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Background/Objectives: Near-infrared photoimmunotherapy (NIR-PIT) was recently approved for the treatment of unresectable locally advanced or recurrent head and neck cancers in Japan; however, only one clinical dose has been validated in clinical trials, potentially resulting in excessive or insufficient dosing. Moreover, IRDye700X (IR700) fluorescence intensity plateaus during treatment, indicating a particular threshold for the antitumor effects. Therefore, we investigated the NIR laser dose across varying tumor sizes and irradiation methods until the antitumor effects of the fluorescence decay rate plateaued. Methods: Mice were subcutaneously transplanted with A431 xenografts and categorized into control, clinical dose (cylindrical irradiation at 100 J/cm², frontal irradiation at 50 J/cm²), and evaluation groups. The rate of tumor IR700 fluorescence intensity decay to reach predefined rates (−0.05%/s or −0.2%/s) until the cessation of light irradiation was calculated using a real-time fluorescence imaging system. Results: The evaluation group exhibited antitumor effects comparable to those of the clinical dose group at a low irradiation dose. Similar results were observed across tumor sizes and irradiation methods. Conclusions: In conclusion, the optimal antitumor effect of NIR-PIT is achieved when the fluorescence decay rate reaches a plateau, indicating the potential to determine the appropriate dose for PIT using a real-time fluorescence monitoring system.

Abstract The development of multiple squamous cell carcinomas (SCC) in the upper aerodigestive tract, which includes the oral cavity, pharynx, larynx, and esophagus, is explained by field cancerization and is associated with alcohol consumption and cigarette smoking. We reviewed the association between alcohol consumption, multiple Lugol‐voiding lesions, and field cancerization, mainly based on the Japan Esophageal Cohort study. The Japan Esophageal Cohort study is a prospective cohort study that enrolled patients with esophageal SCC after endoscopic resection. Enrolled patients received surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months. The Japan Esophageal Cohort study showed that esophageal SCC and head and neck SCC that developed after endoscopic resection for esophageal SCC were associated with genetic polymorphisms related to alcohol metabolism. They were also associated with Lugol‐voiding lesions grade in the background esophageal mucosa, the score of the health risk appraisal model for predicting the risk of esophageal SCC, macrocytosis, and score on alcohol use disorders identification test. The standardized incidence ratio of head and neck SCC in patients with esophageal SCC after endoscopic resection was extremely high compared to the general population. Drinking and smoking cessation is strongly recommended to reduce the risk of metachronous esophageal SCC after treatment of esophageal SCC. Risk factors for field cancerization provide opportunities for early diagnosis and minimally invasive treatment. Lifestyle guidance of alcohol consumption and cigarette smoking for esophageal precancerous conditions, which are endoscopically visualized as multiple Lugol‐voiding lesions, may play a pivotal role in decreasing the incidence and mortality of esophageal SCC.

Abstract The Japan Gastroenterological Endoscopy Society (JGES) held four serial symposia between 2021 and 2022 on state‐of‐the‐art issues related to advanced diagnostic endoscopy of the upper gastrointestinal tract. This review summarizes the four core sessions and presents them as a conference report. Eleven studies were discussed in the 101st JGES Core Session, which addressed the challenges and prospects of upper gastroenterological endoscopy. Ten studies were also explored in the 102nd JGES Core Session on advanced upper gastrointestinal endoscopic diagnosis for decision‐making regarding therapeutic strategies. Moreover, eight studies were presented during the 103rd JGES Core Session on the development and evaluation of endoscopic artificial intelligence in the field of upper gastrointestinal endoscopy. Twelve studies were also discussed in the 104th JGES Core Session, which focused on the evidence and new developments related to the upper gastrointestinal tract. The endoscopic diagnosis of upper gastrointestinal diseases using image‐enhanced endoscopy and AI is one of the most recent topics and has received considerable attention. These four core sessions enabled us to grasp the current state‐of‐the‐art in upper gastrointestinal endoscopic diagnostics and identify future challenges. Based on these studies, we hope that an endoscopic diagnostic system useful in clinical practice is established for each field of upper gastrointestinal endoscopy.

