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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.

Computer-aided diagnosis systems for polyp characterization are commercially available but cannot recognize subtypes of sessile lesions. This study aimed to develop a computer-aided diagnosis system to characterize polyps using non-magnified white-light endoscopic images.A total of 2249 non-magnified white-light images from 1030 lesions including 534 tubular adenomas, 225 sessile serrated adenoma/polyps, and 271 hyperplastic polyps in the proximal colon were consecutively extracted from an image library and divided into training and testing datasets (4:1), based on the date of colonoscopy. Using ResNet-50 networks, we developed a classifier (1) to differentiate adenomas from serrated lesions, and another classifier (2) to differentiate sessile serrated adenoma/polyps from hyperplastic polyps. Diagnostic performance was assessed using the testing dataset. The computer-aided diagnosis system generated a probability score for each image, and a probability score for each lesion was calculated as the weighted mean with a logThe area under the curve of classifier (1) for adenomas was equivalent to E1 and superior to E2 (classifier 86%, E1 86%, E2 69%; classifier vs. E2, p 0.001). In contrast, the area under the curve of classifier (2) for sessile serrated adenoma/polyps was inferior to both experts (classifier 55%, E1 68%, E2 79%; classifier vs. E2, p 0.001).The classifier (1) developed using white-light images alone compares favorably with experts in differentiating adenomas from serrated lesions. However, the classifier (2) to identify sessile serrated adenoma/polyps is inferior to experts.

Endoscopic submucosal dissection (ESD) of colorectal lesions was invented in Japan, but postoperative management including hospital stay has not been reconsidered due to the Japanese insurance system. To explore appropriate postoperative management after colorectal ESD, we reviewed short-term outcomes after ESD in non-selected consecutive patients.Patients who underwent colorectal ESD from April 2013 to September 2020 in one institution were reviewed. The primary outcome measure was the occurrence of adverse events stratified by the Clavien-Dindo classification with five grades. A logistic regression model with the Firth procedure was applied to investigate predictors of severe (grade III or greater) adverse events.A total of 330 patients (female 40%, male 60%; median 72 years; IQR 65-80 years) with colorectal lesions (median 30 mm, IQR 23-40 mm; colon 77%, rectum 23%; serrated lesion 4%, adenoma 47%, mucosal cancer 30%, invasive cancer 18%) was evaluated. The en bloc resection rate was 97%. The median dissection time was 58 min (IQR: 38-86). Intraprocedural perforation occurred in 3%, all successfully treated by endoscopic clipping. No delayed perforations occurred. Postprocedural bleeding occurred in 3% on days 1-10 (median day 2); all were controlled endoscopically. Severe adverse events included only delayed bleeding. In analyzing severe adverse events in a multivariate logistic regression model with the Firth procedure, antithrombotic agent use (No serious adverse events occurred in this series. Four days of hospitalization may be too long for the majority of patients after ESD.

Endoscopic submucosal dissection (ESD) is a widely used treatment for early gastrointestinal cancer. However, colon ESD remains challenging. Previous studies on colon ESD using the traction method used a small sample, single-center design, providing insufficient evidence of this procedure's efficacy. We thus aimed to investigate the efficacy and safety of the traction method in colon ESD in this multicenter randomized trial.We conducted a prospective, multicenter, randomized, two-arm controlled trial at 10 facilities in Japan. A 1:1 allocation was conducted for the conventional ESD (C-ESD) and traction ESD (T-ESD) groups. The primary end-point was ESD procedure time.We included 128 C-ESD and 123 T-ESD cases from April 2020 to August 2021. The median procedure times for C-ESD and T-ESD were 61 (40-100) and 53 (40-76) min (P = 0.18), respectively, and no significant differences were observed between the groups. Subgroup analysis showed that the median procedure times for patients with a lesion diameter of ≥30 mm in the C-ESD and T-ESD groups were 89 (57-80) and 69 (50-104) min (P = 0.05), respectively, and for nonexpert operators were 81 (62-120) and 64 (52-109) min (P = 0.07), respectively.The traction method did not contribute to a significantly shortened ESD procedure time. However, this method may be useful when the tumor diameter is large or if the procedure is conducted by nonexpert endoscopists.

