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Recently, Helicobacter pylori (HP)-uninfected gastric mucosal cancer has been reported; however, the clinicopathological and molecular features of HP-uninfected gastric cancer have not been elucidated.We evaluated the clinicopathological, immunohistochemical, and genetic alterations in HP-uninfected early gastric adenocarcinoma using next-generation sequencing (NGS).Among 968 primary early gastric carcinomas, 64 (6.6%) were HP-uninfected gastric adenocarcinoma and were pathologically classified as gastric adenocarcinoma of fundic-gland type (GA-FG, n = 39), differentiated gastric adenocarcinoma (DGA, n = 16), and signet-ring cell carcinoma (SRCC, n = 9). Based on the expression profile of the mucin core protein, DGAs were classified into a gastrointestinal phenotype showing either MUC5AC or MUC6 expression and MUC2 or CD10 expression simultaneously (n = 5), and a gastric phenotype (n = 11) showing either MUC5AC or MUC6 expression. All DGAs with a gastrointestinal phenotype shared similar endoscopic characteristics, such as reddish depressed lesions in the antrum. In contrast, DGAs with a gastric phenotype exhibited several distinct endoscopic features, including a raspberry-shaped appearance and whitish flat-elevated appearance; the former expressed only MUC5AC and the latter exhibited co-expression of MUC5AC and MUC6. Among 16 HP-uninfected DGAs, seven were subjected to NGS. APC was recurrently mutated in DGA (42.9%) and was enriched in DGAs with a gastrointestinal phenotype (75%).Overall, HP-uninfected gastric adenocarcinomas showed distinct clinicopathologic and endoscopic characteristics. Furthermore, HP-uninfected DGAs, especially those with a gastrointestinal phenotype, may be characterized by recurrent APC mutations.

Summary Our study aimed to compare the treatment outcomes between endoscopic submucosal dissection (ESD) with an insulated-tip knife (ESD-IT) and a needle-type knife (ESD-N) for large superficial esophageal neoplasms, as no study of this kind has been previously reported. We used the dataset of a multicenter, randomized controlled trial that compared conventional ESD (C-ESD) and traction-assisted ESD (TA-ESD) for superficial esophageal neoplasms. We compared the procedural outcomes between ESD-IT and ESD-N in a post hoc analysis and conducted sub-analyses based on traction assistance and electrical knife type. We included 223 (EST-IT, n = 169; ESD-N, n = 54) patients with no significant differences in baseline characteristics. The operator handover rate due to ESD difficulties was significantly higher in ESD-N (ESD-IT = 0.6% vs. ESD-N = 13.0%, P = 0.001), while the injection volume was significantly higher in ESD-IT than in ESD-N (40.0 vs. 20.5 mL, P 0.99; and complication rate: 1.8% vs. 3.7%, P = 0.60 for ESD-IT and ESD-N, respectively). In the sub-analyses, the handover rate was significantly lower with TA-ESD than with C-ESD for ESD-N (3.2% vs. 26.1%, P = 0.034), and a significantly smaller injection volume was used in TA-ESD than in C-ESD for ESD-IT (31.5 vs. 47.0 mL, P

Background and Aim Magnifying endoscopy (ME) diagnostic algorithm for early gastric cancer (EGC) relies on qualitative features such as microvascular (MV) architecture and microsurface structure; however, it is a “static” diagnostic algorithm that uses still images. ME can visualize red blood cell flow within subepithelial microvessels in real time. Here, we evaluated the utility of using the MV blood flow rate in combination with ME for the diagnosis of EGC as a retrospective study. Methods Patients with differentiated‐type EGC (n = 10) or patchy redness (n = 10) underwent ME with blue laser imaging. The mean MV blood flow rates of EGC, patchy redness, and background mucosa were calculated by the mean movement distance of one tagging red blood cell using split images of ME with blue laser imaging videos. We compared the mean MV blood flow rate between EGC, patchy redness, and background mucosa and also calculated the MV blood flow imaging ratio (inside lesion/background mucosa) between EGC and patchy redness. Results Mean MV blood flow rate was significantly lower in EGC (1481 μm/s; range 1057–1762) than in patchy redness (3859 μm/s; 2435–5899) or background mucosa (4140.6 μm/s; 2820–6247) (P

Background: Gastric adenocarcinoma of foveolar type (GA-FV) is a raspberry-shaped gastric cancer (RSGC) and garners much attention as H. pylori (Hp)-uninfected gastric cancer. However, the classification and clinicopathological and endoscopic features of RSGCs in Hp-uninfected patients are poorly defined. We designed a new histopathological classification of RSGC and compared them via endoscopic and clinicopathological characteristics. Summary: From 996 patients with early gastric cancers resected by endoscopy in our hospital, we studied 24 RSGC lesions from 21 (2.4%) Hp-uninfected patients. RSGCs were classified into 3 histological types as follows: GA-FV (n = 19), gastric adenocarcinoma of fundic gland type (GA-FG, n = 2), and gastric adenocarcinoma of fundic gland mucosa type (GA-FGM, n = 3). Most of the lesions were found at the greater curvature of the upper or middle third of the stomach. GA-FV lesions were homogeneously reddish and frequently accompanied with a whitish area around the tumor and an irregular microvascular (MV) pattern; these features were confirmed histopathologically by the presence of homogeneous neoplastic foveolar epithelium with foveolar hyperplasia around the tumors. GA-FG lesions might be heterogeneously reddish with a submucosal tumor shape and regular MV pattern; these were confirmed by the presence of covered or mixed nonneoplastic epithelium on deeper regions of tumors. GA-FGM lesions might be homogeneously reddish and occasionally had a submucosal tumor shape and irregular MV pattern; these were confirmed by the presence of homogeneous neoplastic foveolar epithelium on deeper regions of the tumors. Key Messages: RSGCs in Hp-uninfected patients are classified into 3 histopathological types. For accurate diagnosis of RSGCs, it may be necessary to fully understand endoscopic features of these lesions based on these histological characteristics and to take a precise biopsy.