Abstract Background Hypoxic microenvironment is prominent in advanced esophageal squamous cell carcinoma (ESCC). However, it is unclear whether ESCC becomes hypoxic when it remains in the mucosal layer or as it invades the submucosal layer. We aimed to investigate whether intramucosal (Tis‐T1a) or submucosal invasive (T1b) ESCC becomes hypoxic using endoscopic submucosal dissection samples. Methods We evaluated the expression of hypoxia markers including hypoxia inducible factor 1α (HIF‐1α), carbonic anhydrase IX (CAIX), and glucose transporter 1 (GLUT1) by H‐score and vessel density by microvessel count (MVC) and microvessel density (MVD) for CD31 and α‐smooth muscle actin (α‐SMA) with immunohistochemical staining (n = 109). Further, we quantified oxygen saturation (StO2) with oxygen saturation endoscopic imaging (OXEI) (n = 16) and compared them to non‐neoplasia controls, Tis‐T1a, and T1b. Results In Tis‐T1a, cccIX (13.0 vs. 0.290, p

Abstract Radiotherapy (RT) plus immunotherapy is a promising modality; however, the therapeutic effects are insufficient, and the molecular mechanism requires clarification to further develop combination therapies. Here, we found that the RNA virus sensor pathway dominantly regulates the cellular immune response in NSCLC and ESCC cell lines. Notably, transposable elements (TEs), especially long terminal repeats (LTRs), functioned as key ligands for the RNA virus sensor RIG-I, and the mTOR–LTR–RIG-I axis induced the cellular immune response and dendritic cell and macrophage infiltration after irradiation. Moreover, RIG-I-dependent immune activation was observed in ESCC patient tissue. scRNA sequencing and spatial transcriptome analysis revealed that radiotherapy induced the expression of LTRs, and the RNA virus sensor pathway in immune and cancer cells; this pathway was also found to mediate tumour conversion to an immunological hot state. Here, we report the upstream and ligand of the RNA virus sensor pathway functions in irradiated cancer tissues.

Before the development of double-balloon enteroscopy (DBE), the standard management of small-bowel polyposis was surgical resection. This is an invasive procedure that could lead to short bowel syndrome. In the 21st century, several new enteroscopy techniques were distributed worldwide, including DBE, single-balloon enteroscopy, spiral enteroscopy, and motorized spiral enteroscopy. These devices enable the diagnoses and endoscopic interventions in the entire small bowel, even in patients with a history of laparotomy. In patients with Peutz–Jeghers syndrome (PJS), endoscopic ischemic polypectomy with clips or a detachable snare is the preferred method for managing pedunculated polyps because it is less likely to cause adverse events than conventional polypectomy. Although polyps in patients with PJS always recur, repeat endoscopic resection can reduce the total number and mean size of polyps in the long-term clinical course. Endoscopic reduction of small-bowel intussusception caused by PJS polyps can be successfully performed using DBE without surgery. A transparent hood is useful for securing a visual field during the treatment of small-bowel polyps, and minimal water exchange method is recommended to facilitate deep insertion. Familial adenomatous polyposis (FAP) is a genetic disorder that increases the risk of developing colorectal cancer. Because jejunal and ileal polyps in patients with FAP have the potential to develop into cancer via the adenoma–carcinoma sequence, periodical surveillance, and endoscopic resection are needed for them, not only polyps in the duodenum. In cases of multiple small-bowel polyps in patients with FAP, cold snare polypectomy without retrieval is an acceptable treatment option for polyps that are 10 mm or smaller in size. Additional good pieces of evidence are necessary to confirm these findings because this narrative review mostly includes retrospective observational studies from single center, case reports, and expert reviews.

The drug efficacy evaluation of tumor-selective photosensitive substances was expected to be enabled by imaging the fluorescence intensity in the tumor area. However, fluorescence observation is difficult during treatments that are performed during gastrointestinal endoscopy because of the challenges associated with including the fluorescence filter in the camera part. To address this issue, this study developed a device that integrates a narrow camera and a laser diffuser to enable fluorescence imaging through a forceps port. This device was employed to demonstrate that a laser diffuser with an NIR fluorescence imaging sensor could be delivered through a 3.2 mm diameter port. In addition, fluorescence images of Cetuximab-IR700 were successfully observed in two mice, and the fluorescence intensity confirmed that the fluorescence decayed within 330 s. This device is expected to have practical application as a tool to identify the optimal irradiation dose for tumor-selective photosensitive substances under endoscopy.

Abstract Background Endoscopic balloon dilation (EBD) is an effective, minimally invasive treatment for Crohn's disease (CD) related intestinal strictures. However, restenosis frequently occurs and requires repetitive EBD or surgical resection. Since previous studies could not evaluate restenosis based on stricture diameter, factors affecting restenosis after EBD were unclear. This study aimed to identify these factors by precisely measuring the diameter of small intestinal strictures in patients with CD. Methods This single‐center retrospective study enrolled patients with CD with de novo small intestinal strictures who underwent two double‐balloon enteroscopy sessions (EBD and follow‐up) between January 2016 and October 2021. Clinical and endoscopic data were obtained from electronic medical records. A calibrated small‐caliber‐tip transparent hood was used to precisely measure stricture diameters. Multivariate analysis was performed to identify factors associated with restenosis. Results Forty‐eight patients (37 male) were analyzed. The total number of strictures detected decreased from 162 to 143. The mean diameter of all strictures and the narrowest stricture in each patient increased significantly from 8.6 to 9.8 mm and from 7.6 to 8.7 mm, respectively. Thirty‐two (67%) patients developed endoscopic restenosis. Multivariate analysis showed that the presence of ulcers at the follow‐up session was a risk factor for restenosis (odds ratio 9.4, p = 0.01). Patients with complete mucosal healing at both sessions (n = 21) showed significant improvement in the narrowest stricture (+1.7 mm, p = 0.001). Conclusions Maintenance of complete mucosal healing is significantly associated with avoiding restenosis after EBD in CD‐related small intestinal strictures.

