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Developments of endoscopic techniques brought the possibility of endoscopic resection for gastrointestinal stromal tumors (GISTs) of larger sizes. We aim to compare safety and short-term outcomes between endoscopic and laparoscopic resections of gastric GISTs with a diameter of 2-5 cm.This is a single-center, retrospective cohort study. The clinical data, perioperative conditions, and the adverse events of patients who underwent endoscopic or laparoscopic resection for gastric GIST of 2-5 cm in Zhongshan Hospital, Fudan University, from January 2016 to December 2020 were retrospectively reviewed.A total of 346 patients were reviewed; 12 patients who failed to accomplish the planned procedure were excluded; 182 underwent laparoscopic resection; and 152 underwent endoscopic resection. Significant differences exist in the tumor size between the laparoscopic group (3.43 ± 0.86 cm) and the endoscopic group (2.78 ± 0.73 cm) (P 0.01). Compared with laparoscopic resection, endoscopic resection was associated with faster recovery (P 0.01), shorter hospital stays (P 0.01), and lower cost (P 0.01). The incidence of Clavien-Dindo grade II-V adverse events in the endoscopic group (3/152) was significantly lower than that in the laparoscopic group (12/182) (P = 0.04). After a propensity score matching analysis, the endoscopic group showed similar incidences of complications with the laparoscopic group, while the advantages over laparoscopic resection in postoperative hospital stay, time to first oral intake, and hospitalization expenses remained significant (P 0.01).Endoscopic resection is a safe and cost-effective method for 2-5 cm of gastric GISTs compared with laparoscopic resection.

Supplementary Data from Human Leukocyte Antigen-G Protein Expression Is an Unfavorable Prognostic Predictor of Hepatocellular Carcinoma following Curative Resection

Gastrointestinal stromal tumors (GIST) are mostly seen in the stomach. Clinical data on GISTs ≤ 2 cm with 5 mitosis/50 HPFs are limited. This study aimed to analyze small GISTs with high histological grades to gain a more comprehensive understanding of their clinical characteristics with long-term follow-up.This was a nested cohort study of patients with gastric GISTs ≤ 2 cm and 5 mitosis/50 HPFs. Individuals with endoscopically resected gastric specimens diagnosed as GISTs between January 2008 and July 2019 were enrolled. We analyzed baseline clinicopathological characteristics, perioperative characteristics, risk of recurrence, and metastasis during follow-up.A total of 55 patients diagnosed with gastric GISTs ≤ 2 cm and 5 mitosis/50 HPFs were enrolled. The mean tumor size was 1.6 ± 0.4 cm (median 1.7 cm, range 0.8-2.0 cm). ESD was performed in 33 patients (60.0%) and EFTR in 22 patients (40.0%). Mean mitotic figures were 8.9/50 HPFs. Postoperative bleeding in one patient (1.8%) was the only severe adverse event. The mean follow-up period was 61.2 ± 33.9 months (median 53 months, range 13-133 months). Five patients (5/55, 9.1%) received additional therapies, including partial gastrectomy and adjuvant Imatinib. Only two patients (2/55, 3.6%) showed signs of recurrence. We observed no significant difference regarding baseline clinical characteristics and recurrence among GISTs with mitosis 10/50 HPF and ≥ 10/50 HPF. No patient had signs of metastasis during follow-up.Endoscopic resection of gastric GISTs ≤ 2 cm with 5 mitosis/50 HPFs has a low risk of recurrence and metastasis in the long term. Endoscopic resection of GISTs is safe and feasible.

Immune-mediated neuroinflammation has been proposed to underlie the loss of lower esophageal sphincter (LES) myenteric neurons in achalasia. However, the immune status and key pathogenic immune subpopulations remain unclear. This study aims to evaluate the inflammatory status of patients with achalasia and their correlation with clinical characteristics, and further explore the key pathogenic subpopulations.We investigated the complete blood cell count and inflammatory markers in a large population of patients with achalasia (n=341) and healthy controls (n=80). The subpopulations of lymphocytes were analyzed by flow cytometry. Immunofluorescence was used to determine immune cell infiltration in the LES. Transcriptome changes of the key subpopulation were determined by RNA sequencing analysis.NLR, MLR, CRP, globulin, IL-6 and IL-10 were significantly elevated in patients with achalasia. MLR and globulin were positively correlated with disease duration. The absolute count and percentage of CD8+ T cells in peripheral blood and its infiltration around ganglion in the LES were significantly increased in achalasia. Transcriptome analysis indicated that CD8+ T cells were activated and proliferative. In addition to multiple inflammatory pathways, regulation of neuroinflammatory response pathway was also significantly up-regulated in achalasia. GSEA analysis revealed a close association with autoimmune diseases.Patients with achalasia suffered from chronic low-grade inflammation with dysregulated immune cells and mediators associated with disease duration. CD8+ T cells might be the key pathogenic subpopulation of achalasia. Our results provide an important immune cell signature of the pathogenesis of achalasia.

