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Introduction: Eosinophils in the esophageal epithelium are unevenly distributed in eosinophilic esophagitis (EoE). Esophageal eosinophilia (EE) may be observable by endocytoscopy (EC). This study aimed to evaluate the diagnostic performance of EC for the diagnosis of EE., Methods: A total of 33 EoE patients underwent EC with methylene blue staining from March 2020 to April 2021. A total of 194 EC images with corresponding biopsies were obtained. Three findings of EC, increased squamous cells (item I), increased inflammatory cells (item II), and cells with bilobed nuclei (item III), were established. These findings were reviewed by two endoscopists to diagnose EE. Another four endoscopists reviewed the images for interobserver agreement., Results: When all three items were met by EC, the sensitivity and the accuracy for the diagnosis of EE were 88% and 76%, respectively. The integrated diagnostic odds ratios (ORs) for the diagnosis of EE of the four endoscopists were significant (OR: 3.98, 95% CI: 2.94-5.40, p < 0.001). The results were similar when only item III was met. Interobserver agreement was good for item III to diagnose EE (kappa value = 0.653)., Discussion/conclusion: The diagnostic performance of EC for EE is acceptable and has good interobserver agreement. It may be useful for targeted biopsy in EoE patients., (© 2023 S. Karger AG, Basel.)

Background: The utility of endoscopic ultrasonography (EUS) in predicting tumor depth among superficial nonampullary duodenal epithelial tumors (SNADETs) is unclear. The aim was to compare EUS with conventional endoscopy (CE) for the evaluation of tumor invasion of SNADETs., Methods: A retrospective analysis was performed on consecutive 174 lesions/169 patients with duodenal dysplasia or adenocarcinoma with invasion up to submucosa who underwent both CE and EUS before endoscopic (n = 133) or surgical (n = 41) treatment. Endoscopic staging by CE was performed based on the characteristic endoscopic criteria of submucosal invasion (irregular surface, submucosal tumor [SMT]-like marginal elevation, and fusion of converging folds). The diagnostic performance of each test was compared with the final histology., Results: The sensitivity and accuracy of estimating the depth were higher for CE compared to that of EUS (99.4% vs. 89.4%, p < 0.01 and 97.7% vs. 87.9%, p < 0.01, respectively). Univariate analysis of endoscopic factors revealed that tumor diameter, red color, SMT-like appearance, and hypoechogenicity were factors related to advanced histology. Multivariate analysis revealed that the presence of SMT-like appearance based on CE was an independent factor to predict submucosal invasion (p = 0.025). Gross morphology of the combined type was associated to incorrect diagnosis of EUS (p = 0.007). Among 3 cases in which EUS overestimated the tumor depth, carcinoma extension in submucosal Brunner's gland or nontumorous submucosal cystic dilation was observed., Conclusion: EUS may not be necessary, and CE may be sufficient for determining the optimal therapeutic strategy for SNADETs., (© 2022 S. Karger AG, Basel.)

Introduction: Fusobacterium and several bacteria are reported to be associated with colorectal cancer (CRC). However, their relationship and whether they cause CRC or are just adapted to the cancerous environment is not known. We approached this subject by investigating the correlation and distribution of the bacteria throughout the colon in patients with CRC and elucidated the relationship between microbiota and CRC., Methods: Twenty-five patients with CRC who underwent colonoscopy for endoscopic submucosal dissection or surgery were prospectively enrolled. Fecal samples were taken before bowel preparation, and mucosal samples were collected from three sites (tumor surface, tumor-adjacent mucosa, and cecum) during colonoscopy using a cytology brush. The microbiota was identified and analyzed by sequencing of the 16S rRNA gene of the V3-V4 region. We evaluated the correlation between the bacteria based on network analysis and the distribution of Fusobacterium in the colon., Results: A network consisting of many bacteria was found in all sites; especially, oral origin bacteria including Fusobacterium formed a positively correlated network on tumor surface. Streptococcus showed a significantly higher relative abundance on tumor surface than in feces. The relative abundance of Fusobacterium had significant positive correlations between tumor surface and feces, tumor-adjacent mucosa, and cecum., Conclusion: In patients with CRC, many bacteria were correlated with each other, and Fusobacterium and oral origin bacteria formed a positively correlated network on tumor surface. Fusobacterium was equally distributed on tumor surface and throughout the lumen and mucus in the colon. In the colon where Fusobacterium is widely distributed, Fusobacterium would adhere to the tumor surface and be correlated with oral origin bacteria to make a microenvironment that is favorable for CRC., (© 2022 S. Karger AG, Basel.)

