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Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an essential endoscopic tissue sampling method for diagnosing pancreatobiliary diseases; however, determining the presence of target specimens mixed in the blood by conventional observation is challenging due to the small size of the obtained sample. This study investigated the usefulness of a target sample check illuminator (TSCI) that emits a specific wavelength of light to determine the presence of target specimens. Twenty-seven patients who underwent EUS-FNA at our hospital were included. Conventional white light observation was performed for the collected samples, followed by TSCI; six people evaluated the presence of the target specimen on a 5-point scale. The target specimen discrimination score using TSCI (median: 5) was significantly higher than that using conventional white light observation (median: 1) (p < 0.001). No significant difference was observed in the discrimination score between the evaluator (novice vs. expert, p = 0.162) and puncture needle (22G vs. 25G, p = 0.196). The discriminability of TSCI in the samples obtained using EUS-FNA was significantly higher than that of conventional observation. TSCI does not depend on the evaluator or puncture needle for the identification of the target specimen; hence, it can provide a good pathological specimen and may contribute to the improvement of the diagnostic ability.

Screening endoscopy has advanced to facilitate improvements in the detection and prognosis of gastric cancer. However, most early gastric cancers (EGCs) have subtle morphological or color features that are difficult to detect by white-light imaging (WLI); thus, even well-trained endoscopists can miss EGC when using this conventional endoscopic approach. This review summarizes the current and future status of linked color imaging (LCI), a new image-enhancing endoscopy (IEE) method, for gastric screening. LCI has been shown to produce bright images even at a distant view and provide excellent visibility of gastric cancer due to high color contrast relative to the surrounding tissue. LCI delineates EGC as orange-red and intestinal metaplasia as purple, regardless of a history of Helicobacter pylori (Hp) eradication, and contributes to the detection of superficial EGC. Moreover, LCI assists in the determination of Hp infection status, which is closely related to the risk of developing gastric cancer. Transnasal endoscopy (ultra-thin) using LCI is also useful for identifying gastric neoplastic lesions. Recently, several prospective studies have demonstrated that LCI has a higher detection ratio for gastric cancer than WLI. We believe that LCI should be used in routine upper gastrointestinal endoscopies.

BackgroundPostoperative complications related to gastric conduit reconstruction are still common issues after McKeown esophagectomy. A novel endoscopic grading system is desired to predict anastomotic complications after McKeown esophagectomy.Aims and MethodsThe purpose of this study was prospectively to evaluate the safety and efficacy of endoscopic examinations of the anastomotic region in the acute period after esophagectomy.Endoscopic examinations were performed on postoperative days (PODs) 1 and 8. The severity of the ischemic area was prospectively validated and classified into four categories according to the novel endoscopic mucosal ischemic grading system (EMIGS). ResultsFifteen patients (25.9%) developed anastomotic complications after esophagectomy. The negative predictive values for anastomotic complications, leakage, and strictures in EMIGS grades C or D were extremely high on POD 8 after esophagectomy (95.1%, 100%, and 95.1%, respectively). In the multivariate analysis, EMIGS grades C or D on POD 8 had a significant correlation with anastomotic complications after esophagectomy (odds ratio [OR]: 67.0; 95% confidence interval [CI]: 6.5-688.4; P < 0.01). EMIGS grades C or D on POD 8 after esophagectomy were associated with developing anastomotic leakage and strictures after esophagectomy in the univariate logistic regressions analysis (OR: 2.1 x 107; 95%CI:9.0 – infinity; PConclusionsThe application of endoscopic classification to mucosal ischemia after McKeown esophagectomy yielded suboptimal accuracy in predicting anastomotic complications.Trial registration: Clinical Trial.gov Registry, ID: NCT02937389, Registration date: Oct 17, 2015

Alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) are widely used as tumor markers to diagnose hepatocellular carcinoma (HCC). Some advanced HCCs demonstrate neither AFP nor DCP. This study investigated the characteristics and prognosis of AFP (

