[Gastric-type adenocarcinoma consisting of signet-ring cell carcinoma and adenocarcinoma of the fundic gland type:a case report].

After endoscopic treatment for esophageal cancer, a 65-year-old male underwent surveillance esophagogastroduodenoscopy. A 12-mm discolored flat lesion was noted on the greater curvature of the middle gastric body. Magnifying endoscopy with blue laser imaging demonstrated an irregular papillary surface. Biopsy revealed atypical cells with mucus and irregularly distributed nuclei. The lesion was diagnosed as a gastric-type neoplasm with low atypia. Thereafter, endoscopic submucosal dissection (ESD) was conducted and specimen was sent for biopsy. The ESD specimen suggested a signet-ring cell carcinoma with MUC5AC-positive phenotype and adenocarcinoma of the fundic gland type, with MUC6 positivity and pepsinogen I positivity in the shallow and deeper layers, respectively. Moreover, the cervical region of fundic glands demonstrated a transformation zone of the signet-ring cell carcinoma into an adenocarcinoma of the fundic gland type. Herein, we report this rare case along with a literature review.

Conventional versus underwater endoscopic resection for superficial non-ampullary duodenal epithelial tumours.

BACKGROUND AND OBJECTIVE: Several endoscopic resection methods have been developed as less invasive treatments for superficial non-ampullary duodenal epithelial tumours. This study aimed to compare outcomes of conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours, including resection depth and rate of the muscularis mucosa contained under the lesion. METHODS: This single-centre retrospective cohort study conducted from January 2009 to December 2021 enrolled patients who underwent conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours and investigated their clinicopathological outcomes using propensity score matching. RESULTS: Of the 285 superficial non-ampullary duodenal epithelial tumours, 98 conventional endoscopic mucosal resections and 187 underwater endoscopic mucosal resections were included. After propensity score matching, 64 conventional endoscopic mucosal resections and 64 underwater endoscopic mucosal resections were analysed. The R0 resection rate was significantly higher in underwater endoscopic mucosal resection cases than in conventional endoscopic mucosal resection cases (70.3% vs. 50.0%; P = 0.030). In the multivariate analysis, a lesion diameter > 10 mm (odds ratio 7.246; P = 0.001), being in the 1st-50th treatment period (odds ratio 3.405; P = 0.008), and undergoing conventional endoscopic mucosal resection (odds ratio 3.617; P = 0.016) were associated with RX/R1 resection. Furthermore, in underwater endoscopic mucosal resection cases, the R0 rate was significantly higher for lesions diameter ≤10 mm than >10 mm, and was significantly higher in the 51st-treatment period than in the 1st-50th period. Conventional endoscopic mucosal resection and underwater endoscopic mucosal resection cases showed no significant difference in resection depth and muscularis mucosa containing rate. CONCLUSIONS: Underwater endoscopic mucosal resection may be more acceptable than conventional endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours ≤ 10 mm. A steep early learning curve may be acquired for underwater endoscopic mucosal resection. Large multicentre prospective studies need to be conducted to confirm the effectiveness of underwater endoscopic mucosal resection.

Clinical Background Factors as Predictors of the Efficacy of 5-Aminosalicylic Acid Suppositories in Patients with Ulcerative Colitis.

Introduction: Although the efficacy of 5-aminosalicylic acid (ASA) suppositories for ulcerative colitis (UC) has been reported in many studies, many studies have also described poor adherence to 5-ASA suppository regimens. We aimed to identify the clinical background factors that influence adherence to 5-ASA suppositories to improve adherence and efficacy of the treatment. Methods: We conducted a retrospective cohort study of 61 patients with active UC who were using 5-ASA suppositories. All patients underwent endoscopy and rectal biopsy for histological diagnosis prior to 5-ASA suppository treatment. The efficacy of 5-ASA suppository treatment was compared in relation to clinical background factors (sex, age, disease duration, disease type, clinical activity, Ulcerative Colitis Endoscopic Index of Severity, histological activity, serum C-reactive protein level, concomitant use of immunomodulators, history of steroid use, and dose of oral 5-ASA). Results: The efficacy of 5-ASA suppositories was significantly related to low Lichtiger Colitis Activity Index (LCAI) scores and proctitis type prior to its use. In terms of sex, females tended to show higher efficacy. Multivariate logistic regression analysis using these three factors showed high predictive value for the efficacy of 5-ASA suppositories (AUC, 0.788; sensitivity, 87.2%; and specificity, 63.7%). Conclusion: This study is the first to extract clinical background factors for predicting the efficacy of 5-ASA suppositories. The use of 5-ASA suppositories in patients who are expected to show efficacy will be effective in improving patient co-operation.

