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Simple Summary: Throughout the years, endoscopic technologies have advanced to facilitate better assessment of gastric lesions and early detection of gastric cancer. With improvements in conventional white light endoscopy, we have also witnessed the development of newer endoscopic diagnostic modalities, giving rise to several classifications for early gastric cancer. Different endoscopic classifications of early gastric based on several endoscopic diagnostic modalities were included in this review. In addition to this, newer and novel endoscopic classifications that were specifically developed for the stomach for assessing and diagnosing gastric lesions have also been included. Illustrative representations of each classification have also been provided to aid readers in better understanding of these endoscopic classifications of early gastric cancer. Endoscopic technologies have been continuously advancing throughout the years to facilitate improvement in the detection and diagnosis of gastric lesions. With the development of different endoscopic diagnostic modalities for EGC, several classifications have been advocated for the evaluation of gastric lesions, aiming for an early detection and diagnosis. Sufficient knowledge on the appearance of EGC on white light endoscopy is fundamental for early detection and management. On the other hand, those superficial EGC with subtle morphological changes that are challenging to be detected with white light endoscopy may now be clearly defined by means of image-enhanced endoscopy (IEE). By combining magnifying endoscopy and IEE, irregularities in the surface structures can be evaluated and highlighted, leading to improvements in EGC diagnostic accuracy. The main scope of this review article is to offer a closer look at the different classifications of EGC based on several endoscopic diagnostic modalities, as well as to introduce readers to newer and novel classifications, specifically developed for the stomach, for the assessment and diagnosis of gastric lesions. [ABSTRACT FROM AUTHOR]

Background: Esophagogastric junctional (EGJ) cancer occurs in the mucosa near the esophagogastric junction, and has characteristics of both esophageal and gastric malignancies; its optimal treatment strategy is controversial. Methods: We conducted a single-center retrospective cohort study of the patients who underwent curative surgery with lymphadenectomy for EGJ cancer. Tumor specimens were categorized by histology and location into four types—centered in the esophagus < 5 cm from EGJ (type E), which were subtyped as (i) squamous-cell carcinoma (SQ) or (ii) adenocarcinoma (AD); (iii) any histological tumor centered in the stomach < 5 cm from EGJ, with EGJ invasion (type Ge); (iv) any histological tumor centered in the stomach < 5 cm from EGJ, without EGJ invasion (type G)—and classified by TNM system; these were compared to patients' clinicopathological characteristics and survival outcomes. Results: A total of 92 EGJ cancer patients were studied. Median follow-up of surviving patients was 35.5 months. Tumors were categorized as 12 type E (SQ), 6 type E (AD), 27 type Ge and 47 type G; of these 7 (58.3%), 3 (50%), 19 (70.4%) and 14 (29.8%) and 23 patients, respectively, had lymph node metastases. No patients with type E (AD) and Ge tumors had cervical lymph node metastasis; those with type G tumors had no nodal metastasis at cervical and mediastinal lymph nodes. Multivariate analysis showed that type E (AD) tumor was an independent prognostic factor. Conclusions: We should distinguish type Ge tumor from type E (AD) tumor because of the clinicopathological and prognostic differentiation. Extended gastrectomy with or without lower esophagectomy according to tumor location and lower mediastinal and abdominal lymphadenectomy are recommended for EGJ cancer. [ABSTRACT FROM AUTHOR]

