A comparative study of demarcation line diagnostic performance between non-magnifying observation with white light and non-magnifying observation with narrow-band light for early gastric cancer.

BACKGROUND AND AIMS: With the improvement in endoscopic equipment functions, narrow-band imaging (NBI) for endoscopic observation of the stomach, which is an organ with a large lumen, is now feasible. Studies evaluating the NBI utility without magnifying endoscopy to diagnose the invasion extent for the demarcation line identification in early gastric cancer have not been reported. This study aimed to investigate the demarcation line diagnostic performance of NBI in early gastric cancer compared to that of white-light imaging (WLI) using prospectively collected consecutive specimens from early gastric cancer patients. METHODS: Thirty consecutive lesions were collected from patients who underwent endoscopic submucosal dissection for early gastric cancer. Next, 30 NBI and 30 WLI images, each with the same degree of gastric wall extension, angle, and layout for one lesion, were selected, and a total of 60 images were prepared for testing. The early gastric cancer invasion ranges in the endoscopic images was plotted using the web-developed software, and 264 independent endoscopists, unaware of the diagnosis, performed the web tests, with the concordance rates between the ranges of responses. After estimating the actual early gastric cancer invasion ranges, the NBI and WLI results were compared. RESULTS: The concordance rates for NBI and WLI images were 43.1% (95% confidence interval [CI] 42.5-43.7%) and 37.2% (95% CI 36.6-37.7%), respectively, showing that the concordance rate for NBI was significantly higher than that for WLI. CONCLUSION: This study suggested that NBI was more useful for identifying demarcation lines than WLI.

Diagnosis of histological type of early gastric cancer by magnifying narrow-band imaging: A multicenter prospective study.

Objectives: Distinguishing undifferentiated-type from differentiated-type early gastric cancers (EGC) is crucial for determining the indication of endoscopic resection. We aimed to investigate the diagnostic performance of white-light endoscopy (WLE) and magnifying narrow-band imaging (M-NBI) for the histological type of EGC. Methods: In this multicenter prospective study, patients with histologically proven cT1 EGC, macroscopically depressed or flat type, size ≥5 mm, and without erosion/ulcer, were recruited. The diagnostic criterion of WLE for undifferentiated-type EGC was pale color. The M-NBI algorithm was created based on microsurface and microvascular patterns, and lesions with absent microsurface pattern and opened-loop microvascular patterns were diagnosed as undifferentiated-type. The center of the lesion was defined as the evaluation point and was initially evaluated by WLE, then by M-NBI, and a biopsy specimen was taken as a reference standard. The primary and key secondary endpoints were overall diagnostic accuracy and specificity, respectively. Results: In total, 167 lesions (122 differentiated-type and 45 undifferentiated-type EGCs) in 167 patients were analyzed. The overall accuracy, sensitivity, specificity, and positive likelihood ratio of WLE for undifferentiated-type cancer were 80%, 69%, 84%, and 4.4, respectively, and those of M-NBI were 82%, 53%, 93%, and 7.2, respectively. There was no significant difference in overall accuracy (p = 0.755), but specificity was significantly higher in M-NBI (p = 0.041). Conclusions: The use of M-NBI did not improve the accuracy of WLE for the diagnosis of depressed/flat undifferentiated-type EGCs but improved the specificity. It may reduce surgical overtreatment by preventing misdiagnosis of differentiated-type EGC as undifferentiated-type.

Visualization of Absorbed Lipid in the Normal Duodenal Epithelium Using Magnifying Endoscopy with Narrow-Band Imaging.

BACKGROUND: Subepithelial microvascular pattern cannot be visualized on the surface of adenoma and carcinoma by magnifying endoscopy due to a white opaque substance (WOS), which consists of minute lipid droplets accumulated in the neoplastic epithelium. AIMS: We aimed to investigate whether the WOS is visualized in the duodenum after exogenous fat loading (FL) administration in an open-label, randomized, controlled study. METHODS: The patients scheduled to undergo endoscopic therapy for gastric epithelial neoplasms were enrolled in the study. They were randomly assigned to the FL or non-FL group. An initial (before FL administration) and follow-up (after two to three weeks) endoscopic examinations were conducted to observe the duodenal mucosa using magnifying narrow-band imaging. Each patient in the FL group consumed 250 ml of Ensure H® four hours before the follow-up examination. Two experienced endoscopists determined the grade of the WOS. FL test results were judged positive for patients who showed a higher grade at the follow-up examination than at the initial examination. The rate of positive test results was compared between the two groups. RESULTS: Twenty patients (10 in the FL and 10 in the non-FL groups) were included. FL test results were positive for all 10 patients in the FL group, while they were negative for all 10 patients in the non-FL group (P < 0.001 by Fisher's exact test). CONCLUSIONS: Lipids loaded onto normal duodenal epithelium were absorbed, and the absorbed lipid droplets appeared as WOS on magnifying narrow-band imaging.

