Diagnostic accuracy of magnetically guided capsule endoscopy with a detachable string for detecting oesophagogastric varices in adults with cirrhosis: prospective multicentre study.

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.

IGF-1-mediated FOXC1 overexpression induces stem-like properties through upregulating CBX7 and IGF-1R in esophageal squamous cell carcinoma.

Substantial evidence attests to the pivotal role of cancer stem cells (CSC) in both tumorigenesis and drug resistance. A member of the forkhead box (FOX) family, FOXC1, assumes significance in embryonic development and organogenesis. Furthermore, FOXC1 functions as an overexpressed transcription factor in various tumors, fostering proliferation, enhancing migratory capabilities, and promoting drug resistance, while maintaining stem-cell-like properties. Despite these implications, scant attention has been devoted to its role in esophageal squamous cell carcinoma. Our investigation revealed a pronounced upregulation of FOXC1 expression in ESCC, correlating with a poor prognosis. The downregulation of FOXC1 demonstrated inhibitory effects on ESCC tumorigenesis, proliferation, and tolerance to chemotherapeutic agents, concurrently reducing the levels of stemness-related markers CD133 and CD44. Further studies validated that FOXC1 induces ESCC stemness by transactivating CBX7 and IGF-1R. Additionally, IGF-1 activated the PI3K/AKT/NF-κB and MEK/ERK/NF-κB pathways through its binding to IGF-1R, thereby augmenting FOXC1 expression. Conversely, suppressing FOXC1 impeded ESCC stemness induced by IGF-1. The presence of a positive feedback loop, denoted by IGF-1-FOXC1-IGF-1R, suggests the potential of FOXC1 as a prognostic biomarker for ESCC. Taken together, targeting the IGF-1-FOXC1-IGF-1R axis emerges as a promising approach for anti-CSC therapy in ESCC.

Transcription factor 3 promotes migration and invasion potential and maintains cancer stemness by activating ID1 expression in esophageal squamous cell carcinoma.

Transcription factor 3 (TCF3) is a member of the basic Helix - Loop - Helix (bHLH) transcription factor (TF) family and is encoded by the TCF3 gene (also known as E2A). It has been shown that TCF3 functions as a key transcription factor in the pathogenesis of several human cancers and plays an important role in stem cell maintenance and carcinogenesis. However, the effect of TCF3 in the progression of esophageal squamous cell carcinoma (ESCC) is poorly known. In our study, TCF3 was found to express highly and correlated with cancer stage and prognosis. TCF3 was shown to promote ESCC invasion, migration, and drug resistance both from the results of in vivo and in vitro assays. Moreover, further studies suggested that TCF3 played these roles through transcriptionally regulating Inhibitor of DNA binding 1(ID1). Notably, we also found that TCF3 or ID1 was associated with ESCC stemness. Furthermore, TCF3 was correlated with the expression of cancer stemness markers CD44 and CD133. Therefore, maintaining cancer stemness might be the underlying mechanism that TCF3 transcriptionally regulated ID1 and further promoted ESCC progression and drug resistance.

Muscular injury as an independent risk factor for esophageal stenosis after endoscopic submucosal dissection of esophageal squamous cell cancer.

