Association between occurrence of multiple white and flat elevated gastric lesions and oral proton pump inhibitor intake.

BACKGROUND/AIMS: Multiple white and flat elevated lesions (MWFL) that develop from the gastric corpus to the fornix may be strongly associated with oral antacid intake. Therefore, this study aimed to determine the association between the occurrence of MWFL and oral proton pump inhibitor (PPI) intake and clarify the endoscopic and clinicopathological characteristics of MWFL. METHODS: The study included 163 patients. The history of oral drug intake was collected, and serum gastrin levels and anti-Helicobacter pylori immunoglobulin G antibody titers were measured. Upper gastrointestinal endoscopy was performed. The primary study endpoint was the association between MWFL and oral PPI intake. RESULTS: In the univariate analyses, MWFL were observed in 35 (49.3%) of 71 patients who received oral PPIs and 10 (10.9%) of 92 patients who did not receive oral PPIs. The occurrence of MWFL was significantly higher among patients who received PPIs than in those who did not (p<0.001). Moreover, the occurrence of MWFL was significantly higher in patients with hypergastrinemia (p=0.005). In the multivariate analyses, oral PPI intake was the only significant independent factor associated with the presence of MWFL (p=0.001; odds ratio, 5.78; 95% confidence interval, 2.06-16.2). CONCLUSION: Our findings suggest that oral PPI intake is associated with the presence of MWFL (UMINCTR 000030144).

Efficacy of endoscopy under general anesthesia for the detection of synchronous lesions in oro-hypopharyngeal cancer.

BACKGROUND/AIMS: Image-enhanced endoscopy can detect superficial oro-hypopharyngeal squamous cell carcinoma; however, reliable endoscopy of the pharyngeal region is challenging. Endoscopy under general anesthesia during transoral surgery occasionally reveals multiple synchronous lesions that remained undetected on preoperative endoscopy. Therefore, we aimed to determine the lesion detection capability of endoscopy under general anesthesia for superficial oro-hypopharyngeal squamous cell carcinoma. METHODS: This retrospective study included 63 patients who underwent transoral surgery for superficial oropharyngeal squamous cell carcinoma between April 2005 and December 2020. The primary endpoint was to compare the lesion detection capabilities of preoperative endoscopy and endoscopy under general anesthesia. Other endpoints included the comparison of clinicopathological findings between lesions detected using preoperative endoscopy and those newly detected using endoscopy under general anesthesia. RESULTS: Fifty-eight patients (85 lesions) were analyzed. The mean number of lesions per patient detected was 1.17 for preoperative endoscopy and 1.47 for endoscopy under general anesthesia. Endoscopy under general anesthesia helped detect more lesions than preoperative endoscopy did (p<0.001). The lesions that were newly detected on endoscopy under general anesthesia were small and characterized by few changes in color and surface ruggedness. CONCLUSION: Endoscopy under general anesthesia for superficial squamous cell carcinoma is helpful for detecting multiple synchronous lesions.

Magnifying endoscopy with narrow-band imaging for diagnosis of subtype of gastric intestinal metaplasia.

BACKGROUND AND AIM: Patients with incomplete gastric intestinal metaplasia (GIM) have a higher risk of gastric cancer (GC) than those with complete GIM. We aimed to clarify whether micromucosal patterns of GIM in magnifying endoscopy with narrow-band imaging (M-NBI) were useful for diagnosis of incomplete GIM. METHODS: We enrolled patients with a history of endoscopic resection of GC or detailed inspection for suspicious or definite GC. The antrum greater curvature and corpus lesser curvature were regions of interest. Areas with endoscopic findings of light blue crest and/or white opaque substance (WOS) were defined as endoscopic GIM, and subsequent M-NBI was applied. Micromucosal patterns were classified into Foveola and Groove types, and targeted biopsies were performed on GIM with each pattern. GIM was classified into complete and incomplete types using mucin (MUC)2, MUC5AC, MUC6, and CD10 immunohistochemical staining. The primary endpoint was the association between micromucosal pattern and histological subtype. The secondary endpoint was endoscopic findings associated with incomplete GIM. RESULTS: We analyzed 98 patients with 156 GIMs. Univariate analysis (odds ratio [OR] 3.4, P = 0.004), but not multivariate analysis (OR 0.87, P = 0.822), demonstrated a significant association between micromucosal pattern and subtype. The antrum (OR 3.7, P = 0.006) and WOS (OR 43, P = 0.002) were independent predictors for incomplete GIM. The WOS had 69% sensitivity and 93% specificity. CONCLUSIONS: The M-NBI micromucosal pattern is not useful for diagnosis of GIM subtype. WOS is a promising endoscopic indicator for diagnosis of incomplete GIM. (UMIN-CTR000041119).

A case of early gastric cancer in a patient with gastric juvenile polyposis diagnosed by magnifying endoscopy and resected by endoscopic submucosal dissection.

