Underwater endoscopic papillectomy for a small neuroendocrine tumor of the ampulla of Vater.

Neuroendocrine tumors (NETs) of the ampulla of Vater are rare. Therefore, there is a lack of comprehensive information regarding their pathogenesis. We herein present the case of a patient with a 5-mm ampullary NET who demonstrated the presence of lymphatic invasion after undergoing endoscopic papillectomy. A 44-year-old woman was referred to our hospital for treatment of a grade 1 NET in the ampulla of Vater. Endoscopic ultrasonography revealed a hypoechoic mass within the submucosal layer without obvious infiltration into the common bile duct or the main pancreatic duct. We performed underwater endoscopic papillectomy (UEP) to remove the tumor with a negative margin. Pathological evaluation of the resected specimen showed a grade 1 NET with a negative margin. However, pancreaticoduodenectomy was subsequently performed because of the risk of lymph node metastasis, which was expected due to the significant number of NET cells infiltrating the endothelium of the lymphatic vessels. No lymph node metastasis or recurrence was observed during the 26-month follow-up period. UEP is a useful method to achieve complete resection for diagnostic and therapeutic purposes. UEP may be a novel option for endoscopic treatment of ampullary NET.

Characteristics of Gastric Mucosa-Associated Microbiota in Patients with Early Gastric Cancer After Successful Helicobacter pylori Eradication.

BACKGROUND: Helicobacter pylori (H. pylori) is widely recognized as a definite carcinogen in gastric cancer (GC). Although H. pylori eradication reduces the risk of GC, GC recurrence has been detected even after successful H. pylori eradication. Recently, the analysis of gut microbiota was reported. AIMS: This study aimed to evaluate the correlation between gastric mucosa-associated microbiota (G-MAM) and early gastric cancer (EGC) after successful H. pylori eradication. METHODS: In this pilot study, G-MAM were collected during the esophagogastroduodenoscopy of 17 patients, receiving H. pylori eradication therapy at least 5 years ago. The patients were divided into those with EGC (the EGC group, 8 patients) and those without EGC (the NGC group, 9 patients). Microbial samples in the greater curvature of the pyloric site were obtained using an endoscopic cytology brush, and the G-MAM profiles of each sample were analyzed using 16S rRNA V3-V4 gene sequencing. RESULTS: Between the two groups, there was no significant difference in the median age, sex, median period after successful eradication of H. pylori, the α diversity, and the average abundance at the phylum level. At the genus level, the average abundance of Unclassified Oxalobacteraceae, Capnocytophaga, and Haemophilus was significantly lower in the EGC group than in the NGC group (0.89 vs. 0.14%, P < 0.01, 0.28 vs. 0.00%, P < 0.01 and 5.84 vs. 2.16%, P = 0.034, respectively). CONCLUSIONS: We demonstrated alternations in the profiles of G-MAM between the two groups. Our results suggest that G-MAM may influence carcinogenesis after successful H. pylori eradication.

Effect of concomitant use of G-CSF and myelosuppressive chemotherapy on bone marrow and peripheral granulocytes in a mouse model.

Granulocyte-colony stimulating factor (G-CSF) stimulates bone marrow progenitor cell proliferation and enhances neutrophil production. Exogenous G-CSF administration is indicated for chemotherapy-induced neutropenia management. However, there is a paucity of basic research examining the effects of the concomitant use of G-CSF and chemotherapy on myeloid cells in vivo. Whether concomitant G-CSF and chemotherapy adversely affect myeloid cell proliferation have not been determined. Herein, we examined the effects of the concomitant use of pegfilgrastim and 5-fluorouracil on myeloid cells and peripheral blood cells in mouse models. Balb/c mice were treated intraperitoneally with 5-fluorouracil (20 µg/g b.w.) or a vehicle as a control for 5 days, and pegfilgrastim was administered subcutaneously at 1 µg/g b.w. on day 3. As a result, we demonstrated that the concomitant use of pegfilgrastim suppressed the 5-fluorouracil-induced decrease of granulocytic cells in both bone marrow and peripheral blood in mice. To assess the clinical efficacy of early administration of pegfilgrastim during docetaxel, cisplatin, and 5-fluorouracil therapy in patients with esophageal cancer, we retrospectively identified 42 consecutive patients treated with this regimen. The incidence of both febrile neutropenia and grade 4 neutropenia was significantly lower in patients who received pegfilgrastim than in those who did not receive it (P = 0.002 and P = 0.002, respectively). These results suggest that the concomitant use of pegfilgrastim and chemotherapy, consisting of continuous infusions of 5-fluorouracil, improved chemotherapy-induced neutropenia without detrimental effects on proliferating myeloid granulocytic cells.