A new endoscopic scoring system corresponding to histological healing using linked color imaging in ulcerative colitis: the SOUL study.

Background and study aims An important therapeutic aim in ulcerative colitis (UC) is endoscopic remission. Although an endoscopic score with white light imaging (WLI) is mainly used to evaluate endoscopic findings, the usefulness of linked color imaging (LCI) has been reported. We evaluated the relationship between LCI and histopathological findings and attempted to establish a new LCI endoscopic evaluation index for UC. Patients and methods This study was conducted at Kyorin University, Kyoto Prefectural University, and Fukuoka University Chikushi Hospital. Ninety-two patients with a Mayo endoscopic subscore (MES) ≤ 1 who underwent colonoscopy for UC in clinical remission were included. LCI index was defined as redness (R) (Grade 0-2), area of inflammation (A) (Grade 0-3), and lymphoid follicles (L) (Grade 0-3). Histological healing was defined as Geboes score < 2B.1. Endoscopic and histopathological scores were determined by central judgment. Results In 92 patients, 85 biopsies from the sigmoid colon and 84 biopsies from the rectum (total 169 biopsies) were evaluated. There were 22, 117, and 30 cases of Grades 0, 1, and 2, respectively in LCI index-R; 113, 34, 17, and five cases of Grades 0, 1, 2, and 3, respectively, in LCI index-A; and 124, 27, 14, and four cases of Grades 0, 1, 2, and 3, respectively, in LCI index-L. Histological healing was achieved in 84.0 % of the cases (142 of 169), and there were significant associations with histological healing or non-healing in LCI index-R ( P  = 0.013) and A ( P  = 0.0014). Conclusions A new LCI index is useful for predicting histological healing in UC patients with MES ≤ 1 and clinical remission.

Papillary thyroid carcinoma with aggressive fused follicular and solid growth pattern: A unique histological subtype with high-grade malignancy?

Papillary thyroid carcinoma (PTC) is usually indolent; however, some rare subtypes of PTCs, such as columnar cell and hobnail subtypes, carry poor prognosis as an intermediate malignancy between differentiated carcinoma and anaplastic carcinoma. We present the case of a 56-year-old Japanese woman having PTC with aggressive behavior showing characteristic histological features of a predominantly fused follicular and focally solid (FFS) pattern. The fused follicular pattern is cribriform-like without intermingled vessels. This PTC with FFS pattern included frequent mitotic figures, necrosis, lymphovascular invasion, and metastases with high clinical stage. The tumor cells were broadly positive for antibodies to TTF-1, PAX8, and bcl-2, and negative for cyclin D1. Ki-67 labeling index was approximately 10%, and there was occasional positivity of p53. Targeted next generation sequencing analysis only detected a NRAS mutation (Q61K); there was no mutation and no translocation of other genes including BRAF and RET/PTC. To our knowledge, this is first report that PTC shows aggressive FFS growth pattern. The tumor is possibly included in the new category of differentiated high-grade thyroid carcinoma in the World Health Organization 2022 classification, or in a novel subtype of PTC owing to its characteristic histological feature and intermediate malignancy between differentiated carcinoma and anaplastic carcinoma.