Abstract Objectives Recent innovations in prophylactic treatment with steroids have overcome the issue of esophageal stricture after endoscopic submucosal dissection (ESD), except in entire circumferential esophageal squamous cell carcinoma (EC‐ESCC). Current Japanese guidelines weakly recommend performing ESD for clinical epithelial/lamina propria EC‐ESCC with a longitudinal extension

Summary: Trochanteric femur fractures have traditionally been treated surgically with compression hip screws or cephalomedullary nails. With the increasing use of cephalomedullary nails, potential complications from this technique have surfaced. One of them is the potential for varus malreduction of trochanteric femur fractures, known as the “wedge effect”, which is the distraction of fracture fragments generated during reamer and nail passage resulting in varus malalignment at the neck-shaft angle. Although trochanteric nonunion in the non-elderly is exceedingly rare, we experienced one such case after nailing due to the wedge effect that was subsequently successfully treated with a compression hip screw without bone grafting. Therefore, in the case of stable pertrochanteric fractures (AO/OTA 31A1) in younger patients, compression hip screw surgery may be the better choice of initial surgery to avoid later nonunion.

Background and study aims: Radial incision and cutting (RIC) is indicated for refractory benign esophageal strictures after curative treatment for esophageal cancer and has shown favorable short-term outcomes. However, re-stricture after RIC may occur in the long term, and RIC is performed repeatedly in such cases, but the efficacy and safety of repeated RIC are unclear. Therefore, we aimed to demonstrate the efficacy and safety of the repeated RIC for refractory benign esophageal strictures after surgical and non-surgical treatment. Patients and methods: Between April 2008 and September 2019, we enrolled patients who were treated with the first RIC for benign esophageal strictures. The RIC was indicated for the refractory stricture and repeatedly performed for re-refractory esophageal stricture after RIC. We retrospectively evaluated the 6-month refractory stricture-free rate, and adverse events (AEs) in the first RIC and repeated RICs. Results: Forty-six patients (39 men, 7 women; median age, 71 years, range 49–85) were included. RIC was performed once in 24 patients (non-repeated RIC group) and two or more times in 22 patients (repeated RIC group). In all patients, the 6-month refractory stricture-free rate after the first RIC were 42.3 %. In the repeated RIC group, the 6-month refractory stricture-free rate after the first and repeated RICs were 18.2 % vs 18.2 %, respectively. No AEs were noted. Conclusions: Repeated RIC could be effective in the short-term and safe even for patients with refractory benign esophageal stricture after the first RIC. However, it cannot be considered curative treatment for refractory stricture because of poor long-term results.

Abstract Background While esophageal squamous cell carcinoma (ESCC) is the predominant histological type in Japan, concern has been expressed over an increase in the proportion of esophageal adenocarcinoma (EAC), especially in middle‐aged populations. This study aimed to assess long‐term trends in esophageal cancer incidence by histological type. Methods We used data from three population‐based cancer registries in Japan with 10,642 esophageal cancer cases diagnosed between 1993 and 2014. The multiple imputation approach was used to impute a specific histological type (ESCC, EAC, and others) for cases with “Unknown” or missing status. We calculated the age‐standardized incidence rates by histological type from 1993 to 2014 and fitted age‐period‐cohort models to estimate the annual percent changes (APCs) and adjusted incidence rate ratios (IRRs). Results After imputation of missing data, the largest mean APC increase was seen in the incidence of EAC in men aged 40–49 years (7.1%) followed by those aged 50–59 years (5.5%). The age‐period‐cohort analysis showed that men who were born in the 1960s and later were more likely to develop EAC relative to men who were born in 1950–1959 (1960–1969 cohort, IRR: 1.42; 1970–1974 cohort, IRR: 2.23), with a period effect indicating a constant increase after 2003. For women, no significant trend in EAC incidence was observed. Conclusions The incidence of EAC has increased more prominently compared with that of ESCC, especially in men aged 40–59 years, suggesting the impact of increasing obesity in men and a reduction in H. pylori prevalence in Japan.

Background and Aims: Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. Methods: This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. Results: LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). Conclusion: Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676.