Introduction: Patients with esophageal squamous cell carcinoma (ESCC) have various comorbidities. Thus, it is necessary to determine the appropriateness of performing treatment based on the patient's general condition., Aim: This study aimed to clarify the prognostic predictors of ESCC indicated for endoscopic submucosal dissection (ESD)., Methods: This retrospective study enrolled 241 patients with superficial ESCC endoscopically diagnosed as ESD-indicated lesions at the Nagoya University Hospital between January 2007 and December 2017. We evaluated the 3- and 5-year overall survival (OS) rates and prognostic predictors, such as the Prognostic Nutritional Index (PNI), Charlson Comorbidity Index (CCI), Psoas Muscle Index, and Controlling Nutritional Status score. Furthermore, we created a score-based classification using the prognostic predictors identified by multivariate analysis, and the 3- and 5-year OS rates were compared among the calculated scores., Results: In the multivariate analysis, PNI < 45 (hazard ratio [HR]: 2.39; 95% confidence interval [CI]: 1.28-4.46; p = 0.006) and CCI ≥ 3 (HR: 4.42; 95% CI: 2.40-8.12; p < 0.001) were significantly associated with the OS. Based on the HR, 0 and 1 were assigned to PNI and 0, 2, and 4 were assigned to CCI, and the score classification of 0-5 points was created. The 3- and 5-year OS rates in patients with a score 3 were significantly higher than in those with scores 4 and 5. As a result of scoring, the prognosis was stratified; the 3- and 5-year OS rates in patients with scores 4 and 5, that is, CCI ≥ 6, were clearly low, at approximately 10%., Conclusions: CCI and PNI can be prognostic predictors of patients with superficial ESCC indicated for ESD. Observation without ESD might be an acceptable strategy among patients with CCI ≥ 6., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Introduction: Endoscopic criteria for the diagnosis of superficial nonampullary duodenal epithelial tumors (SNADETs) are lacking. The aim of this study was to explore the usefulness of endocytoscopy (ECS) in the duodenum., Methods: A total of 77 ECS images stained by methylene blue and 58 images with double staining of methylene blue and crystal violet were obtained from 20 patients. Images were classified into 3 grades based on nuclear and villi atypia: EC A, B, and C. Diagnostic performance of ECS classification to predict histology and interobserver agreement was evaluated. The performance was compared between staining methods and ×520 or ×936 zoom., Results: With methylene blue staining, high rates of accuracy, sensitivity, specificity, and positive predictive value (PPV) over 90% were achieved for tumor and nontumor diagnosis as assessed by EC A versus EC B. High rates of accuracy, sensitivity, PPV, and negative predictive value over 90% were achieved for the differentiation between the diagnosis of the Vienna category 3 and 4/5 as assessed by EC B versus C. The accuracy rate of interpreting ECS images with ×936 zoom among 10 endoscopists was 82%, and the interobserver agreement rate was 0.803 (Kendall's coefficient of concordance). In the ×936 zoom group, methylene blue staining was significantly associated with higher accuracy rate (odds ratio 1.76 [1.06-2.92], p value 0.0297). No benefit was observed by double staining., Conclusions: ECS diagnosis with methylene blue provides a high accuracy rate and good interobserver agreement to predict histology of SNADETs., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Introduction: Dysphagia is a common symptom that occurs in patients with diabetes mellitus (DM). There have been few prospective observational studies on esophageal motility disorders in DM using high-resolution manometry (HRM). This study aimed to clarify the characteristics of esophageal motility disorders using HRM in patients with dysphagia and compare them between DM and non-DM patients., Methods: Patients with dysphagia were prospectively recruited between October 2018 and July 2019. Patients (n = 89) underwent esophagogastroduodenoscopy and HRM and completed the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. Manometry parameters and motility disorder classifications were compared between DM and non-DM patients. We also investigated the differences in clinical backgrounds and questionnaire scores among DM patients with normal and abnormal manometry results., Results: A higher prevalence of esophageal motility disorder was observed in DM patients (60%, 21/35) compared to non-DM patients (29.6%, 16/54) (p = 0.001). The prevalence of minor disorders such as ineffective esophageal motor disorder and fragmented peristalsis was significantly higher (45 vs. 11%), and the distal contractile integral, integrated relaxation pressure, and contractile front velocity values were lower in the DM group. Among DM patients, those with abnormal esophageal motility had a significantly higher prevalence of neuropathy, retinopathy, and nephropathy, as well as higher reflux or constipation scores on the GSRS, than those with normal results., Conclusions: Among patients with dysphagia, the frequency of minor esophageal motility disorders was higher in DM patients than in non-DM patients. Abnormal esophageal motility related to poor esophageal clearance was associated with higher prevalence of diabetic complications., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Introduction: We aimed to compare the efficacy of endoscopic ultrasound elastography (EUS-EG) with that of magnifying chromoendoscopy (MCE) and endoscopic ultrasonography (EUS) for the diagnosis of the depth of invasion in colorectal neoplasms. This is an important clinical issue as the depth of invasion is associated with the risk of metastasis., Methods: Consecutive patients with suspected superficial colorectal neoplasms, evaluated by MCE, EUS, and EUS-EG, for whom endoscopic submucosal dissection was considered, were enrolled in 2018 (derivation study) and in 2019-2020 (validation study). The primary clinical endpoint was the diagnostic yield differentiating intramucosal and shallow submucosal neoplasms from deep submucosal (dSM) and advanced colorectal cancers. In addition, inter- and intra-observer agreements of the elastic score of colorectal neoplasm (ES-CRN) were evaluated by 2 expert and 2 non-expert endoscopists., Results: Thirty-one (33 lesions) and 50 (55 lesions) patients were enrolled in the derivation and validation studies, respectively. Sensitivity, specificity, positive, and negative predictive values, and accuracy of assessment of the depth of submucosal or deeper invasion in the derivation and validation groups were as follows: EUS-EG, 100/88.2/86.7/100/93.3% and 77.8/86.1/73.7/88.6/83.3%; MCE, 66.7/94.4/90.9/77.3/81.8% and 84.2/91.4/84.2/91.4/88.9%; and EUS, 93.3/77.8/77.8/93.3/84.8% and 89.5/65.7/58.6/92.0/74.1%, respectively. For the 2 expert endoscopists, interobserver agreement for the ES-CRN (first and second assessments) in the derivation group was 0.84 and 0.78, respectively; these values were 0.73 and 0.49, respectively, for the 2 non-expert endoscopists., Discussion/conclusion: All 3 modalities presented similar diagnostic yield. Inter- and intra-observer agreements of the ES-CRN were substantial, even for non-expert endoscopists. Therefore, EUS-EG may be a useful modality in determining the depth of invasion in colorectal neoplasms., (© 2020 The Author(s). Published by S. Karger AG, Basel.)