BACKGROUND AND AIMS: Stenosis after esophageal endoscopic submucosal dissection (ESD) has a high incidence, and muscular injury is an important risk factor for esophageal stenosis. Hence, this study aimed to classify muscular injury degrees and investigate their association with postoperative stenosis. METHODS: This retrospective study included 1033 patients with esophageal mucosal lesions treated with ESD between August 2015 and March 2021. Demographic and clinical parameters were analyzed, and stenosis risk factors were identified using multivariate logistic regression. A novel muscular injury classification system was proposed and used to investigate the association between different muscular injury degrees and postoperative stenosis. Finally, a scoring system was established to predict muscular injury. RESULTS: Of 1033 patients, 118 (11.4%) had esophageal stenosis. The multivariate analysis demonstrated that the history of endoscopic esophageal treatment, circumferential range, and muscular injury were significant risk factors for esophageal stenosis. Patients with type II muscular injuries tended to develop complex stenosis (n = 13 [36.1%], P < .05), and type II muscular injuries were more likely to predispose patients to severe stenosis than type I (73.3% and 92.3%, respectively). The scoring system showed that patients with high scores (3-6) were more likely to have muscular injury. The score model presented good discriminatory power in the internal validation (area under the receiver-operating characteristic curve, .706; 95% confidence interval, .645-.767) and goodness-of-fit in the Hosmer-Lemeshow test (P = .865). CONCLUSIONS: Muscular injury was an independent risk factor for esophageal stenosis. The scoring system demonstrated good performance in predicting muscular injury during ESD.

Assessment of Autologous Blood marker localIzation and intraoperative coLonoscopy localIzation in laparoscopic colorecTal cancer surgery (ABILITY): a randomized controlled trial.

BACKGROUND: Laparoscopic colorectal surgery has been proved to have similar oncological outcomes with open surgery. Due to the lack of tactile perception, surgeons may have misjudgments in laparoscopic colorectal surgery. Therefore, the accurate localization of a tumor before surgery is important, especially in the early stages of cancer. Autologous blood was thought a feasible and safe tattooing agent for preoperative endoscopic localization but its benefits remain controversial. We therefore proposed this randomized trial to the accuracy and safety of autogenous blood localization in small, serosa-negative lesion which will be resected by laparoscopic colectomy. METHODS: The current study is a single-center, open-label, non-inferiority, randomized controlled trial. Eligible participants would be aged 18-80 years and diagnosed with large lateral spreading tumors that could not be treated endoscopically, malignant polyps treated endoscopically that required additional colorectal resection, and serosa-negative malignant colorectal tumors (≤ cT3). A total of 220 patients would be randomly assigned (1:1) to autologous blood group or intraoperative colonoscopy group. The primary outcome is the localization accuracy. The secondary endpoint is adverse events related to endoscopic tattooing. DISCUSSION: This trial will investigate whether autologous blood marker achieves similar localization accuracy and safety in laparoscopic colorectal surgery compared to intraoperative colonoscopy. If our research hypothesis is statistically proved, the rational introduction of autologous blood tattooing in preoperative colonoscopy can help improve identification of the location of tumors for laparoscopic colorectal cancer surgery, performing an optimal resection, and minimizing unnecessary resections of normal tissues, thereby improving the patient's quality of life. Our research data will also provide high quality clinical evidence and data support for the conduction of multicenter phase III clinical trials. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, NCT05597384. Registered 28 October 2022.

No-touch endoscopic full-thickness resection technique for gastric gastrointestinal stromal tumors.

BACKGROUND : There remain concerns regarding the technical feasibility of endoscopic resection for large gastrointestinal stromal tumors (GISTs), mainly relating to the risk of tumor rupture and the adequacy of the resection margins. This study aimed to evaluate the feasibility and therapeutic outcomes of the newly developed no-touch endoscopic full-thickness resection (NT-EFTR) technique for GISTs. METHODS : In this retrospective study, 92 patients with gastric GISTs undergoing NT-EFTR were included. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. RESULTS : The median tumor size was 2.5 cm and en bloc resection was achieved in all patients with negative surgical margins. The median time of the NT-EFTR procedure was 59.5 minutes. Large tumors (> 3.0 cm), extraluminal tumor growth pattern, and large gastric defects were significant contributors to long operative times. Patients were discharged within 4 days postoperatively. During follow-up, all patients were free from local recurrence and distant metastasis. CONCLUSIONS : NT-EFTR was a feasible method for the resection of gastric GISTs and can be expected to achieve complete radical resection. Large tumors with extraluminal growth and large gastric defects impact procedural difficulty.