Background and study aims Intussusception caused by intestinal polyps in patients with Peutz-Jeghers syndrome usually requires laparotomy. Patients following successful endoscopic reduction using double-balloon endoscopy (DBE) have been reported. The aim of this study was to evaluate the feasibility of endoscopic treatment of intussusception. Patients and methods We retrospectively reviewed patients who underwent DBE for intussusception due to small intestine polyps in patients with Peutz-Jeghers syndrome from January 2004 to June 2020. Results Twenty-seven (antegrade 22, retrograde 5) DBEs were performed in 19 patients with 25 sites of intussusception identified during the study period. If the intussusception remained once the endoscope reached the site, endoscopic reduction of the intussusception was performed as needed (15 sites). Ultimately, endoscopic resections (8 sites) or ischemic polypectomies (16 sites) of the polyp causing the intussusception were completed at 24 sites. Only one site could not be treated endoscopically and was treated surgically. The final per-site and per-patient success rates of endoscopic treatment were 96 % (24/25) and 95 % (18/19) respectively. Two patients developed mild acute pancreatitis and one patient developed intussusception after the procedures, both of which were treated non-operatively. Conclusions Endoscopic treatment of intussusception is feasible to avoid laparotomy in patients with Peutz-Jeghers syndrome.

Background and study aims Gastric endoscopic submucosal dissection (ESD) is a highly technical procedure mainly due to the distinctive shape of the stomach and diverse locations of lesions. We developed a new gastric ESD training model (G-Master) that could accurately recreate the location of the stomach and assessed the reproducibility of located lesions in the model. Methods The model comprises a simulated mucous membrane sheet made of konjac flour and a setting frame, which can simulate 11 locations of the stomach. We assessed the reproducibility of each location in the model by assessing the procedure speed and using a questionnaire that was distributed among experts. In the questionnaire, each location was scored on a six-point scale for similarity of locations. Results The mean score for all locations was high with > 4 points. Regarding locations, lower anterior and posterior walls had medium scores with 3 to 4 points. The procedure speed was slower in the greater curvature of the upper and middle gastric portions, where ESD is considered more difficult than the overall procedure speed. Conclusions The new gastric ESD training model appears to be highly reproducible for each gastric location and its application for training in assuming actual gastric ESD locations.

Abstract Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real‐world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1–75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2–357). Adverse events occurred in 12.7%. Life‐threatening complications occurred in 0.5%, but there were no treatment‐related deaths. During a median follow‐up period of 46.1 months (range 1–113), the 3‐year overall survival rate, relapse‐free survival rate, cause‐specific survival rate, and larynx‐preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.

Abstract Background The Cryoballoon focal ablation system (CbFAS) for dysplastic Barrett’s esophagus is simple, time-saving and has high therapeutic efficacy. This study aimed to evaluate the technical feasibility and tissue damage with combination therapy of endoscopic resection (ER) and CbFAS in porcine models. Methods Three pigs (A, B, and C) were included, and all ER procedures were performed by endoscopic mucosal resection using the Cap method (EMR). Combination therapy for each pig was performed as follows: (a) CbFAS was performed for a post-EMR mucosal defect for Pig A; (b) CbFAS for post-EMR scar for Pig B, and (c) EMR for post-CbFAS scar for Pig C. All pigs were euthanized at 32 days after the initial procedure, and the tissue damage was evaluated. Results All endoscopic procedures were followed as scheduled. None of the subjects experienced anorexia, rapid weight loss, bleeding, and perforation during the observation period. They were euthanized at 32 days after the initial endoscopic procedure. On histological assessment, there was little difference between the tissue that was treated with CbFAS alone and that treated with CbFAS in combination with ER. Conclusion Combination therapy with ER and CbFAS can be technically feasible, and its outcome was not significantly different from CbFAS alone in terms of tissue damage.

Abstract Little is known about the incidence of metachronous advanced neoplasia (AN) following resection of submucosal invasive colorectal cancer (SM-CRC). Here, we aimed to assess the occurrence of metachronous AN following SM-CRC resection. We retrospectively reviewed consecutive patients who underwent SM-CRC resection at an academic medical center between 2005 and 2013. Among 343 patients, 250 (72.9%) underwent surgical resection or endoscopic resection followed by surgical resection and 93 (27.1%) underwent only endoscopic resection. During a median follow-up period of 61.5 months, the overall incidence of metachronous AN was 7.6%, and the cumulative incidence at 5 years was 6.1%. The cumulative incidence was significantly higher in the endoscopic resection group than in surgical resection group, in patients with colonic disease than in those with rectal disease, and in patients with synchronous AN than in those without. Multivariate analysis revealed that synchronous AN was the only significant risk factor for metachronous AN (HR 4.35; 95% CI 1.88–10.1). These findings imply that depending on synchronous AN, a surveillance protocol following SM-CRC resection can be changed for better detection of metachronous AN.