Proton Pump Inhibitors Enhance the Antitumor Effect of Chemotherapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Vacuolar ATPase (V-ATPase) is involved in cancer development. The use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in certain cancers. This study aimed to evaluate the effect of PPIs on chemotherapy for esophageal cancer. METHODS: To investigate the effects of PPIs on esophageal cancer cells, human KYSE50 and 70 cells were plated and 3 PPIs (lansoprazole, esomeprazole, vonoprazan) were added at various concentrations with 5-Fluorouracil (5-FU) to the corresponding cells for a cell viability assay. To investigate the effects of PPI treatment on patients undergoing 5-FU-based therapy in the clinical setting, we retrospectively analyzed the clinical outcomes and chemotherapy-related adverse events in 40 esophageal cancer patients who received 5-FU chemotherapy in our hospital between May 2013 and April 2017. RESULTS: In the viability assays, all PPIs significantly enhanced the cytotoxic effect of 5-FU on the two esophageal cancer cell lines. In the clinical study, PPI-treated patients showed better overall survival (OS) than patients managed without PPI treatment. A multivariate analysis revealed that PPI treatment was independently associated with OS (p = 0.009, HR, 0.33; 95% CI, 0.12-0.76). CONCLUSIONS: PPI treatment may safely enhance chemosensitivity in esophageal cancer patients.

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.

Water-soluble dietary fiber alleviates cancer-induced muscle wasting through changes in gut microenvironment in mice.

Cancer cachexia and the associated skeletal muscle wasting are considered poor prognostic factors, although effective treatment has not yet been established. Recent studies have indicated that the pathogenesis of skeletal muscle loss may involve dysbiosis of the gut microbiota and the accompanying chronic inflammation or altered metabolism. In this study, we evaluated the possible effects of modifying the gut microenvironment with partially hydrolyzed guar gum (PHGG), a soluble dietary fiber, on cancer-related muscle wasting and its mechanism using a colon-26 murine cachexia model. Compared with a fiber-free (FF) diet, PHGG contained fiber-rich (FR) diet-attenuated skeletal muscle loss in cachectic mice by suppressing the elevation of the major muscle-specific ubiquitin ligases Atrogin-1 and MuRF1, as well as the autophagy markers LC3 and Bnip3. Although tight-junction markers were partially reduced in both FR and FF diet-fed cachectic mice, the abundance of Bifidobacterium, Akkermansia, and unclassified S24-7 family increased by FR diet, contributing to the retention of the colonic mucus layer. The reinforcement of the gut barrier function resulted in the controlled entry of pathogens into the host system and reduced circulating levels of lipopolysaccharide-binding protein (LBP) and IL-6, which in turn led to the suppression of proteolysis by downregulating the ubiquitin-proteasome system and autophagy pathway. These results suggest that dietary fiber may have the potential to alleviate skeletal muscle loss in cancer cachexia, providing new insights for developing effective strategies in the future.

Treatment with broad-spectrum antibiotics upregulates Sglt1 and induces small intestinal villous hyperplasia in mice.

Although extensive evidence indicates that the gut microbiota plays a crucial role in regulating glucose homeostasis, the exact regulatory mechanism remains unclear. This study aimed to investigate the effect of broad-spectrum antibiotics on the expression of glucose transporters, histomorphology of the small intestine, and glucose metabolism in mice. C57BL/6 mice were administered drinking water with or without a broad-spectrum antibiotic combination for 4 weeks. Thereafter, an oral glucose tolerance test was performed. Body weight, small intestine histopathology, mRNA levels of glucose transporters (SGLT1 and GLUT2) and intestinal transcription factors (CDX1 and CDX2) were evaluated. SGLT1 and CDX1 were upregulated in the small intestine upon antibiotic administration compared with that in the control group. The height and surface area of the jejunal villi were significantly higher upon antibiotic administration than in the control group. Fasting glucose levels were significantly higher upon antibiotic administration than in the control group. The present results indicate that treatment with broad-spectrum antibiotics upregulates SGLT1 and CDX1 and induces hyperplasia in the small intestine, thus increasing fasting blood glucose levels. Our results further the current understanding of the effects of broad-spectrum antibiotics on the gut microbiota and glucose homeostasis that may have future clinical implications.