Sarcopenia comprises a low skeletal muscle index (SMI) and low muscle strength (MS) or low physical function. Many sarcopenia biomarkers have been reported. With Crohn’s disease (CD), a low SMI is predictive of intestinal complications. Therefore, many CD studies have reported that sarcopenia is defined by SMI alone. This study investigated the sarcopenia frequency by assessing the SMI and MS of Japanese patients with CD and biomarkers predicting a low SMI. We evaluated the SMI using a bioelectrical impedance analysis, handgrip strength, and C-reactive protein, albumin, interleukin-6, tumor necrosis factor-α, growth differentiation factor (GDF)-8, and GDF-15 levels as biomarker candidates for 78 CD patients at our hospital. Sarcopenia and a low SMI were observed in 7.7% and 42.3% of the patients, respectively. There was a significant difference in the GDF-15 levels of the low SMI group and normal group according to the multivariate analysis (P = 0.028; odds ratio [OR], 1.001; 95% confidence interval [CI] 1.000–1.002). When evaluated by sex, males exhibited a negative correlation between the GDF-15 level and SMI (Pearson’s r = − 0.414; P = 0.0031), and the multivariate analysis indicated a significant difference in the GDF-15 levels (P = 0.011; OR, 1.001; 95% CI 1.000–1.002). GDF-15 levels may indicate a low SMI with CD.

This study constructed a simplified post-endoscopic submucosal dissection (ESD) prediction model with a prognostic nutritional index (PNI). A total of 449 patients who underwent gastric ESD was included, divided with a ratio of 2:1, and assigned to the model or validation cohort. A prediction model of post-ESD (modified BEST-J score) was constructed using the model cohort. The modified BEST-J score was evaluated by comparing its accuracy to the BEST-J score in the validation cohort. Within 4 weeks of ESD, melena, hematemesis, or a 2 g/dL or greater decrease in hemoglobin level that required esophagogastroduodenoscopy was defined as post-ESD bleeding. In the model cohort, 299 patients were enrolled and 25 (8.4%) had post-ESD bleeding. Independent risk factors for post-ESD bleeding were use of P2Y12RA, tumor size > 30 mm, location of lesion at lower one-third of the stomach, and PNI ≤ 47.9. Constructing the modified BEST-J score based on these variables, the sensitivity, specificity, and positive likelihood ratio were 73.9%, 78.1%, and 3.37. When comparing the modified BEST-J score to the BEST-J score in the validation cohort, no significant difference was observed by ROC-AUC (0.77 vs. 0.75, p = 0.81). Modified BEST-J score can predict post-ESD bleeding more simply, with the same accuracy as the BEST-J score.

OBJECTIVES Gastrointestinal (GI) perforations are one of the major adverse events of endoscopic procedures. Polyglycolic acid (PGA) sheets with fibrin glue have been reported to close GI perforations. However, its clinical outcome has not yet been fully investigated; thus, we conducted a multicenter retrospective observational study to assess the efficacy of PGA sheeting for GI perforation. METHODS The medical records of patients who underwent PGA sheeting for endoscopic GI perforations between April 2013 and March 2018 in 18 Japanese institutions were retrospectively analyzed. PGA sheeting was applied when the clip closure was challenging or failed to use. Perforations were filled with one or several pieces of PGA sheets followed by fibrin glue application through an endoscopic catheter. Nasal or percutaneous drainage and endoscopic clipping were applied as appropriate. Clinical outcomes after PGA sheeting for intraoperative or delayed perforations were separately evaluated. RESULTS There were 66 intraoperative and 24 delayed perforation cases. In intraoperative cases, successful closure was attained in 60 cases (91%). The median period from the first sheeting to diet resumption was 6 days (interquartile range [IQR], 4-8.8 days). Large perforation size (≥ 10 mm) and duodenal location showed marginal significant relationship to higher closure failure of intraoperative perforations. In delayed perforation cases, all cases had successful closure. The median period from the first sheeting to diet resumption was 10 days (IQR, 6-37.8 days). No adverse events related to PGA sheeting occurred. CONCLUSION Endoscopic PGA sheeting could be a therapeutic option for GI perforations related to GI endoscopic procedures.

