non-SC lesions by univariate analysis revealed that the incidence of redness (72% vs 41%, respectively, P < 0.001) and a flat or depressed type of lesion (58% vs 44%, respectively, P = 0.013) was significantly higher in the SC group. Using non-magnified NBI endoscopy, the incidence of a brownish area was significantly higher for SC lesions (79% vs 57%, respectively, P < 0.001). On magnified NBI endoscopy, the incidence of IBE (68% vs 33%, P < 0.001) and microvascular proliferation (82% vs 51%, P < 0.001), dilation (90% vs 76%, P = 0.002), and irregularity (82% vs 31%, P < 0.001) was also significantly higher for the SC compared with the non-SC lesions. Multivariate analysis revealed that the incidence of redness (P = 0.022) on CWL endoscopy and IBE (P < 0.001) and microvascular irregularities (P < 0.001) on magnified NBI endoscopy was significantly higher in SC than non-SC lesions. Redness alone exhibited significantly higher sensitivity and significantly lower specificity for the diagnosis of SC compared with redness plus IBE and microvascular irregularities (72% vs 52%, P = 0.002; and 59% vs 92%, P < 0.001, respectively). The accuracy of redness plus IBE and irregularities for the diagnosis of SC was significantly greater than using redness alone (82% vs 62%, respectively, P < 0.001). CONCLUSION: Redness, IBE, and microvascular irregularities appear to be closely related to SC lesions. Magnified NBI endoscopy may increase the diagnostic accuracy of CWL endoscopy for SC.