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 (PS4), blood transfusion, a low eGFR, poor view of the whole rectum on endoscopy, and the use of monopolar hemostatic forceps.

Significance of rescue hybrid endoscopic submucosal dissection in difficult colorectal cases.

BACKGROUND/AIMS: Hybrid endoscopic submucosal dissection (ESD), in which an incision is made around a lesion and snaring is performed after submucosal dissection, has some advantages in colorectal surgery, including shorter procedure time and preventing perforation. However, its value for rescue resection in difficult colorectal ESD cases remains unclear. This study evaluated the utility of rescue hybrid ESD (RH-ESD). METHODS: We divided 364 colorectal ESD procedures into the conventional ESD group (C-ESD, n=260), scheduled hybrid ESD group (SH-ESD, n=69), and RH-ESD group (n=35) and compared their clinical outcomes. RESULTS: Resection time was significantly shorter in the following order: RH-ESD (149 [90-197] minutes) >C-ESD (90 [60-140] minutes) >SH-ESD (52 [29-80] minutes). The en bloc resection rate increased significantly in the following order: RH-ESD (48.6%), SH-ESD (78.3%), and C-ESD (97.7%). An analysis of factors related to piecemeal resection of RH-ESD revealed that the submucosal dissection rate was significantly lower in the piecemeal resection group (25% [20%-30%]) than in the en bloc resection group (40% [20%-60%]). CONCLUSION: RH-ESD was ineffective in terms of curative resection because of the low en bloc resection rate, but was useful for avoiding surgery.

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.

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.

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.

Giant Brunner's gland hamartoma diagnosed via endoscopic mucosal resection: A case report.

We report the case of a patient with a giant Brunner's gland hamartoma that was pathologically diagnosed by endoscopic mucosal resection. A 69-year-old woman presented with intermittent abdominal pain, and imaging revealed a smooth saccular submucosal tumor, 40 mm in diameter, on the anterior wall of the duodenal bulb. Brunner's gland and smooth muscle tissue were observed on endoscopic ultrasound-guided fine-needle aspiration biopsy, which resulted in the preoperative diagnosis of a duplication cyst. However, subsequent endoscopic mucosal resection established a final histopathological diagnosis of Brunner's gland hamartoma.

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.

Efficacy of endoscopic clip closure for nonperforated muscle layer exposure during esophageal endoscopic submucosal dissection.

Exposure of the muscle layer during endoscopic submucosal dissection (ESD) in the esophagus can lead to complications such as fever and pain. Although closure with endoscopic clips is widely used when perforation is a major complication, its value when the exposed muscle layer is not perforated is unclear. Data for 104 lesions in 104 patients who underwent esophageal ESD between 2008 and 2020 were retrospectively analyzed. Patients with multiple tumors, those who experienced procedure-related adverse events such as aspiration pneumonitis, perforation during ESD, or delayed bleeding, and those in whom the muscle layer was not exposed were excluded. The clinical course of inflammation after ESD in patients in whom the muscle layer was exposed was examined according to whether endoscopic clips were used for closure. A significantly greater number of patients had a temperature ≤ 37.5°C in the clip closure group than in the nonclip closure group (≤37.5°C/≥37.6°C, 47/14 vs. 25/18, respectively, P = 0.040). Furthermore, significantly more patients in the clip closure group had a white blood cell count ≤10,000/µL (≤10,000/µL/>10,000/µL, 51/10 vs. 21/22, P < 0.001) and a C-reactive protein level < 1.0 mg/dL (<1.0 mg/dL/≥1.0 mg/dL, 40/21 vs. 36/7, P = 0.040) in the 24 hour post-ESD. The results were not changed after propensity score matching. Closure with endoscopic clips reduces inflammation after esophageal ESD with nonperforated muscle layer exposure. Even if there is no obvious perforation during ESD, closure of the exposed muscle layer with endoscopic clips may contribute to the clinical course post-ESD.

Long-term outcomes of esophageal squamous cell carcinoma with invasion depth of pathological T1a-muscularis mucosae and T1b-submucosa by endoscopic resection followed by appropriate additional treatment.