Background and study aims Small polyps are occasionally missed during colonoscopy. This study was conducted to validate the diagnostic performance of a polyp-detection algorithm to alert endoscopists to unrecognized lesions. Methods A computer-aided detection (CADe) algorithm was developed based on convolutional neural networks using training data from 1991 still colonoscopy images from 283 subjects with adenomatous polyps. The CADe algorithm was evaluated on a validation dataset including 50 short videos with 1-2 polyps (3.5 ± 1.5 mm, range 2-8 mm) and 50 videos without polyps. Two expert colonoscopists and two physicians in training separately read the same videos, blinded to the presence of polyps. The CADe algorithm was also evaluated using eight full videos with polyps and seven full videos without a polyp. Results The per-video sensitivity of CADe for polyp detection was 88% and the per-frame false-positive rate was 2.8%, with a confidence level of ≥30%. The per-video sensitivity of both experts was 88%, and the sensitivities of the two physicians in training were 84% and 76%. For each reader, the frames with missed polyps appearing on short videos were significantly less than the frames with detected polyps, but no trends were observed regarding polyp size, morphology or color. For full video readings, per-polyp sensitivity was 100% with a per-frame false-positive rate of 1.7%, and per-frame specificity of 98.3%. Conclusions The sensitivity of CADe to detect small polyps was almost equivalent to experts and superior to physicians in training. A clinical trial using CADe is warranted.

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.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 lt; 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).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.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.

The aim of this study is to investigate the feasibility of bowel preparation using a hypertonic laxative (polyethylene glycol with ascorbic acid, PEG + Asc) for CT colonography (CTC) and to examine the volume limit of laxative. In one institution, patients who met the indications for CTC were enrolled and randomly assigned to CTC with regimen A (800 ml PEG + Asc), B (600 ml PEG + Asc), or C (400 ml PEG + Asc). Sodium diatrizoate was given orally for fecal tagging. On the previous day, patients ate low-residue meals and took the assigned lavage solution after dinner. A reader blinded to the preparation graded residual stool/fluid and fecal tagging quality in six segments of the colorectum. The primary outcome was a proportion of colon segments without stool. One hundred twenty segments in 20 patients with each regimen were needed to show a non-inferiority margin of 15%, assuming 85% of no stool. A total of 360 segments in 60 patients were analyzed. There were 83% of segments with no stool in regimen A, 89% in regimen B, and 88% in regimen C. Using the delta method, the 95% confidence interval of the risk difference (6.7%) between regimens A and B was − 2.2% to 15.6%, and the risk difference (5.0%) between regimens A and C was − 4.1% to 14%, both within the non-inferiority margin. Residual fluid and fecal tagging quality were also within the non-inferiority margin. No adverse events occurred. A novel CTC regimen using hypertonic laxative demonstrated optimal colon cleansing effectiveness even with the lowest volume of laxative (UMIN000022851). • A novel CTC regimen using a hypertonic laxative is feasible. • The lowest volume of laxative provides excellent colon imaging. • However, the lowest volume of laxative did not improve patient acceptance.

The neutrophil-to-lymphocyte ratio (NLR) has been reported to be an independent prognostic factor of unresectable advanced or metastatic colorectal cancer (uCRC). However, few studies have documented changes in NLR during chemotherapy. The current study analyzed whether a change in NLR during chemotherapy in patients with uCRC could be used as a prognostic biomarker. The present retrospective study enrolled 71 patients who received first-line chemotherapy for uCRC between April 2012 and April 2019. The exclusion criteria were as follows: Acute infection or systemic inflammatory disease, duration of first-line chemotherapy

Cold snare polypectomy is being increasingly adopted; however, there are few reports of cold snare polypectomy regarding antithrombotic therapy.This study aimed to investigate the real-world safety of cold snare polypectomy during antithrombotic therapy.We collected data from consecutive patients undergoing cold snare polypectomy in a single hospital between 2013 and 2017. Indications for cold snare polypectomy were any ≤ 10 mm polyp. The primary outcome was delayed bleeding. We compared rates of delayed bleeding between patients with and without antithrombotic therapy and analyzed risk factors for delayed bleeding using binary logistic regression model with firth procedure.In 2152 patients (mean age 67.6 years; male 1411), 4433 colorectal polyps (mean diameter 5.0 mm) underwent cold snare polypectomy. Clipping during the procedure was performed for 5.8%. Delayed bleeding occurred in 0.51% (11/2152) of patients and 0.25% (11/4433) of polyps, but no major delayed bleeding occurred. A total of 244 (11%) patients received antithrombotic therapy. Patients on antithrombotic therapy were older (p 0.001), more likely male (p 0.001) and had cold snare polypectomy in the proximal colon (p = 0.011). The rate of delayed bleeding was higher in patients on antithrombotic therapy (1.64% vs. non-antithrombotic therapy 0.37%, p = 0.009). Larger polyp size ( 5 mm), use of clips, and antithrombotic therapy were significant risk factors for delayed bleeding. There was no clear association between specific antithrombotic agents and delayed bleeding.Delayed bleeding after cold snare polypectomy was rare even in patients with antithrombotic therapy, and no major delayed bleeding occurred.

