Efficacy of endoscopic surveillance for pharyngeal mucosa during endoscopic resection for pharyngeal carcinoma: a multicenter prospective study.

INTRODUCTION: Since patients with pharyngeal squamous cell carcinoma (SCC) often have multiple pharyngeal lesions, evaluation of pharyngeal lesions before endoscopic resection (ER) is important. However, detailed endoscopic observation of the entire pharyngeal mucosa under conscious sedation is difficult. We examined the usefulness of endoscopic surveillance with narrow band imaging (NBI) and lugol staining for detection of pharyngeal sublesions during ER for pharyngeal SCC under general anesthesia (endoscopic surveillance during treatment; ESDT). METHODS: From January 2021 through June 2022, we examined 78 patients who were diagnosed with superficial pharyngeal SCC and underwent ER. They underwent the ESDT and for patients who were diagnosed with new lesions of pharyngeal SCC or high-grade dysplasia (HGD) that were not detected in the endoscopic examination before treatment, ER were performed simultaneously for new lesions and the main lesions. The primary endpoint of this study was the detection rate of new lesions of pharyngeal SCC or HGD in the ESDT. RESULTS: Fifteen of the 78 patients were diagnosed as having undetected new pharyngeal lesions in the ESDT and 10 (12.8%) (95% CI 6.9-22.2%) were histopathologically confirmed to have new lesions of pharyngeal SCC or HGD. Among the 13 lesions of SCC or HGD, 8 were found by NBI observation; however, 5 were undetectable using NBI but detectable by lugol staining. All of the 13 lesions had endoscopic findings of pink color sign on lugol staining. CONCLUSIONS: Endoscopic surveillance for pharyngeal sublesions during ER for pharyngeal SCC is feasible and useful.

A simpler diagnostic algorithm of the Japan Esophageal Society classification for Barrett's esophagus-related superficial neoplasia.

BACKGROUND: We previously developed a Japan Esophageal Society Barrett's Esophagus (JES-BE) magnifying endoscopic classification for superficial BE-related neoplasms (BERN) and validated it in a nationwide multicenter study that followed a diagnostic flow chart based on mucosal and vascular patterns (MP, VP) with nine diagnostic criteria. Our present post hoc analysis aims to further simplify the diagnostic criteria for superficial BERN. METHODS: We used data from our previous study, including 10 reviewers' assessments for 156 images of high-magnifying narrow-band imaging (HM-NBI) (67 dysplastic and 89 non-dysplastic histology). We statistically analyzed the diagnostic performance of each diagnostic criterion of MP (form, size, arrangement, density, and white zone), VP (form, caliber change, location, and greenish thick vessels [GTV]), and all their combinations to achieve a simpler diagnostic algorithm to detect superficial BERN. RESULTS: Diagnostic accuracy values based on the MP of each single criterion or combined criteria showed a marked trend of being higher than those based on VP. In reviewers' assessments of visible MPs, the combination of irregularity for form, size, or white zone had the highest diagnostic performance, with a sensitivity of 87% and a specificity of 91% for dysplastic histology; in the assessments of invisible MPs, GTV had the highest diagnostic performance among the VP of each single criterion and all combinations of two or more criteria (sensitivity, 93%; specificity, 92%). CONCLUSION: The present post hoc analysis suggests the feasibility of further simplifying the diagnostic algorithm of the JES-BE classification. Further studies in a practical setting are required to validate these results.

Rio de Janeiro Global Consensus on Landmarks, Definitions, and Classifications in Barrett's Esophagus: World Endoscopy Organization Delphi Study.