Abstract The diagnosis of gastrointestinal stromal tumor (GIST) using conventional endoscopy is difficult because submucosal tumor (SMT) lesions like GIST are covered by a mucosal layer. Near-infrared hyperspectral imaging (NIR-HSI) can obtain optical information from deep inside tissues. However, far less progress has been made in the development of techniques for distinguishing deep lesions like GIST. This study aimed to investigate whether NIR-HSI is suitable for distinguishing deep SMT lesions. In this study, 12 gastric GIST lesions were surgically resected and imaged with an NIR hyperspectral camera from the aspect of the mucosal surface. Thus, the images were obtained ex-vivo. The site of the GIST was defined by a pathologist using the NIR image to prepare training data for normal and GIST regions. A machine learning algorithm, support vector machine, was then used to predict normal and GIST regions. Results were displayed using color-coded regions. Although 7 specimens had a mucosal layer (thickness 0.4–2.5 mm) covering the GIST lesion, NIR-HSI analysis by machine learning showed normal and GIST regions as color-coded areas. The specificity, sensitivity, and accuracy of the results were 73.0%, 91.3%, and 86.1%, respectively. The study suggests that NIR-HSI analysis may potentially help distinguish deep lesions.

Background and study aims Endoscopic submucosal dissection (ESD) is a standard method for minimally invasive resection of superficial gastrointestinal tumors. The pocket creation method (PCM) facilitates ESD regardless of location in the gastrointestinal tract. The aim of this systematic review and meta-analysis is to evaluate the effectiveness and safety of ESD for superficial neoplasms in the upper and lower gastrointestinal tract comparing the PCM to the non-PCM. Methods Randomized controlled, prospective, and retrospective studies comparing the PCM with the non-PCM were included. Outcomes included en bloc resection, R0 resection, dissection speed, delayed bleeding and perforation. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) using the Mantel-Haenszel random effect model were documented. Results Eight studies including gastric, duodenal, and colorectal ESD were included. The en bloc resection rate was significantly higher in the PCM group than the non-PCM group (OR 3.87, 95 %CI 1.24–12.10 P = 0.020). The R0 resection rate was significantly higher in the PCM group than the non-PCM group (OR 2.46, 95 %CI 1.14–5.30, P = 0.020). The dissection speed was significantly faster in the PCM group than the non-PCM group (mean difference 3.13, 95 % CI 1.35–4.91, P

Background and study aims Gel immersion endoscopy is a novel technique for securing the visual field during endoscopy. Clinical application of a dedicated gel for this technique with an appropriate viscosity to prevent mixing with blood and its efficacy was reported. The aim of this study was to evaluate changes in gel viscosity and flow rate under different conditions. Methods The viscosity of the gel after injection and flow rate were measured under various conditions changing the injection route and method. Gel viscosity was measured at 25, 10, and 4 °C. Results A decrease in gel viscosity was found when the gel was injected via the water jet channel compared to the accessory channel. The flow rate and decrease in viscosity of the gel injected via the water jet channel were 220 mL/min and 63.2 %, while when injected via the accessory channel with a clip device inserted were 560 mL/min and 35.8 %. When the gel was kept at a low temperature, the viscosity increased. Conclusions Gel injection via the accessory channel should be the first choice for efficient use considering the viscosity and flow rate.

Abstract Objective Photoacoustic (PA) imaging is a novel noninvasive technique that offers high‐contrast tomographic imaging with ultrasound‐like resolution at depths of centimeters, enabling visualization of deep small vessels. The aim of this pilot study was to survey the characteristics of deep vessel networks in the mucosa of neoplastic gastrointestinal (GI) lesions using PA imaging. Methods Specimens of patients who had undergone surgical and endoscopic resection for GI lesions were included in this study. The PA/ultrasound imaging system for clinical research is characterized by a technology that can superimpose a PA image over an ultrasound image. Three‐dimensional PA images were acquired for the resected specimen before fixation. The stomach and colon of live pigs were incised, and the walls were scanned from the mucosa. Results A total of 32 specimens (nine esophageal, 12 gastric, 11 colorectal) were scanned. The pathological diagnoses were adenomas (n = 2), intramucosal cancers (n = 14), and invasive cancers (n = 16). The deep vessel networks of all lesions could be visualized. In the intramucosal lesions, the deep vessel network was similar to that of a normal tissue. In invasive cancers, the thick and prominent vessel network was visible in the surface layer of esophageal cancers, infiltrated area of gastric cancers, and surface layer and infiltrated area of colorectal cancers. In the images of living pigs, visualizing the vascular network deeper than the submucosa in both the stomach and large intestine was possible. Conclusion Our study confirmed that the deep vessel networks of neoplastic GI lesions were visible by PA imaging.