Background and study aims Magnifying endoscopy with narrow band imaging (M-NBI) has made a huge contribution to endoscopic diagnosis of early gastric cancer (EGC). However, we sometimes encountered false-negative cases with M-NBI diagnosis (i. e., M-NBI diagnostic limitation lesion: M-NBI-DLL). However, clinicopathological features of M-NBI-DLLs have not been well elucidated. We aimed to clarify the clinicopathological features and histological reasons of M-NBI-DLLs. Patients and methods In this single-center retrospective study, M-NBI-DLLs were extracted from 456 EGCs resected endoscopically at our hospital. We defined histological types of M-NBI-DLLs and analyzed clinicopathologically to clarify histological reasons of M-NBI-DLLs. Results Of 456 EGCs, 48 lesions (10.5 %) of M-NBI-DLLs were enrolled. M-NBI-DLLs was classified into four histological types as follows: gastric adenocarcinoma of fundic-gland type (GA-FG, n = 25), gastric adenocarcinoma of fundic-gland mucosal type (GA-FGM, n = 1), differentiated adenocarcinoma (n = 14), and undifferentiated adenocarcinoma (n = 8). Thirty-nine lesions of M-NBI-DLLs were H. pylori-negative gastric cancers (39/47, 82.9 %). Histological reasons for M-NBI-DLLs were as follows: 1) completely covered with non-neoplastic mucosa (25/25 GA-FG, 8/8 undifferentiated adenocarcinoma); 2) well-differentiated adenocarcinoma with low-grade atypia (1/1 GA-FGM, 14/14 differentiated adenocarcinoma); 3) similarity of surface structure (10/14 differentiated adenocarcinoma); and 4) partially covered and/or mixed with a non-neoplastic mucosa (1/1 GA-FGM, 6/14 differentiated adenocarcinoma). Conclusions Diagnostic limitations of M-NBI depend on four distinct histological characteristics. For accurate diagnosis of M-NBI-DLLs, it may be necessary to fully understand endoscopic features of these lesions using white light imaging and M-NBI based on these histological characteristics and to take a precise biopsy.

Objective The association between frailty and abdominal symptoms has not been evaluated. Methods We conducted a hospital-based, retrospective cross-sectional study of consecutive outpatients ≥65 years old at the Department of Gastroenterology, Juntendo Tokyo Koto Geriatric Medical Center from 2017 to 2019. Patients were included in the study if all of the following information was available from their medical records: patient's profile, the evaluation of osteoporosis, sarcopenia, frailty, nutritional status, findings of upper gastrointestinal endoscopy, and questionnaire results for abdominal symptoms [Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) and Constipation Scoring System (CSS)]. We divided the subjects into frailty and non-frailty groups and investigated the risk factors for frailty. Results Of the 313 eligible study subjects [134 men (42.8%) and 179 women (57.2%); mean age, 75.7±6.0 years; mean body mass index, 22.8±3.6 kg/m2], frailty was noted in 71 cases (22.7%). In a univariate analysis, an older age (p

Background and Aim Magnifying endoscopy with narrow‐band imaging (ME‐NBI) has made a huge contribution to clinical practice. However, acquiring skill at ME‐NBI diagnosis of early gastric cancer (EGC) requires considerable expertise and experience. Recently, artificial intelligence (AI), using deep learning and a convolutional neural network (CNN), has made remarkable progress in various medical fields. Here, we constructed an AI‐assisted CNN computer‐aided diagnosis (CAD) system, based on ME‐NBI images, to diagnose EGC and evaluated the diagnostic accuracy of the AI‐assisted CNN‐CAD system. Methods The AI‐assisted CNN‐CAD system (ResNet50) was trained and validated on a dataset of 5574 ME‐NBI images (3797 EGCs, 1777 non‐cancerous mucosa and lesions). To evaluate the diagnostic accuracy, a separate test dataset of 2300 ME‐NBI images (1430 EGCs, 870 non‐cancerous mucosa and lesions) was assessed using the AI‐assisted CNN‐CAD system. Results The AI‐assisted CNN‐CAD system required 60 s to analyze 2300 test images. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the CNN were 98.7%, 98%, 100%, 100%, and 96.8%, respectively. All misdiagnosed images of EGCs were of low‐quality or of superficially depressed and intestinal‐type intramucosal cancers that were difficult to distinguish from gastritis, even by experienced endoscopists. Conclusions The AI‐assisted CNN‐CAD system for ME‐NBI diagnosis of EGC could process many stored ME‐NBI images in a short period of time and had a high diagnostic ability. This system may have great potential for future application to real clinical settings, which could facilitate ME‐NBI diagnosis of EGC in practice.