Mucosal Addressin Cell Adhesion Molecule 1 Expression Reflects Mucosal Inflammation and Subsequent Relapse in Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: Mucosal addressin cell adhesion molecule 1 [MAdCAM-1] is upregulated in the vascular endothelium of the colonic mucosa in ulcerative colitis [UC]. Although the association between MAdCAM-1 expression and mucosal inflammation has been discussed, the association with the clinical course of UC patients has not been reported. In this study we investigated not only the association between mucosal MAdCAM-1 expression and mucosal inflammation, but also its association with subsequent relapse in UC patients with clinical remission. METHODS: Eighty UC patients in remission who visited Kyoto Prefectural University of Medicine for follow-up for 2 years were included. Biopsy samples were collected during colonoscopy, and transcriptional expression levels of UC-related cytokines and MAdCAM-1 were quantified using real-time polymerase chain reaction. MAdCAM-1 mRNA expression and protein expression by immunohistochemistry were compared in patients who subsequently relapsed and those who remained in remission and were examined in relation to endoscopic findings, histological activity and cytokine expression. RESULTS: MAdCAM-1 expression was correlated with endoscopic severity, and significantly elevated in histologically active mucosa than inactive mucosa. Furthermore, MAdCAM-1 expression levels were closely correlated with those of several cytokines. MAdCAM-1 mRNA and protein expression were significantly higher in the relapse group than in the remission group, indicating that MAdCAM-1 expression in the mucosa is already elevated in UC patients in clinical remission who subsequently relapse. CONCLUSIONS: MAdCAM-1 expression in the colonic mucosa of UC patients is related to mucosal inflammation and subsequent relapse; it may serve as a marker for both relapse and therapeutic effectiveness in UC.

Surgical intervention for non-small-cell lung cancer with minimal malignant pleural effusion.

PURPOSE: We assessed the clinical significance of minimal malignant pleural effusion (MPE) using liquid-based cytology (LBC) and immunocytochemistry and reviewed the postoperative outcomes of patients with non-small-cell lung cancer (NSCLC). METHODS: We reviewed 240 patients with cM0 NSCLC who underwent lobectomy. Carcinoembryonic antigen (CEA) immunocytochemistry was performed with LBC to aid in the diagnosis of minimal MPE. We assessed the efficacy of this diagnostic method, relevant clinical factors, and postoperative outcomes. RESULTS: LBC showed positive results in two patients and suspicious results in 21. Of the 21 patients, immunocytochemistry showed minimal MPE in 10 (47.6%); therefore, a total of 12 patients (5%) showed minimal MPE. Minimal MPE is associated with an older age, increased consolidation tumor ratio, and adenocarcinoma histology. The 12 patients with minimal MPE had a 3-year overall survival rate of 90%. Postoperative recurrence was observed in seven patients (58.3%), four of whom were treated with epidermal growth factor receptor-tyrosine kinase inhibitors or immune checkpoint inhibitors, while three are still undergoing treatment, with a survival of 2.2, 2.5 and 5.5 years. CONCLUSIONS: CEA immunocytochemistry offers high sensitivity for the diagnosis of minimal MPE. Surgical intervention may be considered for select patients with NSCLC showing minimal MPE.

Clinicopathological features of appendiceal goblet cell adenocarcinoma in Japan: a multicenter retrospective study.

PURPOSE: In the 5th edition of the World Health Organization classification, appendiceal goblet cell adenocarcinoma (GCA) is categorized separately from neuroendocrine tumors and other appendiceal adenocarcinomas. We clarified the clinicopathological characteristics of Japanese appendiceal GCA. METHODS: We designed a retrospective multicenter cohort study and retrieved the data of patients with appendiceal neoplasms and histologically diagnosed appendiceal goblet cell carcinoid (GCC) treated from January 2000 to December 2017 in Japan. The available GCC slides were reviewed and diagnosed with a new grading system of GCA. RESULTS: A total of 922 patients from 43 institutions were enrolled; of these, 32 cases were patients with GCC (3.5%), and 20 cases were ultimately analyzed. The 5-year survival rate was 61.4% (95% confidence interval: 27.4-83.2), and the median survival time was 93.1 months. For peritoneal metastasis, regional lymph node metastasis was a significant factor (p = 0.04), and Grade 3 was a potential factor (p = 0.07). No peritoneal metastasis was observed in either T1/2 patients (n = 2) or Grade 1 patients (n = 4). We were unable to detect any significant factors associated with regional lymph node metastasis. CONCLUSION: For peritoneal metastasis, regional lymph node metastasis was a significant factor, and Grade 3 was a potential factor.

Anoctamin 5 regulates the cell cycle and affects prognosis in gastric cancer.