BACKGROUND & AIMS: Despite the significant advances made in the diagnosis and treatment of Barrett's esophagus (BE), there is still a need for standardized definitions, appropriate recognition of endoscopic landmarks, and consistent use of classification systems. Current controversies in basic definitions of BE and the relative lack of anatomic knowledge are significant barriers to uniform documentation. We aimed to provide consensus-driven recommendations for uniform reporting and global application. METHODS: The World Endoscopy Organization Barrett's Esophagus Committee appointed leaders to develop an evidence-based Delphi study. A working group of 6 members identified and formulated 23 statements, and 30 internationally recognized experts from 18 countries participated in 3 rounds of voting. We defined consensus as agreement by ≥80% of experts for each statement and used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool to assess the quality of evidence and the strength of recommendations. RESULTS: After 3 rounds of voting, experts achieved consensus on 6 endoscopic landmarks (palisade vessels, gastroesophageal junction, squamocolumnar junction, lesion location, extraluminal compressions, and quadrant orientation), 13 definitions (BE, hiatus hernia, squamous islands, columnar islands, Barrett's endoscopic therapy, endoscopic resection, endoscopic ablation, systematic inspection, complete eradication of intestinal metaplasia, complete eradication of dysplasia, residual disease, recurrent disease, and failure of endoscopic therapy), and 4 classification systems (Prague, Los Angeles, Paris, and Barrett's International NBI Group). In round 1, 18 statements (78%) reached consensus, with 12 (67%) receiving strong agreement from more than half of the experts. In round 2, 4 of the remaining statements (80%) reached consensus, with 1 statement receiving strong agreement from 50% of the experts. In the third round, a consensus was reached on the remaining statement. CONCLUSIONS: We developed evidence-based, consensus-driven statements on endoscopic landmarks, definitions, and classifications of BE. These recommendations may facilitate global uniform reporting in BE.

Natural History of Small Gastric Subepithelial Lesions Less than 20 mm: A Multicenter Retrospective Observational Study (NUTSHELL20 Study).

BACKGROUND AND AIM: Small gastric subepithelial lesions (SELs) are sometimes encountered in daily esophagogastroduodenoscopy (EGD) practice, but whether once-annual or twice-annual endoscopy can provide sufficient follow-up remains unclear. Because follow-up based on small-SEL characteristics is important, this study clarified the natural history of gastric SELs less than 20 mm. METHODS: This retrospective multicenter observation study conducted at 24 Japanese hospitals during April 2000 to March 2020 examined small gastric SELs of ≤20 mm diameter. The primary outcome was the rate of size increase of those SELs detected using EGD, with growth times assessed irrespective of SEL pathological diagnoses. RESULTS: We examined 824 cases with tumors of 1-5 mm diameter in 298 (36.2%) cases, 6-10 mm in 344 (41.7%) cases, 11-15 mm in 112 (13.6%) cases, and 16-20 mm in 70 (8.50%) cases. An increase of small gastric SELs was observed in 70/824 patients (8.5%). The SELs larger than 6 mm increased, even after 10 years. No-change and increasing groups had no significantly different malignant findings at diagnosis. In cases of gastrointestinal stromal tumors (GISTs), internal cystic change in endoscopic ultrasound (EUS) is a risk factor for an increased tumor size. The predictive tumor growth cutoff size at initial diagnosis was 13.5 mm. CONCLUSIONS: Small gastric SELs less than 20 mm have an approximately 8.5% chance of increase. Predictive markers for GIST growth are tumor size ≥13.5 mm and internal cystic change in EUS.

Making Hematochezia of Unknown Origin Known: A Retrospective Analysis.

INTRODUCTION: Hematochezia is observed frequently in daily practice. However, natural hemostasis often prevents identification of the bleeding source during observations. This study was conducted to clarify risk factors related to rebleeding in hematochezia patients without an identified cause of bleeding. METHODS: We analyzed patients who were admitted to Dokkyo Medical University Hospital during April 1, 2009, through March 31, 2015, with the chief complaint of hematochezia. Main outcome measures included the rebleeding rate and the period until rebleeding in hematochezia patients without an identified bleeding source. RESULTS: We selected 159 patients for analyses. Rebleeding was observed in 46 (28.9%) of 159 patients. The median period until first rebleeding was 166 days (2-3,046 days). Univariate analysis indicated that risk factors for rebleeding were male gender (p = 0.029), higher age (p = 0.023), antithrombotic medicines (p = 0.047), lower hemoglobin on admission (p = 0.024), and the presence of diverticula (p = 0.002). Multivariate analysis indicated the presence of diverticula (p = 0.023) and male gender (p = 0.043) as rebleeding risk factors. DISCUSSION/CONCLUSION: In patients with hematochezia of unknown origin, risk factors for rebleeding indicated in this study, especially the presence of diverticula and male gender, should be given particular attention by physicians.

Measuring optimal ultrasound speed using endoscopic ultrasound in patients with chronic pancreatitis, including early stage.