A prediction model and nomogram for technical difficulty of peroral endoscopic myotomy.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is a promising endoscopic technique for achalasia. We aimed to establish a regression model and develop a simple nomogram to predict the technical difficulty of POEM in a single center with large volume cases. METHODS: 3385 achalasia patients treated with POEM were included, and the technical difficulty was systemically evaluated. All of them were randomized into the training cohort (n = 1693) or internal validation cohort (n = 1692). Then, the prediction model and nomogram were proposed based on multivariate logistic regression analysis in the training cohort and assessed in the validation cohort. RESULTS: Of 3385 patients, technical difficulty happened in 417 (12.32%) cases. In the training stage, six factors were weighted based on the ß coefficient from the regression model, including age, disease duration, sigmoid esophagus, mucosal edema, submucosal fibrosis, and tunnel length. The patients were categorized into low-risk (< 0.1), medium-risk (0.1-0.25), and high-risk (> = 0.25) groups. Our score model performed satisfying discrimination with the areas under the receiver-operating characteristic curve (AUC) of 0.743 (95% confidence interval (CI), 0.701-0.785) and calibration with goodness of fit in the Hosmer-Lemeshow test (P = 0.088) in internal validation. CONCLUSIONS: The prediction model and nomogram demonstrated good performance in predicting the technical difficulty of POEM.

Predictors of difficult endoscopic resection of submucosal tumors originating from the muscularis propria layer at the esophagogastric junction.

BACKGROUND: Endoscopic resection approaches, including endoscopic submucosal dissection (ESD), submucosal tunneling endoscopic resection (STER) and endoscopic full-thickness resection (EFTR), have been widely used for the treatment of submucosal tumors (SMTs) located in the upper gastrointestinal tract. However, compared to SMTs located in the esophagus or stomach, endoscopic resection of SMTs from the esophagogastric junction (EGJ) is much more difficult because of the sharp angle and narrow lumen of the EGJ. SMTs originating from the muscularis propria (MP) in the EGJ, especially those that grow extraluminally and adhere closely to the serosa, make endoscopic resection even more difficult. AIM: To investigate the predictors of difficult endoscopic resection for SMTs from the MP layer at the EGJ. METHODS: A total of 90 patients with SMTs from the MP layer at the EGJ were included in the present study. The difficulty of endoscopic resection was defined as a long procedure time, failure of en bloc resection and intraoperative bleeding. Clinicopathological, endoscopic and follow-up data were collected and analyzed. Statistical analysis of independent risks for piecemeal resection, long operative time, and intraoperative bleeding were assessed using univariate and multivariate analyses. RESULTS: According to the location and growth pattern of the tumor, 44 patients underwent STER, 14 patients underwent EFTR, and the remaining 32 patients received a standard ESD procedure. The tumor size was 20.0 mm (range 5.0-100.0 mm). Fourty-seven out of 90 lesions (52.2%) were regularly shaped. The overall en bloc resection rate was 84.4%. The operation time was 43 min (range 16-126 min). The intraoperative bleeding rate was 18.9%. There were no adverse events that required therapeutic intervention during or after the procedures. The surgical approach had no significant correlation with en bloc resection, long operative time or intraoperative bleeding. Large tumor size (≥ 30 mm) and irregular tumor shape were independent predictors for piecemeal resection (OR: 7.346, P = 0.032 and OR: 18.004, P = 0.029, respectively), long operative time (≥ 60 min) (OR: 47.330, P = 0.000 and OR: 6.863, P = 0.034, respectively) and intraoperative bleeding (OR: 20.631, P = 0.002 and OR: 19.020, P = 0.021, respectively). CONCLUSION: Endoscopic resection is an effective treatment for SMTs in the MP layer at the EGJ. Tumors with large size and irregular shape were independent predictors for difficult endoscopic resection.

Endoscopic radial incision versus endoscopic balloon dilation as initial treatments of benign esophageal anastomotic stricture.

