MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs.

BACKGROUND: Endoscopic submucosal dissection (ESD) is the current standard treatment for early-stage esophageal neoplasms. However, the postoperative esophageal stricture after extensive mucosal dissection remains a severe challenge with limited effective treatments available. In this study, we introduced a chitosan/gelatin (ChGel) sponge encapsulating the adipose mesenchymal stem cells (ADMSCs)-derived exosomes (ChGelMSC-Exo) for the prevention of esophageal stenosis after ESD in a porcine model. RESULTS: Pigs were randomly assigned into (1) ChGelMSC-Exo treatment group, (2) ChGelPBS group, and (3) the controls. Exosome treatments were applied immediately on the day after ESD as well as on day 7. Exosome components crucial for wound healing were investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and small RNA sequencing. ChGelMSC-Exo treatment significantly reduced mucosal contraction on day 21, with less fiber accumulation and inflammatory infiltration, and enhanced angiogenesis when compared with the control and ChGelPBS groups. The anti-fibrotic effects following MSC-Exo treatment were further found to be associated with the anti-inflammatory M2 polarization of the resident macrophages, especially within the M2b subset characterized by the reduced TGFß1 secretion, which sufficiently inhibited inflammation and prevented the activation of myofibroblast with less collagen production at the early stage after ESD. Moreover, the abundant expression of exosomal MFGE8 was identified to be involved in the transition of the M2b-macrophage subset through the activation of MFGE8/STAT3/Arg1 axis. CONCLUSIONS: Our study demonstrates that exosomal MFGE8 significantly promotes the polarization of the M2b-macrophage subset, consequently reducing collagen deposition. These findings suggest a promising potential for MSC-Exo therapy in preventing the development of esophageal stricture after near-circumferential ESD.

Rapid Endoscopic Diagnosis of Benign Ulcerative Colorectal Diseases With an Artificial Intelligence Contextual Framework.

BACKGROUND & AIMS: Benign ulcerative colorectal diseases (UCDs) such as ulcerative colitis, Crohn's disease, ischemic colitis, and intestinal tuberculosis share similar phenotypes with different etiologies and treatment strategies. To accurately diagnose closely related diseases like UCDs, we hypothesize that contextual learning is critical in enhancing the ability of the artificial intelligence models to differentiate the subtle differences in lesions amidst the vastly divergent spatial contexts. METHODS: White-light colonoscopy datasets of patients with confirmed UCDs and healthy controls were retrospectively collected. We developed a Multiclass Contextual Classification (MCC) model that can differentiate among the mentioned UCDs and healthy controls by incorporating the tissue object contexts surrounding the individual lesion region in a scene and spatial information from other endoscopic frames (video-level) into a unified framework. Internal and external datasets were used to validate the model's performance. RESULTS: Training datasets included 762 patients, and the internal and external testing cohorts included 257 patients and 293 patients, respectively. Our MCC model provided a rapid reference diagnosis on internal test sets with a high averaged area under the receiver operating characteristic curve (image-level: 0.950 and video-level: 0.973) and balanced accuracy (image-level: 76.1% and video-level: 80.8%), which was superior to junior endoscopists (accuracy: 71.8%, P < .0001) and similar to experts (accuracy: 79.7%, P = .732). The MCC model achieved an area under the receiver operating characteristic curve of 0.988 and balanced accuracy of 85.8% using external testing datasets. CONCLUSIONS: These results enable this model to fit in the routine endoscopic workflow, and the contextual framework to be adopted for diagnosing other closely related diseases.

Curative endoscopic full-thickness resection of a fundic gland-type gastric adenocarcinoma.

Video 1Summary of the presented case. Macroscopic images of the lesion in a white-light endoscopy and narrow-band imaging and in an underwater view followed by scenes from the resection with circular marking, submucosal injection, circumferential incision, and submucosal dissection using a multi-bend double-channel endoscope, as well as clip traction, controlled full-thickness dissection, and inspection of the defect plus closure of the defect with the clip-and-loop technique.

Endoscopic ultrasonography-guided gastroenterostomy versus uncovered duodenal metal stenting for unresectable malignant gastric outlet obstruction (DRA-GOO): a multicentre randomised controlled trial.