OBJECTIVES: Ultrasound speed (USS) correction improves image quality by estimating the optimal USS correcting the deviation from a predetermined USS. This study assessed USS differences between chronic pancreatitis (CP), early CP (ECP), and normal pancreas when using endoscopic ultrasound (EUS). The usefulness of measuring optimal USS was evaluated for patients with CP, including early stage patients. METHODS: This study enrolled 116 consecutive patients for whom USS was measured using an EUS system. The USS correction principle is generation of a B-mode image by changing the USS in all ranges while correcting the delay in the received data. Final diagnoses were made according to the Japanese diagnostic criteria for CP in 2019. They were classified as CP, ECP, or normal. We compared USS applied for these three groups. RESULTS: The medians and ranges of USS values for patients in the normal, ECP, and CP groups were 1506.0 (1407-1600) m/s, 1580.0 (1520-1630) m/s, and 1574.0 (1537-1610) m/s, respectively. The USS values of the ECP and CP groups were significantly higher than those of the normal group (P < 0.001). Analyses of the receiver operating characteristic curve in the normal pancreas, ECP, and CP revealed the area as 0.957, with specificity and sensitivity of 95.9% and 87.5%, respectively, using the USS of 1535 m/s as a cut-off. CONCLUSION: Measurement of USS might be particularly useful for distinguishing between normal and ECP imaging.

A Case of Stevens-Johnson Syndrome Complicated with Multimatrix System Mesalamine in Ulcerative Colitis.

A 41-year-old man was treated with prednisolone (PSL) and multimatrix (MMX) mesalamine for remission induction therapy of ulcerative colitis. PSL was tapered due to successful remission induction treatment. During the treatment course, ocular foreign body sensation, eyelid swelling, ocular conjunctiva hyperemia, facial redness and swelling, watery nasal discharge, stomatitis, anal pain, and reddish puffiness on the bilateral dorsum of the hands appeared, and he was diagnosed with Stevens-Johnson syndrome (SJS). SJS was improved by PSL treatment and intravenous immunoglobulin. MMX mesalamine was the causative agent by drug-induced lymphocyte stimulation test. This is the first reported case of SJS with MMX mesalamine.

Evaluation of the risk of metachronous multiple squamous cell carcinoma of the head and neck after transoral surgery based on the genetic polymorphisms of alcohol dehydrogenase 1B and aldehyde dehydrogenase 2.

Patients with superficial head and neck squamous cell carcinoma (HNSCC) can be completely treated by techniques of transoral surgery (TOS). The aim of this study was to evaluate the risk of metachronous multiple HNSCC arising after TOS based on alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2). We registered patients who underwent TOS for superficial HNSCC. Buccal cell samples were obtained by using a cotton swab to examine two single nucleotide polymorphisms in ADH1B and ALDH2 genotyping. We used Cox proportional hazards models to examine the risk of metachronous HNSCC. A total of 198 patients who underwent TOS for HNSCC were evaluated. In multivariate analysis, risks for second HNSCC were ADH1B*1/*1 [hazard ratio (HR), 1.88; 95% confidence interval (CI), 1.11-3.19; P = 0.02], ALDH2*1/*2 (HR, 2.11; 95% CI, 1.00-5.16; P = 0.048) and alcohol consumption before TOS (HR, 1.17; 95% CI, 1.06-1.27; P = 0.01). The 5-year incidence rates of second primary HNSCC in the temperance group and the non-temperance group were 20.8 and 46.5%, respectively (HR, 0.54; 95% CI, 0.31-0.92; P = 0.02). Cumulative development rates of third HNSCC in the temperance group and non-temperance group at 10 years were 11.3 and 36.1%, respectively (HR, 0.19; 95% CI, 0.03-0.65; P = 0.006). ADH1B*1/*1, ALDH2*1/*2 and moderate or heavy alcohol consumption before treatment are independent risk factors of metachronous HNSCC. Since it was shown that temperance decreased the incidences of second and third metachronous HNSCC, advice to discontinue alcohol drinking is necessary.

Diagnostic yield of fourth-generation endocytoscopy for esophageal squamous lesions using a modified endocytoscopic classification.