Measurement of intragastric pressure: an objective method to ascertain whether gastric wall extension is sufficient for assessment of the non-extension sign.

Background and study aims The optimal intragastric pressure (IP) for strong gastric wall extension is unclear. We aimed to develop an accurate method to measure IP using endoscopy and determine the pressure required for strong gastric wall extension. Methods An in vitro experiment using an endoscope with a rubber attached at its tip was conducted. The process of inserting the pressure measurement probe into the forceps channel was skipped, and the tube of the pressure measurement device was directly connected to the forceps channel. In vivo, the pressure in 51 consecutive patients at the time of strong gastric wall extension was measured. Strong extension of the gastric wall was defined as when the folds in the greater curvature were flattened as a result of sufficient extension of the gastric wall by insufflated air during upper gastrointestinal endoscopy. The IP at that time was measured. Results In vitr o , 20 mL of tap water was injected once into the forceps channel and then aspirated for 10 seconds. Pressure measurement after irrigation of the forceps channel as well as the measurement by inserting the probe procedure were accurately performed. In vivo, among the 51 included patients, the mean IP (range) was 14.7 mmHg (10-23). Strong extension of the gastric wall was obtained in 96.1 % of patients when the IP was 20 mmHg. Conclusions We developed an accurate method to measure IP using upper gastrointestinal endoscopy. Strong extension of the gastric wall was obtained in almost all patients when the IP was 20 mmHg.

Histological Architecture of Gastric Epithelial Neoplasias That Showed Absent Microsurface Patterns, Visualized by Magnifying Endoscopy with Narrow-Band Imaging.

BACKGROUND/AIMS: The objective of this study was to elucidate the histological structure of the absent microsurface patterns (MSPs) that were visualized by magnifying endoscopy with narrow-band imaging (M-NBI). METHODS: The study included consecutive gastric epithelial neoplasias for which M-NBI findings and histological findings could be compared on a one-to-one basis. The lesions were classified as absent MSPs and present MSPs based on the findings obtained using M-NBI. Of the histopathological findings for each lesion that corresponded to M-NBI findings, crypt opening densities, crypt lengths, crypt opening diameters, intercrypt distances, and crypt angles were measured and compared. RESULTS: Thirty-six lesions were included in the analysis; of these, 17 lesions exhibited absent MSP and 19 lesions exhibited present MSP. Comparing the histological measurements for absent MSPs vs. present MSPs, median crypt opening density was 0.9 crypt openings/mm vs. 4.8 crypt openings/mm (p<0.001), respectively. The median crypt length, median crypt opening diameter, median intercrypt distance, and median crypt angle were 80.0 µm vs. 160 µm (p<0.001), 40.0 µm vs. 44.2 µm (p=0.09), 572.5 µm vs. 166.7 µm (p<0.001), and 21.6 degrees vs. 15.5 degrees (p<0.001), respectively. CONCLUSION: Histological findings showed that lesions exhibiting absent MSPs had lower crypt opening density, shorter crypt length, greater intercrypt distance, and larger crypt angle.

Histological subtype of gastric adenocarcinoma: two cases of mixed fundic and pyloric mucosa-type adenocarcinoma.