Gastric juvenile polyposis (GJP) is frequently associated with the development of gastric cancer. However, there are no reports of gastric cancer in patients with GJP diagnosed using magnifying endoscopy with narrow-band imaging (M-NBI) and successfully treated by endoscopic submucosal dissection (ESD). A 50-year-old woman was referred to our hospital. Conventional white-light endoscopy revealed numerous aggregated polyps with reddish and whitish areas in the gastric cardia. M-NBI revealed a regular microvascular pattern (MVP) and regular microsurface pattern (MSP) in the reddish area of the lesion, and they were diagnosed as non-cancerous polyps. There was a clear demarcation line between the reddish and whitish areas, with irregular MVP plus irregular MSP in the whitish area, which was diagnosed as early gastric cancer. The horizontal extent of the cancer was precisely identified using M-NBI, and the en bloc resection of cancerous lesions was performed using ESD. Histopathological examination of the resected specimen showed that the reddish area comprised a hyperplastic foveolar epithelium. Conversely, the whitish area was diagnosed as a well-differentiated adenocarcinoma. The cancer was limited to the mucosa, lymphovascular invasion was negative, and horizontal and vertical margins were free from cancerous tissue. According to surveillance endoscopy, there has been no recurrence 11 years after ESD. This is the first report demonstrating that M-NBI is useful for making a precise diagnosis of cancer in juvenile polyposis and that ESD can be an option for the treatment of such a cancer.

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.

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.

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.

Nature of a white opaque substance visualized by magnifying endoscopy in colorectal hyperplastic polyps.

Background and study aims A white opaque substance (WOS) has been observed in the epithelia of gastric, duodenal, and colorectal epithelial adenomas and carcinomas, using magnifying endoscopy (ME). The WOS has been reported to be derived from a dense accumulation of minute lipid droplets in the epithelium. This study aimed to investigate whether the WOS in colorectal hyperplastic polyps was derived from lipid droplets accumulated in the epithelium, as observed in the case of gastric, duodenal, and colorectal epithelial neoplasms. Patients and methods We analyzed 30 consecutive patients who were positive for the WOS, as visualized in colorectal hyperplastic polyps by ME with narrow-band imaging and 30 consecutive patients who were negative for the WOS. Biopsy specimens obtained from the polyps were immunostained with anti-adipophilin antibody to determine the correlation between the presence of the WOS and that of lipid droplets in the epithelium. Results In all patients, the epithelial cells were histologically positive for adipophilin. However, the area of adipophilin-positive epithelial cells in the WOS-positive group was significantly larger than that in the WOS-negative group ( P  < 0.001). The density of the WOS was strongly and positively correlated with the area of adipophilin-positive cells. Conclusions This study reveals that the WOS visualized in the superficial layers of colorectal hyperplastic polyps is produced by a dense accumulation of minute lipid droplets in the epithelia of the polyps.

Erratum: Nature of a white opaque substance visualized by magnifying endoscopy in colorectal hyperplastic polyps.

[This corrects the article DOI: 10.1055/a-1452-9669.].

A case of gastric signet-ring cell carcinoma with a long-term retrospective follow-up of 17 years.

A man in his 60s underwent esophagogastroduodenoscopy (EGD) for gastric cancer screening in 2006. A pale, oval, depressed lesion, 8 mm in diameter, was seen in the greater curvature of the gastric antrum. The patient was followed up every 1-2 years. EGD performed 13 years after 2006 showed the lesion with an irregular margin. Histopathological diagnosis of a target biopsy was signet-ring cell carcinoma. The lesion was resected by endoscopic submucosal dissection. The resected specimen was 8 × 3 mm in size, and histopathological examination showed type 0-IIc, signet-ring cell carcinoma, pT1a, Ly0, V0, UL0, pHM0, pVM0. The patient had no history of Helicobacter pylori infection. The serum anti-H. pylori IgG antibody test result and the urea breath test result was negative. Histopathological examination did not reveal the presence of H. pylori. No evidence of atrophic gastritis on endoscopy was found. Based on these findings, the patient was confirmed as not having H. pylori infection. We retrospectively reviewed all previous endoscopic images and confirmed that the lesion was already present in the images taken 17 years ago. To our knowledge, this is the longest retrospective follow-up (17 years) of gastric signet-ring cell carcinoma remaining in the mucosa, without H. pylori infection.

Usefulness of vessel plus surface classification system for the diagnosis of early gastric cancer after Helicobacter pylori eradication.

