Anti-acid treatment for ulcerated early gastric cancer may be a treatment option avoiding unnecessary gastrectomy: a cohort study.

Diagnosing the invasion depth of ulcerated early gastric cancer is usually inaccurate, especially for endoscopists in primary care clinics who are often not experts in this area. In reality, many patients with open ulcers who can be treated with endoscopic submucosal dissection (ESD) are referred for surgery. Materials and methods: Twelve patients with ulcerated early gastric cancer who were treated with proton pump inhibitors, including vonoprazan, and underwent ESD were included in the study. Conventional endoscopic and narrow-band images were evaluated by five board-certified endoscopists (two physicians: A, B, and three gastrointestinal surgeons: C, D, and E). They assessed the invasion depth, and the results were compared with the pathologic diagnosis. Results: The accuracy of the invasion depth diagnosis was 38.3%. According to the pretreatment diagnosis of invasion depth, gastrectomy was recommended for 41.7% (5/12) of the cases. However, histological examination revealed that additional gastrectomy was required in only one case (8.3%). Thus, in four out of five patients unnecessary gastrectomy could be avoided. Post-ESD mild melena occurred in only one case, and there was no case of perforation. Conclusion: Antiacid treatment contributed to avoid unnecessary gastrectomy in four out of five patients for whom gastrectomy was indicated based on an inaccurate pretreatment diagnosis of the invasion depth.

Development of supercooling preservation method of adherent cultured human cells.

Cryopreservation of mammalian cells is an important technology; however, freezing damage due to osmotic pressure differences and ice crystal formation is inevitable. In addition, cryopreserved cells cannot be used immediately after thawing in many cases. Therefore, in this study, we developed a method for supercooling and preserving adherent cells using a precision temperature-controlled CO2 incubator. The effects of the cooling rate from 37 to -4°C, the warming rate from -4 to 37°C and a preservation solution on cell viability after storage were examined. Human hepatocarcinoma-derived cell line HepG2 cells, preserved with HypoThermosol FRS at -4°C with a cooling rate of -0.028°C/min (24 h from 37°C to -4°C) and warming to 37°C at a rate of +1.0°C/min (40 min from -4 to 37°C), displayed high cell viability after 14 days of preservation. The superiority of supercooling preservation at -4°C was demonstrated by comparing the obtained results with that of refrigerated preservation at +4°C. Cells preserved for 14 days under optimal conditions showed no cell shape abnormalities and may be used for experiments immediately after thawing. The optimized supercooling preservation method determined in this study is suitable for the temporary preservation of adherent cultured cells.

Malignant melanoma in the stomach treated with endoscopic submucosal dissection: a case report.

The initial appearance of malignant melanoma localized in the stomach has never been reported previously. We encountered a patient with gastric melanoma in the stomach, which was histologically confirmed to be confined to the mucosa. Case Presentation: The patient, when in her 40s, had undergone surgery for malignant melanoma of the left heel. However, there were no detailed records of pathological findings. The patient had a 4-mm black elevated lesion in her stomach observed on esophagogastroduodenoscopy after the eradication of Helicobacter pylori. A year later, esophagogastroduodenoscopy showed that the lesion had increased to 8 mm. A biopsy was performed, but no malignancy was found; the patient continued to be followed up. Esophagogastroduodenoscopy performed at the 2-year follow-up revealed that the melanotic lesion had increased to 15 mm, and biopsy was performed and revealed a malignant melanoma. Clinical Discussion: Endoscopic submucosal dissection was performed for gastric malignant melanoma. The margin of the resected malignant melanoma was negative; vascular and lymphatic invasions were not observed, and the lesion was confined to the mucosa. Conclusion: We suggest that even if the first biopsy of a melanotic lesion shows no evidence of malignancy, the lesion should be closely monitored. This is the first reported case of endoscopic submucosal dissection of localized gastric malignant melanoma confined to the mucosa.

Gel immersion endoscopic mucosal resection in early gastric cancer with bleeding: A case report.

