Endoscopic program with a scoring system for surveillance of metachronous esophageal cell carcinoma for older patients considering risk factors after endoscopic resection.

BACKGROUND: This study evaluated the association between the risk factors and prognosis for metachronous esophageal squamous cell carcinoma (ESCC) after endoscopic resection (ER) of esophageal cancer in older patients. METHODS: We conducted a retrospective observational study of 127 patients with ESCC who underwent ER from 2015 to 2020. Patients were classified as non-older (≤ 64 years), early older (65-74 years), and late older (≥ 75 years). We analyzed factors associated with poor overall survival and metachronous ESCC after ER using multivariate Cox regression analysis. A metachronous ESCC prediction scoring system was examined to validate the surveillance endoscopy program. RESULTS: Body mass index (BMI) and Charlson Comorbidity Index (CCI) were significant risk factors for poor overall survival in the multivariate analysis (p = 0.050 and p = 0.037, respectively). Multivariate analysis revealed that age of < 64 years, Lugol-voiding lesions (grade B/C), and head and neck cancer were significantly related to metachronous ESCC (p = 0.035, p = 0.035, and p = 0.014, respectively). In the development cohort, BMI < 18.5 kg/m2, CCI > 2, age < 64 years, Lugol-voiding lesions (grade B/C), and head and neck cancer were significantly related to metachronous ESCC, and each case was assigned 1 point. Patients were classified into low (0, 1, and 2) and high (> 3) score groups based on total scores. According to Kaplan-Meier curves, the 3-year overall survival was significantly lower in the high-score group than in the low-score group (91.5% vs. 100%, p = 0.012). CONCLUSIONS: We proposed an endoscopic surveillance scoring system for metachronous ESCC considering BMI and CCI in older patients.

Risk of map-like redness development after eradication therapy for Helicobacter pylori infection.

BACKGROUND: Map-like redness is a newly identified endoscopic risk factor for gastric cancer in patients who received Helicobacter pylori eradication therapy. However, the incidence rate of map-like redness in patients who received eradication, and the risk factors for the development of map-like redness remain unclear. We hence aimed to investigate the incidence rate of map-like redness at 1-year post H. pylori eradication, and evaluated its associations with map-like redness and gastric cancer in relation with gastric condition. MATERIALS AND METHODS: Endoscopic severity of gastritis and map-like redness were retrospectively evaluated according to the Kyoto Classification of Gastritis in patients who had undergone endoscopy before and after H. pylori eradication therapy. RESULTS: The incidence rate of map-like redness for all 328 patients at a mean of 1.2 ± 0.6 years after eradication was 25.3% (95% confidence interval [CI]: 20.7%-30.4%). Patients who developed map-like redness were older, had more severe atrophy and intestinal metaplasia, a higher total score of the Kyoto Classification of Gastritis both before and after eradication, and a higher rate of gastric cancer history than patients who did not have map-like redness. On multivariate analysis, risk of map-like redness was increased in patients with intestinal metaplasia (odds ratio [OR]: 2.794, 95% CI: 1.155-6.757) and taking acid inhibitors (OR: 1.948, 95% CI: 1.070-3.547). Characteristics of H. pylori-positive patients with gastric cancer history were patients who were older (OR: 1.033, 95% CI: 1.001-1.066), taking acid inhibitors (OR: 4.456, 95% CI: 2.340-8.484), and with occurrence of map-like redness after eradication therapy (OR: 2.432, 95% CI: 1.264-4.679). CONCLUSIONS: Map-like redness is observed in one fourth of patients at 1-year post eradication. Patients who developed map-like redness were found to have severe intestinal metaplasia and taking acid inhibitors, and hence such patients require increased attention at surveillance endoscopy.

Rebleeding Risk of Acute Hemorrhagic Rectal Ulcer: A Multicenter Retrospective Study.