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.

Enhanced Visibility in Evaluating Gastric Cancer and Helicobacter pylori-Associated Gastritis Using Linked Color Imaging with a Light-Emitting Diode Light Source.

BACKGROUND: In Japan, laser light source (Laser) endoscopy is widely available, and the characteristics of light-emitting diode light source (LED) endoscopy have not been clarified. AIMS: We assessed the visibility of early gastric cancers (EGCs) and Helicobacter pylori (H. pylori)-associated gastritis for LED endoscopy compared with laser endoscopy using white-light imaging (WLI) and linked color imaging (LCI). METHODS: We assessed 99 lesions between February 2019 and March 2020. The visibility was scored from four (excellent visibility) to one (poor visibility) by evaluating videos including EGCs and gastric mucosa captured using WLI and LCI with LED endoscopy (LED-WLI and LED-LCI, respectively) and laser endoscopy (Laser-WLI and Laser-LCI, respectively). The primary end point was the non-inferiority of the visibility of EGCs and H. pylori-associated gastritis between LED-/Laser-WLI and LED-/Laser-LCI. RESULTS: The visibility scores of EGCs for LED-/Laser-WLI and LED-/Laser-LCI were 3.14/2.97 and 3.39/3.35, respectively. The visibility scores of H. pylori-associated gastritis [intestinal metaplasia (IM), diffuse redness (DR), regular arrangement of collecting venules (RAC) and map-like redness (MR)] for LED-/Laser-WLI and LED-/Laser-LCI were 3.05/2.85 and 3.60/3.50 (IM), 2.76/2.50 and 2.96/2.86 (DR), 2.69/2.44 and 2.77/2.62 (RAC) and 2.97/2.75 and 3.39/3.27 (MR). Non-inferiority was demonstrated for visualizing EGCs and H. pylori-associated gastritis. CONCLUSIONS: LED-WLI and LED-LCI can be used to visualize EGCs and H. pylori-associated gastritis with non-inferiority to Laser-WLI and Laser-LCI. Furthermore, even with LED, LCI was more effective than WLI for evaluating EGCs and H. pylori-associated gastritis. Therefore, LED endoscopy can be used to detect EGCs and evaluate H. pylori-associated gastritis accurately.

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.

Improved Visibility of Early Gastric Cancer after Successful Helicobacter pylori Eradication with Image-Enhanced Endoscopy: A Multi-Institutional Study Using Video Clips.

The visibility and diagnostic accuracy of early gastric cancer (EGC) after Helicobacter pylori (HP) eradication have been reported to improve using image-enhanced endoscopy (IEE) compared with white light imaging (WLI). The present study clarified the appropriate IEE for the detection and diagnosis of EGC in clinical settings. This prospective and cross-sectional study evaluated the visibility of EGC and endoscopic findings of gastric mucosa after successful HP eradication (n = 31) using videos with WLI and IEE. Three endoscopists evaluated high-definition videos in a randomized order. The mean visibility scores (MVSs) on linked color imaging (LCI) for atrophic border, intestinal metaplasia, map-like redness, and EGC were the highest among each modality (3.87 ± 0.34, 3.82 ± 0.49, 3.87 ± 0.50, and 3.35 ± 0.92, respectively). The MVSs with blue laser imaging (BLI) were highest for magnifying view of the demarcation line (DL), microsurface pattern (MSP), and microvascular pattern (MVP) for EGC (3.77 ± 0.49, 3.94 ± 0.25, and 3.92 ± 0.34, respectively). LCI had the highest visibility among findings of gastric mucosa and EGC after HP eradication, and BLI had the highest visibility of MVP, MSP, and DL in magnifying observation. These results suggest that LCI observation in the entire stomach and further magnifying BLI are the best methods for detecting and diagnosing EGCs after HP eradication, respectively.