The tumour microenvironment (TME) plays an important role in cancer development, progression, and metastasis. Various cytokines are present in the TME in oesophageal cancer. Oesophageal stricture is a major complication of endoscopic submucosal dissection (ESD) for oesophageal cancer, and inflammatory cytokines are closely related to its pathogenesis. However, the cytokine crosstalk involved in the oesophageal cancer TME and post-ESD stricture has not been fully elucidated. This study investigated the comprehensive cytokine dynamics following ESD in patients with oesophageal cancer. In addition, the effect of a novel preventive technique for post-ESD stricture, autologous cell sheet engraftment, on cytokine levels was evaluated. Various pro-inflammatory and anti-tumorigenic cytokines were elevated in patients with oesophageal cancer, and ESD transiently influenced cytokine concentrations. IL-1β and TNF-α, two major pro-inflammatory cytokines that induce oesophageal stricture, were significantly suppressed by cell sheet engraftment. In conclusion, this study revealed the distinct cytokine dynamics after ESD in patients with oesophageal cancer, together with the effect of autologous cell sheet engraftment on cytokine fluctuation. These results can accelerate research on the TME and therapeutic strategies for oesophageal cancer.

Gastroesophageal reflux disease (GERD) in systemic sclerosis (SSc) can significantly reduce a patient's quality of life. GERD in SSc is occasionally resistant to conventional anti-acid treatment. Vonoprazan is an H+/K+-ATPase blocker that is approved in Japan for treatment of GERD. The aim of the present study was to evaluate the efficacy of vonoprazan in SSc-related GERD. The frequency scale for symptoms of GERD (FSSG) scores were collected before and after vono-prazan treatment in 15 SSc patients with GERD. Additionally, endoscopic esophagogastroduodenoscopy was performed in select patients. Conventional proton pump inhibitors or hista-mine-2 receptor antagonists had been previously administered in 93% (14/15) of the patients. Although the baseline esophago-gastroduodenoscopy examination did not show severe erosion in the majority of patients,the mean total FSSG score before vonoprazan treatment was notably high (25.2±10.7) compared to a normal score of, Biomedical Reports, 14(2), pp.1-8; 2020

While retrospective studies have compared the efficacy of anti?tumour necrosis factor (TNF) agents and tacrolimus (TAC) in ulcerative colitis (UC), information regarding first-time use of these agents is limited. The aim of our study was to investigate the short- and long-term efficacy of anti-TNF agents [adalimumab (ADA) and infliximab (IFX)] and TAC in anti-TNF agent- and TAC-naive steroid-refractory UC patients. We evaluated 150 steroid-refractory UC patients receiving anti-TNF agents (IFX: n = 30, ADA: n = 41) or TAC (n = 79) at eight institutions in Japan. Clinical response rates at 8 weeks were 73.2% and 75.9% while remission rates were 30.1% and 25.3% in the anti-TNF and TAC groups, respectively. Logistic regression analysis showed the male sex and higher C-reactive protein to be independent factors for response to anti-TNF agents and TAC, respectively. Use of TAC was an independent factor for relapse. No differences in response to the treatment or relapse were observed between IFX and ADA. In conclusion, TAC and anti-TNF agents promoted similar short-term effects, but anti-TNF agents ensured better long-term outcomes at first-time treatment of steroid-refractory UC patients., Scientific Reports, 10(1), art.no.12546; 2020