While hospitalized due to severe aortic stenosis, an 84-year-old woman developed repeated bleeding from angiodysplasia in the stomach leading to a diagnosis of Heyde syndrome. Following transcatheter aortic valve implantation (TAVI), there was no recurrence of bleeding from the angiodysplasia, and the decrease in von Willebrand factor levels that caused Heyde syndrome also improved. It was felt that the TAVI was able to prevent the recurrence of gastrointestinal bleeding due to angiodysplasia in Heyde syndrome.

Gastric adenocarcinoma of foveolar type (GA-FV) is a raspberry-shaped gastric cancer (RSGC) and garners much attention as H. pylori (Hp)-uninfected gastric cancer. However, the classification and clinicopathological and endoscopic features of RSGCs in Hp-uninfected patients are poorly defined. We designed a new histopathological classification of RSGC and compared them via endoscopic and clinicopathological characteristics.From 996 patients with early gastric cancers resected by endoscopy in our hospital, we studied 24 RSGC lesions from 21 (2.4%) Hp-uninfected patients. RSGCs were classified into 3 histological types as follows: GA-FV (n = 19), gastric adenocarcinoma of fundic gland type (GA-FG, n = 2), and gastric adenocarcinoma of fundic gland mucosa type (GA-FGM, n = 3). Most of the lesions were found at the greater curvature of the upper or middle third of the stomach. GA-FV lesions were homogeneously reddish and frequently accompanied with a whitish area around the tumor and an irregular microvascular (MV) pattern; these features were confirmed histopathologically by the presence of homogeneous neoplastic foveolar epithelium with foveolar hyperplasia around the tumors. GA-FG lesions might be heterogeneously reddish with a submucosal tumor shape and regular MV pattern; these were confirmed by the presence of covered or mixed nonneoplastic epithelium on deeper regions of tumors. GA-FGM lesions might be homogeneously reddish and occasionally had a submucosal tumor shape and irregular MV pattern; these were confirmed by the presence of homogeneous neoplastic foveolar epithelium on deeper regions of the tumors. Key Messages: RSGCs in Hp-uninfected patients are classified into 3 histopathological types. For accurate diagnosis of RSGCs, it may be necessary to fully understand endoscopic features of these lesions based on these histological characteristics and to take a precise biopsy.

Background/Aims: Early gastric cancer after Helicobacter pylori (Hp) eradication is difficult to demarcate. We used the vessel plus surface classification system (VSCS) to determine whether magnifying endoscopy with narrow-band imaging (ME-NBI) could demarcate differentiated-type early gastric cancers after Hp eradication, and to identify causes of an unclear demarcation line (DL). Methods: Among 100 lesions of differentiated-type early gastric cancer resected endoscopically, 34 lesions in the Hp-eradicated group and 66 in the Hp-infected group were retrospectively compared. Clinicopathological factors and ME-NBI findings, including the presence or absence of the DL, were examined. Histopathologically, histological gastritis, the surface structure at the tumor border, well-differentiated adenocarcinoma with low-grade atypia (tub1-low), and non-neoplastic epithelium (NE) coverage rate on the tumor surface and at the tumor border were evaluated. Results: DL (–) cases were more frequent in the Hp-eradicated group (11.8%, 4/34) than in the Hp-infected group (1.5%, 1/66; p < 0.05). The Hp-eradicated group had a higher NE coverage rate than the Hp-infected group (p < 0.05). All DL (–) cases had tub1-low or NE at the tumor border. Conclusion: ME-NBI with VSCS can identify the DL in most patients (88.2%) with differentiated-type early gastric cancer after Hp eradication.

To identify areas that are difficult to access by the single scope at the time of endoscopic submucosal dissection (ESD) and examine the effectiveness, en-bloc, R0 resection, and perforation rate after changing to multibending scope at the same site.When the direct visualization of the submucosal layer became impossible with Q260J or in the position where the device became vertical and peeling became impossible in parallel, we decided to change to the multibending 2TQ260M scope to record the position where the change was effective and the perforation rate.A total of 315 lesions were studied. Of the 12 sites, ESD was completed using the Q260J alone at four sites. The 2TQ260M scope was used with greater frequency at the fornix (88.9%) and on the line of the lesser curvature of the stomach (37.1%). In the cases with observed perforations (0.9%), the submucosal layer was not elevated due to the adhesion caused by strong fibrosis. None of the cases involving the change to 2TQ260M was ineffective, nor were perforations observed, and all resected specimens were en-bloc and R0 resections.The success rate of this scope may help clinicians perform ESD with greater understanding.