Adenocarcinomas with differentiation towards fundic or pyloric glands are rare histological subtypes. We herein describe two cases of new histological subtypes: mixed fundic and pyloric mucosa-type adenocarcinoma detected in Helicobacter pylori uninfected patients. The first patient was a woman in her 40s. A glossy, reddish, nodular lesion with a flat elevated whitish area was detected at the gastric fundus. When the nodular lesion was visualised with magnifying narrow-band imaging (M-NBI), an absent microvascular pattern plus an irregular microsurface pattern with a demarcation line was observed. The second patient was a woman in her 60s. A glossy, reddish, elevated lesion was detected at the gastric body. M-NBI finding was a regular microvascular pattern plus a regular microsurface pattern with a demarcation line. Histological examination of the resected specimens from both cases showed a very well- to well-differentiated adenocarcinoma which has differentiation towards the mixed fundic and pyloric mucosa. The histological and serological findings of both cases indicated the absence of H. pylori infection. The present two cases demonstrate further evidence of a new histological subtype of gastric adenocarcinoma: mixed fundic and pyloric mucosa-type adenocarcinoma, which has distinct characteristic endoscopic findings.

Guidelines for endoscopic diagnosis of early gastric cancer.

The Japan Gastroenterological Endoscopy Society developed the Guideline for Endoscopic Diagnosis of Early Gastric Cancer based on scientific methods. Endoscopy for the diagnosis of early gastric cancer has been acknowledged as a useful and highly precise examination, and its use has become increasingly more common in recent years. However, the level of evidence in this field is low, and it is often necessary to determine recommendations based on expert consensus only. This clinical practice guideline consists of the following sections to provide the current guideline: [I] Risk stratification of gastric cancer before endoscopic examination, [II] Detection of early gastric cancer, [III] Qualitative diagnosis of early gastric cancer, [IV] Diagnosis to choose the therapeutic strategy for gastric cancer, [V] Risk stratification after endoscopic examination, and [VI] Surveillance of early gastric cancer.

Irregularly branched microvessels as visualized by magnifying endoscopy: a reliable marker for predicting deep submucosal invasion of superficial esophageal squamous cell carcinoma.

Background and study aims Magnifying endoscopy with narrow-band imaging (M-NBI) is reported to be useful in diagnosing invasion depth of superficial esophageal squamous cell carcinoma (SCC), but accurate diagnosis of deep submucosal invasion (SM2) has remained difficult. However, we discovered that irregularly branched microvessels observed with M-NBI are detected in SM2 cancers with high prevalence. Thus, this retrospective study aimed to investigate the diagnostic performance of irregularly branched microvessels as visualized by M-NBI for predicting SM2 cancers. Patients and methods Patients with superficial esophageal SCC lesions that were endoscopically or surgically resected at our hospital between September 2005 and December 2014 were included. Endoscopic findings by M-NBI of these lesions were presented to an experienced endoscopist who was unaware of the histopathological diagnosis and who then judged whether irregularly branched microvessels were present. Using the invasion depth according to postoperative histopathological diagnosis as the gold standard, we determined the diagnostic performance of the presence of irregularly branched microvessels as an indicator for SM2 cancers. Results A total of 302 superficial esophageal SCC lesions (228 patients) were included in the analysis. When irregularly branched microvessels were used as an indicator of SM2 cancers, the diagnostic accuracy was 94.0 % (95 % confidence interval [CI]: 91.1-96.1 %), sensitivity was 79.4 % (95 % CI: 66.6-88.4 %), specificity was 95.9 % (95 % CI: 94.3-97.0 %), positive predictive value was 71.1 % (95 % CI: 59.6-79.1 %), and negative predictive value was 97.3 % (95% CI: 95.7-98.5 %). Conclusions Irregularly branched microvessels may be a reliable M-NBI indicator for the diagnosis of cancers with deep submucosal invasion.

Learning Effect of Diagnosing Depth of Invasion Using Non-Extension Sign in Early Gastric Cancer.

BACKGROUND: Determining the depth of invasion is important when considering therapeutic strategies for early gastric cancer (EGC). We determined the effects of learning the non-extension sign, that is, an index of T1b2 in EGC, on identifying its depth of invasion. METHODS: Endoscopic images of 40 EGC cases (20 showing positive non-extension sign on endoscopy as T1b2 and 20 showing negative non-extension sign on endoscopy as T1a-T1b1) were randomly displayed on PowerPoint. Participants read endoscopy findings (pretest) and attended a 60-min lecture on how to read the non-extension sign. Then, they read the same images using the non-extension sign as the marker (posttest). The primary endpoint was a change in accuracy rate for determining the depth of invasion before and after attending the lecture, for nonexperts (< 80%). RESULTS: Among 35 endoscopists, 12 were nonexperts; their test results were used for analyses. Accuracy rates for pretest and posttest among nonexperts were 75.2 and 82.5%, respectively, showing a significant increase in the accuracy rate after learning to read the non-extension sign (p = 0.003). CONCLUSION: Nonexperts' diagnostic ability to determine the depth of invasion of EGC improved by learning to read the non-extension sign. Thus, the non-extension sign is considered a simple and useful diagnostic marker.