BACKGROUND AND AIM: We aim to evaluate the efficacy and safety of endoscopic radial incision (ERI) versus endoscopic balloon dilation (EBD) treatment of naïve, recurrent, and refractory benign esophageal anastomotic strictures. METHODS: One hundred and one ERI, 145 EBD, and 42 ERI combined with EBD sessions were performed in 136 consecutive patients with benign esophageal anastomotic stricture after esophagectomy at Zhongshan Hospital from January 2016 to August 2021. Baseline characteristics, operational procedures, and clinical outcomes data were retrospectively evaluated. Parameters and recurrence-free survival (RFS) were compared between ERI and EBD in patients with naïve or recurrent or refractory strictures. Risk factors for re-stricture after ERI were identified using univariate and multivariate analyses. RESULTS: Twenty-nine ERI versus 68 EBD sessions were performed for naïve stricture, 26 ERI versus 60 EBD for recurrent strictures, and 46 ERI versus 17 EBD for refractory stricture. With comparable baseline characteristics, RFS was greater in the ERI than the EBD group for naïve strictures (P = 0.0449). The ERI group had a lower 12-month re-stricture rate than the EBD group (37.9% vs 61.8%, P = 0.0309) and a more prolonged patency time (181.5 ± 263.1 vs 74.5 ± 82.0, P = 0.0233). Between the two interventions, recurrent and refractory strictures had similar RFS (P = 0.0598; P = 0.7668). Multivariate analysis revealed initial ERI treatment was an independent predictive factor for lower re-stricture risk after ERI intervention (odds ratio = 0.047, P = 0.001). Few adverse events were observed after ERI or EBD (3.0% vs 2.1%, P = 0.6918). CONCLUSIONS: ERI is associated with lower re-stricture rates with better patency and RFS compared with EBD for naive strictures.

ETV5 overexpression promotes progression of esophageal squamous cell carcinoma by upregulating SKA1 and TRPV2.

Esophageal squamous cell carcinoma (ESCC) is notorious for the rapid progression especially early tumor metastasis due to the unclear mechanism. Recently, ETV5 attracts much attention for its potential role as an oncogenic transcription factor involved in multiple cancers. However, no one reported the mechanism behind the association between ETV5 expression and esophageal squamous cell carcinoma progression. In this study, we found that ETV5 was upregulated in ESCC both from online database and our ESCC tissues and ETV5 was associated with tumor staging and prognosis. Knockdown of ETV5 or its downstream genes SKA1 and TRPV2 significantly suppress ESCC cells migration and invasion, respectively. Additionally, in vivo study showed knockdown of ETV5 inhibited tumor metastasis. Further experiments unveiled ETV5 could transcriptionally upregulate the expression of SKA1 and TRPV2 and further activate MMPs in ESCC progression. In conclusion, ETV5 was associated with ESCC tumor staging and ESCC prognosis clinically. ETV5 promoted metastasis of ESCC by activating MMPs through augmenting the transcription of SKA1 and TRPV2. ETV5 was likely to be a novel oncogene and therapeutic target in ESCC.

Endoscopic resection of upper GI extraluminal tumors (with videos).

BACKGROUND AND AIMS: Endoscopic resection is a feasible treatment for GI extraluminal tumors but remains a challenging procedure with limited data. In this study, we assessed the safety and efficacy of endoscopic resection for extraluminal tumors in the upper GI tract. METHODS: From May 2016 to December 2021, 109 patients undergoing endoscopic resection for extraluminal tumors in the upper GI tract were retrospectively included. Clinicopathologic characteristics, procedure-related parameters, adverse events (AEs), and follow-up outcomes were analyzed. RESULTS: The en-bloc tumor resection rate was 94.5% and en-bloc retrieval rate 86.2%. Statistical analysis revealed tumor size ≥3.0 cm and irregular shape as significant risk factors for piecemeal extraction. Resection time and suture time were 46.8 ± 33.6 minutes and 20.6 ± 20.1 minutes, respectively. Large tumor size was significantly associated with a longer procedure duration. Five patients (4.6%) experienced major AEs, including recurrent laryngeal nerve injury, hydrothorax, major bleeding, local peritonitis, duodenal leakage, and repeat endoscopic surgery for tumor extraction. Minor AEs occurred in 13 patients (11.9%). Irregular tumor shape and tumor location (duodenum) were significantly associated with AE occurrence. Mean postoperative hospital stay was 4.7 ± 3.3 days. No recurrence or metastasis was observed during the mean follow-up period of 31.8 ± 15.2 months. CONCLUSIONS: Endoscopic resection is a safe and feasible therapeutic approach for upper GI extraluminal tumors. Tumor size, shape, and location impact the difficulty and safety of the procedure. Endoscopic resection of duodenal tumors is also feasible but associated with an increased risk of AEs compared with tumors in other locations.