Background and aims: Oxygen saturation (OS) imaging is a novel technique that directly measures and visualizes the tissue oxygen saturation at the surface of the GI tract. Our purpose was to evaluate the ability of OS imaging to visualize the action mode of photodynamic therapy (PDT). Methods: Eight patients with local recurrence after chemoradiotherapy for esophageal cancer were enrolled. OS imaging observation was performed before PDT, after 100 J/cm2 illumination and illumination completion, and on the second day. Results: OS imaging showed an extreme change in the hypoxic state in the illuminated area, although the change was near invisible on white-light imaging. The median tissue oxygen saturation value at the tumor lesion was 61.5% (range, 36%-91%) before PDT and significantly decreased immediately after illumination: 11% (range, 0%-57%) after 100 J/cm2 illumination, 1% (range, 0%-6%) at PDT completion, and 2% (range, 0%-12%) on the second day. Conclusions: OS imaging could be a useful tool to visualize changes after PDT.

The small bowel had long been considered a dark unapproachable tunnel until the invention of capsule endoscopy and doubleballoon enteroscopy in the 21st century, which revolutionized the diagnosis and management of small bowel diseases, including bleeding. Various imaging modalities such as computed tomographic enterography, angiography, capsule endoscopy, and balloonassisted enteroscopy play vital roles in the diagnosis and management of small bowel bleeding. The choice of modality to use and timing of application differ according to the availability of the modalities, patient’s history, and physician’s experience. Small bowel bleeding is managed using different strategies as exemplified by medical treatment, interventional radiology, endoscopic therapy, or surgical intervention. Balloon-assisted enteroscopy enables endoscopic interventions to control small bowel bleeding, including electrocautery, argon plasma coagulation, clip application, and tattooing as a prelude to surgery. In this article, we clarify the recent approaches to the optimal diagnosis and management of patients with small bowel bleeding.

Abstract Background Monopolar instruments are generally used in colorectal endoscopic mucosal resection (EMR). Bipolar instruments have previously been reported to be as safe as monopolar instruments. We sought to compare the safety of the monopolar and bipolar snare and hemostatic forceps in an animal model. Methods We created 5-mm, 10-mm, and 15-mm target lesions on an ex vivo porcine rectum. Two lesions of each size were resected via monopolar polypectomy (M-P), monopolar EMR (M-E), bipolar polypectomy (B-P), and bipolar EMR (B-E). We performed a pathological evaluation of the conditions of perforation and the effects of burning on the tissues. In addition, we burned the muscularis propria covered with submucosal layer using monopolar and bipolar hemostatic forceps and performed pathological evaluations. Results Polypectomy and EMR were performed in a total of 24 target lesions. A perforation was found on histology in one case of M-P and one case of M-E after removing target lesions of 15 mm in diameter. There were no perforations during endoscopic resection using the bipolar snare. The thermal denaturation in B-P did not reach the muscularis propria layer regardless of the size of the target lesion. Although thermal damage after using monopolar hemostatic forceps was extensive, thermal denaturation was only seen on the surface of the submucosal layer when bipolar hemostatic forceps were used. Conclusions Bipolar instruments cause less damage to the tissue than monopolar instruments. Our results also suggest that bipolar instruments may be safer than monopolar instruments in endoscopic procedures for colorectal lesions.

Backgrounds and study aims Gel immersion endoscopy is a novel technique to secure the visual field during endoscopy. The aim of this study was to develop a dedicated gel for this technique. Methods To identify appropriate viscoelasticity and electrical conductivity, various gels were examined. Based on these results, the dedicated gel “OPF-203” was developed. Efficacy and safety of OPF-203 were evaluated in a porcine model. Results In vitro experiments showed that a viscosity of 230 to 1900 mPa·s, loss tangent (tanδ) ≤ 0.6, and hardness of 240 to 540 N/cm2 were suitable. Ex vivo experiments showed electrical conductivity ≤ 220 μS/cm is appropriate. In vivo experiments using gastrointestinal bleeding showed that OPF-203 provided clear visualization compared to water. After electrocoagulation of gastric mucosa in OPF-203, severe coagulative necrosis was not observed in the muscularis but limited to the mucosa. Conclusions OPF-203 is useful for gel immersion endoscopy.