Background: There are a number of reports that demonstrate the high diagnostic accuracy of colon capsule endoscopy (CCE) for polyp detection. However, some colorectal polyps are missed on CCE, and the clinical factors influencing those missed polyps are still unknown., Objective: The aim of this study was to elucidate the clinical factors related to missing colorectal polyp on CCE by using per-polyp analysis., Methods: We performed a retrospective multi-center study of 53 consecutive patients who underwent both CCE and colonoscopy (CS) within 3 months from January 2014 to -December 2017. Of those patients, we analyzed 151 polyps detected on CCE, and 149 polyps detected on CS diagnosed as neoplasm according to histopathological result., Results: The capsule excretion rate was 81%. One hundred three polyps were detected on both CS and CCE, 46 polyps (31%) were missed on CCE, and 48 polyps were considered false positive on CCE when CS result was considered as the gold standard. Per-polyp sensitivity and positive predictive value on CCE were 69.1 and 68%. On multiple logistic analysis, only the segmental transit time on CCE was identified as the independent factor influencing missed polyp on CCE., Conclusions: The clinical factor related to missing colorectal polyp on CCE was the segmental transit time., (© 2019 S. Karger AG, Basel.)

Objective: To evaluate the efficacy and safety of alternate-day administration of S-1 as second-line chemotherapy for unresectable pancreatic cancer in a multicenter, randomized, phase II study., Methods: Patients with histologically proven, unresectable pancreatic cancer treated with chemotherapy not including S-1 as first-line therapy were randomly assigned to receive either daily or alternate-day treatment with S-1. The primary end point was overall survival (OS), and the secondary end points were progression-free survival (PFS), time to treatment failure (TTF), response rate, and adverse events., Results: A total of 77 patients were enrolled, of which 75 were included in the final analysis. The median OS was 4.5 months in the daily group and 4.4 months in the alternate-day group (HR 1.178; 95% CI 0.741-1.875), with no significance in PFS and TTF. The response rate was 2.8% in the daily group and 0% in the alternate-day group. Grade 3 or higher adverse events occurred with significantly higher incidence in the daily group (47.2 vs. 25.6%, p = 0.044)., Conclusion: As a second-line chemotherapy for unresectable pancreatic cancer, although the efficacy in both groups was comparable and we can expect fewer toxicities with alternate-day administration of S-1, the noninferiority of alternate-day treatment to daily treatment with S-1 was not verified., (© 2018 S. Karger AG, Basel.)

Background/aims: Balloon-assisted endoscopy allows us to diagnose gastrointestinal (GI) stromal tumors (GISTs) in the small bowel including endoscopic ultrasonography and taking biopsy. The aim of this study was to retrospectively clarify clinical and endoscopic characteristics of small bowel GISTs using double-balloon endoscopy (DBE)., Methods: We reviewed 25 patients who underwent DBE and were diagnosed with GISTs. The risk of GISTs was stratified using the National Institute of Health (NIH) consensus criteria. We evaluated the available DBE route, the diagnostic yield of biopsy examination, and the relationship between endoscopic characteristics and recurrence-free survival (RFS)., Results: Of all 25 patients, 23 had any endoscopic findings related to GIST. They were detected using the antegrade approach in 91.3%. GISTs were classified into high risk (n = 7), intermediate risk (n = 4), low risk (n = 10), and very low risk (n = 4) based on surgical specimens. The diagnostic result of biopsy was 46.7% (7/15), but it was difficult to predict the NIH risk group. Endoscopic characteristics were not associated with RFS. The NIH risk group was significantly associated with RFS., Conclusions: Antegrade DBE was preferable for exploring small bowel GIST, but the diagnostic ability of biopsy examination was limited., (© 2017 S. Karger AG, Basel.)