Aims: We aimed to clarify the endoscopic/clinicopathological features of superficial non-ampullary duodenal epithelial tumors (SNADETs) based on their mucin phenotypes. Methods: We analyzed 62 SNADET lesions and classified them based on mucin phenotypic expression. Endoscopic and clinicopathological findings were compared according to mucin phenotypes. Results: Eleven lesions had the gastric phenotype (GP) and 43 lesions had the intestinal phenotype (IP). All GP lesions were located in the first portion of the duodenum, while most IP lesions (72.1%) were located in the second portion (p < 0.01). Tumor size was significantly larger in the GP than in the IP group (14.4 mm vs. 10.2 mm, p < 0.05). Reddish color (72.7% in GP vs. 37.2% in IP, p < 0.05), type 0-I (72.7% vs. 11.6%, p < 0.01), lobular/granular pattern (81.8% vs. 4.7%, p < 0.01), and category 4/5 in Vienna classification (81.8% vs. 30.2%, p < 0.01) were observed significantly more often in the GP than in the IP group. Regarding findings of magnifying endoscopy with narrow-band imaging (M-NBI), white opaque substance (22.2% in GP vs. 89.7% in IP, p < 0.01) and light blue crest (0% vs. 43.6%, p < 0.05) were significantly less frequently observed in the GP group. Oval-shaped marginal epithelium (66.7% vs. 17.9%, p < 0.01), dense pattern (55.6% vs. 2.6%, p < 0.01), and dilatation of the intervening part (100% vs. 12.8%, p < 0.01) were more frequently observed in the GP group. Conclusions: SNADETs showed distinct endoscopic/clinicopathological features according to the mucin phenotype. Tumor location, coloration, macroscopic type, and endoscopic findings including M-NBI are useful to distinguish the mucin phenotypes of SNADETs.

The aim of the present study was to evaluate symptomatic reflux esophagitis (RE) in proton pump inhibitor (PPI) users. The present study conducted a hospital-based, retrospective cross-sectional study of consecutive RE cases in PPI users at Juntendo University Hospital recruited between 2008 and 2016. Eligible patients were PPI users with a complete patient profile, who completed the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) questionnaire, and who underwent upper gastrointestinal endoscopy for the examination of RE, hiatal hernia (HH) and endoscopic gastric mucosal atrophy (EGA). The patients with RE who were administered PPIs were divided into two groups: Those with symptomatic RE (FSSG≥8) and those with non-symptomatic RE (FSSG

The aim of the present study was to investigate the efficacy of a potassium-competitive acid blocker (PCAB) named vonoprazan (VPZ) for improving symptoms in patients with reflux esophagitis (RE), non-erosive reflux disease (NERD), and functional dyspepsia (FD). A hospital-based, retrospective study of outpatients in our department (Department of Gastroenterology, University of Juntendo, Tokyo, Japan) between March 2015 and August 2016 was performed. The patients who were experiencing heartburn, acid regurgitation, gastric pain, and/or a heavy feeling in the stomach of at least moderate severity at baseline were treated with 20 mg VPZ once daily for 4 weeks. The patients completed the global overall symptom (GOS) scale to determine their symptom severity at baseline and after the 4 week treatment period. The proportions of patients with RE, NERD, and FD achieving improvement of their symptoms, defined as a GOS scale score of 1 (‘no problem’) or 2 (‘minimal problem’), were evaluated. During 4 weeks of VPZ therapy, changes in the gastroesophageal reflux disease (GERD) score, which was defined as the total points for heartburn and acid regurgitation on the GOS scale in patients with RE and NERD, and in the FD score, which was defined as the total points for gastric pain and a heavy feeling in the stomach on the GOS scale in patients with FD, were also evaluated. A total of 88 eligible cases were included in the present study, comprising 20 patients with RE, 25 patients with NERD, and 43 patients with FD. The rates of symptomatic improvement in patients with RE, NERD, and FD were 75.0, 60.0, and 48.8%, respectively. For the patients who were first administered VPZ, the rates of symptomatic improvement were 90.9, 66.7, and 58.8% in patients with RE, NERD, and FD, respectively. For those patients who were resistant to 8 weeks of proton pump inhibitor therapy, the rates of symptomatic improvement were 55.6, 53.8, and 42.3% in patients with RE, NERD, and FD, respectively. The GERD score in patients with RE and NERD, and the FD score in FD patients, were decreased after 4 weeks of VPZ therapy (P