OBJECTIVES: Endocytoscopy (EC) is an ultra-high magnification endoscopy designed to provide in vivo histologic assessment. This study aimed to evaluate the diagnostic yield of the newly developed fourth-generation EC for esophageal squamous lesions by using a modified EC classification. METHODS: A total of 2548 EC images of 57 esophageal targeted areas between June 2015 and October 2017 were retrospectively collected. Two lesions with low-quality images were excluded. Only EC images were independently reviewed by two expert and two non-expert endoscopists. The lesions were classified according to a three-tier modified EC classification. We used a multilevel logistic regression to analyze the data. RESULTS: The sensitivity and specificity of diagnosing non-squamous cell cancer (SCC) vs SCC were 82.5% and 83.0% by the experts; 90.1% and 75.0% by non-experts. The interobserver agreement among the four raters was good (kappa statistic 0.59). The diagnostic accuracy of experts and non-experts was similar (P = 0.16 for specificity and P = 0.20 for sensitivity). The sensitivity and specificity of EC for non-neoplasia vs neoplasia were 88.7% and 74.6% by experts; 90.3 and 52.1% by non-experts. The interobserver agreement among the four raters was moderate (kappa statistic 0.44). The specificity of experts was higher compared to non-experts, although the difference did not reach statistical significance (P = 0.08 for specificity and P = 0.93 for sensitivity). CONCLUSIONS: Fourth-generation EC offers acceptable diagnostic accuracy and reliability in both experts and non-experts, especially when diagnosing SCC lesions.

Diagnostic utility of a novel magnifying endoscopic classification system for superficial Barrett's esophagus-related neoplasms: a nationwide multicenter study.

BACKGROUND: Currently, no classification system using magnification endoscopy for the diagnosis of superficial Barrett's esophagus (BE)-related neoplasia has been widely accepted. This nationwide multicenter study aimed to validate the diagnostic accuracy and reproducibility of the magnification endoscopy classification system, including the diagnostic flowchart developed by the Japan Esophageal Society-Barrett's esophagus working group (JES-BE) for superficial Barrett's esophagus-related neoplasms. METHODS: The JES-BE acquired high-definition magnification narrow-band imaging (HM-NBI) images of non-dysplastic and dysplastic BE from 10 domestic institutions. A total of 186 high-quality HM-NBI images were selected. Thirty images were used for the training phase and 156 for the validation (test) phase. We invited five non-experts and five expert reviewers. In the training phase, the reviewers discussed how to correctly predict the histology based on the JES-BE criteria. In the validation phase, they evaluated whether the criteria accurately predicted the histology results according to the diagnostic flowchart. The validation phase was performed immediately after the training phase and at 6 weeks thereafter. RESULTS: The sensitivity and specificity for all reviewers were 87% and 97%, respectively. Overall accuracy, positive predictive value, and negative predictive value were 91%, 98%, and 83%, respectively. The overall strength of inter-observer and intra-observer agreements for dysplastic histology prediction was κ = 0.77 and κ = 0.83, respectively. No significant difference in diagnostic accuracy and reproducibility between experts and non-experts was found. CONCLUSION: The JES-BE classification system, including the diagnostic flowchart for predicting dysplastic BE, is acceptable and reliable, regardless of the clinician's experience level.

Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer.

The Japan Gastroenterological Endoscopy Society has developed endoscopic submucosal dissection/endoscopic mucosal resection guidelines. These guidelines present recommendations in response to 18 clinical questions concerning the preoperative diagnosis, indications, resection methods, curability assessment, and surveillance of patients undergoing endoscopic resection for esophageal cancers based on a systematic review of the scientific literature.

A Case of Lung Abscess Caused by Double Immunosuppressive Therapy to Treat Ulcerative Colitis.

A 25-year-old man was admitted to our institution for remission induction therapy to treat a 12-year condition of ulcerative colitis (UC). Previously, he was treated with drugs, such as mesalamine, immunomodulators, prednisolone (PSL), and anti-TNFα anti-body, but remission was not maintained. Therefore, we started remission induction therapy with 20 mg/day of tofacitinib (TOF) to inhibit the action of Janus kinase. On the 29th day after TOF administration, he developed a lung abscess with high fever. A chronic bulla was already present in his lung; therefore, the lung abscess was likely formed due to a combination of the bulla being present and the pharmacological effects of TOF. Our report is significant as it highlights the compounding association between TOF and PSL therapy and bulla presence with the rare adverse effect of developing an abscess.