Submucosal Tunneling Endoscopic Resection for Submucosal Tumors in the Proximal Esophagus.

BACKGROUND: Submucosal tunneling endoscopic resection (STER) is widely applied for treatment of gastrointestinal submucosal tumors (SMTs) originating from the muscularis propria layer. However, the tumor location within the proximal esophagus makes STER a challenge for the endoscopists. The aim of this study was to summarize the technique skill and evaluate the outcomes of proximal esophageal STER. STUDY DESIGN: A total of 72 patients with SMTs in the proximal esophagus undergoing STER were included from February 2019 to March 2021. Imaging 3-dimensional reconstruction was used for patients with large SMTs. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. RESULTS: In this study, all the tumors were removed completely and no gross disease was remaining. The en bloc resection was achieved in 90.28% of patients, and the complications rate was 6.95%. Three-dimensional reconstruction was used for 30 patients (41.67%) with large SMTs (transverse diameter >2.0 cm). Based on statistical analysis, tumors with irregular shape and larger size were the significant contributors to piecemeal resection. Larger tumors increase the risk of long operation time, and irregular tumor shapes increase the risk of complications. The median hospitalization time was 4 days. All of the complications were cured by conservative treatment. A median follow-up of 12 months was available, and all patients were free from local recurrence or distant metastasis during the study period. CONCLUSIONS: STER is an effective and safe methodology for the resection of proximal esophageal SMTs. Tumor size and shape mainly impact the piecemeal resection rate, STER-related complications, and procedural difficulty.

Submucosal tunneling endoscopic septum division for esophageal diverticulum with a median follow-up of 39 months: a multicenter cohort study.

BACKGROUND AND AIMS: Submucosal tunneling endoscopic septum division (STESD) is an endoscopic minimally invasive technique for treating esophageal diverticulum. The objectives of this study were to evaluate the safety and efficacy of STESD and its impact on patients' quality of life. METHODS: This study included consecutive patients who underwent STESD for esophageal diverticulum from April 2016 to August 2020 in 2 centers (Zhongshan Hospital, Fudan University and Tianjin First Central Hospital). Esophagogram and endoscopic examination were performed before STESD and 30 days after STESD. Patients completed the 36-item Short Form survey (SF-36) before STESD and 1 year after surgery. Clinical symptoms were assessed via telehealth every 6 months until August 2021. Costamagna and Eckardt scores were used to evaluate changes in symptoms. RESULTS: Twenty-one patients were included. Mucosal injury 1 to 2 cm below the septum occurred in 2 patients. No severe surgical adverse events were observed. Median duration of follow-up was 39 months (range, 12-63). Total SF-36 scores increased from 118.7 ± 18.6 before STESD to 132.4 ± 9.1 at 1 year after the procedure (P = .007). SF-36 subscales of general health (P = .002), vitality (P = .004), social functioning (P = .030), and mental health (P = .020) improved significantly after STESD. The mean Costamagna score decreased from 3.83 ± 1.33 to 1.67 ± 1.51 (P = .010), whereas the mean Eckardt score decreased from 3.50 ± .90 to 1.25 ± 1.76 (P = .002). One patient developed symptom recurrence at 10 months after STESD. CONCLUSIONS: STESD is a safe and valid endoscopic minimally invasive surgery for esophageal diverticulum, which can reduce symptoms and improve quality of life.