Daisuke Asaoka,1 Akihito Nagahara,2 Mariko Hojo,1 Kenshi Matsumoto,1 Hiroya Ueyama,1 Kohei Matsumoto,1 Kentaro Izumi,1 Tsutomu Takeda,1 Hiroyuki Komori,1 Yoichi Akazawa,1 Yuji Shimada,2 Taro Osada,1 Sumio Watanabe1 1Department of Gastroenterology, University of Juntendo, School of Medicine, Tokyo, 2Department of Gastroenterology, Juntendo University Shizuoka Hospital, Shizuoka, Japan Background: Because of a change in lifestyle, especially adoption of westernized eating habits, lifestyle-related diseases have become increasingly prevalent. The aim of this study was to investigate the association of medications for lifestyle-related diseases with reflux esophagitis (RE).Methods: We conducted a hospital-based, cross-sectional retrospective study of consecutive outpatients who received an upper gastrointestinal endoscopy in our department from February 2008 to November 2014, which was performed by one specialist who was a member of the Japan Gastroenterological Endoscopy Society. We investigated the patient profile, Helicobacter pylori (H. pylori) infection status, medications for lifestyle-related diseases (including calcium channel blockers, statins, and bisphosphonates), and upper gastrointestinal endoscopic findings (RE, hiatal hernia, Barrett’s mucosa, and endoscopic gastric mucosal atrophy [EGA]). Patients with gastrectomy, peptic ulcer disease, gastric or esophageal malignant disease, and those who used proton pump inhibitors or histamine-2 receptor antagonists were excluded. We divided the subjects into a group without RE (RE(–)) and a RE (RE(+)) group as judged by endoscopy, and investigated the risk factors for RE.Results: Of 1,744 consecutive cases, 590 cases (300 males and 290 females; mean age 60.5±13.2 years) were eligible. RE(–) and RE(+) cases numbered 507 and 83, respectively. Bivariate analysis showed significant positive associations of RE with male sex, body mass index (BMI), calcium channel blockers, Barrett’s mucosa, hiatal hernia and negative associations of RE with H. pylori positivity, EGA. Multivariate analysis showed significant positive associations of RE with BMI (odds ratio [OR]: 1.20, 95% confidence interval [95% CI]: 1.10–1.29), use of calcium channel blockers (OR: 2.12, 95% CI: 1.16–3.87), Barrett’s mucosa (OR: 2.97, 95% CI: 01.64–5.38), hiatal hernia (OR: 3.13, 95% CI: 1.79–5.47) and negative associations of RE with H. pylori positivity (OR: 0.20, 95% CI: 0.07–0.57), use of statins (OR: 0.42, 95% CI: 0.18–0.96), and EGA (OR: 0.83, 95% CI: 0.70–0.98).Conclusion: Calcium channel blockers were positively associated with RE and statins were negatively associated with RE, while bisphosphonates were not associated with RE. Keywords: reflux esophagitis, calcium channel blockers, statins, bisphosphonates, H. pylori, hiatal hernia, Barrett’s mucosa, endoscopic gastric mucosal atrophy

AIM To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation (GCED). METHODS We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer (CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital. GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate. RESULTS Six cases (5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases (139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC (66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED (positivity, 83.3%), immunohistochemically. CONCLUSION Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological features of this highly malignant type of cancer.

It has been indicated that proton pump inhibitor (PPI) use is associated with a loss of the anti-fracture efficacy of alendronate (AD). However, there are few prospective studies that have investigated the efficacy of AD on lumbar bone mineral density (BMD) in osteoporotic patients who are using PPIs. Thus, the aim of the present study was to investigate the efficacy of alfacalcidol (AC) and AD on lumbar BMD in osteoporotic patients using PPIs. A prospective, randomized, active control study enrolled such osteoporotic patients (age, ≥50 years). The patients were randomly assigned to receive AC (1 µg/day) or AD (35 mg/week) and were followed up for one year. Patient profiles were maintained, and lumbar BMD, bone-specific alkaline-phosphatase (BAP) and collagen type-I cross-linked N-telopeptide (NTX), upper gastrointestinal endoscopy results, and the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) were evaluated. Percentage changes in lumbar BMD, NTX, BAP, and change in FSSG score from baseline to the end of one year of treatment were investigated. Sixteen patients were eligible for analysis (eight assigned to receive AC, eight assigned to receive AD). The percentage change in lumbar BMD from baseline to the end of treatment was −0.4±4.0% for the AC group vs. 6.8±6.3% for the AD group (P=0.015). No significant percentage change of BAP and NTX between the two groups was observed. Subsequent to one year of treatment, the FSSG score did not change from the baseline values for either study group, and no new bone fractures or esophagitis were observed in either group of patients. The findings demonstrated that in osteoporotic patients using concomitant PPIs, there was a greater increase in lumbar BMD after one year of treatment with AD compared with AC. However, the number of study subjects was small; thus, further, large prospective studies are required to determine the effect of AD in osteoporotic patients using concomitant PPIs.

The aim of the present study was to investigate the association between the severity of constipation and sarcopenia in elderly adults. We conducted a single-center university hospital-based, retrospective cross-sectional study of consecutive outpatients aged ≥65 years from 2017 to 2020. Patients were included in the study if all of the following information were available from medical records: Patient's profile (age, sex, body mass index), laxative/prokinetics use, evaluation of sarcopenia, nutritional status, and questionnaires concerning the severity of constipation [Constipation Scoring System (CSS)], abdominal symptom-related quality of life (QOL) (Izumo scale) and stool shape [Bristol Stool Form Scale (BSFS)]. Multiple regression analysis of risk factors for high CSS score was performed. The results revealed that of the 310 eligible study subjects, [149 men (48.1%) and 161 women (51.9%); mean age, 75.7±6.1 years; mean body mass index, 23.0±3.6 kg/m2], sarcopenia was noted in 83 cases (26.8%). The CSS score was significantly higher in the sarcopenia group than that noted in the non-sarcopenia group (4.9±4.9 vs. 3.6±3.6, P=0.009). The CSS score was significantly associated with the albumin level (r=-0.148), lymphocyte count (r=-0.118), CONUT score (r=0.130), reflux-related QOL score (r=0.155), upper abdominal pain-related QOL score (r=0.171), fullness-related QOL score (r=0.299), constipation-related QOL score (r=0.615), diarrhea-related QOL score (r=0.235) and BSFS score (r=-0.114). In multiple regression analysis, independent predictors for CSS score were sarcopenia [standardized partial regression coefficient (β)=0.107, P=0.032], constipation-related QOL score (β=0.537, P