An Asian consensus on standards of diagnostic upper endoscopy for neoplasia.

BACKGROUND: This is a consensus developed by a group of expert endoscopists aiming to standardise the preparation, process and endoscopic procedural steps for diagnosis of early upper gastrointestinal (GI) cancers. METHOD: The Delphi method was used to develop consensus statements through identification of clinical questions on diagnostic endoscopy. Three consensus meetings were conducted to consolidate the statements and voting. We conducted a systematic literature search on evidence for each statement. The statements were presented in the second consensus meeting and revised according to comments. The final voting was conducted at the third consensus meeting on the level of evidence and agreement. RESULTS: Risk stratification should be conducted before endoscopy and high risk endoscopic findings should raise an index of suspicion. The presence of premalignant mucosal changes should be documented and use of sedation is recommended to enhance detection of superficial upper GI neoplasms. The use of antispasmodics and mucolytics enhanced visualisation of the upper GI tract, and systematic endoscopic mapping should be conducted to improve detection. Sufficient examination time and structured training on diagnosis improves detection. Image enhanced endoscopy in addition to white light imaging improves detection of superficial upper GI cancer. Magnifying endoscopy with narrow-band imaging is recommended for characterisation of upper GI superficial neoplasms. Endoscopic characterisation can avoid unnecessary biopsy. CONCLUSION: This consensus provides guidance for the performance of endoscopic diagnosis and characterisation for early gastric and oesophageal neoplasia based on the evidence. This will enhance the quality of endoscopic diagnosis and improve detection of early upper GI cancers.

Long-term outcomes of endoscopic resection and metachronous cancer after endoscopic resection for adenocarcinoma of the esophagogastric junction in Japan.

BACKGROUND AND AIMS: Endoscopic resection (ER) of superficial adenocarcinoma of the esophagogastric junction (AEGJ) has been shown to be safe and effective. However, long-term data in patients undergoing ER for superficial AEGJ in Japan are still limited. The aim of this study was to determine the effect of ER on survival and occurrence of metachronous cancer of patients with superficial AEGJ. METHODS: A retrospective analysis of patients who underwent or endoscopic submucosal dissection (ESD) for superficial AEJG in 13 centers in Japan was performed. The patients were classified as either low risk or high risk for lymph node metastasis based on histologic features. The incidence of metachronous AEGJ as well as overall survival and disease-specific survival rates were calculated. RESULTS: A total of 372 patients who underwent ER were included, in which 277 patients were low risk and 95 high risk for lymph node metastasis. Five-year cumulative incidences of local recurrence were 13% and .5% in the EMR and ESD groups, respectively (P < .01). Six AEGJ deaths were observed in the high-risk group and none in the low-risk group. The 5-year overall survival rates in the low-risk group without additional treatment, the high-risk group with additional treatment, and the high-risk group without additional treatment were 93.9%, 77.7%, and 81.6%, respectively. The 5-year disease-specific survival rates in the 3 groups were 100%, 94.4%, and 92.8%, respectively. The 5-year cumulative incidence of metachronous AEGJ in 316 patients without additional treatment was 1.1%. CONCLUSIONS: Favorable long-term outcomes with ER were observed in patients with AEGJ who met the low-risk criteria for lymph node metastasis. ESD was a reasonable and effective treatment in Japanese patients.

Peroral endoscopic myotomy and fundoplication: a novel NOTES procedure.

BACKGROUND: Peroral endoscopic myotomy (POEM) has become the minimally invasive endoscopic treatment for achalasia; however, gastroesophageal reflux (GER) post-POEM has been reported. A pilot study was conducted in which an endoscopic fundoplication was added to the standard POEM (POEM + F) procedure to overcome this issue. We report the technical details of POEM + F and short-term safety results. METHODS: POEM + F was performed in 21 patients. After completing myotomy, the endoscope was advanced from the submucosal tunnel into the peritoneal cavity. A partial mechanical barrier was created by retracting the anterior gastric wall at the esophagogastric junction with the use of endoclips and an endoloop. RESULTS: POEM + F was technically feasible in all cases and created a visually recognizable fundoplication. The clinical course after POEM + F was uneventful. No immediate or delayed complications occurred. CONCLUSION: POEM + F may help mitigate the post-POEM incidence of GER and serve as a minimally invasive endoscopic alternative to a laparoscopic Heller-Dor procedure. This is the largest case series of peroral natural orifice transluminal endoscopic surgery without laparoscopic assistance in the human foregut.