BACKGROUND: Endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) is a novel endoscopic method to palliate malignant gastric outlet obstruction. We aimed to assess whether the use of EUS-GE with a double balloon occluder for malignant gastric outlet obstruction could reduce the need for reintervention within 6 months compared with conventional duodenal stenting. METHODS: The was an international, multicentre, randomised, controlled trial conducted at seven sites in Hong Kong, Belgium, Brazil, India, Italy, and Spain. Consecutive patients (aged ≥18 years) with malignant gastric outlet obstruction due to unresectable primary gastroduodenal or pancreatobiliary malignancies, a gastric outlet obstruction score (GOOS) of 0 (indicating an inability in intake food or liquids orally), and an Eastern Cooperative Oncology Group performance status score of 3 or lower were included and randomly allocated (1:1) to receive either EUS-GE or duodenal stenting. The primary outcome was the 6-month reintervention rate, defined as the percentage of patients requiring additional endoscopic intervention due to stent dysfunction (ie, restenosis of the stent due to tumour ingrowth, tumour overgrowth, or food residue; stent migration; or stent fracture) within 6 months, analysed in the intention-to-treat population. Prespecified secondary outcomes were technical success (successful placement of a stent), clinical success (1-point improvement in gastric outlet obstruction score [GOOS] within 3 days), adverse events within 30 days, death within 30 days, duration of stent patency, GOOS at 1 month, and quality-of-life scores. This study is registered with ClinicalTrials.gov (NCT03823690) and is completed. FINDINGS: Between Dec 1, 2020, and Feb 28, 2022, 185 patients were screened and 97 (46 men and 51 women) were recruited and randomly allocated (48 to the EUS-GE group and 49 to the duodenal stent group). Mean age was 69·5 years (SD 12·6) in the EUS-GE group and 64·8 years (13·0) in the duodenal stent group. All randomly allocated patients completed follow-up and were analysed. Reintervention within 6 months was required in two (4%) patients in the EUS-GE group and 14 (29%) in the duodenal stent group [p=0·0020; risk ratio 0·15 [95% CI 0·04-0·61]). Stent patency was longer in the EUS-GE group (median not reached in either group; HR 0·13 [95% CI 0·08-0·22], log-rank p<0·0001). 1-month GOOS was significantly better in the EUS-GE group (mean 2·41 [SD 0·7]) than the duodenal stent group (1·91 [0·9], p=0·012). There were no statistically significant differences between the EUS-GE and duodenal stent groups in death within 30 days (ten [21%] vs six [12%] patients, respectively, p=0·286), technical success, clinical success, or quality-of-life scores at 1 month. Adverse events occurred 11 (23%) patients in the EUS-GE group and 12 (24%) in the duodenal stent group within 30 days (p=1·00); three cases of pneumonia (two in the EUS-GE group and one in the duodenal stent group) were considered to be procedure related. INTERPRETATION: In patients with malignant gastric outlet obstruction, EUS-GE can reduce the frequency of reintervention, improve stent patency, and result in better patient-reported eating habits compared with duodenal stenting, and the procedure should be used preferentially over duodenal stenting when expertise and required devices are available. FUNDING: Research Grants Council (Hong Kong Special Administrative Region, China) and Sociedad Española de Endoscopia Digestiva.

Partially covered versus uncovered pyloro-duodenal stents for unresectable malignant gastric outlet obstruction: Randomized controlled study.