Background and study aims The Japan Narrow-band imaging (NBI) Expert Team (JNET) classification was proposed for evaluating colorectal lesions. However, it remains unknown whether the JNET classification can be applied to magnifying endoscopy with image-enhanced endoscopies other than NBI. This study aimed to compare the diagnostic ability of JNET classification by magnifying endoscopy with blue laser imaging (ME-BLI) and with ME-NBI. Patients and methods We retrospectively assessed consecutive patients diagnosed per the JNET classification by ME-BLI (BLI group) or ME-NBI (NBI group) between March 2014 and June 2017. We compared the diagnostic value of JNET classification between the groups with one-to-one propensity score matching. Results Four hundred and seventy-one propensity score-matched pairs of lesions were analyzed. In the BLI and NBI groups, the overall diagnostic accuracies were 92.1 % and 91.7 %, respectively, and those for differentiating between neoplastic and non-neoplastic polyps were 96.6 % and 96.8 %, respectively. The positive predictive value by each JNET classification in BLI vs. NBI group was 90.6 % vs. 96.2 % in Type 1, 94.3 % vs. 94.6 % in Type 2A, 57.7 % vs. 42.3 % in Type 2B, and 100 % vs. 91.7 % in Type 3. The negative predictive value was 97.0 % vs. 96.9 % in Type 1, 88.1 % vs. 82.8 % in Type 2A, 98.0 % vs. 98.2 % in Type 2B, and 98.5 % vs. 98.7 % in Type 3. No statistical difference in the diagnostic results was found between the groups. Conclusions The diagnostic ability of the JNET classification by ME-BLI and ME-NBI was comparable, with the former also applicable for diagnosis of colorectal lesions.

ObjectivesOxygen saturation (OS) imaging is a new method of endoscopic imaging that has clinical applications in oncology which can directly measure tissue oxygen saturation (Sto2) of the surface of gastrointestinal tract without any additional drugs or devices. This imaging technology is expected to contribute to research into cancer biology which leads to clinical benefit such as prediction to efficacy of chemotherapy or radiotherapy. However, adherent substances on tumors such as blood and white coating, pose a challenge for accurate measurements of the StO2 values in tumors. The aim of this study was to develop algorithms for discriminating between the tumors and their adherent substances, and to investigate whether it is possible to evaluate the tumor specific StO2 values excluding adherent substances during OS imaging.MethodsWe plotted areas of tumors and their adherent substances using white-light images of 50 upper digestive tumors: blood (68 plots); reddish tumor (83 plots); white coating (89 plots); and whitish tumor (79 plots). Scatter diagrams and discriminating algorithms using spectrum signal intensity values were constructed and verified using validation datasets. StO2 values were compared between the tumors and tumor adherent substances using OS images of gastrointestinal tumors.ResultsThe discriminating algorithms and their accuracy rates (AR) were as follows: blood vs. reddish tumor: Y> - 4.90X+7.13 (AR: 95.9%) and white coating vs. whitish tumor: Y< -0.52X+0.17 (AR: 96.0%). The StO2 values (median, [range]) were as follows: blood, 79.3% [37.8%-100.0%]; reddish tumor, 74.5% [62.0%-86.9%]; white coating, 73.8% [42.1%-100.0%]; and whitish tumor, 65.7% [53.0%-76.3%].ConclusionsOS imaging is strongly influenced by adherent substances for evaluating the specific StO2 value of tumors; therefore, it is important to eliminate the information of adherent substances for clinical application of OS imaging.

Dysbiotic microbiota contributes to the pathogenesis of Crohn’s disease (CD) by regulating the immune system. Although pro-inflammatory microbes are probably enriched in the small intestinal (SI) mucosa, most studies have focused on fecal microbiota. This study aimed to examine jejunal and ileal mucosal specimens from patients with CD via double-balloon enteroscopy. Comparative microbiome analysis revealed that the microbiota composition of CD SI mucosa differs from that of non-CD controls, with an increased population of several families, including Enterobacteriaceae, Ruminococcaceae, and Bacteroidaceae. Upon anaerobic culturing of the CD SI mucosa, 80 bacterial strains were isolated, from which 9 strains representing 9 distinct species (Escherichia coli, Ruminococcus gnavus, Klebsiella pneumoniae, Erysipelatoclostridium ramosum, Bacteroides dorei, B. fragilis, B. uniformis, Parabacteroides distasonis, and Streptococcus pasteurianus) were selected on the basis of their significant association with CD. The colonization of germ-free (GF) mice with the 9 strains enhanced the accumulation of TH1 cells and, to a lesser extent, TH17 cells in the intestine, among which an E. coli strain displayed high potential to induce TH1 cells and intestinal inflammation in a strain-specific manner. The present results indicate that the CD SI mucosa harbors unique pro-inflammatory microbiota, including TH1 cell-inducing E. coli, which could be a potential therapeutic target.