Objective Acute hemorrhagic rectal ulcer (AHRU) is characterized by sudden, painless, and massive bleeding from rectal ulcers. To date, few studies have analyzed the risk factors for AHRU rebleeding. In this study, we clarified the risk factors of rebleeding after initial hemostasis of AHRU through a multicenter study. Methods A total of 149 patients diagnosed with AHRU between January 2015 and May 2020 at 3 medical centers were enrolled. We retrospectively investigated the following factors: age, sex, body mass index (BMI), performance status (PS), Charlson Comorbidity Index (CCI), comorbidities, medications, laboratory examinations, endoscopic findings, view of the entire rectum on endoscopy, hemostasis method, blood transfusion history, shock, instructions for posture change after initial hemostasis, and clinical course. Results Rebleeding was observed in 35 (23%) of 149 patients. A multivariate analysis showed that significant factors for rebleeding were PS 4 [odds ratio (OR), 5.23; 95% confidence interval (CI), 1.97-13.9; p=0.001], a blood transfusion history (OR, 3.66; 95% CI, 1.41-9.51; p=0.008), low an estimated glomerular filtration rate (eGFR) levels (OR, 0.98; 95% CI, 0.97-0.99; p=0.001), poor view of the whole rectum on endoscopy (OR, 0.33; 95% CI, 0.12-0.90; p=0.030), and use of monopolar hemostatic forceps (OR, 4.89; 95% CI, 1.37-17.4; p=0.014). Conclusion Factors associated with rebleeding of AHRU were a poor PS (PS 4), blood transfusion, a low eGFR, poor view of the whole rectum on endoscopy, and the use of monopolar hemostatic forceps.

Factors associated with long-term efficacy of lubiprostone for chronic constipation.

The prevalence of chronic constipation in Japan is increasing, and is presently almost 1 in 5 people. Because constipation is common, especially in older patients, to avoid adverse events and polypharmacy, simple treatments at low doses are generally desired. Although the chloride channel activator lubiprostone is candidate drug that may solve these problems, factors associated with the long-term efficacy of lubiprostone monotherapy for chronic constipation in treatment-naive patients remain unclear. We here retrospectively investigated the clinical characteristics and factors of patients who achieved long-term constipation improvement with lubiprostone monotherapy. Seventy-four patients with chronic constipation treated with lubiprostone monotherapy (24 or 48 µg/day) from January 2017 to August 2018 were reviewed. Patient characteristics and clinical time-courses were compared between those who sustained improvement for 6 months, and those who became refractory to treatment. In 54 patients (76.1%), constipation improved by lubiprostone administration for 6 months. On multivariate analysis, a significant clinical factor associated with sustained improvement was a starting lubiprostone dose of 24 µg/day (odds ratio: 5.791; 95% confidence interval: 1.032-32.498; p = 0.046). A starting lubiprostone dose of 24 µg/day has efficacy to improve chronic constipation and to prevent adverse events of nausea and diarrhea in Japanese patients.

Visibility of early gastric cancers by texture and color enhancement imaging using a high-definition ultrathin transnasal endoscope.

We evaluated whether texture and color enhancement imaging (TXI) using a high-definition ultrathin transnasal endoscope (UTE) improves the visibility of early gastric cancer (EGC) compared with white-light imaging (WLI). This study included 31 EGCs observed by TXI mode 2 using a high-definition UTE prior to endoscopic submucosal dissection. The first outcome was to compare the color differences based on Commission Internationale de l'Eclairage L*a*b* color space between EGCs and the surrounding mucosa by WLI and TXI using the UTE (objective appearance of EGC). The second outcome was to assess the visibility of EGCs by WLI and TXI using the UTE in an image evaluation test performed on 10 endoscopists (subjective appearance of EGC). Color differences between EGCs and non-neoplastic mucosa were significantly higher in TXI than in WLI in all EGCs (TXI: 16.0 ± 10.1 vs. WLI: 10.2 ± 5.5 [mean ± standard deviation], P < 0.001). Median visibility scores evaluated by 10 endoscopists using TXI were significantly higher than those evaluated using WLI (TXI: 4 [interquartile range, 4-4] vs. WLI: 4 [interquartile range, 3-4], P < 0.001). TXI using high-definition UTE improved both objective and subjective visibility of EGCs compared with WLI.