Background/Aims: To compare white light imaging (WLI) with linked color imaging (LCI) and blue LASER imaging (BLI) in endoscopic findings of Helicobacter pylori presently infected, previously infected, and uninfected gastric mucosae for visibility and inter-rater reliability. Methods: WLI, LCI and BLI bright mode (BLI-bright) were used to obtain 1,092 endoscopic images from 261 patients according to the Kyoto Classification of Gastritis. Images were evaluated retrospectively by 10 experts and 10 trainee endoscopists and included diffuse redness, spotty redness, map-like redness, patchy redness, red streaks, intestinal metaplasia, and an atrophic border (52 cases for each finding, respectively). Physicians assessed visibility as follows: 5 (improved), 4 (somewhat improved), 3 (equivalent), 2 (somewhat decreased), and 1 (decreased). Visibility was assessed from totaled scores. The inter-rater reliability (intraclass correlation coefficient) was also evaluated. Results: Compared with WLI, all endoscopists reported improved visibility with LCI: 55.8% for diffuse redness; LCI: 38.5% for spotty redness; LCI: 57.7% for map-like redness; LCI: 40.4% for patchy redness; LCI: 53.8% for red streaks; LCI: 42.3% and BLI-bright: 80.8% for intestinal metaplasia; LCI: 46.2% for an atrophic border. For all endoscopists, the inter-rater reliabilities of LCI compared to WLI were 0.73–0.87. Conclusion: The visibility of each endoscopic finding was improved by LCI while that of intestinal metaplasia was improved by BLI-bright.

A 70-year-old man with a growing liver tumor had undergone subtotal gastrectomy with pancreaticoduodenectomy for gastric cancer (T4b P0 H0 N1, Stage IIIB) 30 months before admission to our hospital. Enhanced computed tomography revealed two hypervascular nodules in segments 4 and 8. After histological diagnosis of small liver metastases from gastric cancer in segment 8, the patient underwent open microwave coagulation therapy (MCT) for the tumor (diameter: 30 mm) in segment 4. MCT was performed by using 1.5-cm and 3-cm monopolar needle electrodes with 22 times of puncture under the condition of 100 W × 60 sec. Liver abscess developed at the MCT site; however, it was decreased with percutaneous drainage. The patient is alive, without tumor recurrence even after 15 years since the MCT. This successful case proves that appropriate MCT is a promising treatment for patients with gastric liver metastases.

Background.Endoscopic submucosal dissection (ESD) of esophageal tumors can cause stenosis, yet the effect of esophageal ESD on motility remains unclarified. This study aimed to compare esophageal motility and symptoms, before and after ESD, using high-resolution manometry (HRM) and symptom scoring.Methods.Twenty-eight patients with 35 cT1a cancers were prospectively enrolled between December 2014 and February 2016. Pre- and post-ESD symptom score and HRM were recorded. Based on circumferential resection (CR), patients were divided into group A (n=17, n=11, 2/3 CR or greater). HRM parameters evaluated were distal contractile integral (DCI), contractile front velocity (CFV), intrabolus pressure, integrated relaxation pressure, distal latency, and peristaltic breaks.Results.Symptom scores worsened after ESD in 8/11 patients in group B, and 0/17 patients in group A. There was no significant difference in any HRM parameter after ESD in the whole study group but mean DCI tended to increase (p=0.07). In group B, DCI increased significantly after ESD (p=0.04), and CFV tended to decrease after ESD (p=0.08).Conclusions.DCI tended to increase after esophageal ESD. ESD affected the symptom score and esophageal motility in cases with 2/3 CR or greater. This trial is registered withUMIN000015829.

Early gastric cancer after Helicobacter pylori (Hp) eradication is difficult to demarcate. We used the vessel plus surface classification system (VSCS) to determine whether magnifying endoscopy with narrow-band imaging (ME-NBI) could demarcate differentiated-type early gastric cancers after Hp eradication, and to identify causes of an unclear demarcation line (DL).Among 100 lesions of differentiated-type early gastric cancer resected endoscopically, 34 lesions in the Hp-eradicated group and 66 in the Hp-infected group were retrospectively compared. Clinicopathological factors and ME-NBI findings, including the presence or absence of the DL, were examined. Histopathologically, histological gastritis, the surface structure at the tumor border, well-differentiated adenocarcinoma with low-grade atypia (tub1-low), and non-neoplastic epithelium (NE) coverage rate on the tumor surface and at the tumor border were evaluated.DL (-) cases were more frequent in the Hp-eradicated group (11.8%, 4/34) than in the Hp-infected group (1.5%, 1/66; p0.05). The Hp-eradicated group had a higher NE coverage rate than the Hp-infected group (p0.05). All DL (-) cases had tub1-low or NE at the tumor border.ME-NBI with VSCS can identify the DL in most patients (88.2%) with differentiated-type early gastric cancer after Hp eradication.