Gel immersion endoscopy was developed by Yano for the treatment of bleeding. In this case, we performed gel immersion endoscopic mucosal resection to treat a bleeding gastric cancer. An 80-year-old man, with chronic renal failure and on aspirin treatment for ischemic heart disease, underwent endoscopic treatment for multiple early gastric cancers on the anterior and posterior walls of the pyloric ring. An endoscopic submucosal dissection was performed for gastric cancer on the anterior wall; however, the removal of the cancer on the posterior wall was complicated by tumor prolapse and bleeding. Gel formulation (VISCOCLEAR® Otsuka Pharmaceutical Factory, Inc., Tokushima, Japan) was used to immerse the bleeding tumor and subsequently facilitate the endoscopic mucosal resection. Various factors, such as the use of antithrombotic medication and underlying renal disease, can increase the risk of bleeding during endoscopic gastric cancer resection. If bleeding persists, the resection margin becomes obscured. Gel formulations, such as VISCOCLEAR®, can be applied to control bleeding and improve visibility. In this case, gel immersion was useful for endoscopic mucosal resection of the bleeding tumor. The use of gel immersion endoscopic resection should be considered for the treatment of early gastric cancer, however further cases should be evaluated.

Localizing spontaneously hemostatic colonic diverticular bleeding using VISCOCLEAR gel: A case report.

Colonic diverticular bleeding is the most common type of gastrointestinal bleeding. We report a case of an 82-year-old man with a chief complaint of melena. Enhanced computed tomography showed multiple diverticula, and water-assisted colonoscopy could not help identify the diverticulum responsible for bleeding. We injected VISCOCLEAR, a novel gel formulation, into the digestive tract endoscopically and successfully localized the bleeding point. Moreover, the use of VISCOCLEAR secured a clear visual field with reduced glare, as seen in the digital endoscopic image. Subsequently, we performed hemostatic clipping. The course after the endoscopic treatment was unremarkable. In this case, we could identify the exposed bleeding vessels in the diverticulum using VISCOCLEAR and perform hemostatic clipping. We intend to evaluate the effectiveness of VISCOCLEAR further by analyzing a series of cases.

Eosinophilic esophagitis induced by sublingual immunotherapy with cedar pollen: a case report.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease associated with eosinophilic infiltration of the esophageal mucosa mostly due to exposure to allergens. However, the causes and pathogenesis of EoE are not fully understood. We encountered a case of EoE that was triggered by sublingual immunotherapy (SLIT) for cedar pollen allergy. A 40-year-old man who was treated with Japanese cedar pollen tablet SLIT for cedar pollen allergy developed heartburn 3 weeks after the initiation of the treatment. He took vonoprazan for the heartburn, but the heartburn did not improve. Then, esophagogastroduodenoscopy was performed; it revealed longitudinal furrows and white spots on the esophageal mucosa, decreased vascular permeability, and erosions. Consequently, the patient was diagnosed with EoE. Heartburn and chest discomfort disappeared 1 week after the discontinuation of Japanese cedar pollen tablet SLIT, and the patient tested positive for drug allergy to Japanese cedar pollen tablet SLIT. In this study, we found that if heartburn persists during SLIT for cedar pollen allergy, and does not improve on administration of vonoprazan or proton pump inhibitors, EoE should be suspected. In addition, the occurrence of EoE due to drug allergy is indicated.

Cronkhite-Canada Syndrome Successfully Treated by Corticosteroids before Presenting Typical Ectodermal Symptoms.

Cronkhite-Canada syndrome (CCS) is a rare disease characterized by diffuse gastrointestinal polyposis with chronic diarrhea and ectodermal change, but its etiology is unknown. We present a case at the age of 26 years complaining of epigastralgia and weight loss. Endoscopic examination revealed extensive diffuse polypoid lesions of the stomach and the terminal ileum, all of which showed hyperplastic polyps pathologically. There were no polypoid lesions in his colon. He has no family history of diffuse gastrointestinal polyposis. Diffuse gastrointestinal hyperplastic polyposis without any hereditary association led us to suspect this case as CCS although he did not show chronic diarrhea and any ectodermal symptoms such as onychodystrophy, alopecia, and hyperpigmentation. After initiation of a corticosteroid therapy, his epigastralgia disappeared and he gained appetite and weight, accompanied by normalization of serum albumin levels. Endoscopic examination 1 year after initiation of corticosteroid therapy revealed a decrease in the number of gastric polyposis and those inflammations. This rare young case may suggest that early therapeutic intervention with corticosteroids could improve the prognosis of CCS, preventing not only malnutrition but also appearance of several ectodermal symptoms.

Effects of vonoprazan on gastric PH and clinical course after gastric ESD: A retrospective and prospective study.