Background: The identification of circulating tumour cells (CTCs) in peripheral blood is a useful approach to estimate prognosis, monitor disease progression, and measure treatment effects in various malignancies. However,clinical relevance of CTCs is controversial. We attempted to detect viable CTCs in the peripheral blood of gastric cancer patients using a telomerase-specific viral agent.Methods: We took a 7.5-ml blood sample from 65 treatment-negative gastric cancer patients before surgery and10 healthy volunteers. We detected viable CTCs in the blood samples after incubating them with a telomerase specific,replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein (GFP) gene (OBP-401). GFP-positive CTCs were defined as having a diameter of at least 7.735 μm; this threshold was determined by receiver operating characteristic curve analysis. GFP-positive cells were counted under a fluorescence microscope.Results: There was a significant difference in overall survival among the patients with 0–4 and those with ≥5GFP-positive CTCs in the stage I–IV disease group and stage II–IV advanced disease group. The number of GFP-positive CTCs was not related to cancer stage. Among the pathological findings, the number of GFP-positive CTCs was only significantly related to venous invasion, although there were trends towards more GFP-positive CTCs with disease progression (tumour depth, lymph node metastasis, distant metastasis, lymphatic invasion, and histological type).Conclusions: There was a significant relationship between the number of GFP-positive CTCs and overall survival in the patients with gastric cancer. The detection of CTCs using OBP-401 may be useful for prognostic evaluation.Trial registration: University Hospital Medical Information Network in Japan, UMIN000002018. [ABSTRACT FROM AUTHOR]

Background. Bile juice plays a major role in duodenogastroesophageal reflux (DGERD). Several devices to directly measure the bile concentration have been proposed. We aimed to ex-vivo evaluate the bile concentration by narrow band imaging (NBI). Method. From six surgical cholecystectomies, the content of the gallbladders was aspirated and the total biliary acid (TBA) concentration was evaluated. 2 mL was employed for serial twofold dilutions. Each dilution was scoped. Images on white light (WL) and NBI were captured and grouped accordingly to NBI-appearance and TBA-concentration. Results. Nondiluted bile had a TBA-concentration of 61965 ± 32989 μmol/L. Final dilution (1 : 4096) had 1.16 μmol/L. NBI and correspondent WL images were grouped into seven groups, and an NBI/Bile scale was created. Conclusion. The scale showed that not only NBI scale but also white light scale could be useful to predict the bile concentration. This initial study shows that NBI has a potential role in the detection of DGERD and further investigation is warranted to distinguish the presence and the concentration of bile, especially at very low TBA concentrations. [ABSTRACT FROM AUTHOR]

Background/Objectives: Esophageal achalasia is an archetypal esophageal motility disorder characterized by abnormal peristalsis of the esophageal body and impaired lower esophageal sphincter (LES) relaxation. Methods: In this study, the mRNA expression of docking proteins 1 and 2 (DOK1 and DOK2, respectively) were analyzed and the mechanisms underlying achalasia onset were investigated. Results: DOK1 and DOK2 mRNA levels significantly increased in the LES of patients with achalasia. Moreover, significant correlations were observed between IL-1β and DOK1, IL-1β and DOK2, ATG16L1 and DOK1, and HSV1-miR-H1-3p and DOK2 expression levels. However, a correlation between ATG16L1 and DOK2 or between HSV-miR-H1-3p and DOK1 expression was not observed. In addition, a positive correlation was observed between patient age and DOK1 expression. Microarray analysis revealed a significant decrease in the expression of hsa-miR-377-3p and miR-376a-3p in the LES muscle of patients with achalasia. Conclusions: These miRNAs possessed sequences targeting DOK. The upregulation of DOK1 and DOK2 expression induces IL-1β expression in the LES of achalasia patients, which may contribute to the development of esophageal motility disorder. [ABSTRACT FROM AUTHOR]

Peroral endoscopic myotomy (POEM) is an established treatment for primary achalasia. It has gained endorsement from the American Society for Gastrointestinal Endoscopy with increasing clinical acceptance since the fi rst procedure, performed in Japan in 2008. The fi rst successful POEM in the UK was performed in November 2013 at King’s College Hospital and this article presents the fi rst UK case series. Prospective data were collected at 3 and 12–24 months for consecutive patients undergoing POEM. Post-POEM gastro-oesophageal refl ux health-related quality of life scale (GORD-HRQoL) score was recorded. Statistical comparisons were made using paired non-parametric testing. In an initial series of 33 consecutive prospectively followed patients (12 female; 49.5±13 years; median follow-up 9 (3–28) months; 58% having had previous intervention), a 91% success rate has been achieved at 3 months. To date, 16 patients have reached the 12-month time point, with 13 (81%) sustaining response. This case series compares well with international cohorts and demonstrates excellent long-term safety and favourable effi cacy. [ABSTRACT FROM AUTHOR]

The article presents information on the 76th Congress of the Japanese Gastric Cancer Association which was held at the Yonago Convention Center in Tottori, Japan during March 4-6, 2004. Six speakers made presentations. Professor Y. Kitagawa explained the historical background and the current status of sentinel node (SN) biopsy for gastric cancer. After the presentations, five updated subjects of interest for SN biopsy were discussed by six speakers. In the last part of the discussion, the necessity for multicenter trials in order to advance the clinical application of SN biopsy in gastric cancer surgery in Japan was reconfirmed by all speakers and by the audience at the symposium.