Self-study of the non-extension sign in an e-learning program improves diagnostic accuracy of invasion depth of early gastric cancer.

Background and study aims We developed an e-learning program for endoscopic diagnosis of invasion depth of early gastric cancer (EGC) using a simple diagnostic criterion called non-extension sign, and the contribution of self-study quizzes to improvement of diagnostic accuracy was evaluated. Methods We conducted a prospective randomized controlled study that recruited endoscopists throughout Japan. After completing a pretest, the participants watched video lectures and undertook post-test 1. The participants were then randomly allocated to either the self-study or non-self-study group, and participants in the first group completed the self-study program that comprised 100-case quizzes. Finally, participants in both groups undertook post-test 2. The primary endpoint was the difference in post-test 2 scores between the groups. The perfect score for the tests was set as 100 points. Results A total of 423 endoscopists completed the pretest and were enrolled. Post-test 1 was completed by 415 endoscopists and 208 were allocated to the self-study group and 207 to the non-self-study group. Two hundred and four in the self-study group and 205 in the non-self-study group were included in the analysis. Video lectures improved the mean score of post-test 1 from 72 to 77 points. Participants who completed the self-study quizzes showed significantly better post-test 2 scores compared with the non-self-study group (80 vs. 76 points, respectively, P  < 0.0001). Conclusions Our e-learning program showed that self-study quizzes consolidated knowledge of the non-extension sign and improved diagnostic ability of endoscopists for invasion depth of EGC.

Crohn's disease-specific mortality: a 30-year cohort study at a tertiary referral center in Japan.

BACKGROUND: In this study, survival and cause of death were investigated in patients with Crohn's disease (CD) at a tertiary referral center. METHODS: A database was created based on the medical records of 1108 CD patients who had a history of visiting our hospital to investigate background characteristics, cumulative survival rates from diagnosis, causes of death, and the standardized mortality ratio (SMR) for each cause of death. A follow-up questionnaire survey of patients followed up inadequately was also conducted. The cumulative survival rate from diagnosis was determined using the life table method and compared with that of a sex- and age-matched population model from the year 2000. RESULTS: The study included 1108 patients whose mean age at diagnosis was 25.6 ± 10.8 years. The mean duration of follow-up was 14.6 ± 9.4 years, and there were 52 deaths. The cumulative survival rate was significantly lower 25 years after the diagnosis of CD (91.7%) than in the standard population model (95.7%). SMRs for both all causes [3.5; 95% confidence interval (CI): 2.7-4.6] and CD-specific causes (36.7; 95% CI 26.1-51.6) were high. Among the CD-specific causes, SMRs were especially high for small intestine and colorectal cancers, gastrointestinal diseases including intestinal failure (IF), perioperative complications, and amyloidosis. CONCLUSION: The SMRs for both all causes and CD-specific causes were high in CD patients. CD-specific causes including intestinal cancer, IF, perioperative complications, and amyloidosis showed especially high SMRs.

Trough level of infliximab is useful for assessing mucosal healing in Crohn's disease: a prospective cohort study.

BACKGROUND/AIMS: Decreased trough levels of infliximab (TLI) and antibodies to infliximab (ATI) are associated with loss of response (LOR) in Crohn's disease. Two prospective studies were conducted to determine whether TLI or ATI better correlates with LOR (Study 1), and whether TLI could become a predictor of mucosal healing (MH) (Study 2). METHODS: Study 1 was conducted in 108 patients, including those with LOR and remission to compare ATI and TLI in discriminating the 2 conditions based on receiver operating characteristic (ROC) curve analyses. Study 2 involved 35 patients who were evaluated endoscopically. RESULTS: In Study 1, there were no differences between the 2 assays in ROC curve analyses; the TLI cutoff value for LOR was 2.6 µg/mL (sensitivity, 70.9%; specificity, 79.2%), and the ATI cutoff value was 4.9 µg/mL (sensitivity, 65.5%; specificity, 67.9%). The AUROC (area under the ROC curve) of TLI was greater than that of ATI. AUROC was useful for discriminating between the 2 conditions. In Study 2, the TLI was significantly higher in the colonic MH group than in the non-MH group (2.7 µg/mL vs. 0.5 µg/mL, P=0.032). CONCLUSIONS: TLI is better than ATI for clinically diagnosing LOR, and a correlation was observed between TLI and colonic MH.

