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Barrett's esophagus arises in the process of wound healing in distal esophageal epithelium damaged by gastroesophageal reflux disease. Differentiation of fibroblast into myofibroblasts, a smooth muscle cell-like phenotype and tissue contraction are crucial processes in wound healing. No study has evaluated mechanism by which luminal esophageal nitric oxide (NO) affect Rho-associated coiled coil-forming protein kinase (Rho-ROCK) signaling pathway, a key factor of tissue contraction, in stromal fibroblasts to develop Barrett's esophagus. Using esophageal fibroblasts, we performed collagen-based cell contraction assays and evaluated influence of Rho-ROCK signaling in the exposure to acidic bile salts and NOC-9, which is an NO donor. We found that enhanced cell contraction induced by acidic bile salts was inhibited by NO, accompanied by decrease in phosphorylated myosin light chain expression and stress fiber formation. NO directly

Hyperspectral Imager Suite (HISUI) is a hyperspectral sensor for a remote sensing on the International Space Station (ISS). HISUI is composed of one radiometer that obtains spectral images of 185 bands from the visible to shortwave-infrared region with the ground sampling distance (GSD) of 20 meters for the cross track and 31 meters for the along track. The sensor system is the follow-on mission of the Advanced Space-borne Thermal Emission and Reflection Radiometer (ASTER) in the visible to shortwave infrared region. The observation data of the hyperspectral sensor is expected to an important role in the future spatial-spectral data for the resource exploration, disaster monitoring, environmental observation, agriculture, forestry and fisheries, etc. The tests of a flight model of HISUI have been carried out successfully in 2019 and HISUI is operating on the ISS. This paper describes the design and the performances of the flight model of HISUI and also presents radiometric performances in orbit.

Background: With the ongoing growth of the aged population, the number of elderly patients suffering from gastric cancer has increased in Japan. Since the frequency of lymph node metastasis (LNM) in patients after endoscopic submucosal dissection (ESD) with endoscopic curability (eCura) C-2 for early gastric cancer (EGC) is relative low, the following question can be raised: “Is additional gastrectomy required for elderly patients with such criteria for ESD?” Summary: For therapeutic decision-making after ESD with eCura C-2, the risk of all-cause mortality and impaired quality of life (QoL) should thus be evaluated. Risk stratification of LNM and gastric cancer-specific mortality was established by the eCura system; however, it remains unclear how much these categories and treatment selection affect all-cause mortality. The contribution of prognostic tools for predicting all-cause mortality was noted to vary across the studies of patients with EGC; thus, further studies that investigate comprehensive geriatric assessment (CGA) may be required. Regarding the QoL, studies on elderly patients remain to be lacking. Furthermore, one of the issues with CGA and QoL tools is that they are time consuming. Key Messages: Combined evaluation of risk stratification of gastric cancer-specific mortality by the eCura system and risk of nongastric cancer-related mortality and impaired QoL may be the current optimal method to decide treatment strategy after ESD with eCura C-2 for EGC among elderly patients. A large-scale prospective study that investigates CGA domains is required to identify predictors of all-cause mortality and impaired QoL, and a more easily usable tool should be developed.