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic intestinal diseases of unknown etiology that present with variable disease extents and outcomes. The use of biomarkers for the diagnosis and management of IBDs is considered beneficial. Palmitoleic acid (PO) is an adipose tissue-derived mono-unsaturated free fatty acid that potentially serves as a lipokine in metabolic and inflammatory diseases. The aim of this study was to investigate the significance of PO levels in the serum of patients with UC and CD. The study included patients with UC (n = 22), patients with CD (n = 35), and controls (n = 22). The levels of serum PO were analyzed using gas chromatography. The association of serum PO levels with the clinical features and disease outcomes in IBD was examined. Serum PO levels were significantly higher in patients with CD than in controls, whereas no difference in these levels was observed between patients with UC and controls. Serum PO levels were significantly associated with the CD activity index. Additionally, high serum PO levels were associated with an increased risk of surgical intervention requirement during follow-up. In a pilot study with a few patients, high PO levels were observed in the mesenteric tissue in the active disease site of patients with CD (n = 7) compared with those with colon cancer (n = 6). Elevated serum PO levels might serve as a marker for local inflammation and prognosis in patients with CD., Scientific Reports, 11, art. no. 16260; 2021

Aim: Sarcopenic dysphagia has become an urgent matter of debate in our aging society. However, little is known about the relationship between sarcopenia and dysphagia in patients with liver cirrhosis. Our aim was to assess sarcopenia and dysphagia among elderly patients with cirrhosis using two easy-to-use screening tests, i.e., the eating assessment tool-10 and the finger-ring test. Methods: The eating assessment tool-10, handgrip strength, skeletal muscle mass index, computed tomography, and the finger-ring test were included in our analysis. One hundred patients with cirrhosis and without a history of aspiration pneumonia were divided into the elderly (≥75 years) and non-elderly (, Archives of Gerontology and Geriatrics, 95, art. no. 104430; 2021

Introduction Cultured stratified epithelial cell sheets have been clinically utilized as transplantable grafts for the regeneration of epithelial tissues, such as the esophagus, cornea, skin, and intraoral cavity. These cell sheets are expected to gain widespread use as regenerative medicine products and save many patients. For this purpose, establishing and disseminating the stale protocol of fabricating the cell sheet is crucial. The fabrication of cultured stratified epithelial cell sheets consists of many important steps, and since the patients’ epithelial cell conditions vary widely and are sometimes unstable, the qualities of the epithelial cell grafts are likewise potentially unstable. Therefore, in this paper, we report the stable protocol for fabrication of the transplantable cell sheet particularly from patient-derived oral mucosal tissues. Methods Serum extracted from blood and buccal mucosal tissue were collected in Nagasaki University and transported to Tokyo Women's Medical University. Oral mucosal epithelial cells were collected by minimum trypsin method, and this treatment was studied whether to be a critical procedure. After 14 days cultivation, cultured cells were examined whether to be transplantable as cell sheets. Results We successfully transported buccal mucosal tissue and serum without damage and contamination. Oral mucosal epithelial cells were collected with high viability by minimum trypsin method. Finally, we succeeded to stably fabricate oral mucosal epithelial cell sheets in all 10 patients. Conclusions We established a stable protocol for the fabrication of human oral mucosal epithelial cell sheets and their transportation in clinical settings in this study. These methodologies could also be basis for transplantation therapy using cultured cell sheets of various types other than oral mucosal epithelial cell and will contribute largely to the future development of regenerative medicine., Highlights • A stable protocol for fabricating oral mucosal cell sheets.

Background and study aims: Endoscopic submucosal dissection (ESD) of the pharyngeal region has not been well accepted, although ESD of the gastrointestinal tract is a standard procedure for treating early cancers. However, early detection and treatment of pharyngeal cancers is highly beneficial because surgical resection can be highly invasive and cause serious cosmetic deformities, swallowing disorders, dysgeusia, and speech defects. On the other hand, application of an anchored clip with surgical thread during ESD of the gastrointestinal tract has been reported to be beneficial. This pilot case series reveals the usefulness and clinical feasibility of applying a clip with thread in ESD of the pharyngeal region.