OBJECTIVES: Endoscopic resection (ER) is indicated for a wide range of superficial esophageal squamous cell carcinomas (ESCCs). We examined the long-term outcomes in patients with pathological (p) invasion of ESCC into the T1a-muscularis mucosae (MM) and T1b-submucosa (SM) after ER, for which data on prognosis are limited. METHODS: Of the 1217 patients with superficial ESCC who underwent ER, 225 patients with a pathological diagnosis of ESCC invasion into the MM, minute submucosal invasion ≤200 µm (SM1), or massive submucosal invasion (SM2) were included. In patients with lymphovascular invasion, droplet infiltration, or SM2 invasion, additional treatments, including chemoradiation (CRT) or esophagectomy with two- to three-field lymph node dissection, were recommended. The median observation period was 66 months (interquartile range 48-91 months). RESULTS: In total, there were 151, 28, and 46 pT1a-MM, pT1b-SM1, and pT1b-SM2 cases, respectively. Metastatic recurrence was observed in 1.3%, 10.7%, and 6.5% patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Of the eight patients with metastatic recurrence, six were successfully treated, and two died of ESCC. The 5-year overall survival rates were 84.1%, 71.4%, and 67.4%, the 5-year relapse-free survival rates were 82.8%, 64.3%, and 65.2%, and the 5-year disease-specific survival rates were 100%, 96.4%, and 99.1% in patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Multivariate analysis showed that additional CRT and esophagectomy, and T1b-SM2 were positively and negatively associated with overall survival, respectively. CONCLUSIONS: Endoscopic resection preceding appropriate additional treatments resulted in favorable outcomes. Many cases of metastatic recurrence in this cohort could be successfully treated.

Artificial intelligence diagnostic system predicts multiple Lugol-voiding lesions in the esophagus and patients at high risk for esophageal squamous cell carcinoma.

BACKGROUND: It is known that an esophagus with multiple Lugol-voiding lesions (LVLs) after iodine staining is high risk for esophageal cancer; however, it is preferable to identify high-risk cases without staining because iodine causes discomfort and prolongs examination times. This study assessed the capability of an artificial intelligence (AI) system to predict multiple LVLs from images that had not been stained with iodine as well as patients at high risk for esophageal cancer. METHODS: We constructed the AI system by preparing a training set of 6634 images from white-light and narrow-band imaging in 595 patients before they underwent endoscopic examination with iodine staining. Diagnostic performance was evaluated on an independent validation dataset (667 images from 72 patients) and compared with that of 10 experienced endoscopists. RESULTS: The sensitivity, specificity, and accuracy of the AI system to predict multiple LVLs were 84.4 %, 70.0 %, and 76.4 %, respectively, compared with 46.9 %, 77.5 %, and 63.9 %, respectively, for the endoscopists. The AI system had significantly higher sensitivity than 9/10 experienced endoscopists. We also identified six endoscopic findings that were significantly more frequent in patients with multiple LVLs; however, the AI system had greater sensitivity than these findings for the prediction of multiple LVLs. Moreover, patients with AI-predicted multiple LVLs had significantly more cancers in the esophagus and head and neck than patients without predicted multiple LVLs. CONCLUSION: The AI system could predict multiple LVLs with high sensitivity from images without iodine staining. The system could enable endoscopists to apply iodine staining more judiciously.

Incidence of metachronous gastric cancer in patients whose primary gastric neoplasms were discovered after Helicobacter pylori eradication.

BACKGROUND AND AIMS: The incidence of metachronous gastric cancer (MGC) in patients whose primary gastric neoplasm is discovered after Helicobacter pylori eradication remains unclear. Here, we evaluated the long-term effect of previous H pylori eradication on development of MGC after endoscopic submucosal dissection (ESD). METHODS: We analyzed prospectively collected data of consecutive patients with successful H pylori eradication more than 1 year before (eradicated group, 180 patients) or after (control group, 602 patients) initial curative ESD. These patients were also followed by endoscopy for over 2 years. Propensity score matching and inverse probability of treatment weighting (IPTW) were used to adjust for confounding variables during data analysis. The main outcome was the incidence of MGC after initial ESD. RESULTS: In a propensity-matched analysis of 174 pairs, the incidence of MGC was similar in the 2 cohorts (33.9 per 1000 person-years vs 40.8 per 1000 person-years in the control group, P = .454) at a median follow-up of 4.1 years (interquartile range, 3.0-5.6). Incidences were also similar in the 2 groups when data were analyzed using IPTW, even after exclusion of 123 patients with successful H pylori eradication <5 years before initial ESD. Multiple Cox regression analysis revealed age, differentiated-type histology, and initial multiplicity were predictors of MGC in patients after initial curative ESD. CONCLUSIONS: The frequency of follow-up surveillance after initial curative ESD should be kept constant, irrespective of whether H pylori eradication is performed before or after initial curative ESD.

Novel ex vivo training model for freehand insertion using a double-bending peroral direct cholangioscope.