OBJECTIVES: The aim of the current study was to compare the efficacy of partially covered duodenal stent (PCDS) vs. uncovered duodenal stent (UCDS) in patients suffering from unresectable primary malignant gastric outlet obstruction (GOO). METHODS: This was a prospective international randomized controlled study conducted in 10 high-volume institutions. Consecutive patients suffering from malignant GOO were recruited. The primary outcome measurement was the reintervention rate. Secondary outcomes included technical and clinical success, 30-day adverse events, 30-day mortality, causes of stent dysfunction, and the duration of stent patency. RESULTS: Between March 2017 and October 2020, 115 patients (59 PCDS, 56 UCDS) were recruited. The 1-year reintervention was not significantly different (PCDS vs. UDCS = 12/59, 20.3% vs. 14/56, 25%, P = 0.84). There was a trend to fewer patients with tumor ingrowth in the PCDS group (6/59 [10.2%]) vs. 13/56 [23.2%], P = 0.07). There were no significant differences in the technical success (100% vs. 100%, P = 1), clinical success (91.5% vs. 98.2%, P = 0.21), procedural time (21.5 [interquartile range [IQR] 17-30] vs. 20.0 [IQR 15-34.75], P = 0.62), hospital stay (4 [IQR 3-12] vs. 5 [IQR 3-8] days, P = 0.81), 30-day adverse events (18.6% vs. 14.3%, P = 0.62), or 30-day mortality (6.8% vs. 5.2%, P = 1.00). CONCLUSION: The use of PCDS was associated with a lower risk of tumor ingrowth but did not improve on reintervention rates or stent patency. Both kinds of stents could be used in this group of patients.

Effect of Real-Time Computer-Aided Polyp Detection System (ENDO-AID) on Adenoma Detection in Endoscopists-in-Training: A Randomized Trial.

BACKGROUND: The effect of computer-aided polyp detection (CADe) on adenoma detection rate (ADR) among endoscopists-in-training remains unknown. METHODS: We performed a single-blind, parallel-group, randomized controlled trial in Hong Kong between April 2021 and July 2022 (NCT04838951). Eligible subjects undergoing screening/surveillance/diagnostic colonoscopies were randomized 1:1 to receive colonoscopies with CADe (ENDO-AID[OIP-1]) or not (control) during withdrawal. Procedures were performed by endoscopists-in-training with <500 procedures and <3 years' experience. Randomization was stratified by patient age, sex, and endoscopist experience (beginner vs intermediate level, <200 vs 200-500 procedures). Image enhancement and distal attachment devices were disallowed. Subjects with incomplete colonoscopies or inadequate bowel preparation were excluded. Treatment allocation was blinded to outcome assessors. The primary outcome was ADR. Secondary outcomes were ADR for different adenoma sizes and locations, mean number of adenomas, and non-neoplastic resection rate. RESULTS: A total of 386 and 380 subjects were randomized to CADe and control groups, respectively. The overall ADR was significantly higher in the CADe group than in the control group (57.5% vs 44.5%; adjusted relative risk, 1.41; 95% CI, 1.17-1.72; P < .001). The ADRs for <5 mm (40.4% vs 25.0%) and 5- to 10-mm adenomas (36.8% vs 29.2%) were higher in the CADe group. The ADRs were higher in the CADe group in both the right colon (42.0% vs 30.8%) and left colon (34.5% vs 27.6%), but there was no significant difference in advanced ADR. The ADRs were higher in the CADe group among beginner (60.0% vs 41.9%) and intermediate-level (56.5% vs 45.5%) endoscopists. Mean number of adenomas (1.48 vs 0.86) and non-neoplastic resection rate (52.1% vs 35.0%) were higher in the CADe group. CONCLUSIONS: Among endoscopists-in-training, the use of CADe during colonoscopies was associated with increased overall ADR. (ClinicalTrials.gov, Number: NCT04838951).

Intelligent surgical workflow recognition for endoscopic submucosal dissection with real-time animal study.

Recent advancements in artificial intelligence have witnessed human-level performance; however, AI-enabled cognitive assistance for therapeutic procedures has not been fully explored nor pre-clinically validated. Here we propose AI-Endo, an intelligent surgical workflow recognition suit, for endoscopic submucosal dissection (ESD). Our AI-Endo is trained on high-quality ESD cases from an expert endoscopist, covering a decade time expansion and consisting of 201,026 labeled frames. The learned model demonstrates outstanding performance on validation data, including cases from relatively junior endoscopists with various skill levels, procedures conducted with different endoscopy systems and therapeutic skills, and cohorts from international multi-centers. Furthermore, we integrate our AI-Endo with the Olympus endoscopic system and validate the AI-enabled cognitive assistance system with animal studies in live ESD training sessions. Dedicated data analysis from surgical phase recognition results is summarized in an automatically generated report for skill assessment.