Delineation of the extent of early gastric cancer by magnifying narrow-band imaging and chromoendoscopy: a multicenter randomized controlled trial.

BACKGROUND: Accurate delineation of tumor margins is necessary for curative resection of early gastric cancer (EGC). The objective of this multicenter, randomized, controlled study was to compare the accuracy with which magnifying narrow-band imaging (M-NBI) and indigo carmine chromoendoscopy delineate EGC margins. METHODS: Patients with EGC ≥ 10 mm undergoing endoscopic or surgical resection were enrolled. The oral-side margins of the lesions were first evaluated with conventional white-light endoscopy in both groups and then delineated by either chromoendoscopy or M-NBI. Biopsies were taken from noncancerous and cancerous mucosa, each at 5 mm from the margin. Accurate delineation was judged to have been achieved when the histological findings in all biopsy samples were consistent with endoscopic diagnoses. The primary end point was the difference in rate of accurate delineation between the two techniques. RESULTS: Data on 343 patients were analyzed. The accurate delineation rate (95 % confidence interval) was 85.7 % (80.4 - 91.0) in the chromoendoscopy group (n = 168), and 88.0 % (83.2 - 92.8) in the M-NBI group (n = 175; P = 0.63). Lower third tumor location (odds ratio [OR] 2.9; P = 0.01), nonflat macroscopic type (OR 4.4; P < 0.01), and high diagnostic confidence (OR 3.6; P < 0.001) were associated with accurate delineation, whereas use of M-NBI was not (OR 1.2; P = 0.39). Even after adjustment for identified confounders, the difference in accurate delineation between the groups was not significant (OR 1.0; P = 0.82). CONCLUSIONS: M-NBI does not offer superior delineation of EGC margins compared with chromoendoscopy; the two methods appear to be clinically equivalent.

Clinical predictors of histologic type of gastric cancer.

BACKGROUND AND AIMS: Gastric cancer is classified into differentiated and undifferentiated types according to the degree of glandular differentiation. Undifferentiated-type early gastric cancer (EGC) carries a higher risk of lymph-node metastasis than differentiated type, and therefore the indication criteria for endoscopic resection differ. This study aimed to clarify the ability of clinical predictors to distinguish between differentiated-type and undifferentiated-type EGCs. METHODS: This was a post hoc study of a multicenter prospective trial carried out in 5 Japanese hospitals, including 343 patients with cT1 EGC of ≥10 mm. According to the protocol, age, sex, and endoscopic findings of cancer (diameter, location, macroscopic type, and invasion depth) were evaluated, and the final diagnosis was confirmed from resected specimens. We evaluated the associations between these clinical factors and the histologic type of cancer and calculated the ability of the factors to diagnose differentiated-type EGC. The diagnostic ability of forceps biopsy was also calculated as a reference. RESULTS: Multivariate analysis identified older age (≥72 years), male sex, larger tumor size (>30 mm), elevated type, and shallower invasion depth (cT1a) as independent significant predictors for differentiated-type EGC, with elevated type showing the highest positive likelihood ratio. The sensitivity, specificity, accuracy, and positive and negative likelihood ratios of elevated type for differentiated-type EGC were 24%, 99%, 38%, 15.7, and 0.77, respectively, compared with 96%, 86%, 95%, 7.0, and 0.04 for forceps biopsy. CONCLUSIONS: Endoscopic elevated type is a significant predictor for differentiated-type EGC and may exclude undifferentiated-type EGC without the need for forceps biopsy.

Extending magnifying NBI diagnosis of intestinal metaplasia in the stomach: the white opaque substance marker.