Objectives Although many patients with early gastric cancers (EGCs) die of non-gastric cancer-related causes, the association of the risk categories of lymph node metastasis (LNM) with all-cause mortality remains unclear. We aimed to clarify the predictors of early and late mortality, separately. Methods Patients with endoscopic resection or gastrectomy for EGCs between 2003 and 2017 were retrospectively enrolled. We analyzed predictors for early and late mortality, including risk categories of LNM, treatment method, and nine non-cancer-related indices, separately, with a cut-off value of three years. Results We enrolled 1,439 patients with a median follow-up period of 79 months. The five-year overall survival rate was 86.8%. In the multivariate Cox analysis, the most important predictors for early and late mortality were age ≥ 85 years [hazard ratio (HR), 2.88 and 4.54, respectively] and Eastern Cooperative Oncology Group Performance Status ≥ 2 (HR, 3.00 and 4.19, respectively). Charlson comorbidity index ≥ 2 (HR, 2.76 and 1.99, respectively), American Society of Anesthesiologists Physical Status ≥ 3 (HR, 2.35 and 1.79, respectively), and C-reactive protein/albumin ratio ≥ 0.028 (HR, 2.30 and 1.58, respectively) were also predictors for both early and late mortality. Male (HR, 2.26), intermediate- (HR, 2.12)/high-risk (HR, 1.85) of LNM in eCura system, and sarcopenia evaluated by the psoas muscle mass index (HR, 1.70) were predictors for early mortality. Conclusion The combined assessment of multiple predictors might help to predict early and/or late mortality in patients with EGCs. The eCura system was associated with early mortality.

Although endoscopic submucosal dissection (ESD) is a minimally invasive treatment method for upper gastrointestinal (GI) tumors, patients undergoing upper GI ESD sometimes fall into a serious condition from complications. Thus, it is important to fully understand how to prevent complications when performing upper GI ESD. One of the major complications in esophageal and gastric ESD is intraoperative perforation. To prevent this complication, blind dissection should be avoided. Traction-assisted ESD is a useful technique for maintaining good endoscopic view. This method was proven to reduce the incidence of intraoperative perforation, which would become a standard technique in esophageal and gastric ESD. In gastric ESD, delayed bleeding is the most common complication. Recently, a novel prediction model (BEST-J score) consisting of 10 factors with four risk categories for delayed bleeding in gastric ESD was established, and a free mobile application is now available. For reducing delayed bleeding in gastric ESD, vonoprazan ≥20 mg/day is the sole reliable method in the current status. Duodenal ESD is still challenging with a much higher frequency of complications, such as perforation and delayed bleeding, than ESD in other organs. However, with the development of improved devices and techniques, the frequency of complications in duodenal ESD has been decreasing. To prevent intraoperative perforation, some ESD techniques, such as using the distal tips of the Clutch Cutter, were developed. An endoscopic mucosal defect closure technique would be mandatory for preventing delayed complications. However, several unresolved issues, including standardization of duodenal ESD, remain and further studies are demanded.

The present report describes an extremely rare case of Barrett's adenocarcinoma (BAC) with a squamous cell carcinoma (SCC) component. A 55-year-old man was diagnosed with esophageal adenocarcinoma on Barrett's esophagus. The patient underwent endoscopic submucosal dissection, but the pathology revealed deep submucosal invasive, moderately differentiated tubular adenocarcinoma and focal SCC with vascular invasion. In addition, morphological transition between adenocarcinoma and SCC components was confirmed. The patient underwent additional surgery, which revealed lymph node metastasis, and then received S-1 adjuvant chemotherapy. Based on the pathological findings, the transdifferentiation process may have a role in the histogenesis of this tumor.

Background: There has been no study that has directly measured the esophageal reflux factors in Barrett’s adenocarcinoma (BA) using 24-h multichannel intraluminal impedance-pH monitoring (24-h MII-pH). We aimed to clarify the esophageal reflux factors in Barrett’s esophagus (BE) and BA and the factors that determine the location of BA with 24-h MII-pH. Methods: We performed 24-h MII-pH in 26 patients with superficial BA treated endoscopically (BA group) and 13 patients with BE (BE group) and examined the esophageal reflux factors (esophageal acid exposure time [AET], bolus exposure (acid, weakly acid, and alkaline), and number of reflux episodes. In the BA group, there were 16 cases in which the lesions were localized in an area in contact with the esophagogastric junction (EGJ; EGJ group), and 10 cases in which the lesions were proximal to the BE and separated from the EGJ (non-EGJ group). Results: Total reflux in the bolus exposure in the BA group showed higher values compared to that in the BE group. The total of acid and weakly acid reflux of bolus exposure was significantly higher in the BA group than that in the BE group. The BA group also had greater numbers of total reflux episodes than the BE group. As for the cancer locations in BE, the cases in which the lesions were located proximally and separated from the EGJ had more AET and total reflux and acid reflux indicated by bolus exposure compared to the lesions adjacent to the EGJ. Conclusions: Stronger gastro-esophageal reflux appeared to be an important factor in the development of adenocarcinoma from BE. In addition, the cancer location in BE may be related to the intensity of esophageal reflux.