Figure 10.1 illustrates the organization of this chapter. We begin with a brief review of colon anatomy and an overview of general information on colorectal cancers (CRCs). In Sect. 1.2, we introduce the details of colonoscopy, the most important tool for the screening, diagnosis, and therapy of CRCs.

Small intestinal hemorrhage due to diverticulum is a relatively rare condition among gastrointestinal hemorrhages. We report a case of diverticular hemorrhage of the terminal ileum that was successfully treated by ultra-selective transcatheter arterial embolization using a triaxial system. A 25-year-old man was referred to our hospital due to melena. Abdominal contrast-enhanced computed tomography demonstrated marked extravasation of contrast medium in a diverticulum of the terminal ileum. We immediately attempted transcatheter arterial embolization after onset of hemorrhagic hypovolemic shock. Angiogram of the superior mesenteric artery revealed apparent hemorrhage at the end of the ileocolic artery. We performed embolization with 2 platinum coils using a triaxial system via the vasa recta of the terminal ileum. This procedure stopped extravasation of contrast medium. Postoperative course was uneventful, and he was discharged four days postoperatively. The triaxial system may facilitate high diagnostic ability to accurately identify target arteries of the ileal diverticular hemorrhage.

Background and study aims Colorectal cancers (CRC) with deep submucosal invasion (T1b) could be metastatic lesions. However, endoscopic images of T1b CRC resemble those of mucosal CRCs (Tis) or with superficial invasion (T1a). The aim of this study was to develop an automatic computer-aided diagnosis (CAD) system to identify T1b CRC based on plain endoscopic images. Patients and methods In two hospitals, 1839 non-magnified plain endoscopic images from 313 CRCs (Tis 134, T1a 46, T1b 56, beyond T1b 37) with sessile morphology were extracted for training. A CAD system was trained with the data augmented by rotation, saturation, resizing and exposure adjustment. Diagnostic performance was assessed using another dataset including 44 CRCs (Tis 23, T1b 21) from a third hospital. CAD generated a probability level for T1b diagnosis for each image, and > 95 % of probability level was defined as T1b. Lesions with at least one image with a probability level > 0.95 were regarded as T1b. Primary outcome is specificity. Six physicians separately read the same testing dataset. Results Specificity was 87 % (95 % confidence interval: 66–97) for CAD, 100 % (85–100) for Expert 1, 96 % (78–100) for Expert 2, 61 % (39–80) for both gastroenterology trainees, 48 % (27–69) for Novice 1 and 22 % (7–44) for Novice 2. Significant differences were observed between CAD and both novices (P = 0.013, P = 0.0003). Other diagnostic values of CAD were slightly lower than of the two experts. Conclusions Specificity of CAD was superior to novices and possibly to gastroenterology trainees but slightly inferior to experts.

Automatic polyp detection is reported to have a high false-positive rate (FPR) because of various polyp-like structures and artifacts in complex colon environment. An efficient polyp's computer-aided detection (CADe) polyp detection system should have a high sensitivity and a low FPR (high specificity). Convolutional neural networks have been implemented in colonoscopy-based automatic polyp detection and achieved high performance in improving polyp detection rate. However, complex colon environments caused excessive false positives are going to prevent the clinical implementation of CADe systems. To reduce false positive rate, we proposed an automatic polyp detection algorithm, combined with YOLOv3 architecture and active learning. This algorithm was trained with colonoscopy videos/images from 283 subjects. Through testing with 100 short and 9 full colonoscopy videos, the proposed algorithm shown FPR of 2.8 % and 1.5 %, respectively, similar sensitivities of expert endoscopists.

We report 2 cases of advanced colorectal cancer achieving complete response by FOLFOXIRI plus bevacizumab. Case 1 was a 65-year-old male diagnosed with descending colon cancer with multiple liver metastases. Six courses of FOLFOXIRI plus bevacizumab were administered after laparoscopic-assisted left hemicolectomy. Ten partial hepatectomies and 1 radiofrequency ablation were performed as the liver metastases resolved. A pathological complete response was confirmed. Adjuvant chemotherapy was not administered, and recurrence-free survival was 21 months after hepatectomy. Case 2 was a 77-yearold male diagnosed with rectal cancer invading the pelvic wall and sacral foramen with bilateral lateral lymph node metastasis. Additionally, there was a cancer embolism in the right internal iliac vein. Six courses of FOLFOXIRI plus bevacizumab were administered, and the cancer tissue was absent on subsequent CT and MRI. The cancer was scarred by colonoscopy, and the biopsy showed no malignant cells. Six courses of FOLFIRI plus panitumumab were administered as second-line chemotherapy, and the patient survived without any recurrence after 12 months from initiation of chemotherapy.