BACKGROUND: Vonoprazan has been more widely used for artificial ulcers after endoscopic submucosal dissection (ESD) for early gastric cancer; however, no reports have examined intragastric pH during ESD. The present study aimed to measure gastric pH at the time of ESD and the clinical course afterwards for patients treated with vonoprazan the night before undergoing ESD. MATERIALS AND METHODS: We examined medication status regarding gastric acid secretion and antithrombotic drugs, post-ESD bleeding as a perioperative complication, and the timing of upper gastrointestinal endoscopy after ESD and ulcer healing in 156 patients who underwent gastric ESD at our hospital from January 2014 to December 2019. The gastric pH was measured at the time of ESD after administration of 20 mg vonoprazan on the night before gastric ESD. RESULTS: There were 14 cases of post-ESD bleeding in patients treated with proton-pump inhibitors (PPIs), including oozing during second-look endoscopy compared to only 1 case of bleeding with vonoprazan administration (p < 0.05). Vonoprazan was also associated with better post-ESD ulcer healing than PPIs. Gastric pH during ESD after vonoprazan administration on the night before gastric ESD was ≥6.96 in all 11 patients. CONCLUSION: Post-ESD bleeding was reduced, and ulcer healing was improved in patients treated with vonoprazan the night before their procedure. Our results suggest high gastric pH during ESD due to vonoprazan administration may be beneficial for hemostasis and ulcer healing following ESD.

Lipopolysaccharides From Non-Helicobacter pylori Gastric Bacteria Potently Stimulate Interleukin-8 Production in Gastric Epithelial Cells.

BACKGROUND: Gastric acid secretion is compromised in chronic Helicobacter pylori (H. pylori) infection allowing overgrowth of non-H. pylori gastric bacteria (NHGB) in the stomach. METHODS: NHGB were isolated from gastric mucosa in selective media and further characterized with biochemical methods and 16S rRNA gene sequencing. Human gastric tissues were studied with indirect immunofluorescence with antibodies against H. pylori and Neisseria subflava (N. subflava). Gastric epithelial cell lines were cocultured with bacteria or incubated with lipopolysaccharides isolated from NHGB, and interleukin-8 released in the media was measured by enzyme-linked immunosorbent assay. Expression of Toll-like receptor (TLR)2, TLR4, it's coreceptor myeloid differentiation factor 2 (MD2), and CD14 in gastric cells was investigated by immunofluorescence microscopy and reverse transcriptase-polymerase chain reaction. RESULTS: Haemophilus species, Neisseria species, Fusobacterium species, and Veillonella species were predominant Gram-negative bacteria coinfected with H. pylori. Lipopolysaccharides from N. subflava potently stimulated interleukin-8 secretion in MKN45 cells which was cancelled by preincubation with polymyxin B. TLR2, TLR4, CD14, and myeloid differentiation factor 2 were expressed in MKN45 cells, though their levels of expression were low. N. subflava adhered to MKN45 cells in vitro and colocalized with H. pylori in the human gastric mucosa. CONCLUSIONS: Our data suggest that N. subflava colonized in the gastric mucosa contribute to gastric inflammation during chronic H. pylori gastritis. TRANSLATIONAL IMPACT: NHGB may perpetuate gastric inflammation and accelerate neoplastic progression in the hypochlorhydric stomach.

Micropatterning Method for Porous Materials Using the Difference of the Glass Transition Temperature between Exposed and Unexposed Areas of a Thick-Photoresist.

A cell culture on a scaffold has the advantages of functionality and easy handling, because the geometry of the cellular tissue is controlled by designing the scaffold. To create complex cellular tissue, scaffolds should be complex two-dimensional (2D) and three-dimensional (3D) structures. However, it is difficult to fabricate a scaffold with a 2D and 3D structure because the shape, size, and fabrication processes of a 2D structure in creating a cell layer, and a 3D structure containing cells, are different. In this research, we propose a micropatterning method for porous materials using the difference of the glass transition temperature between exposed and unexposed areas of a thick-photoresist. Since the proposed method does not require a vacuum, high temperature, or high voltage, it can be used for fabricating various structures with a wide range of scales, regardless of the materials used. Additionally, the patterning area can be fabricated accurately by photolithography. To evaluate the proposed method, a membrane integrated scaffold (MIS) with a 2D porous membrane and 3D porous material was fabricated. The MIS had a porous membrane with a pore size of 4 µm or less, which was impermeable to cells, and a porous material which was capable of containing cells. By seeding HUVECs and HeLa cells on each side of the MIS, the cellular tissue was formed with the designed geometry.

A Liquid-core Liquid-cladding Optical Waveguide Based on Thermal Gradients across the Laminar Flow of Water in Capillary Tubing.