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.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.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).ERI is associated with lower re-stricture rates with better patency and RFS compared with EBD for naive strictures.

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.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.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.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.

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. 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. 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%. 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 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.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.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.STESD is a safe and valid endoscopic minimally invasive surgery for esophageal diverticulum, which can reduce symptoms and improve quality of life.

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.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.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).Repeat esophageal ESD showed favorable short- and long-term outcomes and thus provides an alternative choice for recurrent superficial ESCC.

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.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.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.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.

The approach to paraoesophageal structures and lesions via the oesophagus was initiated by the introduction of peroral endoscopic myotomy (POEM), followed by peroral endoscopic removal of tumours within the muscular layer. We now report a case which suggests that the next step, that is, to remove paraoesophageal tumours not related to the oesophageal wall, would also be possible. This is the case of a 66-year-old male patient with a 4.0×2.0×1.5 cm benign schwannoma from the recurrent laryngeal nerve bulging into the proximal oesophagus, which we removed via a POEM tunnel. The postoperative course was uneventful. Further controlled studies have to show which lesions may be suitable for this expanded approach and also confirm the safety and feasibility of this technique which can be regarded as much less invasive than operative minimal invasive alternatives. Due to the complicated anatomy of the mediastinum, mediastinal masses represent a heterogeneous group of tumours.1 2 Characteristic location of the mass establishes a useful differential diagnosis that aids in planning the diagnostic evaluation. Video-assisted thoracoscopic surgery and conventional open surgery are the currently available treatments for these patients with benign lesions in whom removal is considered to be indicated, also for clarification of the diagnosis.3–5 Traditional surgical approach can be associated with substantial trauma, slower recovery, higher complication rate and decreased postoperative quality of life. To overcome these disadvantages, we report on a novel technique, transoesophageal endoscopic surgery, for treating mediastinal tumours. This technique takes advantage of the submucosal tunnelling technique popularised by natural orifice translumenal endoscopic surgery (NOTES). NOTES stimulated with the development of POEM and submucosal tunnelling endoscopic resection (STER), the submucosal or ‘third space’ endoscopy combining minimal invasive surgery and endoscopy. Here we present a rare case of schwannoma originated from the recurrent laryngeal nerve, which we removed via transoesophageal endoscopic surgery …

5‐Hydroxymethylcytosine (5hmC) is a DNA modification that is generated by the oxidation of 5‐methylcytosine (5mC) in a reaction catalyzed by the ten‐eleven translocation (TET) family enzymes. It tends to mark gene activation and affects a spectrum of developmental and disease‐related biological processes. In this manuscript, we present a 5hmC selective chemical labelling technology (hmC‐Seal) to capture and sequence 5hmC‐containing DNA fragments with low input. We tested 10 tumour/adjacent colon cancer tissues and 10 tumour/healthy plasma samples. Furthermore, we tested if this methodology could generate the 5hmC differential genes among cancer patients, healthy controls and precancerous adenoma patients from plasma. Robust cancer‐specific epigenetic signatures were identified for colon cancers. The results show that 5hmC is mainly distributed in gene active regions. The results also indicate the potential application of 5hmC change signals in early stage of colon cancer, even show potential in the diagnosis of precancerous adenoma. We demonstrated the robustness of the 5hmC‐Seal method in tissue and cell‐free DNA (cfDNA) as potential biomarkers. Moreover, this study provides the potential value and feasibility of 5hmC‐Seal approach on colorectal cancer (CRC) early detection. We believe this strategy could be an effective liquid biopsy‐based diagnosis and a potential prognosis method for colon cancer using cfDNA.