Background and aims Intestinal metaplasia (IM) of the stomach is associated with an increased risk of differentiated gastric cancer. While it is important to diagnose IM endoscopically, it can be difficult to observe by white-light endoscopy. In magnifying endoscopy with narrow-band imaging (M-NBI) of the stomach, a light-blue crest (LBC) is widely known to be a useful marker in the endoscopic diagnosis of IM. However, IM that exhibits only white opaque substance (WOS) without an LBC can also occur. The aim of this study was to elucidate whether the presence of WOS on M-NBI of the stomach could serve as a marker of IM in the same way that an LBC does. Methods The subjects were 40 consecutive patients who underwent M-NBI between July and December 2014. The primary endpoint in this study was to evaluate the diagnostic performance of M-NBI for histologically observed IM in WOS- and LBC-positive mucosa. Results The sensitivity and specificity of WOS for histologically diagnosed IM were 50.0 % (95 % confidence interval [CI] 40.0 % - 50.0 %) and 100.0 % (95 %CI 85.0 % - 100.0 %), respectively. Meanwhile, the sensitivity and specificity of LBC were 62.5 % (95 %CI 51.1 % - 65.9 %) and 93.8 % (95 %CI 76.7 % - 98.9 %), respectively. The sensitivity and specificity of WOS and/or LBC (WOS positive and LBC positive, WOS positive and LBC negative, or WOS negative and LBC positive) for histologically diagnosed IM were 87.5 % (95 %CI 76.9 % - 90.9 %) and 93.8 % (95 %CI 77.9 % - 98.9 %), respectively. Conclusions LBC and WOS are both useful markers for endoscopic diagnosis of IM. Combining both markers improves the sensitivity.Clinical trial number: UMINCTR000014453.

Diagnostic performance of conventional endoscopy in the identification of submucosal invasion by early gastric cancer: the "non-extension sign" as a simple diagnostic marker.

BACKGROUND AND AIM: The ability to differentiate between mucosal (M) or microinvasive submucosal (SM1: depth of less than 500 µm) and invasive submucosal (SM2: depth of 500 µm or more) cancer is paramount when choosing the method of treatment for early gastric cancer (EGC). The "non-extension sign" relates to a localized increase in thickness and rigidity due to massive submucosal invasion by a cancer. The present study sought to assess the ability of conventional endoscopy (CE) to correctly identify SM2 cancer using only the non-extension sign. METHODS: This is a retrospective study based on a prospectively collected database. EGCs had been diagnosed according to invasion depth as M-SM1 or SM2. In terms of the endoscopic diagnostic criterion, lesions positive for the non-extension sign were classified as SM2 cancers, while those negative for the non-extension sign were classified as M-SM1 cancers. Histopathological findings were used as the gold standard. RESULTS: We examined a total of 863 lesions from 704 patients, comprising 104 true-positive, 733 true-negative, 9 false-positive, and 17 false-negative lesions. This yielded a sensitivity of 92.0 % (95 % confidence interval (CI), 87.0-97.0 %), a specificity of 97.7 % (95 % CI, 96.7-98.8 %), a positive predictive value of 85.9 % (95 % CI, 79.7-92.1 %), a negative predictive value of 98.8 % (95 % CI, 98.0-99.6 %), and a diagnostic accuracy of 96.9 % (95 % CI, 95.8-98.1 %). CONCLUSION: The non-extension sign may be useful for accurately determining the suitability of minimally invasive endoscopic treatment. Nevertheless, considering the limitations of retrospective analysis, a further prospective study is warranted to confirm the diagnostic reliability of the non-extension sign.

The nature of the white opaque substance within colorectal neoplastic epithelium as visualized by magnifying endoscopy with narrow-band imaging.

Background and study aims: We previously reported our discovery of a white opaque substance (WOS) that is opaque to endoscopic light inside the epithelium while using magnifying endoscopy (ME) to examine gastric epithelial neoplasia. Histopathologic analysis revealed that the WOS comprises minute lipid droplets (LDs) accumulated within the neoplastic epithelium. In addition, the WOS was found in colorectal epithelial neoplasia, although it was unclear whether this WOS corresponded to an accumulation of LDs, as in the stomach. Therefore, the aim of the current study was to elucidate whether the WOS observed in colorectal epithelial tumors comprises LDs. Patients and methods: A consecutive series of 40 WOS-positive and 40 WOS-negative colorectal epithelial tumors was analyzed. One biopsy specimen was taken from each neoplasm. Cryostat sections were stained with oil red O for LD, and sections after formalin-fixation for LD were immunostained with anti-adipophilin antibody. Results: The prevalence of LDs stained with oil red O in WOS-positive vs. WOS-negative lesions was 47.5 % (19/40) vs. 5 % (2/40), respectively (P < 0.001). Furthermore, the WOS coincided with the expression of adipophilin; the prevalence of LDs stained by anti-adipophilin antibody in WOS-positive vs. WOS-negative lesions was 100 % (40/40) vs. 62.5 % (25/40), respectively (P < 0.001). Conclusions: This study elucidated for the first time that endoscopically visualized WOS in colorectal epithelial neoplasia may be composed of LDs accumulated in the neoplastic epithelium.