BACKGROUND: Anoctamin 5 (ANO5)/transmembrane protein 16E belongs to the ANO/ transmembrane protein 16 anion channel family. ANOs comprise a family of plasma membrane proteins that mediate ion transport and phospholipid scrambling and regulate other membrane proteins in numerous cell types. Previous studies have elucidated the roles and mechanisms of ANO5 activation in various cancer types. However, it remains unclear whether ANO5 acts as a plasma membrane chloride channel, and its expression and functions in gastric cancer (GC) have not been investigated. AIM: To examine the role of ANO5 in the regulation of tumor progression and clinicopathological significance of its expression in GC. METHODS: Knockdown experiments using ANO5 small interfering RNA were conducted in human GC cell lines, and changes in cell proliferation, cell cycle progression, apoptosis, and cellular movement were assessed. The gene expression profiles of GC cells were investigated following ANO5 silencing by microarray analysis. Immunohistochemical staining of ANO5 was performed on 195 primary tumor samples obtained from patients with GC who underwent curative gastrectomy between 2011 and 2013 at our department. RESULTS: Reverse transcription-quantitative polymerase chain reaction (PCR) and western blotting demonstrated high ANO5 mRNA and protein expression, respectively, in NUGC4 and MKN45 cells. In these cells, ANO5 silencing inhibited cell proliferation and induced apoptosis. In addition, the knockdown of ANO5 inhibited G1-S phase progression, invasion, and migration. The results of the microarray analysis revealed changes in the expression levels of several cyclin-associated genes, such as CDKN1A, CDK2/4/6, CCNE2, and E2F1, in ANO5-depleted NUGC4 cells. The expression of these genes was verified using reverse transcription-quantitative PCR. Immunohistochemical staining revealed that high ANO5 expression levels were associated with a poor prognosis. Multivariate analysis identified high ANO5 expression as an independent prognostic factor for 5-year survival in patients with GC (P = 0.0457). CONCLUSION: ANO5 regulates the cell cycle progression by regulating the expression of cyclin-associated genes and affects the prognosis of patients with GC. These results may provide insights into the role of ANO5 as a key mediator in tumor progression and/or promising prognostic biomarker for GC.

Investigation on the Inhibitory Effect of Wnt-5a on Colonic Mucosal Inflammation in Patients with Ulcerative Colitis.

BACKGROUND: Recent progress in ulcerative colitis (UC) treatment has been remarkable, and various medications have been applied. However, some patients with UC are refractory to treatment and convert to surgery. AIM: To investigate the role of colonic mucosal Wnt-5a expression in the pathogenesis of UC and the effect of bioactive Wnt-5a peptide on colitis in mice. METHODS: Wnt-5a peptide was intraperitoneally administered to mice every day from the beginning of dextran sulfate sodium (DSS) treatment. The severity of colitis was evaluated based on body weight change, colonic length, and histological scores. Colonic mucosal TNF-α and KC mRNA expression levels were measured. This study included 70 patients with UC in clinical remission. Wnt-5a, TNFα, and IL-8 mRNA expression in the rectal mucosa were measured by quantitative real-time polymerase chain reaction using biopsy materials. Wnt-5a mRNA expression levels were compared between patients who relapsed and those in remission. We examined the correlation of Wnt-5a expression with TNF-α and IL-8 expression. RESULTS: Wnt-5a peptide significantly attenuated the severity of DSS-induced colitis. Moreover, mucosal TNF-α and KC mRNA expression were significantly suppressed by Wnt-5a peptide treatment. Wnt-5a mRNA levels were significantly lower in patients with subsequent relapse than in those who remained in remission. Mucosal Wnt-5a was inversely correlated with TNF α and IL-8 expression. CONCLUSION: Wnt-5a peptide suppressed colitis in mice, and decreased Wnt-5a expression was strongly associated with relapse in patients with UC. Wnt-5a may have an inhibitory effect on mucosal inflammation in UC, and Wnt-5a peptide could be a new therapeutic strategy.

Functions and Clinical Significance of CACNA2D1 in Gastric Cancer.