Effects of Guidelines for Gastroenterological Endoscopy in Patients Undergoing Antithrombotic Treatment on Postoperative Bleeding after Endoscopic Submucosal Dissection for Early Gastric Cancer: A Propensity Score-Matching Analysis.

BACKGROUND: Management of antithrombotic agents during endoscopic treatment changed after the publishing of -Japan Gastroenterological Endoscopy Society guidelines for gastroenterological endoscopy in antithrombotic drug users (GL-2012). OBJECTIVES: We aimed to evaluate the effect of implementing antithrombotic agent management guidelines (GL-2012) on postoperative bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and on the prevention of thromboembolic events. METHODS: A total of 1,264 patients who underwent ESD for EGC at Kyoto Prefectural University Hospital between June 2002 and March 2017 were enrolled and divided into 2 groups: 621 patients before the publication of GL-2012 (Pre-GL group) and 643 patients after (Post-GL group). Relationships between postoperative bleeding and various clinicopathological factors in each group were investigated through propensity score-matching analysis. RESULTS: In the Pre-GL group, antihypertensive agent use (p < 0.01) and upper third of the stomach (p < 0.01) were significantly related to postoperative bleeding in univariate analysis. Antihypertensive agent use (OR 4.6, 95% CI 1.6-12.8) and upper third of the stomach (OR 4.9, 95% CI 1.8-13.4) were significantly related to postoperative bleeding in multivariate analysis. In the Post-GL group, antihypertensive agent use (p < 0.01), dual antiplatelet agents use (p < 0.01), anticoagulant agents use (p < 0.01), and heparin replacement therapy (p < 0.01) were significantly related to postoperative bleeding in univariate analysis. Antihypertensive agent use (OR 3.4, 95% CI 1.1-9.6), dual antiplatelet agents (OR 12.3, 95% CI 2.4-63.0), and heparin replacement therapy (OR 10.2, 95% CI 2.5-41.5) were significantly related to postoperative bleeding in multivariate analysis. CONCLUSIONS: The adherence to GL-2012 might reduce risk of thromboembolic events. On the other hand, dual antiplatelet agents therapy and heparin replacement therapy were the new independent risk factors for ESD postoperative bleeding in EGC after GL-2012. Especially as for heparin replacement therapy, uninterrupted warfarin or a temporary short interruption of direct oral anticoagulants without heparin replacement therapy might be recommended rather than heparin replacement therapy.

Diagnostic Ability of Magnifying Blue Light Imaging with a Light Emitting Diode Light Source for Early Gastric Cancer: A Prospective Comparative Study.

INTRODUCTION: An innovative endoscopic system using 4-color light-emitting diodes (LED) was released between 2016 and 2017 in locations that had not approved laser endoscopes for use, including the United States and Europe. OBJECTIVE: This study compared the diagnostic efficacy between magnifying blue light imaging with an LED light source (LED-BLI) and magnifying blue laser imaging with a laser light source (Laser-BLI) for early gastric cancer (EGC). METHODS: In this prospective, single-center, noninferiority study, 80 gastric lesions were evaluated between January 2017 and July 2017. The magnifying findings of gastric lesions - including the demarcation line (DL), microvascular pattern (MVP), and microsurface pattern (MSP) - were evaluated using Laser-BLI and LED-BLI according to the vessel plus surface classification system (VSCS). The primary end point was to determine whether the diagnostic accuracy of LED-BLI for EGC was noninferior to that of conventional Laser-BLI. RESULTS: Overall, we evaluated 79 gastric lesions histopathologically diagnosed as adenocarcinomas from the specimens obtained via endoscopic submucosal dissection. A DL was observed by Laser-BLI and LED-BLI in 98.7% (78/79) and 96.2% (76/79) of EGCs, respectively. The MVP observed using Laser-BLI and LED-BLI was irregular in 92.4% (73/79) and 89.9% (71/79), respectively. The MSP observed using Laser-BLI and LED-BLI was irregular in 83.5% (66/79) and 82.2% (65/79), respectively. According to the VSCS, diagnosable cancers were found in 94.9% (75/79) and 93.7% (74/79) of cases when using Laser-BLI and LED-BLI, respectively (p = 0.73; difference ratio, 1.2%; 95% CI -8.5 to 6.0%). CONCLUSIONS: LED-BLI could accurately visualize the DL, MVP, and MSP of EGCs and was not inferior to Laser-BLI. Therefore, LED-BLI can be used to diagnose EGC accurately according to the VSCS-based diagnosis criteria.