Landscape of esophageal submucosal tunneling endoscopic resection-related adverse events in a standardized lexicon: a large volume of 1701 cases.

BACKGROUND: Submucosal tunneling endoscopic resection (STER) has been widely applied for esophageal submucosal tumors. This large volume study aims to provide a standard landscape of STER-related AEs for reference. METHODS: 1701 patients with esophageal SMTs undergoing STER were included at Zhongshan Hospital, Fudan University. Data of clinical characteristics and adverse events were collected and analyzed in depth. Adverse events were recorded by ASGE lexicon and graded by ASGE grading/Clavien-Dindo system. Risk factors for major AEs were analyzed by univariate and multivariate logistic regression. RESULTS: Three hundred and twenty (18.8%) patients with 962 cases of adverse events were observed. Accordingly, 84 (5.0%) were classified as major AEs (moderate and severe) by ASGE grading and 37 (2.2%) were classified as major AEs (grades III-V) by Clavien-Dindo grading. First 1 year operation, distance > 6 cm from incision to tumor, piecemeal resection, partially extraluminal location, mucosal injury, and operation time > 60 min were included in the risk score model for major AEs of STER, with 57.1% sensitivity and 87.5% specificity. CONCLUSIONS: STER was a safe procedure for diagnosis and treatment of esophageal SMTs with a total 18.8% incidence of AEs, among which only 5.0% were major AEs requiring therapeutic measurements.

Repeat endoscopic submucosal dissection as salvage treatment for local recurrence of esophageal squamous cell carcinoma after initial endoscopic submucosal dissection.

BACKGROUND AND AIMS: Local recurrence of esophageal squamous cell carcinoma (ESCC) after endoscopic resection does not have an established treatment. The efficacy and safety of repeat endoscopic submucosal dissection (ESD) for recurrent ESCC were determined in the study. METHODS: Forty-three consecutive patients with 45 locally recurrent superficial ESCC lesions undergoing repeat ESD and 909 first ESD lesions for propensity score matching (PSM) at Zhongshan Hospital between January 2011 and January 2020 were retrospectively enrolled. After PSM (1:2), operation-related parameters were compared between repeat ESD and first ESD. In the repeat ESD group, the Kaplan-Meier method and log-rank tests were used for identification of risk factors for local recurrence after repeat ESD. RESULTS: As compared with propensity score-matched first ESD, rates of complete resection (86.7% vs 97.8%, P = .02) and curative resection (86.7% vs 96.7%, P = .06) were lower and procedure duration (54.8 ± 21.7 minutes vs 46.2 ± 20.6 minutes, P = .67) and hospital stay (4.3 ± 1.8 days vs 2.9 ± 1.4 days, P = .25) were longer in the repeat ESD group. The en-bloc resection rate (93.3% vs 98.8%, P > .11) remained comparable. Adverse events including bleeding (4.4% vs 0%, P = .11), perforation (.0% vs .0%, P > .99), and stricture (6.7% vs 2.2%, P = .33) presented with no difference. The 5-year overall survival rate and recurrence-free survival rate for repeat ESD was 100% and 86.0%, respectively. Multiplicity was significantly associated with recurrence after repeat ESD (P = .01). CONCLUSIONS: Repeat esophageal ESD showed favorable short- and long-term outcomes and thus provides an alternative choice for recurrent superficial ESCC.