BACKGROUND: Voltage-gated calcium channels form as a complex of several subunits, among which the function of CACNA2D1, one of the genes encoding the α2δ subunit, remains unclear. The aim of our study was to investigate the role of CACNA2D1 and evaluate the efficacy of amlodipine, a blocker of CACNA2D1, in the treatment of gastric cancer (GC). METHODS: Knockdown experiments were performed on the human GC cell lines MKN7 and HGC27 using CACNA2D1 small interfering RNA (siRNA), and changes in cell proliferation, the cell cycle, apoptosis, migration, and invasion were assessed. The gene expression profiles of cells were examined using a microarray analysis. An immunohistochemical (IHC) analysis was conducted on samples obtained from 196 GC patients who underwent curative gastrectomy. In addition, the antitumor effects of amlodipine were investigated using a xenograft model. RESULTS: Cell proliferation, migration, and invasion were suppressed in CACNA2D1-depleted cells, and apoptosis was induced. The results of the microarray analysis showed that the apoptosis signaling pathway was enhanced via p53, BAX, and caspase 3 in CACNA2D1-depleted cells. A multivariate analysis identified high CACNA2D1 expression levels, confirmed by IHC, as an independent poor prognostic factor in GC patients. Moreover, subcutaneous tumor volumes were significantly smaller in a xenograft nude mouse model treated with a combination of amlodipine and cisplatin than in a model treated with cisplatin alone. CONCLUSIONS: The present study indicates that CACNA2D1 regulates the apoptosis signaling pathway and may have potential as a biomarker for cancer growth and as a therapeutic target for GC.

A Case of Fifteen Simultaneous Rectal Neuroendocrine Tumors and Endocrine Cell Micronests Resected by Both Endoscopic Treatments and Surgery.

Case Report: A 65-year-old man without any symptoms received colonoscopy for cancer screening and underwent cold snare polypectomy (CSP) for a 3-mm rectal lesion at a local clinic. A histopathological examination revealed neuroendocrine tumor (NET) G1 with a positive margin. The patient was referred to our hospital for further treatment. Then, the post-CSP scar was removed by endoscopic submucosal dissection (ESD), with a sufficient endoscopically normal margin. Histopathology showed 4 NETs and endocrine cell micronests (ECMs) distant from the post-CSP scar, with a positive lateral margin. We considered that the possibility of other NETs was high. Additional surgery was performed. After a histopathological examination, 11 NETs and ECMs were found in the whole rectum, without lymph node metastasis. The patient had no recurrence at 24 months after surgery. In the past 10 years, we have experienced 4 cases (including the present case) of multiple rectal NETs among 56 cases of rectal NETs of ≤10 mm (7.1%). None of our 4 cases showed any recurrence (follow-up period: 12-32 months). Conclusions: We herein report a case involving a patient with 15 rectal NETs and ECMs. We reviewed our experience with multiple rectal NETs, and the rate of multiple rectal NETs was 7.1%. Endoscopists should consider that multiple lesions may be present in cases of rectal NET and be aware that some cannot be detected endoscopically.

Mucosal interleukin-8 expression as a predictor of subsequent relapse in ulcerative colitis patients with Mayo endoscopic subscore 0.

BACKGROUND AND AIM: Complete endoscopic mucosal healing is defined as a Mayo endoscopic subscore of 0. Some patients diagnosed with a Mayo endoscopic subscore 0 may present with subsequent clinical relapse. Here, we aimed to demonstrate mucosal cytokine profile as a predictor of clinical relapse in ulcerative colitis patients with a Mayo endoscopic subscore of 0 as a marker of mucosal healing. METHODS: We conducted prospective observational pilot study to examine the relationship between mucosal cytokine expression and subsequent relapse of UC patients diagnosed with a Mayo endoscopic subscore of 0. We enrolled 55 patients, and expression of cytokines tumor necrosis factor-α, interferon γ, interleukin-1ß, interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-7, interleukin-8, interleukin-9, interleukin-10, interleukin-12, interleukin-13, interleukin-15, interleukin-17A, interleukin-17F, interleukin-18, interleukin-21, interleukin-22, interleukin-23, interleukin-27, and interleukin-33 was measured by quantitative real-time PCR using rectal mucosa biopsy materials. Cytokine expression levels were compared between patients who relapsed between March 1, 2016, and March 30, 2020, of the study period and those who remained in remission. RESULTS: Ten cytokines, including interleukin-2, interleukin-4, interleukin-8, interleukin-10, interleukin-12, interleukin-15, interleukin-17A, interleukin-21, interleukin-23, and interleukin-33, were significantly elevated in patients with subsequent relapse compared with those who remained in remission. Interleukin-8 expression was the most useful predictor. CONCLUSIONS: In the rectal mucosa of ulcerative colitis patients with Mayo endoscopic subscore 0, levels of several cytokines were elevated in cases of subsequent relapse. Among these, interleukin-8 expression was the most useful for predicting relapse.