Diagnostic performance of magnifying blue laser imaging versus magnifying narrow-band imaging for identifying the depth of invasion of superficial esophageal squamous cell carcinoma.

Identifying the depth of invasion (DOI) of superficial esophageal squamous cell carcinoma (SESCC) is crucial to determine the indication for endoscopic resection. This retrospective, single-center study aimed to evaluate the diagnostic efficacy of magnifying blue laser imaging (M-BLI) compared with white-light imaging (WLI) or magnifying narrow-band imaging (M-NBI) for identifying the DOI of SESCC. A total of 160 consecutive patients with SESCCs who underwent endoscopic submucosal dissection were enrolled in this study. Still images of the lesion were obtained using WLI, M-BLI and M-NBI prior to endoscopic submucosal dissection. Three endoscopists retrospectively evaluated the DOI using WLI according to non-magnifying findings and using M-BLI and M-NBI images according to the magnifying endoscopic classification of the Japan Esophageal Society. The diagnostic accuracy of each modality was compared using the chi-square test. The DOIs in 160 SESCCs evaluated pathologically were as follows: invasion to the epithelium or lamina propria mucosa in 130, invasion to the lamina muscularis mucosa or submucosa to a depth ≤ 200 µm in 18, and invasion to the submucosa to a depth > 200 µm in 12. The overall diagnostic accuracy rates of WLI, M-BLI, M-NBI, WLI with M-BLI (WLI + M-BLI), and WLI with M-NBI (WLI + M-NBI) were 86.9, 91.2, 90.6, 95.6 and 94.4%, respectively. Significant differences were found between WLI and WLI + M-BLI or WLI + M-NBI (P = 0.006 and P = 0.021, respectively). The concordance of intrapapillary capillary loops between M-BLI and M-NBI was 91.2%. The kappa coefficients for interobserver variability of the three endoscopists for M-BLI and M-NBI were 0.728/0.649/0.792 and 0.729/0.666/0.791, respectively, while those for intraobserver variability were 0.919/0.746/0.778 and 0.736/0.720/0.745, respectively. Similar to M-NBI, M-BLI was useful in predicting the DOI of SESCCs.

Metformin inhibits TGF­ß1­induced epithelial­mesenchymal transition and liver metastasis of pancreatic cancer cells.

Epithelial­mesenchymal transition (EMT) is considered a crucial event in the development of cancer metastasis. Metformin is a drug used in the treatment of type 2 diabetes. Recently, increasing evidence has indicated that metformin possesses anti­tumor activities. However, the effects of metformin on EMT and metastases in pancreatic cancer remain unknown. Thus, the present study investigated whether metformin inhibits EMT of human pancreatic cancer cell lines. Pancreatic cancer cells were stimulated with transforming growth factor ß1 (TGF­ß1), an activator of EMT signaling, with or without metformin. After 48 h, the levels of epithelial and mesenchymal markers were evaluated by western blot analysis, immunocytochemistry and RT­qPCR. Cancer cell migration was evaluated by an in vitro wound healing assay. The cells stimulated with TGF­ß1 acquired an elongated and fusiform morphology, which was inhibited by metformin. The wound healing assay revealed that metformin significantly suppressed the TGF­ß1­stimulated migration of pancreatic cancer cells. Following treatment with metformin, E­cadherin expression (epithelial marker) was upregulated, and the levels of mesenchymal markers were downregulated, which had been increased by TGF­ß1 in these cells. Exposure of the cells to TGF­ß1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF­ß1­induced­EMT through the down­regulation of the Smad pathway in PANC­1 cells and the downregulation of the Akt/mTOR pathway in BxPC­3 cells. In an animal model of surgical orthotopic implantation, metformin inhibited liver metastasis without a significant reduction in the size of the primary pancreatic tumor. On the whole, the findings of the present study suggest that metformin inhibits EMT and cancer metastasis through the Smad or Akt/mTOR pathway.