Background and study aims Submucosal tunneling endoscopic resection (STER) and non-tunneling techniques are two alternative options for the treatment of cardial submucosal tumors (SMTs). We aimed to establish a regression model and develop a simple scoring system (Zhongshan Tunnel Score) to help clinicians make surgical decisions for cardial submucosal tumors. Patients and methods A total of 246 patients who suffered cardial SMTs and received endoscopic resection were included in this study. All of them were randomized into either the training cohort (n = 147) or the internal validation cohort (n = 99). Then, the scoring system was proposed based on multivariate logistic regression analysis in the training cohort and assessed in the validation cohort. Results Of 246 patients, 97 were treated with STER and the others with non-tunneling endoscopic resection. In the training stage, four factors were weighted with points based on the β coefficient from the regression model, including irregular morphology (–2 points), ulcer (2 points), the direction of the gastroscope (–2 points for forward direction and 1 point for reverse direction), and originating from the muscularis propria (–2 points). The patients were categorized into low-score ( –3) groups, and those with low scores were more likely to be treated with STER. Our score model performed satisfying discriminatory power in internal validation (Area under the receiver-operator characteristic curve, 0.829; 95 % confidence interval, 0.694–0.964) and goodness-of-fit in the Hosmer-Lemeshow test (P = .4721). Conclusions This scoring system could provide clinicians the references for making decisions about the treatment of cardial submucosal tumors.

Primary mediastinal cysts are infrequent lesions derived from a variety of mediastinal organs or structures. Complete surgical resection is the treatment of choice even in asymptomatic patients to prevent severe adverse events (AEs) and to establish the diagnosis. Transesophageal endoscopic resection of benign mediastinal tumors has been proven feasible. The aim of this study was to evaluate the feasibility, safety, and efficacy of transesophageal endoscopic surgery for mediastinal cysts.From January 2016 to May 2021, patients with mediastinal cysts who underwent transesophageal endoscopic resection were retrospectively included. Clinicopathologic characteristics, procedure-related parameters, AEs, and follow-up outcomes were analyzed.Ten patients with mediastinal cysts were included in this study. The mean cyst size was 3.3 ± 1.3 cm. Histopathology revealed 3 bronchogenic cysts (30.0%), 4 esophageal duplication cysts (40.0%), 2 gastroenteric cysts (20.0%), and 1 lymphatic cyst (10.0%). All procedures were performed uneventfully without conversion to traditional surgery. En-bloc resection was achieved in 6 patients (60.0%). Aggressive resection was avoided to prevent damage to the surrounding vital organs. Mean resection time and suture time were 58.0 ± 36.4 minutes and 5.4 ± 1.0 minutes, respectively. No major pneumothorax, bleeding, mucosal injury, or fistula occurred. One patient had a transient febrile episode (38.5°C). Mean postoperative hospital stay was 2.7 ± .9 days. No residual or recurrent lesions were observed in any patient during a mean follow-up period of 29.8 ± 19.5 months.Transesophageal endoscopic surgery appears to be a feasible, safe, effective, and much less invasive approach for mediastinal cyst resection. Larger prospective studies are required to fully assess the efficacy and safety of this novel technique.

Background and Aims. Gastric peroral endoscopic myotomy (G-POEM) has been regarded as a novel and minimally invasive therapy for refractory gastroparesis. This study reports the long-term outcomes and possible predictive factors for successful outcomes after G-POEM in an Asian population. Methods. This is a retrospective single-centre study of 16 patients who underwent G-POEM for refractory gastroparesis from August 2016 to October 2017. This study included 11 males and 5 females; in addition, 13 patients had postsurgical gastroparesis, and 3 patients had diabetes. The patients included had severe and refractory gastroparesis, as indicated by a Gastroparesis Cardinal Symptom Index (GCSI) score ≥20, and evidence of a delay on gastric emptying scintigraphy (GES). The primary outcome parameter was an assessment of the long-term clinical efficacy of the procedure. The secondary outcome parameter was the detection of possible predictive factors for success and the determination of cut-off values for such predictors. Results. Technical success was achieved in 100% of the patients, with a mean procedure time of 45.25±12.96 min. The long-term clinical response was assessed in all patients during a median follow-up of 14.5 months. Clinical success was achieved in 13 (81.25%) patients. There was a significant reduction in the GCSI scores and GES values after the procedure compared to the baseline values, with P values of ≤30 had a high sensitivity and a negative predictive value (NPV) of 100% for predicting a successful procedure. GES (half emptying time ≤221.6 min and 2-hour retention ≤78.6%) had a high specificity and a positive predictive value (PPV) of 100%. Conclusions. G-POEM is a safe and effective treatment option with a long-term efficacy of 81.6%. GCSI and GES could serve as good predictive measures.