The first case of SMARCA4-deficient sarcoma of stomach.

SMARCA4-deficient sarcoma was first reported in the chest and recently in the uterus, but not in the stomach. Here, we present a patient diagnosed with SMARCA4-deficient sarcoma of the stomach, using histochemistry. An emergency operation was performed due to perforation of the tumor. However, one month after the operation, two nodes recurred, and six cycles of combination chemotherapy consisting of adriamycin and ifosfamide were administered. The combination chemotherapy showed a remarkable effect, and complete remission was achieved. The patient was alive without recurrence after 48-month follow-up. SMARCA4-deficient sarcoma is an exceedingly rare tumor with an extremely poor therapeutic response to anticancer drugs. Herein, we present the first case of SMARCA4-deficient sarcoma of the stomach, where a complete response to chemotherapy was achieved.

The usefulness of combining the pocket-creation method with a traction device using a scissor-type knife for colorectal endoscopic submucosal dissection.

INTRODUCTION: Technical issues and long procedure time still remain a concern in colorectal endoscopic submucosal dissection (ESD). We examined the usefulness of combining the pocket-creation method (PCM) with a traction device (S-O clip; SO) using a scissor-type knife (Clutch Cutter 3.5 mm; CC) for decreasing ESD procedure time. METHODS: We retrospectively analyzed 95 ESD cases of PCM + SO + CC managed from August 2017 to April 2020 and 103 cases of PCM + CC treated from July 2016 to July 2017. We compared these two groups through propensity score matching. The main outcome was the analysis of the ESD procedure times under various conditions in each group. RESULTS: After matching, 52 cases in the PCM + SO + CC and PCM + CC groups were analyzed. The PCM + SO + CC group showed a significantly shorter ESD procedure time than the PCM + CC group (57.8 ± 31.4 vs. 81.7 ± 33.5 min, p < 0.01). Additionally, the ESD procedure time was significantly shorter in the PCM + SO + CC group than in the PCM + CC group: tumor size (tumor size < 40 mm: 45.6 ± 15.8 vs. 72.7 ± 22.9 min, p < 0.01; tumor size ≥ 40 mm: 83.1 ± 40.1 vs. 111.8 ± 45.3 min, p = 0.04), tumor location (right side: 64.7 ± 33.3 vs. 81.0 ± 29.7 min, p = 0.03; left side: 50.5 ± 28.0 vs. 82.3 ± 36.9 min, p < 0.01), tumor morphology (polypoid: 39.2 ± 18.6 vs. 74.7 ± 28.6 min, p < 0.01; nonpolypoid: 62.3 ± 32.3 vs. 84.5 ± 35.2 min, p < 0.01), endoscopist (expert: 67.3 ± 41.2 vs. 91.9 ± 40.2 min, p = 0.02; nonexpert: 50.4 ± 18.3 vs. 73.6 ± 24.9 min, p < 0.01), and fibrosis (severe fibrosis: 82.0 ± 20.5 vs. 99.8 ± 40.4 min, p = 0.169; non-severe fibrosis: 52.1 ± 23.8 vs. 75.6 ± 29.0 min, p < 0.01). CONCLUSIONS: The combination of the PCM and SO using CC achieved a reduction in the colorectal ESD procedure time.

Linked Color Imaging and Blue Laser Imaging for the Diagnosis of Superficial Non-Ampullary Duodenal Epithelial Tumors.