Background and Objectives: Weakly acidic reflux has been reported as the major cause of symptom occurrence in patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD). This study is aimed at clarifying whether the pH value of weakly acidic reflux affects the induction of symptoms. Methods: We retrospectively evaluated the records of combined multichannel intraluminal impedance and pH monitoring in 57 patients with PPI-refractory NERD. Weakly acidic refluxes were divided into 3 categories based on the pH value of the refluxate: pH 4–5, 5–6, and 6–7. Results: A total of 29 patients were positive in the symptom index. The symptom provocation rate in reflux of pH 4–5 (19%) was much higher than in that of pH 5–6 (11%) and pH 6–7 (12%). In the reflux at pH 4–5, the symptom provocation rate in the proximal reflux was higher than that in the distal reflux (p < 0.05), whereas the reflux at pH 5–6 and pH 6–7 was not significantly different in the symptom provocation rate between the proximal and distal refluxes. Conclusion: Reflux at pH

Background and aim Pooling of liquid in the esophageal lumen can worsen the field of vision and cause liquid reflux to the mouth, which leads to aspiration pneumonia, in esophageal endoscopic submucosal dissection (ESD). We developed a continuous liquid-suction catheter attachment for the endoscope (CLCA) that has multiple tiny holes and can suction the liquid without causing mucosal injury. Thus, we aim to show the efficacy of CLCA in esophageal ESD. Methods This was a single-blinded, randomized controlled trial involving patients with superficial esophageal cancer. The enrolled patients were randomly assigned to the conventional ESD (C-ESD) or ESD with CLCA (CLCA-ESD) groups. Primary endpoint was volume of liquid reflux to the mouth during the ESD procedure. Secondary endpoints were incidence of aspiration pneumonia and procedure time. Results Fifty patients were enrolled in this trial. Volume of liquid reflux to the mouth was significantly lower in the CLCA-ESD group than in the C-ESD group (mean: 10 vs 73 mL, P = 0.010). Furthermore, the incidence of aspiration pneumonia on computed tomography (CT) scan between the two groups was also significantly different (4.0% vs 32.0%, P = 0.023), although no significant difference was observed through chest radiography. In addition, procedure time tended to be shorter in the CLCA-ESD group (P = 0.054). Conclusion This study first showed that use of CLCA in esophageal ESD reduced the volume of liquid reflux to the mouth and contributed to decreased incidence of aspiration pneumonia on CT scan (UMIN000018167).