Targeted Metabolomic Profiling of Plasma Samples in Gastric Cancer by Liquid Chromatography-Mass Spectrometry.

INTRODUCTION: As the high mortality rate of gastric cancer (GC) is due to delayed diagnosis, early detection is vital for improved patient outcomes. Metabolic deregulation plays an important role in GC. Although various metabolite-level biomarkers for early detection have been assessed, there is still no unified early detection method. We conducted a plasma metabolome study to assess metabolites that may distinguish GC samples from non-GC samples. METHODS: Blood samples were collected from 72 GC patients and 29 control participants (non-GC group) at the Tokyo Medical University Hospital between March 2020 and November 2020. Hydrophilic metabolites were identified and quantified using liquid chromatography-time-of-flight mass spectrometry. Differences in metabolite concentrations between the GC and non-GC groups were evaluated using the Mann-Whitney test. The discrimination ability of each metabolite was evaluated by the area under the receiver operating characteristic curve. A radial basis function (RBF) kernel-based support vector machine (SVM) model was developed to assess the discrimination ability of multiple metabolites. The selection of variables used for the SVM utilized a step-wise regression method. RESULTS: Of the 96 quantified metabolites, 8 were significantly different between the GC and non-GC groups. Of these, N1-acetylspermine, succinate, and histidine were used in the RBF-SVM model to discriminate GC samples from non-GC samples. The area under the curve (AUC) of the RBF-SVM model was higher (0.915; 95% CI: 0.865-0.965, p < 0.0001), indicating good performance of the RBF-SVM model. The application of this RBF-SVM to the validation dataset resulted from the AUC of the RBF-SVM model was (0.885; 95% CI: 0.797-0.973, p < 0.0001), indicating the good performance of the RBF-SVM model. The sensitivity of the RBF-SVM model was better (69.0%) than those of the common tumor markers carcinoembryonic antigen (CEA) (10.5%) and carbohydrate antigen 19-9 (CA19-9) (2.86%). The RBF-SVM showed a low correlation with CEA and CA19-9, indicating its independence. CONCLUSION: We analyzed plasma metabolomics, and a combination of the quantified metabolites showed high sensitivity for the detection of GC. The independence of the RBF-SVM from tumor markers suggested that their complementary use would be helpful for GC screening.

Prediction of depth of invasion and lymph node metastasis in superficial pharyngeal cancer by magnifying endoscopy using the Japan Esophageal Society classification.

Backgrounds: The pharynx has no muscularis mucosae, so it is unclear whether diagnostic techniques used for the esophagus can be applied to the pharynx. This study investigated the usefulness of magnifying endoscopy with narrowband imaging using the Japan Esophageal Society (JES) classification for predicting the depth of invasion and lymph node metastasis (LNM) in pharyngeal cancer. Methods: A total of 123 superficial pharyngeal carcinoma lesions that had been observed preoperatively with magnifying endoscopy with narrowband imaging between January 2014 and June 2021 were analyzed. Predictors of subepithelial invasion (SEP) and LNM were sought based on endoscopic findings, including microvascular morphology, using the JES classification. Results: The lesions were divided into carcinoma in situ (n = 41) and SEP (n = 82). Multivariate analysis identified B2-B3 vessels (odds ratio [OR] 6.54, 95% confidence interval [CI] 1.74-24.61, p = 0.005) and a middle/large avascular area (OR 4.15, 95% CI 1.18-14.62, p = 0.027) as independent predictors of SEP. Significant predictors of LNM were protruding type, B2-B3 vessels, middle/large avascular area, SEP, venous invasion, lymphatic invasion, and tumor thickness > 1000 µm. Median tumor thickness increased significantly in the order of B1 < B2 < B3 vessels (B1, 305 µm; B2, 1045 µm; B3, 4043 µm; p < 0.001). The LNM rates for B1, B2, and B3 vessels were 1.6% (1/63), 4.8% (2/42), and 55.6% (10/18), respectively (p < 0.001). Conclusions: Magnifying endoscopy with narrowband imaging using the JES classification could predict the depth of invasion in superficial pharyngeal carcinoma. The JES classification may contribute to the prediction of LNM, suggesting that it could serve as an alternative to tumor thickness.