Introduction Laparoscopic-endoscopic cooperative surgery (LECS) is a minimally invasive surgical technique that combines the advantages of laparoscopic surgery and endoscopic treatment. LECS has been developed for treatment of gastric submucosal tumors and can be applied to superficial non-ampullary duodenal tumors. Here we describe the use of LECS for duodenal mucosal cancer. Materials and Surgical Technique After the placement of five ports, an endoscopic procedure was performed to confirm the tumor location and to place marks around the tumor. The jejunum was then resected 10 cm from the ligament of Treitz, and the connective tissue between the pancreas and duodenum was dissected to close to Vater's papilla. Duodenal resection was performed with a stapling device 2 cm to the oral side of the tumor, with endoscopic confirmation of the duodenal papilla, and duodenal tubular resection was then accomplished. Duodeno-jejunostomy was carried out using the same stapling device. There were no postoperative complications. Discussion This case shows that duodenal tubular resection using LECS enables curability through a minimally invasive procedure that offers the advantages of laparoscopic surgery and endoscopic treatment. This technique is applicable to duodenal lesions such as those due to duodenal mucosal cancers.

Background: Refractory gastroesophageal reflux disease (GERD) may deteriorate patient quality of life (QOL) despite proton pump inhibitor (PPI) therapy. Material/Methods: Nineteen Japanese institutions were surveyed to determine the clinical characteristics and QOL of patients with refractory GERD. Those patients treated with a conventional PPI were switched to 20 mg esomeprazole for 4 weeks. Symptoms and QOL were assessed using Global Overall Symptom and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires at baseline and at 2 and/or 4 weeks of esomeprazole treatment. Results: Of 120 patients who completed the survey, 58 (48.3%) had refractory GERD. Of these, 69.0% were aged >65 years, 79.3% were prescribed a PPI at a standard or high dose, and 22.4% were prescribed a PPI together with another drug. After switching to esomeprazole, patients reported significant improvements in heartburn, acid regurgitation, and excessive belching at 2 weeks using a symptom diary, as well as the total score, reflux, ab dominal pain, and indigestion, which were assessed using the GSRS at 4 weeks. Conclusions: About half of Japanese patients with GERD may be refractory to conventional PPIs. Their reflux-related symp toms are often severe and may impair QOL. Switching to esomeprazole could be used to improve their symptoms and QOL., Medical Science Monitor, 21, pp.4111-4121; 2015

Background: Maintenance of mucosal healing is recommended during the treatment of ulcerative colitis (UC). However, symptoms of UC often do not reflect mucosal disease activity. Fecal markers such as calprotectin, lactoferrin, and hemoglobin have been reported to correlate well with the Mayo endoscopic subscore (MES) and are being considered alternative monitoring tools in endoscopy. Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is a new and more detailed endoscopic scoring system compared to MES. Furthermore, magnifying endoscopic stratification (ME) based on alterations in the mucosal surface pit patterns is noted in UC. However, the association between fecal markers and UCIES and magnifying endoscopy is relatively unexplored. Summary: This study investigated the association between the aforementioned fecal markers and MES, UCEIS, and ME in patients with UC in clinical remission. This prospective study included 60 patients with UC in clinical remission who underwent colonoscopy at the Nagasaki University Hospital between June 2015 and November 2016. A significant correlation was observed between MES and all fecal markers. Notably, the fecal markers correlated well with UCEIS (calprotectin Spearman’s correlation coefficient [r] = 0.54, p < 0.0001; lactoferrin r = 0.56, p < 0.0001; and hemoglobin r = 0.43, p < 0.001). Furthermore, ME findings correlated significantly with calprotectin (r = 0.50, p = 0.0002) and lactoferrin (r = 0.46, p = 0.0006) levels and slightly with hemoglobin (r = 0.28, p = 0.043) levels. Moreover, each cutoff level of fecal calprotectin, lactoferrin, or hemoglobin had a high sensitivity and specificity for the detection of MES = 0, UCEIS = 0, ME = A, for predicting mucosa healing. Key Messages: Fecal markers correlated not only with MES but also with UCEIS and ME and should be useful for monitoring patients with UC in clinical remission.

Initial esophagogastroduodenoscopy (EGD) shows segmental contractions right above the gastro‐esophageal junction, which may be related to the symptoms. A clip was applied during a previously performed manometry. There was no evidence of stricture. High‐resolution manometry before peroral endoscopic myotomy shows a hypercontractile esophagus expressed as distal contractile integral > 8000 mmHg cm s two times out of 10.