Photoimmunotherapy (PIT) is a promising tumor-selective treatment method that uses light-absorbing dye-conjugated antibodies and light irradiation. It has been reported that IR700 fluorescence changes with light irradiation. The purpose of this study was to investigate the fluorescence intensity and antitumor effect of PIT using real-time fluorescence observation of tumors and predict the required irradiation dose. The near-infrared camera system LIGHTVISION was used to image IR700 during PIT treatment. IR700 showed a sharp decrease in fluorescence intensity in the early stage of treatment and almost reached a plateau at an irradiation dose of 40 J/cm. Cetuximab-PIT for A431 xenografts was performed at multiple doses from 0–100 J/cm. A significant antitumor effect was observed at 40 J/cm compared to no irradiation, and there was no significant difference between 40 J/cm and 100 J/cm. These results suggest that the rate of decay of the tumor fluorescence intensity correlates with the antitumor effect by real-time fluorescence imaging during PIT. In addition, when the fluorescence intensity of the tumor plateaued in real-time fluorescence imaging, it was assumed that the laser dose was necessary for treatment.

Abstract Background The treatment of lumbar spinal canal stenosis (LSS) depends on symptom severity. In the absence of severe symptoms such as severe motor disturbances or bowel and/or urinary dysfunction, conservative treatment is generally the first choice for the treatment of LSS. However, we experienced cases of worsening symptoms even after successful conservative treatment. The purpose of this study is to investigate the long-term clinical course of LSS following successful conservative treatment and analyze the prognostic factors associated with symptom deterioration. Methods The study included 60 LSS patients (34 females and 26 males) whose symptoms were relieved by conservative treatment between April 2007 and March 2010 and who were followed up for 5 years or longer. The mean age at admission was 64.8 ± 8.5 years (range, 40–85 years old), and the mean follow-up period was 7.3 years (range, 5.8–9.5 years). We defined “deterioration” of symptoms as the shortening of intermittent claudication more than 50 m compared with those at discharge or the occurrence or progression of lower limb paralysis, and “poor outcome” as the deterioration within 5 years after discharge. The long-term outcome of conservative treatment for LSS was analyzed by Kaplan-Meier analysis. Furthermore, logistic regression analysis was performed to reveal the risk factors of poor outcome for clinical classification, severe intermittent claudication (≤ 100 m), lower limb muscle weakness, vertebral body slip (≥ 3 mm), scoliosis (Cobb angle ≥ 10°), block on myelography, and redundant nerve roots of the cauda equina. Results Thirty-four (56.7%) patients preserved their condition at discharge during the follow-up, whereas 26 patients (43.3%) showed deterioration. Sixteen patients had a decreased intermittent claudication distance, and 10 patients had newly developed or progressive paralysis. The probability of preservation was maintained at 68.3% at 5 years after discharge. Logistic regression analysis demonstrated that only severe intermittent claudication (≤ 100 m) was a significant risk factor of a poor outcome (p = 0.005, odds ratio = 6.665). Conclusions The patients with severe intermittent claudication should be carefully followed up because those are the significant deterioration candidates despite the success in conservative treatment.

An 18-year-old man presented after undergoing multiple investigations for abdominal pain. Retrograde double-balloon enteroscopy showed a protruding red lesion in the ileum with small ulcers, approximately 75 cm proximal to the ileocecal valve, resulting in an intussusception. An inverted Meckel’s diverticulum was strongly suspected. Pressure was applied to the protruding lesion using contrast medium injection after wedging the lumen with a balloon. The intussusception partially reduced, avoiding the need for emergent surgery. Endoscopic tattooing was performed to mark the lesion for subsequent resection. Elective laparoscopy-assisted surgery with minimum laparotomy revealed an inverted Meckel’s diverticulum, which was resected.

Background and study aims This study was designed to clarify clinicopathological, endoscopic, and genetic characteristics of inverted sessile serrated adenomas/polyps. Patients and methods In this retrospective study, we reviewed the pathology reports of patients treated in our hospital between January 2010 and June 2015 and identified sessile serrated adenomas/polyps that were diagnosed with endoscopic resected specimens. Clinicopathological, endoscopic, and genetic features were compared between the inverted and ordinary types. Results Among the 104 sessile serrated adenomas/polyps, 37 lesions were inverted (35.6 %). The inverted types had two patterns of invasion: expansive and infiltrating growth. Expansive growth was observed in 15 cases (40.5 %) and infiltrating in 22 (59.5 %). Regarding the clinicopathological findings and endoscopic characteristics of the inverted types, presence of adherent mucous, location in the right-side colon, an expanded type-II pit pattern, irregularly dilated vessels, and a depression were demonstrated in 89 % (33/37), 73 % (27/37), 54 % (20/37), 75 % (28/37), and 35 % (13/37), respectively. Contrastingly, these were demonstrated in 86 % (58/67), 84 % (56/67), 55 % (37/67), 58 % (39/67), and 0 % (0/67), respectively, in the ordinary type. In the univariate analysis, male sex and a depression in the adenoma/polyp were significantly associated with inverted types (P