Aims An outbreak of coronavirus disease 19 (COVID-19) has altered the dynamic of endoscopic practices. Many guidelines, questionnaires have been published addressing service resumption during the pandemic. Curious about the situation indifferent endoscopic units across the globe, the study was designed to evaluate different aspects of practice resumptionworldwide and their adherence to guidelines. Methods An online questionnaire was created and distributed by national/regional representatives and societies. Redcapplatform was used as the interface;afterwards, Microsoft Excel 2016 and Prism 5 were utilized for data analysis. Results From a total of 307 responses from 47 countries/regions was collected, 290 valid answers were analyzed. Almosthalf (47 %) were in post-peak period by August, 2020. Many units were not designated to be COVID-oriented facility. About15.5 % of centers remained unrecovered, mainly in North and South America;those were recovered, training was still withheld significantly. Nevertheless, opened centers kept safety measurements strictly. Patient load was decreased by 37 %,but waiting list was increased 0-25 %. Among many surveillance methods, body temperature, PCR and chest CT were themost common. 74.8 % increased post-procedural disinfection time and 68.2 % increase in per-case inspection were noted.PPE usage was implemented highly and shortage of these posed as one of the resumption barriers. Post-procedural patientsurveillance was not reinforced. Conclusions The study represented real-time global endoscopic service's adaptation to COVID-19 pandemic. Previouslypublished barriers upon practice resumption remained. Despite Delphi consensus' emphasis on post-procedural surveillance, application was not widely reinforced, raising concerns in disease control.

BACKGROUND AND AIM Traditionally, surgery is the only choice for esophageal foreign bodies (FBs) penetrating into the mediastinum or cervical para-esophageal space. Recent progress in endoscopic techniques and devices has made it possible to perform endoscopic procedures in the mediastinum. Here, we describe a novel method to remove the entirely embedded esophagus-penetrating FBs through an endoscopic approach. METHODS Patients who underwent endoscopic removal of entirely embedded esophagus-penetrating FBs were prospectively enrolled between December 2018 and June 2020. All procedures were performed by using five major steps: localization of the FB; mucosal incision; wound debridement, myotomy, and FB exposure; FB extraction; and closure of the esophageal wound. RESULTS A total of five cases of entirely embedded esophagus-penetrating FBs were evaluated, two in children and three in adults. All FBs were successfully removed and extracted using a therapeutic endoscope and a hook knife or a hybrid knife and a grasping forceps as accessories. The average procedure time was 19.0 ± 12.4 min (range 10-40 min). The major surgical procedure was avoided in all patients. The average length of hospital stay was 3.8 ± 2.5 days (range 2-8 days). There were no severe short-term adverse events after all procedures. During the 1 month and 3 months follow-up, no patient developed long-term adverse events including stenosis of the esophagus and fistula formation. CONCLUSIONS Endoscopic approach was a safe and effective way to remove entirely embedded esophagus-penetrating FBs.

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. 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. 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

Achalasia is characterized by impaired swallowing due to lower esophageal sphincter (LES) dysfunction and an increased risk of esophageal carcinoma. Aflatoxin is a known carcinogen. Esophageal retention is relieved by per oral endoscopic myotomy (POEM), which lowers the esophageal cancer risk. The present study determined whether aflatoxin is involved in the pathogenesis of achalasia or esophageal cancer. A total of 75 patients with achalasia were prospectively enrolled from a tertiary center. Aflatoxin levels in their esophageal contents were measured using ELISA, and esophageal mucosal specimens were immunohistochemically evaluated for Ki67 and p53 expression prior to and 3 months after POEM. The effect of aflatoxin on esophageal contractility was assessed using murine specimens. Aflatoxin was detected in 67 patients before POEM and only 2 patients after POEM. The number of Ki67- and p53-immunopositive cells in the esophageal mucosa significantly decreased after POEM: [Ki67: 27.8% (95% confidence interval (CI), 25.98–29.70) vs. 20.7% (95% CI, 19.78–24.03), P=0.04 and p53: 2.14% (95% CI, 1.85–2.41) vs. 1.45% (95% CI, 1.22–1.68), P=0.03]. In vitro experiments revealed that 500 ng/ml aflatoxin significantly increased the amplitude (P0.05). Aflatoxin was found in most patients with achalasia and was eliminated following POEM. Reduced Ki67 and p53 expression after POEM indicated a decreased risk of carcinogenesis. Aflatoxin accumulation increased LES contractility via cholinergic signaling. Therefore, aflatoxin may maintain achalasia symptoms and increase esophageal cancer risk.