Intracellular mechanisms underlying lipid accumulation (white opaque substance) in gastric epithelial neoplasms: A pilot study of expression profiles of lipid-metabolism-associated genes.

BACKGROUND AND AIM: White opaque substance (WOS) is a novel endoscopic finding in gastric neoplasms, indicating the intracellular accumulation of lipid droplets (LDs). However, gastric lipid metabolism has not been extensively investigated, even in normal mucosa. We investigated the expression profiles of lipid-metabolism-associated genes in gastric neoplasms. METHODS: Thirty-four patients with early gastric cancer or adenoma were enrolled in this study. Paired biopsy samples from tumor and adjacent non-tumor areas were obtained and analyzed by real-time polymerase chain reaction. Endoscopically resected specimens were evaluated histopathologically. RESULTS: Genes associated with ß-oxidation (peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1A, and hydroxyacyl-CoA dehydrogenase), lipoprotein excretion (apolipoprotein B, microsomal triglyceride transfer protein, and acyl-CoA:cholesterol acyltransferase 2), fatty acid transport (fatty acid-binding protein), construction of triglycerides in the endoplasmic reticulum (acyl-CoA:diacylglycerol acyltransferase 1), and LD degradation/lipolysis (comparative gene identification-58, adipose triglyceride lipase) were significantly downregulated in neoplasms compared with non-tumor areas. Pyruvate dehydrogenase lipoamide kinase isozyme 4 (negative regulator of glycolysis) and adipophilin (LD surface component) were also repressed. Conversely, expression levels of genes associated with de novo lipogenesis (sterol regulatory element-binding protein 1c, acyl-CoA:diacylglycerol acyltransferase 2) were significantly enhanced in neoplasms. There was no significant difference in gene expression levels between carcinomas and adenomas, or between WOS-positive and WOS-negative neoplasms. CONCLUSION: Gene expression profiles in neoplasms suggest a predominance of lipid storage (lipogenesis/LD formation) over consumption (ß-oxidation/excretion/lipolysis). Lipid accumulation and WOS in gastric epithelial neoplasms may be caused by impaired mitochondrial oxidation, lipoprotein excretion, and LD degradation.

Lipid is absorbed in the stomach by epithelial neoplasms (adenomas and early cancers): a novel functional endoscopy technique.

BACKGROUND AND STUDY AIMS: The authors have successfully demonstrated that the white opaque substance (WOS) identified in gastric epithelial neoplasms is an accumulation of minute lipid droplets on the epithelial neoplasm. It is not known whether the lipid droplets originate from externally ingested lipids (typically foods). The purpose of this study was to investigate whether the oral ingestion of foods containing emulsified fats increases the density of the WOS in epithelial neoplasms. PATIENTS AND METHODS: We examined 92 gastric epithelial neoplastic lesions in 89 patients. The patients were given emulsified fatty foods before the procedure, and magnifying endoscopy with narrow-band imaging (M-NBI) was used to image the lesions. An increase in WOS density after the ingestion of emulsified fatty foods was defined as a positive fat-loading test result. The patients were divided into the following groups: control group, no emulsified fat administered; group 1, fatty food administered 16 hours prior; group 3, fatty food administered both 16 and 4 hours prior. The proportion of positive fat-loading test results was determined in all groups. RESULTS: The rates of positive fat-loading test results were as follows: control group, 9 %; group 1, 26 %; group 2, 52 %; group 3, 78 %. The increase in the rates of positive fat-loading test results in groups 2 and 3 relative to the rate in the control group was statistically significant (chi-squared test). CONCLUSIONS: This study demonstrated for the first time that the ingestion of external lipids causes lipid droplets to aggregate in situ on the gastric epithelial neoplasm. These results can be used to develop a novel functional endoscopy technique that harnesses the lipid absorption capacity of neoplasms.