Validation of the BEST-J score, a prediction model for bleeding after endoscopic submucosal dissection for early gastric cancer: a multicenter retrospective observational study.

BACKGROUND: A new scoring system, the BEST-J score, using ten risk factors to assign cases to different post-endoscopic submucosal dissection (ESD) risk groups for bleeding, has been shown to be accurate for risk stratification. We first aimed to validate the BEST-J score at four hospitals not specialized in performing ESD and then aimed to identify other risk factors for post-ESD bleeding. METHODS: We evaluated the incidence of post-ESD bleeding in 791 cases of early gastric cancer (EGC) between October 2013 and December 2020 as a retrospective, multi-center observational study conducted at four hospitals. Multivariate logistic regression models to examine the effect of independent variables on post-ESD bleeding firstly included ten possible factors raised by the BEST-J score and secondly included statistically significant (p < 0.01) in univariate analysis. The prediction accuracy of the model was evaluated by receiver-operating characteristic analysis and the areas under the curve (AUC). RESULTS: The incidence of post-ESD bleeding was 4.8% (38/791, 95% confidence interval [CI] 3.4-6.5%). On multivariate analysis, the risk factors were P2Y12 receptor antagonist (odds ratio [OR]: 5.870, 95% CI 1.624-21.219), warfarin (8.382, 1.658-42.322), direct oral anticoagulant (DOAC) (8.980, 1.603-50.322), and tumor location in lower third of stomach (2.151, 1.012-4.571), respectively. When we categorized cases into low-risk by BEST-J score, intermediate-risk, high-risk, and very high-risk groups, the bleeding rates were 2.8%, 7.3%, 12.8%, and 19.0%, respectively. The AUC for our cohort was 0.713 (95% CI 0.625-0.802) for the BEST-J score. In the multivariate analysis in our cohort, the risks were age, body mass index, P2Y12 receptor antagonist, warfarin, DOAC, respectively. DISCUSSION: The BEST-J score is equally accurate in risk stratification of patients with EGC for post-ESD bleeding at non-specialized facilities for ESD as in specialized hospitals. BMI and age may be helpful additional risk factors at hospitals not specialized.

Co-treatment with endoscopic laryngopharyngeal surgery and endoscopic submucosal dissection.

OBJECTIVE: Endoscopic laryngopharyngeal surgery (ELPS) is an effective and minimally invasive treatment for pharyngeal cancers. However, the disadvantages of ELPS are the interference of instruments in the operative field and the difficulty in approaching certain areas. To overcome these drawbacks, we began to perform combination treatment of ELPS and endoscopic submucosal dissection (ESD). The aim of the present study was to compare the efficacies of treatment with ELPS alone and ELPS combined with ESD. METHODS: A total of 103 lesions in 73 patients who underwent pharyngeal ELPS for superficial pharyngeal cancer between August 2014 and January 2020 at our hospital were analyzed. Lesions were divided into the ELPS alone group and ELPS combined with ESD group. Lesion characteristics, technical results, adverse events, and long-term outcomes were analyzed. RESULTS: In the ELPS combined with ESD group, procedure speed was shorter than the ELPS alone group (20.2 ± 10.0 mm2/min vs 13.0 ± 6.6 mm2/min, p < 0.001), and R0 resection rate was higher (67.4% vs 45.6%, p = 0.027). There were no significant differences in tumor size, depth of tumor invasion, and adverse events among the 2 groups. These results remained unchanged after propensity score matching. The overall and cause-specific survival rates at 3 years were 96.7% and 100% for the ELPS combined with ESD group and ELPS alone group, respectively. CONCLUSIONS: Combination treatment of ESD and ELPS enabled more efficient resection than ELPS alone. Cooperative treatment of pharyngeal cancer patients involving gastroenterologists and head and neck surgeons is effective and beneficial, and results in favorable long-term outcomes.