BACKGROUND AND AIM: Several experts of direct peroral videocholangioscopy (D-PVCS) using a conventional ultraslim endoscope have reported its usefulness for the diagnosis and therapy of biliary tract diseases. We have additionally developed a dedicated double-bending D-PVCS technique for freehand scope insertion. In this study, we developed an ex vivo training model for the freehand double-bending D-PVCS technique and compared it with the technique using a conventional ultraslim endoscope. METHODS: The ex vivo model was made for training using a U-shape insertion pattern. A third prototype endoscope and an ultraslim upper gastrointestinal endoscope were used. Two experts and nine non-experts performed D-PVCS using the freehand technique. RESULTS: The two experts could not advance the tip of the endoscope to the hilar portion using the freehand technique, but they could achieve technical successful insertion to the hilar portion with the third prototype cholangioscope using the freehand technique alone. The non-experts could not advance the tip of the endoscope to the bile duct using the freehand technique. On the other hand, two (22.2%) non-experts could advance the tip of the third prototype cholangioscope using the freehand technique before the training conducted by the experts. After the training, all the non-experts could advance the tip of the third prototype cholangioscope to the hilar portion. CONCLUSIONS: The novel ex vivo model using a third prototype cholangioscope was useful for training in the use of the freehand D-PVCS technique.

Surveillance of short-segment Barrett's esophagus using ultrathin transnasal endoscopy.

BACKGROUND AND AIM: Newly developed ultrathin transnasal endoscope, the GIF-XP290N, makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm. We conducted surveillance of subjects with Barrett's esophagus using this ultrathin transnasal endoscopy. In Japan the lower margin of the lower esophageal palisade vessels is defined the gastroesophageal junction in deep inspiration. We diagnose Barrett's esophagus if columnar epithelium is present on the oral side of the gastroesophageal junction. METHODS AND RESULTS: Barrett's esophagus was confirmed in 116 out of 135 subjects (85.9%), with 17 cases of short-segment Barrett's esophagus (SSBE) and 99 of ultra-short-segment Barrett's esophagus. Close observation of the Barrett's esophagus mucosal structural pattern using narrow band imaging revealed 29 cases with an oval or round pattern, 29 with a long straight pattern, 47 with a villous pattern, 8 with a cerebriform pattern, and 6 with an irregular pattern according to Goda classification. Mucosal biopsies from all subjects with SSBE are examined. Histological examination revealed intestinal metaplasia in only eight subjects. We grouped the oval/round and long straight patterns as closed type, and the villous, cerebriform, and irregular patterns as open type. Analysis of the relationship between these mucosal patterns and background factors revealed a significant correlation between intestinal metaplasia and the open-type pattern. CONCLUSION: We consider this new ultrathin transnasal endoscopy to be a useful technique for surveillance of Barrett's esophagus, especially SSBE.

Evaluation of gastric cancer diagnosis using new ultrathin transnasal endoscopy with narrow-band imaging: preliminary study.

BACKGROUND AND AIM: The new developed ultrathin transnasal endoscope, the GIF-XP290N, makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm. In this study, using the GIF-XP290N, we evaluated whether endoscopic diagnosis (discrimination between benign and malignant) of gastric lesions is possible using nonmagnified narrow-band imaging (NBI) endoscopy. METHODS: The subjects were 255 consecutive patients who underwent screening of the gastrointestinal tract using new ultrathin transnasal endoscopy. Their average age was 65.2 ± 11.4 years. The male-female ratio was 2.5:1. All cases were examined using conventional white-light imaging (WLI) and nonmagnified NBI. When a depressed lesion was detected in the stomach, it was examined using WLI, then NBI close examination (at about 3 mm). We observed the mucosal structure of the lesion using close visualization with NBI. Concerning mucosal structural changes, we looked for a clear demarcation line between the lesion and the surrounding mucosa, and loss, irregularity, or nonuniformity of the lesion mucosal microsurface pattern. RESULTS: A total of 52 depressed lesions were examined. The histological diagnosis was cancer for 8 lesions, and noncancer for 44 lesions. WLI examination yielded a sensitivity of 50.0% (4/8), specificity of 63.6% (28/44), and accuracy 61.5% (32/52). On the other hand, NBI close examination yielded a sensitivity of 87.5% (7/8), specificity of 93.2% (41/44), and accuracy of 92.3% (48/52), significantly higher. CONCLUSION: NBI close examination using ultrathin transnasal endoscopy enables mucosal diagnosis even without magnification and was considered to be an effective technique for improving endoscopic diagnosis.