The effect of Andrographis paniculata water extract on palliative management of metastatic esophageal squamous cell carcinoma-A phase II clinical trial.

Patients with metastatic esophageal squamous cell carcinoma (ESCC) have a grave prognosis with limited life expectancy. Here, a phase II clinical trial was conducted to investigate the effect of Andrographis paniculata (AP) on the palliative care of patients with metastatic ESCC. Patients with metastatic or locally advanced ESCC deemed unfit for surgery, and who have already completed palliative chemotherapy or chemoradiotherapy or are not fit for these treatments, were recruited. These patients were prescribed AP concentrated granules for 4 months. They also received clinical and quality of life assessments for clinical response, as well as positron emission tomography-computed tomography at 3 and 6 months after AP treatment for the assessment of tumor volume. Furthermore, the change in gut microbiota composition after AP treatment was studied. From the results, among the 30 recruited patients, 10 completed the entire course of AP treatment, while 20 received partial AP treatment. Patients who completed the AP treatment achieved significantly longer overall survival periods with the maintenance of the quality of life during the survival period when compared to those who could not complete AP treatment. The treatment effect of AP also contributed to the shift of the overall structure of gut microbiota for ESCC patients towards those of healthy individuals. The significance of this study is the establishment of AP as a safe and effective palliative treatment for patients with squamous cell carcinoma of the esophagus. To the best of our knowledge, this is the first clinical trial of AP water extract in esophageal cancer patients demonstrating its new medicinal use.

Endoscopic full-thickness resection (EFTR) compared to submucosal tunnel endoscopic resection (STER) for treatment of gastric gastrointestinal stromal tumors.

Background and study aims Submucosal tunnel endoscopic resection (STER) is being increasingly performed for treatment of gastric gastrointestinal stromal tumor (GIST), while STER has been limited by close dissection within tunnel and risking breach of tumor capsule. Endoscopic full-thickness resection (EFTR) allows resection of GIST with margins to prevent recurrence. This study aimed to compare EFTR against STER for treatment of gastric GIST. Patients and methods We retrospectively reviewed clinical outcomes of patients with gastric GIST who received either STER or EFTR. Patients with gastric GISTs < than 4 cm were included. Clinical outcomes including baseline demographics, perioperative and oncological outcomes were compared between the two groups. Results From 2013 to 2019, 46 patients with gastric GISTs were treated with endoscopic resection, 26 received EFTR and 20 received STER. Most of the GISTs were in the proximal stomach. There was no difference in operative time (94.9 vs 84.9 mins; P  = 0.401), while endoscopic suturing was applied more for closure after EFTR ( P  < 0.0001). Patients after STER had earlier resumption of diet and shorter hospital stay while there was no difference in adverse event rate between two groups. The en-bloc resection rate for EFTR was significantly higher than for STER (100 % vs 80 %; P  = 0.029), while there was no difference in the local recurrence. Conclusions This study demonstrated that although patients who received EFTR had longer hospital stays and slower resumption of diet compared to those who underwent STER, EFTR achieved a significantly higher rate of en-bloc resection compared to STER for treatment of gastric GIST.

Convergent dysbiosis of upper aerodigestive microbiota between patients with esophageal and oral cavity squamous cell carcinoma.

The bidirectional association between primary esophageal squamous cell carcinoma (ESCC) and oral cavity squamous cell carcinoma (OSCC) suggests common risk factors and oncogenic molecular processes but it is unclear whether these two cancers display similar patterns of dysbiosis in their upper aerodigestive microbiota (UADM). We conducted a case-control study to characterize the microbial communities in esophageal lavage samples from 49 ESCC patients and oral rinse samples from 91 OSCC patients using 16S rRNA V3-V4 amplicon sequencing. Compared with their respective non-SCC controls from the same anatomical sites, 32 and 45 discriminative bacterial genera were detected in ESCC and OSCC patients, respectively. Interestingly, 20 of them were commonly enriched or depleted in both types of cancer, suggesting a convergent niche adaptation of upper aerodigestive SCC-associated bacteria that may play important roles in the pathogenesis of malignancies. Notably, Fusobacterium, Selenomonas, Peptoanaerobacter and Peptostreptococcus were enriched in both ESCC and OSCC, whereas Streptococcus and Granulicatelia were commonly depleted. We further identified Fusobacterium nucleatum as the most abundant species enriched in the upper aerodigestive SCC microenvironment, and the higher relative abundances of Selenomonas danae and Treponema maroon were positively correlated with smoking. In addition, predicted functional analysis revealed several depleted (eg, lipoic acid and pyruvate metabolism) and enriched (eg, RNA polymerase and nucleotide excision repair) pathways common to both cancers. Our findings reveal a convergent dysbiosis in the UADM between patients with ESCC and OSCC, suggesting a shared niche adaptation of host-microbiota interactions in the pathogenesis of upper aerodigestive tract malignancies.