[Intra-abdominal bleeding caused after esophagogastroduodenoscopy: a case report].

An 86-year-old man was transferred to the Tokyo Medical University Hospital because of a temporary loss of consciousness and melena. We performed upper gastrointestinal endoscopy, which revealed Mallory-Weiss syndrome caused by a strong vomiting reflex. After an examination, he complained of abdominal pain, and his blood pressure decreased. Abdominal contrast-enhanced computed tomography showed fresh intra-abdominal hemorrhage. We performed transcatheter arterial embolization by using N-butyl-2-cyanoacrylate to control the bleeding from the right gastroepiploic artery. Intra-abdominal hemorrhage after upper gastrointestinal endoscopy is rare, and we report this case with the literature review.

Preparation of micrometer-sized, onionlike multilayered block copolymer particles by two-step AGET ATRP in aqueous dispersed systems: effect of the second-step polymerization temperature.

The polymerization rate, control/livingness, and particle morphology in seeded activators generated by electron transfer for the atom-transfer radical polymerization of styrene with PiBMA-Br macroinitiator particles were investigated at 70, 90, and 110 degrees C. At 110 degrees C, the polymerization proceeded quickly until 60% conversion was reached, but control/livingness was not observed. This seems to be the reason for the high activation rate and spontaneous initiation of styrene, which significantly increased the radical concentration, resulting in a number of radical terminations. As a result, the block copolymer was not sufficiently formed, leading to a sea-island structure. However, at 70 and 90 degrees C, the polymerizations were almost complete in 14 and 7 h, respectively. Control/livingness was maintained, resulting in PiBMA-b-PS. As a result, onionlike multilayered particles were successfully synthesized. These polymerization behaviors were discussed from the viewpoint of the radical concentration and propagation rate coefficient at various temperatures.

Preparation of "mushroom-like" Janus particles by site-selective surface-initiated atom transfer radical polymerization in aqueous dispersed systems.

A versatile approach for the preparation of micrometer-sized, monodisperse, "mushroom-like" Janus polymer particles in aqueous dispersed systems is proposed. The synthetic methodology of the Janus particles consists of the following two steps. The first step is the preparation of spherical poly(methyl methacrylate) (PMMA)/poly(styrene-2-(2-bromoisobutyryloxy)ethyl methacrylate) (P(S-BIEM)) Janus particles based on the internal phase separation induced by solvent evaporation from the solvent droplets dissolving the polymers. The second step is surface-initiated atom transfer radical polymerization (ATRP) of 2-(dimethylamino)ethyl methacrylate (DM) using the Janus particles with ATRP initiator groups at one side of the surface as macroinitiator. As a consequence, mushroom-like PMMA/P(S-BIEM)-graft-poly(DM) Janus particles were prepared, which had pH-responsive property.

Preparation of micrometer-sized, monodisperse "janus" composite polymer particles having temperature-sensitive polymer brushes at half of the surface by seeded atom transfer radical polymerization.

Micrometer-sized, monodisperse polystyrene (PS)/poly[methyl methacrylate-(chloromethyl)styrene] [P(MMA-CMS)] composite particles having hemispherical structure were prepared by solvent evaporation from toluene droplets containing dissolved PS and P(MMA-CMS) dispersed in aqueous solution, which had been prepared using the membrane method. The formation of hemispherical ("Janus") morphology by phase separation between the PS and the P(MMA-CMS) was confirmed by both optical and electron microscopy. Atom transfer radical polymerization (ATRP) of 2-(dimethylamino)ethyl methacrylate (DM) was subsequently carried out in the presence of hemispherical PS/P(MMA-CMS) composite particles in an aqueous dispersed system. After polymerization, the morphology of the particles changed from spherical to "mushroom" shape as observed by scanning electron microscopy, indicating that DM polymerized inside or on the surface of half [P(MMA-CMS) phase] of the particles. 1H NMR spectra were consistent with chloromethyl functional groups in P(MMA-CMS) operating as ATRP initiators in the DM polymerization.