BACKGROUND AND OBJECTIVE: This study aimed to evaluate endoscopic findings using linked color imaging (LCI) and blue laser imaging (BLI) and to determine a diagnostic predictor for duodenal adenocarcinomas. METHODS: All consecutive patients who underwent endoscopic resection for superficial non-ampullary duodenal epithelial tumors (SNADETs) between October 2012 and June 2019 were enrolled in this study. Two highly experienced endoscopists investigated six morphological findings using both white light imaging and LCI and three magnifying endoscopic findings using magnifying BLI (M-BLI). RESULTS: A total of 90 patients with 110 SNADETs, including 87 adenocarcinomas and 23 adenomas, were analyzed in this study. Among the non-magnifying endoscopic findings, the presence of reddish color, orange color on LCI (orange color sign), lobulation, depression, and marginally white opaque substance were found significantly more frequently in adenocarcinomas than in adenomas (p = 0.015, p < 0.001, p = 0.048, p < 0.001, and p = 0.007, respectively). Among the magnifying endoscopic findings, a mixed microsurface pattern (MSP), irregular MSP, and irregular microvascular pattern were found significantly more frequently in adenocarcinomas than in adenomas (p < 0.001, p < 0.001, and p = 0.002, respectively). In the multivariate analysis of all endoscopic findings associated with adenocarcinoma, orange color sign (odds ratio [OR] 10.46; 95% confidence interval [CI]: 1.42-77.08; p = 0.021), mixed MSP (OR 4.66; 95% CI: 1.02-21.40; p = 0.048), and irregular MSP (OR 13.11; 95% CI: 1.41-121.99; p = 0.024) were independent predictors of adenocarcinoma. CONCLUSIONS: The presence of orange color sign on LCI and mixed/irregular MSP on M-BLI were independent diagnostic predictors that were frequently observed in duodenal adenocarcinoma.

TRPV2 Promotes Cell Migration and Invasion in Gastric Cancer via the Transforming Growth Factor-ß Signaling Pathway.

BACKGROUND: Transient receptor potential vanilloid 2 (TRPV2) is a highly Ca2+-permeable ion channel that is involved in a number of cellular processes. It is expressed in various human cancers; however, the role of TRPV2 in gastric cancer (GC) remains poorly understood. METHODS: TRPV2 gene expression was knocked down in GC cell lines by small-interfering RNA (siRNA), and the biological roles of TRPV2 in the proliferation, migration, and invasion of GC cells were then investigated. The gene expression profile of GC was elucidated using a microarray analysis. TRPV2 expression in tumor tissue sections was analyzed by immunohistochemistry. RESULTS: The migration and invasion abilities of GC cells were inhibited by the knockdown of TRPV2. Moreover, the microarray assay revealed that TRPV2 was associated with the transforming growth factor (TGF)-ß signaling pathway. Immunohistochemical staining showed that the strong expression of TRPV2 correlated with lymphatic invasion, venous invasion, pathological T (pT), pathological N (pN), and a poor prognosis in GC patients. CONCLUSIONS: TRPV2 appeared to promote tumor migration and invasion via the TGF-ß signaling pathway, and the strong expression of TRPV2 was associated with a worse prognosis in GC patients.

Blue laser imaging identifies endoscopic findings corresponding to metachronous esophageal squamous cell carcinoma.

BACKGROUND AND STUDY AIM: This study aimed to evaluate endoscopic findings using non-magnifying blue laser imaging (BLI) to determine the risk factors for metachronous esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: All consecutive patients who underwent endoscopic submucosal dissection (ESD) for primary superficial ESCC (SESCC) without a history of ESCC between January 2013 and January 2016 were enrolled. Three highly experienced endoscopists investigated seven endoscopic findings using non-magnifying BLI as follows: (1) a brownish area with unclear margin, (2) white flat deposits, (3) multiple foci of dilated vessels, (4) low capillary permeability, (5) multiple glycogenic acanthosis, (6) horizontal lines, and (7) a nonuniform color tone. Furthermore, Lugol-voiding lesions (LVLs) were graded according to the number of LVLs per endoscopic view (A, no lesions; B, 1-9 lesions; C, ≥ 10 lesions). RESULTS: A total of 102 SESCC patients who underwent ESD were included. Multivariate analyses showed that multiple foci of dilated vessels, low capillary permeability, and a nonuniform color tone were significantly associated with metachronous ESCC (hazard ratio [HR] 2.30; 95% confidence interval [CI] 1.01-5.46; P = 0.049, HR 5.25; 95% CI 1.86-15.01; P = 0.002 and HR 3.17; 95% CI 1.11-9.43; P = 0.032, respectively). The three-year cumulative incidence of metachronous ESCC was significantly higher in patients with low capillary permeability and a nonuniform color tone than in patients without these findings. (41.1% vs. 6.0%, 45.0% vs. 12.7%, respectively, P < 0.001 for both). CONCLUSION: BLI findings of multiple foci of dilated vessels, low capillary permeability, and a nonuniform color tone in the background esophageal mucosa were risk factors for patients with metachronous ESCC after ESD.