Background: Cytokines are being explored as a therapeutic strategy to modulate the tumor microenvironment and facilitate immunotherapy benefit in breast cancer. Here, we investigate a locoregional therapeutic approach whereby cytokines (IRX-2) are administered into the subcutaneous peri-areolar tissue (in an anatomic distribution similar to sentinel lymph node mapping) to facilitate immune cell recruitment/activation within the draining lymph nodes and tumor in ESBC. IRX-2 is derived from ex vivo phytohemagglutinin-stimulated lymphocytes and contains multiple cytokines including IL-1β, IL-2, TNF-α, IFN-γ, IL-6, IL-8, and GM-CSF, with stable concentrations from lot to lot. Preclinically, IRX-2 activates T-cells and natural killer (NK) cells, facilitates antigen presentation, and enhances activity of anti-PD-1/L1 in a SCC7 model. In a preceding head/neck squamous cell carcinoma phase I trial, perilymphatic IRX-2 was safe and increased TILs. Here, we report the final clinical results of a phase Ib trial evaluating the feasibility and immunologic activity of IRX-2 in ESBC. Methods: Beginning 21 days prior to surgical resection, enrolled operable patients with stage I-III ESBC (all subtypes) received the pre-operative IRX-2 regimen consisting of a single low-dose cyclophosphamide (300 mg/m2 to facilitate T-regulatory cell depletion), followed by 10 days of subcutaneous peri-areolar IRX-2 injections into the affected breast (1 mL × 2 at tumor axis and at 90°). Endpoints were feasibility (primary endpoint), stromal TIL (sTIL) count (pre-treatment versus post-treatment, blinded average of two pathologist reads using San Antonio H&E sTIL guidelines), PD-L1 expression (Nanostring) and enumeration of peripheral immune cells by flow cytometry. Results: All patients (n=16/16) completed and tolerated the regimen with no surgical delays or treatment-attributed grade III/IV toxicities. Common adverse events (occurring in >15% subjects) attributed to IRX-2 injections were: injection site reaction (grade 1, n=8/16), bruising (grade 1, n=7/16), and pain (grade 1, n=3/16). Common adverse events attributed to low-dose cyclophosphamide were: fatigue (grade 1, n=5/16) and nausea (grade 1/2, n=3/16). Treatment was associated with an increase in sTIL score (Wilcoxon signed-rank p=.04), with 4/10 sTIL-low tumors (0-10% score) re-categorized to sTIL-moderate (11-50% score). Increases in PD-L1 RNA expression were observed (Wilcoxon signed-rank p=.04) in 12/16 tumors (median 57% increase, range: -53% to 185% increase), as well as increases in Nanostring NK and Th1 cell signatures. In blood, increases in CD4 and CD8 effector T-cell activation (ICOS, HLA-DR, and CD38) and T-reg depletion were observed. Conclusions: IRX-2 was well tolerated with preliminary evidence of sTIL increase, PD-L1 upregulation, and peripheral lymphocyte activation. Based upon these data and preclinical evaluations demonstrating synergy with checkpoint inhibition, the IRX-2 regimen is being evaluated for clinical efficacy in conjunction with pembrolizumab and neoadjuvant chemotherapy (doxorubicin, cyclophosphamide, paclitaxel) in patients with stage II-III triple negative breast cancer. Citation Format: Pucilowska J, Egan JE, Berinstein NL, Moxon N, Aliabadi-Wahle S, Imatani JH, Conlin A, Acheson A, Massimino K, Martel M, Campbell M, Wu Y, Sun Z, Redmond W, Shah M, Urba WJ, Page DB. Perilymphatic IRX-2 cytokine therapy to enhance tumor infiltrating lymphocytes (TILs) and PD-L1 expression preceding curative-intent therapy in early stage breast cancer (ESBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-09-12.

A 66-year-old man with a history of diabetes and dilated cardiomyopathy underwent the implantation of a ventricular assist device (VAD) at the age of 62. He suffered from epigastralgia for a month and then visited our hospital with complaints of severe epigastralgia and hematemesis. A physical examination revealed abdominal distension without rigidity. Laboratory data showed severe systemic inflammation, multiple organ failure, and disseminated intravascular coagulation. Computed tomography showed multifocal thickness of the gastroduodenal wall with surrounding panniculitis, gas in a portal vein and a perigastric vein. Emergency esophago-gastro duodenoscopy (EGD) demonstrated a large erosion in the antrum of the stomach, and penetration surrounded by circumferentially ischemic mucosa in the second and third portions of the duodenum. Based on informed consent, conservative therapy was performed, and his condition improved enabling the start of oral intake on the 37th hospital day. However, 7 days later, there was a relapse of epigastralgia after a meal. Gastrointestinal series and EGD revealed a 10-mm-long pinhole-like stricture at the site. After laparoscopic gastro-jejunal bypass surgery, he has remained in a good condition for 2 years. We demonstrated a rare case of penetration due to severe ischemic duodenitis 4 years after VAD implantation.