Endoscopic treatment of Barrett's esophagus: What can we learn from the Western perspective?

The incidence of Barrett's esophagus (BE)-related neoplasia in Western countries has increased in the past several decades and, even in Eastern countries, it appears to be increasing. Endoscopic therapies are the first-line treatment for BE-related neoplasia; however, there is still no standardized treatment strategy. Most of the data have been published from Western countries where the ultimate goal of treatment is complete eradication of BE mucosa removing subtle synchronous lesions and preventing metachronous neoplasia. A multimodality approach that combines endoscopic resection and radiofrequency ablation (RFA) has been widely accepted in the West. In contrast, the lack of access to RFA treatment in the East has meant that endoscopic resection is the only feasible option. There is a wide divergence in treatment strategies for BE-related neoplasia between the East and the West. It is very important to consider these basic differences in the context of the currently available evidence to date. Therefore, the purpose of this article is to review the recent literature and to provide an overview of the endoscopic treatment options for BE.

Newly developed magnifying endoscopic classification of the Japan Esophageal Society to identify superficial Barrett's esophagus-related neoplasms.

AIM AND METHODS: The Japan Esophageal Society created a working committee group consisting of 11 expert endoscopists and 2 pathologists with expertise in Barrett's esophagus (BE) and esophageal adenocarcinoma. The group developed a consensus-based classification for the diagnosis of superficial BE-related neoplasms using magnifying endoscopy. RESULTS: The classification has three characteristics: simplified, an easily understood classification by incorporating the diagnostic criteria for the early gastric cancer, including the white zone and demarcation line, and the presence of a modified flat pattern corresponding to non-dysplastic histology by adding novel diagnostic criteria. Magnifying endoscopic findings are composed of mucosal and vascular patterns, and are initially classified as "visible" or "invisible." Morphologic features were evaluated for "visible" patterns, and were subsequently rated as "regular" or "irregular," and the histology, non-dysplastic or dysplastic, was predicted. CONCLUSION: We introduce the process and outline of the magnifying endoscopic classification.

Development and Validation of a Classification System to Identify High-Grade Dysplasia and Esophageal Adenocarcinoma in Barrett's Esophagus Using Narrow-Band Imaging.

BACKGROUND & AIMS: Although several classification systems have been proposed for characterization of Barrett's esophagus (BE) surface patterns based on narrow-band imaging (NBI), none have been widely accepted. The Barrett's International NBI Group (BING) aimed to develop and validate an NBI classification system for identification of dysplasia and cancer in patients with BE. METHODS: The BING working group, composed of NBI experts from the United States, Europe, and Japan, met to develop a validated, consensus-driven NBI classification system for identifying dysplasia and cancer in BE. The group reviewed 60 NBI images of nondysplastic BE, high-grade dysplasia, and esophageal adenocarcinoma to characterize mucosal and vascular patterns visible by NBI; these features were used to develop the BING criteria. We then recruited adult patients undergoing surveillance or endoscopic treatment for BE at 4 institutions in the United States and Europe, obtaining high-quality NBI images and performing histologic analysis of biopsies. Experts individually reviewed 50 NBI images to validate the BING criteria, and then evaluated 120 additional NBI images (not previously viewed) to determine whether the criteria accurately predicted the histology results. RESULTS: The BING criteria identified patients with dysplasia with 85% overall accuracy, 80% sensitivity, 88% specificity, 81% positive predictive value, and 88% negative predictive value. When dysplasia was identified with a high level of confidence, these values were 92%, 91%, 93%, 89%, and 95%, respectively. The overall strength of inter-observer agreement was substantial (κ = 0.681). CONCLUSIONS: The BING working group developed a simple, internally validated system to identify dysplasia and EAC in patients with BE based on NBI results. When images are assessed with a high degree of confidence, the system can classify BE with >90% accuracy and a high level of inter-observer agreement.