In this study, we utilized a stainless steel (SUS304) plate for measuring the Raman scattering spectra of body fluid samples. Using this stainless steel plate, we recorded the Raman scattering spectra of 99.5% ethanol and human serum samples by performing irradiation with 785- and 1064-nm lasers. Raman scattering spectra with intensities equal to or greater than those reported previously were obtained. In addition, the Raman scattering spectra acquired using the 1064-nm laser were less influenced by autofluorescence than those obtained via use of the shorter-wavelength laser. Moreover, the shapes of the spectra did not show any dependence on integration time, and denaturation of the samples was minimal. Our method, based on 1064-nm laser and the stainless steel plate, provides performance equal to or better than the methods reported thus far for the measurement of Raman scattering spectra from liquid samples. This method can be employed to rapidly evaluate the components of serum in liquid form without using surface-enhanced Raman scattering. [ABSTRACT FROM AUTHOR]

Background and study aims: Detecting esophageal achalasia remains a challenge. We describe the diagnostic utility of corona appearance, a novel endoscopic finding specific to esophageal achalasia. Patients and methods: Corona appearance and seven conventional endoscopic findings were compared for sensitivity and consistency (κ-value) among 53 untreated esophageal achalasia patients who underwent endoscopy at our hospital. The following criteria had to be met during lower esophageal sphincter examination using the attached ST Hood short-type for positive corona appearance: A) congestion inside the hood, B) ischemic change around the hood, and C) palisade vessels outside the hood. Results: Corona appearance had the highest sensitivity (91%; κ-value, 0.71). Other findings in descending order of sensitivity included 1) functional stenosis of the esophagogastric junction (EGJ; 86%; κ-value, 0.58), 2) mucosal thickening and whitish change (71%; κ-value, 0.27), 3) abnormal contraction of the esophageal body (59%; κ-value, 0.32), 4) dilation of the esophageal lumen (58%; κ-value, 0.53), 5) liquid remnant (57%; κ-value, 0.51), 6) Wrapping around EGJ (49%; κ-value, 0.14), and 7) food remnant (30%; κ-value, 0.88). Even in 22 patients with poor (grade 1) intraluminal expansion, corona appearance had highest sensitivity (88%) compared to other endoscopic findings (κ-value, 0.63). Conclusions: Among endoscopic findings using a ST Hood short-type to diagnose esophageal achalasia, corona appearance had the highest sensitivity and its consistency (κ-value) among endoscopists was substantial compared to other endoscopic findings. Similar results were obtained for esophageal achalasia cases with poor expansion. Endoscopic diagnosis of esophageal achalasia with hood attached is useful. [ABSTRACT FROM AUTHOR]