A liquid-core liquid-cladding optical waveguide based on thermal gradients across laminar flow was built with the laminar flow of water in a stainless capillary tube placed in a heat source. Its characteristics were studied with both experiments and a computational fluid dynamics simulation, firstly showing that it had the nature of a graded index optical fiber.

Adsorption Behavior of Curcumin onto Cetyltrimethylammonium Chloride Reverse Micelles Immobilized on a Glass Surface As Studied by Polarized Visible Attenuated Total Reflection Spectrometry with a Glass Slab Optical Waveguide.

Polarized visible attenuated total reflection spectrometry with a glass slab optical waveguide revealed that when a hydrophobic dye, curcumin, was adsorbed onto the cetyltrimethylammonium chloride (CTAC) reverse micelles immobilized on a glass surface, in an undissociated form, the curcumin was perpendicular to the surface plane, while in a dissociated form, the curcumin was parallel to the plane. This implies that the former may be located in the CTAC monolayer while the latter may be located in the reverse micellar water phase immobilized on the plane.

Recent Progress in the Development of Microfluidic Vascular Models.

The blood vessel is part of the circulatory system, and systemic circulation provides the blood supply to all tissues. Arteries are pathways through which the blood is carried, and the capillaries have a key role in material exchange to maintain the tissue environment. Blood vessels have structures appropriate for their functions, and their sizes and cell types are different. In this review, we introduced recent studies of the microfluidic vascular models. The model structures are classified mainly as poly(dimethylsiloxane) and hydrogel microchannels and self-assembled networks. Basic phenomena and functions were realized in vascular models, including fluid shear stress, cell strain, interstitial flow, endothelial permeation, angiogenesis, and thrombosis. In some models, endothelial cells were co-cultured with smooth muscle cells, pericytes, and fibroblasts in an extracellular matrix. Examples of vascular models involving the brain, lung, liver, kidney, placenta, and cancer were also introduced.

Development of a Microfluidic System Comprising Dialysis and Secretion Components for a Bioassay of Renal Clearance.

We have developed a microfluidic bioassay system that mimics glomerular filtration and tubular secretion in the kidney. The system consists of a peristaltic micropump (heart), a dialysis component (renal corpuscle), and a secretion component (renal proximal tubule). Analytes were separated by size using a dialysis membrane in the dialysis component. Model cells were cultured on a membrane in the secretion component, and active transport mediated by P-glycoprotein (P-gp) was confirmed using the P-gp substrate rhodamine 123 with or without the P-gp inhibitor quinidine sulfate. The system achieved both size separation and selective transport by P-gp on a single microchip. This proof-of-concept model may find applications in drug excretion assays, including studies of drug-drug interactions during tubular secretion.

Efficacy of Vonoprazan-Based Triple Therapy for Helicobacter pylori Eradication: A Multicenter Study and a Review of the Literature.

BACKGROUND: Eradication therapies for Helicobacter pylori infection are advancing as new acid inhibitory reagents approved. The aim of this study was to assess the efficacy and safety of vonoprazan-based triple treatment. MATERIALS AND METHODS: Triple therapy with vonoprazan and two antibiotics (amoxicillin and clarithromycin or metronidazole) received focus in this analysis. We performed a multicenter retrospective study of patients who received vonoprazan-based eradication therapy between February 2015 and February 2016 and conducted a review of the literature. RESULTS: The eradication rate among the 799 patients in our multicenter study was 94.4% (95% confidence interval [CI] 92.6-96.2%) in the per-protocol analysis for first-line treatment (with vonoprazan 20 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg, twice a day for 7 days) and 97.1% (95% CI 93.0-101.1%) for second-line treatment (with vonoprazan 20 mg, amoxicillin 750 mg, and metronidazole 250 mg, twice a day for 7 days). The overall incidence of adverse events was 4.4% in an intention-to-treat analysis with no patients hospitalized. In a literature review, six reports, in which 1380 patients received vonoprazan-based first-line eradication therapy, were included and were all reported by Japanese researchers. The eradication success rates in per-protocol analysis were between 85 and 93%, which was roughly the same among the studies. CONCLUSIONS: Vonoprazan-based triple therapy was effective and safe for Helicobacter pylori eradication in real-world experience, confirmed by a multicenter study and a review of the pertinent literature.

Development of Tetrahydrofuran/Water Optical Waveguide and Its Application to the Observation of Extraction Behavior of 1-Anilino-8-naphtalene Sulfonate at the Tetrahydrofuran/Water Interface.