This chapter focuses on the detailed descriptions of two advanced therapeutic endoscopic techniques: endoscopic full-thickness resection (EFTR) and submucosal tunneling endoscopic resection (STER) for gastrointestinal subepithelial tumors, including indications and contraindications, the procedure steps, procedure-related adverse events, and clinical outcomes. Various approaches for closing the iatrogenic GI wall perforation are highlighted in this chapter.

Background and Aims The management of subepithelial tumors with a predominant extraluminal growth pattern or extra-GI tumors can be challenging and traditionally requires a surgical resection that is not only invasive but may carry a significant risk of morbidity and mortality. We aimed to assess the feasibility, safety, and efficacy of a novel endoscopic technique termed submucosal tunnel endoscopic resection for extraluminal tumors (STER-ET). Methods We prospectively enrolled patients who underwent STER-ET for GI subepithelial tumors with a predominant extraluminal growth pattern or extra-GI tumors located at the level of cardia or the proximal part of the lesser curvature of the stomach seen on cross-sectional imaging between January 2016 and March 2017. Results Eight patients underwent STER-ET. The mean (± standard deviation) tumor size was 2.8 ± 0.6 cm and 2.3 ± 0.8 cm in longest and shortest dimension, respectively. The average procedure time was 67 ± 4.4 minutes. The rates of curative en bloc resection and en bloc retrieval was 100% and 87.5%, respectively. On final histology, 6 tumors were GI stromal tumors, 1 was a schwannoma, and 1 was a foregut cyst. Five patients had capnoperitoneum during the procedure and required abdominal decompression. One patient had a small mucosotomy successfully treated with a hemostatic clip. There were no major adverse events or deaths. The median length of hospital stay was 3 days. There was no residual tumor on surveillance imaging after a mean follow-up period of 10.0 ± 2.1 months. Conclusions STER-ET is a novel technique that appears to be safe and effective in achieving a curative resection for GI subepithelial tumors with a predominantly extraluminal growth pattern or extraluminal tumors in a selected group of patients. However, larger studies are required to validate our finding.

Background and Aims This article systemically describes the landscape of peroral endoscopic myotomy (POEM)-related adverse events (AEs) and compares the different grading systems; and establishes and validates a combined risk factor model and a simplified risk-scoring system to predict POEM-related major AEs. Methods A total of 3135 patients with achalasia treated with POEM were included and the AEs were systemically described and graded. A predictive model and risk-scoring system was developed using logistic regression and then internally validated using bootstrapping approaches. Results A total of 258 out of 3135 patients, accounting for 8.23% of the total patients, presented with 297 AEs. According to Clavien-Dindo grading, 175 (67.83%), 23 (8.91%), 56 (21.71%), 4 (1.55%), and 0 (0.00%) patients were graded as grade I–V, respectively. By American Society of Gastrointestinal Endoscopy lexicon, 175 (67.83%) patients were classified with mild AE, 66 (25.58%) were classified with moderate AE, and 17 (6.59%) were classified with severe AE, respectively. Sixty-eight (2.17%) patients were classified with major AE. Air insufflation, selective myotomy, mucosal injury, and long operation time were selected into the predictive model with an area under the curve of 0.795. They were assigned with scores of 18, 5, 3, and 5 in the risk-scoring system, respectively. By applying the risk scoring system, patients with higher scores had higher rates of major AEs. The model showed little evidence for overfitting and was well-calibrated. Conclusions Based on a systematic landscape analysis, POEM is a safe procedure with low rates of severe AEs. Our prediction model and risk-scoring system demonstrated good performance in predicting major AEs.