Background and Study Aims: Endoscopic diagnosis of esophageal achalasia lacking typical endoscopic features can be extremely difficult. The aim of this study was to identify simple and reliable early indicator of esophageal achalasia. Patients and Methods: This single-center retrospective study included 56 cases of esophageal achalasia without previous treatment. As a control, 60 non-achalasia subjects including reflux esophagitis and superficial esophageal cancer were also included in this study. Endoscopic findings were evaluated according to Descriptive Rules for Achalasia of the Esophagus as follows: (1) esophageal dilatation, (2) abnormal retention of liquid and/or food, (3) whitish change of the mucosal surface, (4) functional stenosis of the esophago-gastric junction, and (5) abnormal contraction. Additionally, the presence of the longitudinal superficial wrinkles of esophageal mucosa, “pinstripe pattern (PSP)” was evaluated endoscopically. Then, inter-observer diagnostic agreement was assessed for each finding. Results: The prevalence rates of the above-mentioned findings (1–5) were 41.1%, 41.1%, 16.1%, 94.6%, and 43.9%, respectively. PSP was observed in 60.7% of achalasia, while none of the control showed positivity for PSP. PSP was observed in 26 (62.5%) of 35 cases with shorter history < 10 years, which usually lacks typical findings such as severe esophageal dilation and tortuosity. Inter-observer agreement level was substantial for food/liquid remnant (k = 0.6861) and PSP (k = 0.6098), and was fair for abnormal contraction and white change. The accuracy, sensitivity, and specificity for achalasia were 83.8%, 64.7%, and 100%, respectively. Conclusion: “Pinstripe pattern” could be a reliable indicator for early discrimination of primary esophageal achalasia. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to clarify the cause of background coloration in the epithelia between each dilated intra papillary capillary loop in esophago-pharyngeal squamous cell carcinoma. Design: This is a single center retrospective study including 124 patients with 160 lesions who underwent esophagogastroduodenoscopy in Nagasaki University Hospital from September 2007 to March 2012; a detailed comparison between endoscopic images and pathology was performed. Immunohistological assessment using anti-human hemoglobin antibody (anti-Hb Ab) was performed to verify the presence of hemoglobin (Hb) component in the cancer cells. Real-time polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) on Hb-β mRNA were performed to assess the production of Hb component within the cancer cells. Results: A strong positivity for anti-Hb Ab was observed in the squamous cell carcinoma area, whereas non-cancerous mucosa showed no immunopositivity for Hb. The concordance rate between anti-Hb Ab immunoreactivity and the presence of BC was as high as 80.9%. The amount of Hb-β mRNA expression was three times higher in cancer tissues compared with the surrounding non-cancerous mucosa. ISH images showed that the expression exclusively occurred in cancer cells, indicating that Hb is probably produced within cancer cells. Conclusions: The background coloration observed is partly due to an extravascular component of Hb. RT-PCR and ISH analyses indicate that Hb is produced within cancer cells. [ABSTRACT FROM AUTHOR]

Background: Per oral endoscopic myotomy (POEM) has been reported to be a new therapeutic option for esophageal achalasia. The possibility that POEM could reduce the risk of developing esophageal squamous cell carcinoma was evaluated. Methods: This was a single-centre, retrospective study. Fifteen consecutive patients with esophageal achalasia who underwent POEM in our institution between August 2010 and January 2012 were enrolled. Ultra-high magnification with endocytoscopy was performed, and both histopathological and immunohistochemical evaluations for Ki-67 and p53 were assessed before and 3 months after POEM. Results: POEM was successfully performed and effectively released the dysphagia symptom in all patients without severe complications. Subjective symptoms (mean Ekcardt score, before 7.4 vs. after 0.5, p<0.05) and manometric pressure studies (mean lower esophageal sphincter pressure), before 82.7 vs. after 22.9 mmHg, p<0.05) showed substantial improvement following POEM. The average numbers of esophageal epithelial nuclei before and after POEM on endocytoscopic images were 128.0 and 78.0, respectively (p<0.05). The mean Ki-67-positive ratio was 26.0 (median 25.4, range, 10.3-33.2) before and 20.7 (median 20.0, 13.1-29.9; p=0.07) after POEM, and the mean p53-positive ratio was 2.35 (median 2.61, 0.32-4.23) before and 0.97 (median 1.49, 0.32-1.56; p<0.05) after POEM. A significant positive correlation was seen between the number of nuclei and the Ki-67-positive ratio (p<0.05). Conclusions: POEM appears to be an effective and less invasive treatment of choice against achalasia and may reduce the risk of esophageal carcinogenesis. Endocytoscopy can be useful for the assessment of esophageal cellular proliferation. [ABSTRACT FROM AUTHOR]