Objective: It was the aim of this study to evaluate the diagnostic utility of Notch-1 immunocytochemistry in distinguishing endometrial glandular and stromal breakdown (EGBD) from endometrial adenocarcinoma in endometrial cytology., Study Design: Samples of normal endometrium, EGBD and endometrial adenocarcinoma were subjected to immunocytochemical staining for Notch-1, and we examined the labeling index (LI) of Notch-1 (the ratio of intranuclear Notch-1-positive cells to total cells). We compared (1) the Notch-1 LI in normal endometrium, (2) the Notch-1 LI between normal endometrium and endometrial adenocarcinoma, and (3) the Notch-1 LI in normal endometrium, EGBD and endometrial adenocarcinoma., Results: In analysis item 1, the LI of Notch-1 was 32.9 ± 8.4, 19.4 ± 8.2 and 12.5 ± 7.5% in proliferative endometrium, secretory endometrium and atrophic endometrium, respectively. In analysis item 2, the LI of Notch-1 in endometrial adenocarcinoma was 45.2 ± 7.4%, which was significantly higher than that in normal endometrium. In analysis item 3, the LI of Notch-1 in EGBD was 31.3 ± 8.3%, which was significantly lower than that in endometrial adenocarcinoma., Conclusion: In conclusion, Notch-1 immunocytochemistry is a useful method for distinguishing between EGBD and endometrial carcinoma in endometrial cytology., (Copyright © 2012 S. Karger AG, Basel.)

Objective: To evaluate the usefulness of collagenase immunocytochemistry as well as its immunohistochemistry in assessing the correlation with prognostic factors in transitional cell carcinoma (TCC) of the urinary bladder., Study Design: We investigated the expression of collagenase in catheterized urine and histologic specimens from 38 patients with TCC and 20 cases with benign lesions of the urinary tract., Results: Thirteen (34.2%) and 17 (44.7%) patients with TCC showed positive expression of collagenase on cytologic and histologic specimens, respectively, whereas in no cases with benign lesions was such expression found (P < .01). Invasive and nonpapillary TCC had higher positive rates than noninvasive and papillary TCC. Grade 3 TCC was positive at a higher rate than was grade 2, whereas there were no positive cases with grade 1. Collagenase expression did not correlate significantly with stage., Conclusion: Collagenase expression in urinary TCC correlated well with tumor growth pattern, pathologic grade and invasiveness of the carcinoma; all are known to be prognostic factors. The application of collagenase immunostaining to urinary cytology is very useful for assessing prognosis in TCC.

Objective: To evaluate the usefulness of endometrial aspiration cytology for the preoperative diagnosis of ovarian carcinoma., Study Design: A total of 210 patients with ovarian carcinoma were investigated by endometrial aspiration cytology., Results: Fifty-five of 210 patients (26.2%) had positive endometrial aspiration cytology. The positive rates of endometrial cytology were 3.9% in stage I, 23.8% in stage II, 36.5% in stage III and 53.3% in stage IV. When classified by histologic type, the positive rates of endometrial cytology in patients with serous adenocarcinoma, mucinous adenocarcinoma, clear cell adenocarcinoma, undifferentiated carcinoma and yolk sac tumor were 38.9%, 11.8%, 21.1%, 16.7% and 16.7%, respectively. One hundred twenty-eight of 210 patients (61.0%) were positive on peritoneal cytology, and 54 of these 128 cases (42.2%) were also positive on endometrial cytology. The positive rates of endometrial cytology were especially high in patients with serous adenocarcinoma (51.2%) and those with clear cell adenocarcinoma (40.0%) among those who were positive on peritoneal cytology. Of 74 patients who were negative on peritoneal cytology, only one (1.4%) with mucinous adenocarcinoma had positive endometrial cytology. Hysterectomy was performed on 130 patients, and the positive rate of endometrial cytology was 100% in 4 patients with endometrial invasion and 15.9% in 126 cases without invasion., Conclusion: Endometrial aspiration cytology can detect ovarian carcinoma cells not only in patients with endometrial involvement but also in patients with positive peritoneal cytology. Endometrial aspiration cytology appears to be useful for the preoperative diagnosis of ovarian carcinoma.