BACKGROUND: It has been reported that it is sometimes difficult to make a diagnosis of gastric cancer detected after Helicobacter pylori (H. pylori) eradication. Therefore, we conducted a study to determine the usefulness of magnifying endoscopy using vessel plus surface classification system for making a diagnosis of early gastric cancer after H. pylori eradication. METHOD: Usefulness of the markers of the vessel plus surface classification system for diagnosing gastric cancer using magnifying endoscopy with narrow-band imaging was investigated for gastric cancer detected after H. pylori eradication (H. pylori-eradicated group) vs. H. pylori-positive gastric cancer (H. pylori-positive group). RESULTS: 85 lesions were included in this study. The H. pylori-eradicated group comprised 27 lesions, whereas the H. pylori-positive group comprised 58 lesions. As for magnified endoscopic findings based on the vessel plus surface classification system, the respective positivity rates in the H. pylori-eradicated group vs. those in the H. pylori-positive group were as follows: demarcation line, 100% (27/27) vs. 100% (58/58); irregular microvascular pattern, 100% (27/27) vs. 100% (58/58); and irregular microsurface pattern, 78% (21/27) vs. 95% (55/58). There was no significant difference in the positivity rates of the demarcation line and irregular microvascular pattern between the groups. The positivity rate of the irregular microsurface pattern was significantly lower in the H. pylori-eradicated group than in the H. pylori-positive group (P=0.03). CONCLUSION: We presume that the microvascular pattern is more useful than the microsurface pattern as a diagnostic marker in cases of gastric cancer detected after H. pylori eradication.

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.

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.

[Tracheobronchitis as an extraintestinal manifestation of Crohn's disease].

A 27-year-old woman with Crohn's disease, who had sustained clinical remission for two years following treatment with mesalazine and nutrition therapy, was admitted to our hospital complaining of dry cough, mild dysphagia, and slight fever. A computed tomography of the chest demonstrated an increase in the thickness of the tracheal wall. Bronchoscopy showed a diffusely erythematous and edematous mucosa with whitish granular lesions in the trachea and main carina. Bronchial biopsy specimens showed epithelioid cell granuloma. We diagnosed tracheobronchitis as an extraintestinal manifestation of Crohn's disease. She was treated with 40mg/day prednisolone. Her symptoms improved immediately. However, dry cough recurred two months after prednisolone treatment, and further treatment with inhaled steroids was prescribed. Tracheobronchial involvement in Crohn's disease is rare, with only 13 cases having been reported. Tracheal involvement should be considered in Crohn's disease patients with respiratory symptoms.

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.

Involvement of herbal medicine as a cause of mesenteric phlebosclerosis: results from a large-scale nationwide survey.

BACKGROUND: Mesenteric phlebosclerosis (MP) is a rare disease characterized by venous calcification extending from the colonic wall to the mesentery, with chronic ischemic changes from venous return impairment in the intestine. It is an idiopathic disease, but increasing attention has been paid to the potential involvement of herbal medicine, or Kampo, in its etiology. Until now, there were scattered case reports, but no large-scale studies have been conducted to unravel the clinical characteristics and etiology of the disease. METHODS: A nationwide survey was conducted using questionnaires to assess possible etiology (particularly the involvement of herbal medicine), clinical manifestations, disease course, and treatment of MP. RESULTS: Data from 222 patients were collected. Among the 169 patients (76.1 %), whose history of herbal medicine was obtained, 147 (87.0 %) used herbal medicines. The use of herbal medicines containing sanshishi (gardenia fruit, Gardenia jasminoides Ellis) was reported in 119 out of 147 patients (81.0 %). Therefore, the use of herbal medicine containing sanshishi was confirmed in 70.4 % of 169 patients whose history of herbal medicine was obtained. The duration of sanshishi use ranged from 3 to 51 years (mean 13.6 years). Patients who discontinued sanshishi showed a better outcome compared with those who continued it. CONCLUSIONS: The use of herbal medicine containing sanshishi is associated with the etiology of MP. Although it may not be the causative factor, it is necessary for gastroenterologists to be aware of the potential risk of herbal medicine containing sanshishi for the development of MP.

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.

Increase in colonic diverticular hemorrhage and confounding factors.

AIM: To classify changes over time in causes of lower gastrointestinal bleeding (LGIB) and to identify factors associated with changes in the incidence and characteristics of diverticular hemorrhage (DH). METHODS: A total of 1803 patients underwent colonoscopy for overt LGIB at our hospital from 1995 to 2013. Patients were divided into an early group (EG, 1995-2006, n = 828) and a late group (LG, 2007-2013, n = 975), and specific diseases were compared between groups. In addition, antithrombotic drug (ATD) use and nonsteroidal anti-inflammatory drug (NSAID) use were compared between patients with and without DH. RESULTS: Older patients (≥ 70 years old) and those with colonic DH were more frequent in LG than in EG (P < 0.01). Patients using ATDs as well as NSAIDs, male sex, obesity (body mass index ≥ 25 kg/m(2)), smoking, alcohol drinking, and arteriosclerotic diseases were more frequent in patients with DH than in those without. CONCLUSION: Incidence of colonic DH seems to increase with aging of the population, and factors involved include use of ATDs and NSAIDs, male sex, obesity, smoking, alcohol drinking, and arteriosclerotic disease. These factors are of value in handling DH patients.

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.