Controlled hypertension under hemostasis prevents post-gastric endoscopic submucosal dissection bleeding: a prospective randomized controlled trial.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a prominent minimally invasive operative technique for treating early gastrointestinal tumors but can result in postoperative bleeding. We conducted a randomized controlled trial to determine whether increasing blood pressure under hemostasis during gastric ESD to identify potential bleeding spots reduces the risk of post-ESD bleeding. METHODS: In this randomized, controlled, single-blinded clinical trial, 309 patients with early gastric cancer who were admitted to a hospital to undergo ESD were recruited from March 2017 to February 2018 and were randomized into intervention and control groups. In the control group, patients underwent normal ESD. In the intervention group, we increased patients' blood pressure to 150 mmHg for 5 min using a norepinephrine pump (0.05 µg/kg/min initial dose) after the specimen was extracted during the ESD operation to identify and coagulate potential bleeding spots with hot biopsy forceps. Our primary outcome was the incidence of postoperative bleeding over 60-day follow-up. RESULTS: The incidence of post-ESD bleeding was lower in the intervention group (1.3%, 2/151) than in the control group (10.1%, 16/158, p = 0.01). Deeper tumor invasion was associated with a higher risk of post-ESD bleeding (5.3% in mucosal/submucosal layer 1 group vs. 12.5% in submucosal layer 2/muscularis propria group, p < 0.001). Multi-factor but not univariate analysis showed that proton pump inhibitor administration three times per day may be a better choice than twice per day. CONCLUSION: Increasing blood pressure under hemostasis during ESD to identify and coagulate potential bleeding spots could reduce the risk of delayed bleeding after gastric ESD.

Short- and long-term outcomes of endoscopic submucosal dissection for superficial esophageal squamous cell cancer in patients with prior gastrectomy.

BACKGROUND: The surgery for esophageal cancer arising after prior gastrectomy is technically difficult with high morbidity and mortality. Endoscopic submucosal dissection (ESD) is a minimally invasive endoscopic treatment for superficial SCC with high curative resection rate. But few studies are concerned about ESD under these circumstances. The aim of this study was to elucidate the short- and long-term outcomes of ESD for superficial esophageal squamous cell cancer (SCC) in patients with prior gastrectomy. METHODS: From January 2009 to January 2019, 37 patients with prior gastrectomy who underwent ESD for superficial esophageal SCC were retrospectively enrolled at the Zhongshan Hospital, Fudan University in Shanghai, China. Rates of en bloc resection, complete resection, curative resection, incidence of postoperative bleeding, perforation and postoperative stricture were evaluated as short-term outcomes. Overall survival, and local recurrence-free survival were evaluated as long-term outcomes. RESULTS: The rate of en bloc resection, complete resection and curative resection were 94.6%, 86.5% and 78.4%, respectively. No perforation was observed. 1 (2.7%) patient experienced postoperative bleeding. During the median observation of 43 months, 3 (8.6%) patients experienced esophageal stricture, successfully managed by balloon dilation. 3(8.6%) patients had local recurrence after ESD with 5-year local recurrence-free survival rate of 91.4%. During the observation period, 4 patients died of other reasons. The 1, 3, 5-year overall survival rates were 97.1%, 97.1% and 91.4%. CONCLUSIONS: The short-term outcomes indicate ESD is technically difficult with lower resection completeness in patients after gastrectomy, while the long-term outcomes are rather favorable.

Submucosal tunneling endoscopic resection for large symptomatic submucosal tumors of the esophagus: A clinical analysis of 24 cases.

BACKGROUND/AIMS: Studies evaluating submucosal tunneling endoscopic resection (STER) for the treatment of upper gastrointestinal submucosal tumors (SMTs) have recently increased. However, the efficacy and safety of STER for the treatment of large symptomatic SMTs in the esophagus have not been well investigated. The aim of the present study was to evaluate the efficacy and safety of STER for the treatment of large symptomatic SMTs in the esophagus. METHODS: A total of 24 patients with large symptomatic SMTs in the esophagus who underwent STER in our hospitals between January 2015 and May 2018 were included in the study. The tumors were confirmed to be of muscularis propria layer origin. Treatment outcomes, complications, and follow-up results were retrospectively analyzed. RESULTS: All 24 lesions were resected en bloc with STER. The mean maximum transverse diameter of the lesions was 4.7 (3.5-6.5) cm. The mean maximum longitudinal diameter of the lesions was 2.1 (1.5-3.0) cm. The mean duration from mucosal incision to complete mucosal closure was 65 (50-115) min. Postoperative pathological diagnosis confirmed 18 cases with leiomyomas, 4 cases with stromal tumors, and 2 cases with schwannomas. There were no major complications. There were no residual lesions or disease recurrence during follow-up. CONCLUSION: STER is safe and effective for the treatment of large symptomatic SMTs of muscularis propria layer origin in the esophagus.