Pure endoscopic resection versus laparoscopic assisted procedure for upper gastrointestinal stromal tumors: Perspective from a surgical endoscopist.

Management of upper gastrointestinal (UGI) tract gastrointestinal stromal tumor (GIST) has evolved significantly over the past two decades. For GIST size smaller than 5 cm, laparoscopic resection has become the current standard. To avoid postoperative gastric deformity and preserve gastric function, laparoscopic endoscopic cooperative surgery (LECS) was developed and various modifications have been reported and utilized successfully. Pure endoscopic resection techniques have also been reported at a similar period of time, which further push the boundary of incisionless surgery in managing these lesions. Both tunneling and nontunneling exposed type endoscopic full thickness resection are well described procedures for resection of small UGI GIST. In this review, a summary of these procedures is provided, and the pros and cons of each technique from the perspective of a surgical endoscopist are discussed in detail. LECS and endoscopic resection are complementary to each other. The choice of technique should be tailored to the location, morphology, and size of the target lesions, taking into account the experience of the laparoscopic surgeons and endoscopists.

Use of over-the-scope clip (OTSC) versus standard therapy for the prevention of rebleeding in large peptic ulcers (size ≥1.5 cm): an open-labelled, multicentre international randomised controlled trial.

INTRODUCTION: Over-the-scope clip (OTSC) has been used recently for primary haemostasis of peptic ulcers. This study aimed to compare the efficacy of OTSC to standard endoscopic therapy in primary treatment of patients with peptic ulcer bleeding that are of size ≥1.5 cm. The target population accounts for only 2.5% of all upper GI bleeders. METHODS: This was a multicentre international randomised controlled trial from July 2017 to October 2020. All patients with Forest IIa or above peptic ulcers of ≥1.5 cm were included. Primary outcome was 30-day clinical rebleeding. Secondary endpoints include 3-day all-cause mortality, transfusion requirement, hospital stay, technical and clinical success, and further interventions. 100 patients are needed to yield a power of 80% to detect a difference of -0.15 at the 0.05 significance level (alpha) using a two-sided Z-test (pooled). RESULTS: 100 patients were recruited. Success in achieving primary haemostasis was achieved in 46/50 (92%) and 48/50 (96%) in the OTSC and conventional arm, respectively. Among patients who had success in primary haemostasis, 2/46 (4.35%) patients in the OTSC arm and 9/48 (18.75%) patients in the conventional arm developed 30-day rebleeding (p=0.03). However, in an intention-to-treat analysis, there was no difference in rebleeding within 30 days (5/50 (10%) OTSC vs 9/50 (18%) standard, p=0.23) or all-cause mortality (2/50 (4%) OTSC vs 4/50 (8%) standard, p=0.68; OR=2.09, 95% CI 0.37 to 11.95). There was also no difference in transfusion requirement, hospital stay, intensive care unit admission and further interventions. CONCLUSION: The routine use of OTSC as primary haemostasis in large bleeding peptic ulcers was not associated with a significant decrease in 30-day rebleeding. TRIAL REGISTRATION NUMBER: NCT03160911.

Droplet nuclei are generated during colonoscopy and are decreased by the use of carbon dioxide and water immersion technique.