Clinical Significance of Lymph Node Dissection and Lymph Node Metastasis in Primary Appendiceal Tumor Patients After Curative Resection: a Retrospective Multicenter Cohort Study.

PURPOSE: Due to its rarity and biological heterogeneity, guidelines for primary appendiceal tumor (PAT) are based on scarce evidence, resulting in no strong recommendations. The present study explored prognosis-related factors, including the timing of lymph node dissection (LND), in PAT patients after curative resection (CR) to determine the optimal surgical therapies. METHODS: We retrospectively collected and analyzed data from 404 patients with PATs who underwent CR at 43 tertiary hospitals from 2000 to 2017. This manuscript is based on revised manuscript during review process. Please, change the bold characters to normal characters in the manuscript. RESULTS: After propensity score matching, there were no marked differences in the recurrence-free survival (RFS) or overall survival (OS) between the primary and secondary LND groups (P = 0.993 and 0.728). A multivariate analysis showed that lymph node metastasis (LNM) was an independent factor for the RFS (hazard ratio [HR] 2.59; 95% confidence interval [CI] 1.09-6.13; P = 0.031) and OS (HR 4.70; 95% CI 1.40-15.76; P = 0.012). There were significant associations between the LNM rates and tumor depth (P < 0.0001) and the histological type (P = 0.006). There was no LNM in patients with low-grade appendiceal mucinous neoplasm (LAMN) or well-differentiated mucinous adenocarcinoma (G1) or patients with any Tis or T1 PATs. CONCLUSIONS: LNM was an independent prognostic predictor in PATs after CR with LND. Tumor depth and histological type were not prognostic predictors but were LNM predictors. Secondary LND based on the pathological findings of resected specimens is considered an acceptable surgical management without a worse prognosis than primary LND, and it may be omitted in LAMN+G1 or in any Tis and T1 PATs.

Effects of the combined use of a scissor-type knife and traction clip on endoscopic submucosal dissection of colorectal tumors: a propensity score-matched analysis.

Background and study aims This study evaluated the technical aspects of colorectal endoscopic submucosal dissection (ESD) with the Clutch Cutter (CC) (Fujifilm Co., Tokyo, Japan), a scissor-type knife, and the S-O clip (SO) as a traction clip, and compared the safety and efficacy to ESD using a needle-type knife. Patients and methods This was a single-center retrospective study. In Study 1, we evaluated 125 ESD patients: 60 using the SO and CC (SO group) and 65 using the CC (CC group). In Study 2, we evaluated 185 ESD patients: the CC group (N = 65) and 120 using the Flush knife BT-S (Flush group) (Fujifilm Co., Tokyo, Japan). In both studies, the clinicopathological features and therapeutic outcomes were compared using a propensity score-matched analysis. Results In 36 pairs of matched patients in Study 1, the rates of en bloc resection, R0 resection, perforation, and postoperative bleeding (POB) were 97.2 %, 88.9 %, 2.8 %, and 0 %, respectively, for the SO group and 100 %, 91.7 %, 0 %, and 0 % for the CC group (not significant). The mean procedure time for the SO group among less-experienced endoscopists was significantly shorter than in the CC group (42 vs. 65 minutes, P  = 0.036). In 49 pairs of matched patients in Study 2, the rates of en bloc resection, R0 resection, perforation, and POB were 100 %, 95.8 %, 0 %, and 0 %, respectively, for the CC group and 98.0 %, 95.8 %, 0 %, and 2.0 % for the Flush group (not significant). The mean procedure time in the CC group among less-experienced endoscopists was significantly shorter than in the Flush group (52 vs. 67 minutes, P  = 0.038). Conclusions CC and the combined use of CC and SO reduced colorectal ESD procedure time among less-experienced endoscopists.