A risk-scoring system to predict clinical failure for patients with achalasia after peroral endoscopic myotomy.

BACKGROUND AND AIMS: We aimed to establish a predictive model and develop a simple risk-scoring system (Zhongshan POEM Score) to help clinicians to characterize high-risk patients for clinical failure after peroral endoscopic myotomy (POEM). METHODS: A total of 1538 patients with achalasia treated with POEM with available follow-up data were included in this study and were randomly classified to the training cohort (n = 769) or internal validation cohort (n = 769). A risk-scoring system was developed using multivariate Cox regression analysis in the training cohort. The system was then internally validated by survival analysis in the validation cohort. RESULTS: During a median follow-up time of 42 months, 109 patients had clinical failure. In the training stage, 3 risk factors for clinical failure were weighted with point values: previous treatment (2 points), intraprocedural mucosal injury (2 points for type I and 6 points for type II), and clinical reflux (3 points). The patients were categorized into low-risk and high-risk groups. In the validation stage, Kaplan-Meier curves differed significantly between the 2 groups. Patients in the high-risk group had a significantly higher risk of clinical failure than those in the low-risk group (hazard ratio, 3.99; 95% confidence interval, 2.31-6.91; P < .001). Satisfactory discrimination and calibration were shown. CONCLUSIONS: This risk-scoring system demonstrated good performance in predicting clinical failure in patients who underwent POEM.

Effect of peroral endoscopic myotomy in geriatric patients: a propensity score matching study.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a safe and effective approach for achalasia. However, the safety, feasibility, perioperative and long-term efficacy in treating geriatric patients has not been well evaluated. METHODS: Data of 2367 patients diagnosed with achalasia and treated with POEM in the Endoscopy Center, Zhongshan Hospital, Fudan University from August 2010 to December 2017 were retrospectively reviewed. Last follow-up was in December 2018. Propensity score matching based on baseline characteristics was used to adjust for confounding. With a caliper of 0.01 in propensity scoring, 139 patients aged ≥ 65 years were matched at a 1:2 ratio with 275 patients aged < 65 years. Perioperative complications and long-term outcomes were compared between the two groups. RESULTS: After propensity score matching, the two groups had similar baseline clinical characteristics and distribution of propensity scores. The mean age was 70.22 years in geriatric patients and 42.02 in younger patients. Technical failure occurred in one geriatric and one non-geriatric patients (p = 0.485). The procedural time in geriatric patients was similar to younger patients [50 (interquartile range (IQR) 36-76) vs. 50 (IQR 36-70) min, p = 0.398]. There were also no significant differences in major perioperative adverse events (2.88% vs. 2.18%, p = 0.663) and hospitalization length (median 3 vs. 3 days, p = 0.488). During a median follow-up period of 41 months (IQR 26-60), mean decrease in Eckardt score and pressure of the LES were 6.63 and 11.9 mmHg in geriatric patients, which were similar to the change in non-geriatric patients (6.49 and 11.6 mmHg, p = 0.652 and 0.872, respectively). Clinical reflux occurred in 23.53% geriatric patients and 21.59% non-geriatric patients (p = 0.724). 5-year success rate of 92.94% was achieved in geriatric patients and 92.61% in younger patients (log-rank p = 0.737). CONCLUSIONS: POEM is a safe and reliable treatment in geriatric achalasia patients with confirmed short-term and long-term efficacy compared with those in non-geriatric patients.