OBJECTIVES Colonic spasm can interfere with colonoscopy, but antispasmodic agents can cause complications. This study aimed to assess the inhibitory effect of topical lidocaine compared with a placebo control. METHODS In five tertiary-care hospitals in Japan, 128 patients requiring endoscopic resection of a colorectal lesion were enrolled and randomly and double-blindly allocated to colonoscopy with topical administration of 2% lidocaine solution 20mL (LID, n = 64) or normal saline 20mL (control, n = 64). During colonoscopy, the assigned solution was applied with a spray catheter near the lesion and the area was observed for three minutes. primary endpoint was the inhibitory effect at three time-points (1, 2 and 3 minutes after dispersion), using a three-point scale (excellent, fair, poor). Secondary endpoints were rebound spasm and adverse events. All endpoints were scored in real time. Serum lidocaine levels were measured in 32 patients (LID 16, control 16). RESULTS There were no significant differences between groups in patient demographics. At all time-points, the proportion of patients with "excellent" scores was greater in LID group than control group, with significant differences observed at 2 minutes (p = 0.02) and 3 minutes (p = 0.02). In LID group, the rate of "excellent" scores increased by 12.5% at 2 minutes and was maintained at 3 minutes. Rebound spasm did not occur in LID group, compared with 15.6% of control group (p = 0.001). There were no adverse events in LID group. All serum lidocaine levels were below detectable levels. CONCLUSIONS Topical lidocaine is an effective and safe method for suppressing colorectal spasm during colonoscopy (UMIN000024733).

Objectives Colonoscopy is the first-line modality to examine the colon even in the very elderly but may have an increased risk of complications. This study aimed to evaluate the efficacy and safety of colonoscopy in the very elderly. Methods Patients ≥85y old, who underwent colonoscopy between September 2010 and August 2012 in two tertiary-care hospitals in Japan were enrolled. Main outcome measures were cecal intubation rate, detection rate of adenomas and cancers, treatment, adverse events, and long-term outcomes. Results A total of 207 colonoscopies were performed in 177 patients (females 72, males 105; maximum age 95 years). Of these, 202 attempted to reach the cecum, with success in 92%. Excluding patients with known colorectal neoplasms, invasive cancers were detected in 12%, including T1 lesions in 2% and T2 or deeper in 9%. No cancers were detected in patients referred for surveillance or mild abdominal symptoms. Cancers were found in 25% of patients with positive fecal immunochemical tests, 22% with altered bowel habits, 21% with anemia, and 18% with hematochezia. Treatment of 29 patients with cancer included surgery in 22, endoscopic resection in two and no treatment (due to comorbidities) in five. There were no complications. During 730 days (mean) of follow up, 27 patients died but only three died from recurrent colorectal cancer. Conclusions Colonoscopy for patients aged ≥85 years is safe. A relatively high detection rate of cancers was found, and most were treatable and even curable. (UMIN000018575).

Background and study aims Mycobacterium tuberculosis is often detected in the feces of patients with active pulmonary tuberculosis. However, no study has examined the small intestine using small bowel capsule endoscopy (SBCE). This study aimed to investigate intestinal abnormalities in patients with active pulmonary tuberculosis.Patients and methods SBCE was performed in sputum/feces smear-positive pulmonary tuberculosis patients. From December 2013 to November 2016, 15 patients were enrolled from a dedicated tuberculous ward. The primary outcome was intestinal abnormalities identified by SBCE.Results Fourteen patients (median age 81 years, range 29 – 91; 3 female) underwent SBCE to the terminal ileum. The video was not recorded for one patient who was excluded from the analysis. Intestinal lesions, including 5 annular ulcers in 4 patients, were observed in 64 % (9/14). In subgroup analysis, prevalence tended to be higher in patients undergoing SBCE within 1 month of anti-tuberculous therapy (P = 0.051). Distribution of small intestinal lesions tended to be distal. Four of five annular ulcers were located close to the ileocecal valve.Conclusion Prevalence of intestinal lesions in patients with pulmonary tuberculosis is higher than expected before (UMIN 000017292)