The reported outcomes of endoscopic resection (ER) for early gastric cancer (EGC) remain limited to several single-institution studies. A multicenter retrospective study was conducted at 11 Japanese institutions concerning their results for ER, including conventional endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). A total of 714 EGCs (EMR, 411; ESD, 303) in 655 consecutive patients were treated from January to December 2001. Technically, 511 of the 714 (71.6%) lesions were resected in one piece. The rate of one-piece resection with ESD (92.7%; 281/303) was significantly higher compared with that for EMR (56.0%; 230/411). Histologically, curative resection was found in 474 (66.3%) lesions. The rate of curative resection with ESD (73.6%; 223/303) was significantly higher compared with that for EMR (61.1%; 251/411). Blood transfusion because of bleeding was required in only 1 patient (0.1%) with EMR of 714 lesions. Perforation was found in 16 (2.2%). The incidence of perforation with ESD (3.6%; 11/303) was significantly higher than that with EMR (1.2%; 5/411). All complications were managed endoscopically, and there was no procedure-related mortality. The median follow-up period was 3.2 years (range, 0.5–5.0 years). In total, the 3-year cumulative residual-free/recurrence-free rate and the 3-year overall survival rate were 94.4% and 99.2%, respectively. The 3-year cumulative residual-free/recurrence-free rate in the ESD group (97.6%) was significantly higher than that in the EMR group (92.5%). ER leads to an excellent 3-year survival in clinical practice and could be a possible standard treatment for EGC. ESD has the advantage of achieving one-piece resection and reducing local residual or recurrent tumor. [ABSTRACT FROM AUTHOR]

Blood tests, which are commonly used for cancer screening, generally have low sensitivity. Here, we developed a novel rapid and simple method to generate silver nanoscale hexagonal columns (NHCs) for use in surface-enhanced Raman scattering (SERS). We reported that the intensity of SERS spectra of clinical serum samples obtained from gastrointestinal cancer patients is was significantly higher than that of SERS spectra of clinical serum samples obtained from non-cancer patients. We estimated the combined constituents on silver NHCs by using a field emission-type scanning electron microscope, Raman microscopes, and a 3D laser scanning confocal microscope. We obtained the Raman scattering spectra of samples of physically fractured cells and clinical serum. No spectra were obtained for chemically lysed cultured cells and DNA, RNA, and protein extracted from cultured cells. We believe that our method, which uses SERS with silver NHCs to detect circulating nucleosomes bound by methylated cell-free DNA, may be successfully implemented in blood tests for cancer screening. [ABSTRACT FROM AUTHOR]

Background: Per oral endoscopic myotomy (POEM) has been reported to be a new therapeutic option for esophageal achalasia. The possibility that POEM could reduce the risk of developing esophageal squamous cell carcinoma was evaluated.Methods: This was a single-centre, retrospective study. Fifteen consecutive patients with esophageal achalasia who underwent POEM in our institution between August 2010 and January 2012 were enrolled. Ultra-high magnification with endocytoscopy was performed, and both histopathological and immunohistochemical evaluations for Ki-67 and p53 were assessed before and 3 months after POEM.Results: POEM was successfully performed and effectively released the dysphagia symptom in all patients without severe complications. Subjective symptoms (mean Ekcardt score, before 7.4 vs. after 0.5, p<0.05) and manometric pressure studies (mean lower esophageal sphincter pressure), before 82.7 vs. after 22.9 mmHg, p<0.05) showed substantial improvement following POEM. The average numbers of esophageal epithelial nuclei before and after POEM on endocytoscopic images were 128.0 and 78.0, respectively (p<0.05). The mean Ki-67-positive ratio was 26.0 (median 25.4, range, 10.3-33.2) before and 20.7 (median 20.0, 13.1-29.9; p=0.07) after POEM, and the mean p53-positive ratio was 2.35 (median 2.61, 0.32-4.23) before and 0.97 (median 1.49, 0.32-1.56; p<0.05) after POEM. A significant positive correlation was seen between the number of nuclei and the Ki-67-positive ratio (p<0.05).Conclusions: POEM appears to be an effective and less invasive treatment of choice against achalasia and may reduce the risk of esophageal carcinogenesis. Endocytoscopy can be useful for the assessment of esophageal cellular proliferation. [ABSTRACT FROM AUTHOR]