OBJECTIVES: The COVID-19 pandemic has raised concerns on whether colonoscopies (CS) carry a transmission risk. The aim was to determine whether CS are aerosol-generating procedures. METHODS: This was a prospective observational trial including all patients undergoing CS at the Prince of Wales Hospital from 1 June to 31 July 2020. Three particle counters were placed 10 cm from each patient's anus and near the mouth of endoscopists and nurses. The particle counter recorded the number of particles of size 0.3, 0.5, 0.7, 1, 5, and 10 µm. Patient demographics, seniority of endoscopists, use of CO2 and water immersion technique, and air particle count (particles/cubic foot, dCF) were recorded. Multilevel modeling was used to test all the hypotheses with a post-hoc analysis. RESULTS: A total of 117 patients were recruited. During CS, the level of 5 µm and 10 µm were significantly higher than the baseline period (P = 0.002). Procedures performed by trainees had a higher level of aerosols when compared to specialists (0.3 µm, P < 0.001; 0.5 µm and 0.7 µm, P < 0.001). The use of CO2 and water immersion techniques had significantly lower aerosols generated when compared to air (CO2 : 0.3, 0.5, and 0.7 µm: P < 0.001; water immersion: 0.3 µm: P = 0.048; 0.7 µm: P = 0.03). There were no significant increases in any particle sizes during the procedure at the endoscopists' and nurses' mouth. However, 8/117 (6.83%) particle count tracings showed a simultaneous surge of all particle sizes at the patient's anus and endoscopists' and nurses' level during rectal extubation. CONCLUSION: Colonoscopy generates droplet nuclei especially during rectal extubation. The use of CO2 and water immersion techniques may mitigate these risks.

Endoscopic ultrasound-guided balloon-occluded gastrojejunostomy bypass, duodenal stent or laparoscopic gastrojejunostomy for unresectable malignant gastric outlet obstruction.

OBJECTIVES: Malignant gastric outlet obstruction (GOO) can be relieved by either laparoscopic gastrojejunostomy (LGJ), endoscopic stenting (SEMS) or endoscopic ultrasound-guided gastrojejunostomy (endoscopic ultrasound-guided balloon-occluded gastrojejunostomy bypass; EPASS). This study aimed to compare the outcomes of the three treatment methods. METHODS: This was a retrospective study of patients who suffered from malignant GOO between January 2012 to November 2020 that received either EPASS, LGJ or SEMS. The outcomes included the technical and clinical success, 30-day adverse events and mortality, pre and post stenting GOO scores (GOOSs), stent patency and causes of stent dysfunction. RESULTS: One hundred and fourteen patients were included (30 EPASS, 35 LGJ, 49 SEMS). The technical success of EPASS, LGJ and SEMS were 93.3%, 100%, 100% (P = 0.058) and clinical success rates were 93.3%, 80%, 87.8% (P = 0.276), respectively. Procedural time was longest for the LGJ group (P < 0.001). The EPASS group had the shortest hospital stay (EPASS 1.5 [1-17], LGJ 7 [2-44], SEMS 5 [2-46] days, P < 0.001). EPASS group also had the lowest rates of recurrent obstruction (EPASS 3.3%, LGJ 17.1%, SEMS 36.7%, P = 0.002) and re-intervention (EPASS 3.3%, LGJ 17.1%, SEMS 26.5%, P = 0.031). The 1-month GOOS was highest in the EPASS group (EPASS 3 [1-3], LGJ 3 [0-3], SEMS 2 [0-3], P = 0.028). CONCLUSION: Endoscopic ultrasound-guided gastrojejunostomy was associated with better clinical outcomes then the other two procedures. The procedure may be the best option provided that the expertise is available.

Telementoring for endoscopic submucosal dissection in vivo training.