GNAQ and GNA11 mutations are thought to be important for the tumorigenesis of uveal melanoma. Although previous studies have reported on mutation rates in cases of uveal melanoma, presently, no such report for the Japanese population exists. In this study, we examined the frequency of GNAQ and GNA11 somatic mutations in cases of uveal melanoma in Japan and their relationship with clinicopathologic features or Ki-67-positive cell rates (Ki-67 labeling index: Ki-67 LI) using immunofluorescence methods. The study involved 19 cases of uveal melanoma. We extracted the template DNA from formalin-fixed, paraffin-embedded specimens using a DNA extraction kit. We amplified the DNA sequences of GNAQ and GNA11 using polymerase chain reaction and analyzed mutations by direct sequencing. We evaluated Ki-67 LI using immunofluorescence methods. The frequencies of GNAQ and GNA11 somatic mutations were 26.3% (5/19) and 31.6% (6/19), respectively. The GNAQ and GNA11 mutations were mutually exclusive, as indicated in previous reports. The frequency of GNA11 mutations was significantly higher in epithelioid cells; however, no significant association between GNAQ mutations and cell type was evident, and there was no significant difference in Ki-67 LI between the mutation-positive and mutation-negative tumors. GNAQ and GNA11 mutations were identified in cases of uveal melanoma in Japan, although at lower frequencies than in white counterparts. The mutation frequency of GNA11 was significantly higher in epithelioid cells.

Background 5-Aminolevulinic acid is a precursor of photosensitizing protoporphyrin IX and has been applied for photodynamic diagnosis of brain and bladder tumors with few side effects. Although most upper gastrointestinal tumors can be detected during photodynamic diagnosis, some tumors containing signet-ring cells cannot be visualized. Here, we aimed to assess whether proteins involved in the absorbance, activation, and turnover of protoporphyrin IX altered the fluorescence signal in gastric cancer. Methods Aminolevulinic acid-mediated photodynamic diagnosis was performed in 23 lesions from 20 patients using an endoscope equipped with a blue laser light that caused red fluorescence emission of photosensitizing protoporphyrin IX. Red fluorescence signal and intensity was assessed during photodynamic diagnosis procedures. Lesions were resected by endoscopic and/or laparoscopic surgery, and specimens were immunostained and assessed for the expression of ATP-binding cassette sub-family G member 2, oligopeptide transporter-1, and coproporphyrinogen oxidase. Results Photodynamic diagnosis was negative in four cases (17.4%). Three cases of photodynamic diagnosis-negative lesions were signet-ring cell carcinomas, and only one case was differentiated adenocarcinoma (intestinal type). Twenty intestinal type, photodynamic diagnosis-positive lesions showed high expression of coproporphyrinogen oxidase, whereas signet-ring cell carcinomas were all negative. Oligopeptide transporter-1 immunoreactivity was significantly higher in tumors of intestinal type. ATP-binding cassette sub-family G member 2 expression tended to be higher in luminal surface tumors than in intestinal type tumors. Conclusion Aminolevulinic acid-mediated photodynamic diagnosis provided good detection of upper gastrointestinal tumors of intestinal type but not diffuse type tumors, such as signet-ring cell carcinomas, possibly owing to coproporphyrinogen oxidase expression.

Esophageal achalasia is a benign esophageal motility disorder resulting from an impaired relaxation of the lower esophageal sphincter. The principles of treatment involve disruption of the sphincter at the esophagogastric junction. Treatment techniques include balloon dilatation, botulinum toxin injection, and surgical myotomy. In 2008, per-oral endoscopic myotomy (POEM) was introduced by Inoue et al. as an endoscopic myotomy with no skin incision. The procedure has been well accepted and widely applied owing to its minimal invasiveness and high cure rates. Moreover, there have been discussions on wider indications for POEM and new technical developments have been reported. The present article reviews the historical background and present status of POEM, as well as future prospects for its application in the treatment of esophageal achalasia.