Can image-enhanced endoscopy improve the diagnosis of Kyoto classification of gastritis in the clinical setting?

Endoscopic diagnosis of Helicobacter pylori (H. pylori) infection, the most common cause of gastric cancer, is very important to clarify high-risk patients of gastric cancer for reducing morbidity and mortality of gastric cancer. Recently, the Kyoto classification of gastritis was developed based on the endoscopic characteristics of H. pylori infection-associated gastritis for clarifying H. pylori infection status and evaluating risk factors of gastric cancer. Recently, magnifying endoscopy with narrow-band imaging (NBI) has reported benefits of the accuracy and reproducibility of endoscopic diagnosis for H. pylori-related premalignant lesions. In addition to NBI, various types of image-enhanced endoscopies (IEEs) are available including autofluorescence imaging, blue laser imaging, and linked color imaging. This review focuses on understanding the clinical applications and the corresponding evidences shown to improve the diagnosis of gastritis based on Kyoto classification using currently available advanced technologies of IEEs.

Efficacy and safety of endoscopic submucosal dissection using a scissors-type knife with prophylactic over-the-scope clip closure for superficial non-ampullary duodenal epithelial tumors.

BACKGROUND AND STUDY AIM: This study aimed to assess the safety and feasibility of endoscopic submucosal dissection (ESD) using a scissors-type knife with prophylactic closure using over-the-scope clip (OTSC) for superficial non-ampullary duodenal epithelial tumors (SNADETs). PATIENTS AND METHODS: Consecutive patients who underwent ESD for SNADETs >10 mm between January 2009 and July 2019 were retrospectively enrolled. We performed ESD using either a needle-type knife (Flush Knife-ESD) or a scissors-type knife (Clutch Cutter-ESD). Mucosal defects were prophylactically closed using three methods: conventional clip, laparoscopic closure, or OTSC. RESULTS: A total of 84 lesions were resected using the Flush Knife-ESD and the Clutch Cutter-ESD (37 and 47 patients, respectively), and conventional clip, laparoscopic closure, and OTSC for mucosal defect closure after ESD were applied in 13, 13, and 56 lesions, respectively. The R0 resection rate was significantly higher in the Clutch Cutter-ESD than that in the Flush Knife-ESD (97.9% vs 83.8%, respectively, P = 0.040). The intraoperative perforation rate was significantly lower in the Clutch Cutter-ESD than in the Flush Knife-ESD (0% vs 13.5%, respectively, P = 0.014). Complete closure rates of conventional clip, laparoscopic closure, and OTSC were 76.9%, 92.3%, and 98.2%, respectively (P = 0.021); and delayed perforation rates were 15.4%, 7.7%, and 1.8%, respectively (P = 0.092). CONCLUSIONS: Endoscopic submucosal dissection using a scissors-type knife with prophylactic OTSC closure is safe and feasible for the low-invasive treatment of SNADETs.

Skeletal muscle mass as a predictor of the response to neo-adjuvant chemotherapy in locally advanced esophageal cancer.

Undernutrition and sarcopenia are associated with a higher incidence of chemotherapy-related toxicity and a poor prognosis in several kinds of cancer, but the impact of sarcopenia on the outcomes of chemotherapy for esophageal cancer remains unclear. Thus, the purpose of this retrospective study was to investigate whether sarcopenia affects the efficacy and toxicities of chemotherapy for advanced esophageal cancer patients. Data were collected from 31 esophageal cancer patients who underwent neo-adjuvant chemotherapy followed by surgery. Body composition was assessed at the start of chemotherapy by bioelectrical impedance analysis, and outcomes of chemotherapy were compared between sarcopenic and non-sarcopenic groups. Of the 31 patients, sarcopenia was observed in 16 (51.6%). The incidence of toxicities was not different between the two groups. However, as for pathologic response, a good therapeutic effect (Grade 2 or higher) was more common in the non-sarcopenic group than in the sarcopenic group (53.3% vs. 25.0%). Multivariate analysis showed that sarcopenia was an independent predictor of poor pathological response (odds ratio 8.02; P = 0.037). The results of this study suggest the potential utility of sarcopenia assessment in neoadjuvant patient selection strategies.