A stable two-phase sheath flow using tetrahydrofuran (THF) for an inner flow and water for an outer flow was formed in a glass capillary, and worked as a stable liquid-core/liquid-cladding optical waveguide (THF/water LLW). Although THF and water were miscible with any ratio, the length of the stable THF/water LLW at 0.9 - 2.1 cm s-1 reached at least 150 mm. The THF/water LLW was applied to the observation of extraction behavior of solvatochromic fluorescence dye, 1-anilino-8-naphtalene sulfonate (ANS), through the THF/water interface. ANS was added to the water phase (clad solution) and its fluorescence, which was excited with the guided light (355 nm) through the LLW, was observed by changing the position of the detector. While the ANS stayed in the region of 70% THF to the end of the LLW without the addition of cationic surfactant, hexadecyltrimethylammonium ion (CTA+) at pH 3 and 11, the ion-pair of ANS and CTA+ was extracted into the higher concentration region of THF with the addition of CTA+ at pH 11.

Development of a Multichannel Dialysis Microchip for Bioassay of Drug Efficacy and Retention.

Here, we developed a multichannel dialysis microchip having three sets of dialysis systems, which consisted of three independent circulation channels with a common micropump. Each dialysis system was composed of a pneumatic micropump (heart), dialysis unit (renal corpuscle), and cell culture chamber (drug target) as well as circulation and dialysate channels to mimic the circulation system. Small molecules were successfully separated in parallel from macromolecules at the dialysis components. Anticancer tests using this microchip showed results that considered both serum protein-binding nature and drug activity. In the anticancer bioassay, the multichannel chip showed similar reproducible and reliable results as those of the single-channel system but with higher throughput.

The clinical importance of "bamboo joint-like appearance" on upper gastrointestinal endoscopy for the diagnosis of Crohn's disease.

Upper gastrointestinal (GI) lesions are frequently reported in Crohn's disease, in which the entire GI tract is affected. In these cases, erosive fissures regularly transversing folds that are longitudinally aligned along the lesser curvature of the gastric body and cardia are described as having a "bamboo joint-like appearance". We designed a blinded experiment in which upper GI imaging without a final diagnosis was checked by three observers to determine the usefulness of the bamboo joint-like appearance in the diagnosis of Crohn's disease. For the three observers, sensitivities of appearance were 30.5%, 56.9%, and 51.4%, while specificities were 99.6%, 98.5%, and 99.3%. Thus, the bamboo joint-like appearance was not useful for the identification of Crohn's disease patients. Nevertheless, patients exhibiting the bamboo joint-like appearance in upper GI imaging should undergo further examination due to the high probability of Crohn's disease.

A novel method for determination of inorganic oxyanions by electrospray ionization mass spectrometry using dehydration reactions.

Novel methods for the determination of inorganic oxyanions by electrospray (ES) ionization mass spectrometry have been developed using dehydration reactions between oxyanions and carboxylic acids at the ES interface. Twelve oxyanions (VO3 (-) , CrO4 (2-) , MoO4 (2-) , WO4 (2-) , BO3 (3-) , SiO3 (2-) , SiO4 (4-) , AsO4 (4-) , AsO2 (-) , SeO4 (2-) , SeO3 (2-) and NO2 (-) ), out of 16 tested, reacted with at least one of four aminopolycarboxylic acids, i.e. iminodiacetic acid (IDA), nitrilotriacetic acid (NTA), trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid and triethylenetetramine-N,N,N',N″,N'″,N'″-hexaacetic acid, at the ES interface to produce the dehydration products that gave intense mass ion responses, sufficient for trace analysis. As examples, trace determinations of Cr(VI) and silica in water samples were achieved after online ion exchange chromatography, where the dehydration product of CrO4 (2-) and NTA (m/z 290) and that of SiO4 (4-) and IDA (m/z 192) were measured. The limits of detection of the respective methods were 17 nM (0.83 ng Cr/ml) for Cr(VI) and 0.17 µM (4.8 ng Si/mL) for SiO4 (4-) .

Patterned Co-culture of Live Cells on a Microchip by Photocrosslinking with Benzophenone.

The patterned coculture of different types of living cells in a microfluidic device is crucial for the analysis of cellular interactions and cell-cell communication. In the present study, cell patterning was achieved by photocrosslinking benzophenone derivatives in a microfluidic channel. Optimization of UV irradiation conditions enabled successful fixation of live cells. In addition, patterning and co-culture of non-adherent K562 cells and adherent RF-6A cells was achieved by successive rounds of patterning. The present approach is expected to be useful for the development of in vitro methods for studying cell signaling.