Endoscopic submucosal dissection (ESD) is widely used as a minimally invasive treatment for large esophageal cancers, but prolonged procedure duration and life-threatening adverse events remain matters of concern. We aimed to determine whether traction-assisted ESD (TA-ESD) is superior to conventional ESD in terms of technical outcomes.A superiority, randomized, phase III trial was conducted at 7 institutions across Japan. Patients with large esophageal cancer (defined as tumor diameter20 mm) were eligible for this study. Enrolled patients were randomly assigned to undergo conventional ESD or TA-ESD. The primary endpoint was ESD procedure duration.Two hundred forty-one patients were recruited and randomized. On applying exclusion criteria, 117 and 116 patients who underwent conventional ESD and TA-ESD, respectively, were included in the baseline analysis. In 1 patient, conventional ESD was discontinued because of severe perforation. Thus, the final analysis included 116 patients per group (primary analysis). The ESD procedure duration was significantly shorter for TA-ESD than for conventional ESD (44.5 minutes vs 60.5 minutes, respectively; P .001). Moreover, no adverse events were noted in the TA-ESD group. The rate of horizontal margin involvement did not differ between the groups (10.3% vs 6.9% for conventional ESD and TA-ESD, respectively; P = .484).TA-ESD was superior to conventional ESD in terms of procedure duration and was not associated with any adverse events. TA-ESD should be considered the procedure of choice for large esophageal cancers. (Clinical trial registration number: UMIN000024080.).

We previously reported that heat shock protein 105 (HSP105) is overexpressed in a variety of human cancers, including colorectal, pancreatic and esophageal cancer and has proven to be a novel biomarker for the immunohistochemical detection of these cancers. In the present study, we used HLA-transgenic mice (Tgm) and the peripheral blood mononuclear cells (PBMCs) of colorectal cancer patients to identify HLA-A2 and HLA-A24-restricted HSP105 epitopes, as a means of expanding the application of HSP105-based immunotherapy to HLA-A2- or HLA-A24-positive cancer patients. In addition, we investigated by ex vivo IFN-γ ELISPOT assay whether the HSP105-derived peptide of cytotoxic T cells (CTLs) exists in PBMCs of pre-surgical colorectal cancer patients. We found that four peptides, HSP105 A2-7 (RLMNDMTAV), HSP105 A2-12 (KLMSSNSTDL), HSP105 A24-1 (NYGIYKQDL) and HSP105 A24-7 (EYVYEFRDKL), are potential HLA-A2 or HLA-A24-restricted CTL HSP105-derived epitopes. HSP105-specific IFN-γ-secreting T cells were detected in 14 of 21 pre-surgical patients with colorectal cancer in response to stimulation with these four peptides. Our study raises the possibility that these HSP105 peptides are applicable to cancer immunotherapy in patients with HSP105-expressing cancer, particularly colorectal cancer.

Background. Previous assessments of technical difficulty and procedure time for endoscopic submucosal dissection (ESD) of gastric neoplasms did not take into account several critical determinants of these parameters. However, two key phases of ESD determine the total procedure time: the mucosal circumference incision speed (CIS) and submucosal dissection speed (SDS). Methods. We included 302 cases of en bloc and R0 resection of gastric neoplasms performed by 10 operators who had completed the training program at our hospital. Twelve locations were classified based on multiple criteria, such as condition of surrounding mucosa, lesion vascularity, presence of submucosal fat, ulcers, scars, fibrosis, and scope and device maneuverability. Lesions in different locations were classified into three groups based on the length of the procedure: fast, moderate, or late. Results. A significant difference was found in CIS and SDS for each location (p<0.01), which demonstrates the validity of this classification system. In several locations, CIS and SDS were not consistent with each other. Conclusion. CIS and SDS did not correspond to each other even for lesions in the same location. Consideration of ESD procedure time for gastric neoplasms requires a more elaborate classification system than that previously reported.

We studied spicular jets over a plage area and derived their dynamic characteristics using Hinode Solar Optical Telescope (SOT) high-resolution images. The target plage region was near the west limb of the solar disk. This location permitted us to study the dynamics of spicular jets without the overlapping effect of spicular structures along the line of sight. In this work, to increase the ease with which we can identify spicules on the disk, we applied the image processing method `MadMax' developed by Koutchmy et al. (1989). It enhances fine, slender structures (like jets), over a diffuse background. We identified 169 spicules over the target plage. This sample permits us to derive statistically reliable results regarding spicular dynamics. The properties of plage spicules can be summarized as follows: (1) In a plage area, we clearly identified spicular jet features. (2) They were shorter in length than the quiet region limb spicules, and followed ballistic motion under constant deceleration. (3) The majority (80%) of the plage spicules showed the cycle of rise and retreat, while 10% of them faded out without a complete retreat phase. (4) The deceleration of the spicule was proportional to the velocity of ejection (i.e. the initial velocity)., 12 pages, 9 figures, accepted for publication in PASJ