The provision of endoscopic training was significantly disrupted during the coronavirus disease (COVID-19) pandemic. It is difficult to provide training on endoscopic submucosal dissection (ESD) due to the complexity of the procedure and the shortage of local trainers. We have designed and conducted a simulation training course with telementoring, incorporating the concept of rapid cycle deliberate practice (RCDP). After a short tutorial on basic setup and maneuvering, the participants undergo 2 h of training on a live anesthetized pig to acquire the necessary skills for ESD. Two overseas experts were involved virtually in real time as telementors. A video camera was set up at each station, and both external and endoscopic views were transmitted live between the animal laboratory and telementors via the Zoom application. The overseas experts actively engaged in the simulation by giving live feedback and instructions to participants using visual aids supported by the meeting application. The training model utilized the concept of RCDP, where repeated immediate feedback and discussion would be carried out to enhance the efficiency of learning. Eighteen trainees were invited to participate in the course, six of them instructed by overseas telementors. Four ESD procedures were performed by participants under telementoring and achieved 100% en bloc resection without perforation. The times required for each ESD were similar with telementoring than that of on-site mentors. The establishment of telementoring has enabled knowledge and skill transfer of complex endoscopic procedures of ESD. With the limitations of international travel, this could be an alternative model allowing remote training, particularly when local experts are not readily available.

Alterations in gut microbiota of esophageal squamous cell carcinoma patients.

BACKGROUND AND AIM: Esophageal squamous cell carcinoma (ESCC) is the most common histological subtype of esophageal cancer worldwide. Patients with ESCC display an altered esophageal microbiota compared with healthy individuals; however, little is known about the gut microbiota in ESCC. METHODS: Here, we characterized the fecal microbiota of 15 ESCC patients and 16 healthy control subjects using 16S rRNA gene sequencing. RESULTS: After controlling for potential confounders, significant alterations in both taxonomic and functional composition of the gut microbiota in ESCC patients were observed. By contrast, alpha diversity of the gut microbiota did not significantly differ between the cases and controls. We observed an enrichment of potentially pro-inflammatory and/or carcinogenic bacteria, such as Butyricimonas, Veillonella, and Streptococcus, and a depletion of butyrate-producing and/or potentially anti-inflammatory bacteria, such as Butyricicoccus, Lachnospiraceae NK4A136 group, and Eubacterium eligens group, in the gut microbiota of ESCC patients. The log-ratios of Streptococcus to Butyricicoccus and Streptococcus to Lachnospiraceae NK4A136 group of the gut microbiota were identified as potential diagnostic biomarkers for ESCC, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.863 (95% confidence interval: 0.707-1.000) and 0.825 (0.673-0.977), respectively. The diagnostic performance of both microbial biomarkers was validated in another ESCC cohort. CONCLUSIONS: This pilot study has revealed an altered gut microbiota in ESCC patients and has paved the way for large-scale prospective cohort studies to examine the causative relationship between ESCC and gut dysbiosis.

Performance of screening tests for esophageal squamous cell carcinoma: a systematic review and meta-analysis.

BACKGROUND AND AIMS: This systematic review and meta-analysis aims to compare the pooled diagnostic accuracy of the currently available esophageal squamous cell carcinoma (ESCC) screening tests. METHODS: A comprehensive literature search of Embase and Medline (up to October 31, 2020) was performed to identify eligible studies. We pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for ESCC screening tools using a bivariate random-effects model. The summary receiver operating characteristic curves with area under the curve (AUC) were plotted for each screening test. RESULTS: We included 161 studies conducted in 81 research articles involving 32,209 subjects. The pooled sensitivity, specificity, and AUC of the major screening tools were respectively as follows: endoscopy (peroral endoscopy): .94 (95% confidence interval [CI], .87-.97), .92 (95% CI, .87-.95), and .97 (95% CI, .96-.99); endoscopy (transnasal endoscopy): .85 (95% CI, .70-.93), .96 (95% CI, .91-.98), and .97 (95% CI, .95-.98); microRNA: .77 (95% CI, .75-.80), .78 (95% CI, .75-.80), and .85 (95% CI, .81-.87); autoantibody: .45 (95% CI, .36-.53), .91 (95% CI, .89-.93), and .84 (95% CI, .81-.87); and cytology: .82 (95% CI, .60-.93), .97 (95% CI, .88-.99), and .97 (95% CI, .95-.98). There was high heterogeneity. CONCLUSIONS: The diagnostic accuracy seemed to be comparable between cytology and endoscopy, whereas autoantibody and microRNAs bear potential as future noninvasive screening tools for ESCC. To reduce ESCC-related death in high-risk populations, it is important to develop a more accurate and less-invasive screening test.