Background This study was performed to clarify the influence of preoperative chemotherapy on liver function and the correlation between histological hepatic injury and the postoperative outcome in patients with colorectal liver metastases who underwent a hepatic resection. Methods Twenty-seven patients who underwent a hepatic resection for colorectal liver metastases were included. Fifteen patients with initially unresectable colorectal liver metastases who were able to undergo a tumor resection after FOLFOX (oxaliplatin plus fluorouracil and leucovorin, with a mean number of 7.7 cycles) were compared to 12 patients who underwent a hepatectomy with no preoperative chemotherapy. The postoperative mortality, morbidity, changes in liver function tests, and pathology of the resected liver were examined. Results Preoperative FOLFOX therapy was significantly associated with the macroscopic appearance of oxaliplatinassociated blue liver (p = 0.02), and a tendency toward sinusoidal dilatation (33.3% in the FOLFOX group versus 8.3% in the no-chemotherapy group, p = 0.056). Preoperative liver function tests showed that the albumin and indocyanine green retention rate at 15 min (ICG-R15) test values were significantly worse after FOLFOX therapy; however, intraoperative events, postoperative liver function test values, and morbidity rates were similar in the two groups. There was no postoperative mortality in any of the patients. Conclusions Although preoperative FOLFOX administration in patients with colorectal liver metastases caused macroscopic blue liver, microscopic sinusoidal dilatationin the liver parenchyma, and a significant decrease in liver function, there was no increase in the morbidity and mortality rates, in comparison to findings in patients without preoperative chemotherapy.

Background and Objectives: It is important to identify prognostic factors in patients with hepatocellular carcinoma (HCC) before hepatectomy. No previous studies have addressed the predictive efficacy of the preoperative doubling times of alpha-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKA-II). Methods: A total of 210 HCC patients who underwent a hepatic resection between 1998 and 2006 were prospectively evaluated. Serum AFP and PIVKA-II levels were measured at least twice before surgery to calculate the doubling times. Nineteen clinical factors that can be examined preoperatively, including the doubling times of AFP and PIVKA-II were investigated to identify prognostic factors for disease-free and overall survival after hepatectomy. Results: There was no relationship between preoperative levels and doubling times of AFP and PIVKA-II. In a multivariate analysis, patients with a doubling time of AFP � 30 days and PIVKA-II � 16 days showed a significantly worse disease-free (P ¼ 0.02, P ¼ 0.03, respectively) and overall survival (P < 0.0001, P ¼ 0.03, respectively). Conclusions: In HCC patients, the doubling times of preoperative serum AFP or PIVKA-II levels are useful tools to predict early postoperative recurrence and a poor prognosis. J. Surg. Oncol. 2010;102:490–496. 2009 Wiley-Liss, Inc.

The purpose of the present study was to investigate the clinical association between serum bile acid level changes and liver hypertrophy in portal vein embolization (PVE). In 31 patients, the serum total bile acid level was prospectively measured before and 1, 3, 5, 7, and 14 days after right PVE. Computed tomographic volumetry was performed before and 25.0 ± 3.6 days after PVE. Portal vein embolization induced the liver hypertrophy with a median increase in the left lobe volume (ILV) of 165 cm3 and a median percentage ILV (%ILV) of 29%. Compared with the pretreatment level, the serum bile acid levels significantly increased on day 3 and day 14 after PVE (p = 0.017 and p = 0.003, respectively). In patients with greater hypertrophy after PVE (ILV > 165 cm3 and %ILV > 30%), the increases in the bile acid level on day 3 were larger than that in those with lesser hypertrophy (p = 0.008 and p = 0.002, respectively). The increase on day 3 positively correlated with the ILV and %ILV (p = 0.003 and p = 0.004, respectively). The serum bile acid levels on day 3, 5, and 7 after PVE increased in patients with %ILV > 30% but not in those with %ILV ≤ 30%. Portal vein embolization increases the serum bile acid level in patients with effective liver hypertrophy in the nonembolized lobe. The increase on day 3 is a useful predictor of effective hypertrophy of the nonembolized lobe. Thus, bile acid signaling may be important for liver regeneration post-PVE.

Background Poorly differentiated hepatocellular carcinoma (HCC) has a malignant potential such as frequent microvascular invasion even if the tumor is smaller than 3 cm in diameter. The aim of this study was to clarify the preoperative predictors of poorly differentiated HCC for safe local ablation therapy. Methods Sixty-six patients underwent a hepatic resection for solitary small-sized HCC (≤3 cm) were included in this study. According to the postoperative histological examination, the patients were divided into a “poorly differentiated group” (n = 17) and a “well/moderately differentiated group” (n = 49). This study investigated the clinicopathological factors and imaging findings, and elucidated the predictive factors of the poorly differentiated type. Results In a univariate analysis, serum hepatitis B surface antigen positive, hepatitis C virus antibody negative, alpha-fetoprotein level, des-γ-carboxy prothrombin level, and a high contrast-to-noise ratio (CNR) in T2-weighted MR imaging were significantly associated with the poorly differentiate type. In a multivariate analysis, a high CNR in T2-weighted MR imaging was the only independent predictor of the poorly differentiated type. In the postoperative pathological findings, portal vein invasion and intrahepatic metastasis were significantly frequent in the poorly differentiated group. Conclusions The CNR in T2-weighted MR imaging is a useful tool to predict poorly differentiated HCC preoperatively. J. Surg. Oncol. 2009;100:121–126. © 2009 Wiley-Liss, Inc.