Background: Unexplained common bile duct (CBD) dilatation may be caused by many etiologies, such as periampullary tumors, a pancreatic neoplasm, choledocholithiasis or an inflammatory stenosis. The aim of this study is to evaluate the diagnostic yield of endoscopic ultrasonography (EUS) in patients with unexplained CBD dilatation, in combination with tumor markers, liver chemistry, symptoms, surgical history and whether there is dilatation of the pancreatic duct (PD). Methods: From January 2016 to July 2017, 115 patients were referred for EUS in our center for CBD dilatation of an unknown etiology. A treatment plan is made based on the EUS result combined with the other clinical information. The final diagnosis is determined by surgical histology or follow-up of at least 3 months. Results: The sensitivity, specificity and accuracy of EUS for patients with choledocholithiasis were 100.0% (10/10), 100.0% (105/105) and 100.0% (115/115), respectively. The sensitivity, specificity and accuracy of EUS for patients with periampullary tumor were 86.5% (32/37), 89.7% (70/78) and 88.7% (102/115), respectively. The sensitivity, specificity and accuracy of EUS for patients with inflammatory stenosis were 88.2% (60/68), 89.4% (42/47) and 88.7% (102/115), respectively. The overall accuracy of EUS for diagnosing an undetermined etiology for CBD dilatation was 88.7% (102/115) and was higher than the accuracy of ultrasound (US) (64.1%), computed tomography (CT) (66.2%), magnetic resonance imaging (MRI) (67.0%) or PET-CT (66.0%). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EUS combined with tumor markers for patients with malignant dilatation of CBD were 91.9% (34/37), 97.4% (76/78), 94.4% (34/36), 96.2% (76/79) and 95.7% (110/115), respectively. PD dilation (P=0.026) and weight loss (P=0.035) had significant predictive values of malignancy. Conclusions: EUS is an effective diagnostic tool for determining the etiology of a CBD dilatation, and offers meaningful information for guiding a treatment plan. EUS used in conjunction with tumor markers has high yield in differentiating benign and malignant CBD dilatation. More attention should be paid to patients with PD dilation or weight loss to prevent misdiagnosis of malignant CBD dilation.

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. 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

Peroral endoscopic myotomy (POEM) has shown excellent results for the treatment of achalasia in adults, but studies for children are limited. The study was aimed to analyze outcomes of peroral endoscopic myotomy (POEM) in children and compared with those in adults in a large multi-center study.Records of consecutive patients with achalasia who underwent POEM at three tertiary centers were reviewed. A total of 130 children were included in this study. The primary outcomes of perioperative outcomes and clinical follow-up data were analyzed.One child (0.8%) experienced technical failure. Five children (3.8%) had major adverse events, including one with pneumothorax requiring drainage, two with delayed mucosa barrier failure, one with readmission, and one with vital-sign instability. Both post-POEM Eckardt score and median LES pressure were significantly lower than their pre-POEM reference values in children (0.7 vs 7.4; 7.0 vs 27.1 mmHg; both P 0.001). During a median follow-up time of 40 months, clinical reflux rate was 27.0% and clinical failure rates at 1, 3, and 5 years were 1.8%, 3.5%, and 4.4% for children. The technical failure, major adverse events, and postoperative clinical reflux were comparable between children and adults (all P 0.05). Kaplan-Meier analysis showed that the risk of clinical failure was lower in children than adults (log-rank test, hazard ratio = 0.37, 95% confidence interval 0.15-0.91, P = 0.023).POEM can be safely performed in children with achalasia, and produce a better clinical response during long-term follow-up compared with that in adults.

Background: Peroral endoscopic myotomy (POEM) has showed excellent results for the treatment of achalasia in adults, but studies of POEM for children are limited. In this study, we comprehensively analyzed outcomes of POEM in children and compared with those in adults in a large multi-center study. Methods: Between August 2010 and December 2015, records of consecutive patients with achalasia who underwent POEM at three tertiary centers were reviewed. A total of 130 children were included in this study. The primary outcomes of perioperative outcomes and clinical follow-up data were analyzed. Findings: One child (0*8%) experienced technical failure. Five children (3*8%) had major adverse events, including one with pneumothorax requiring drainage, two with delayed mucosa barrier failure, one with readmission, and one with vital sign instability. Both post-POEM Eckardt score and median LES pressure were significantly lower than their pre-POEM reference values in children (0*7 vs 7*4; 7*0 vs 27*1 mmHg; both P 0*05). Kaplan-Meier analysis showed that the risk of clinical failure was lower in children than adults (log-rank test, hazard ratio=0*37, 95% confidence interval 0*15-0*91, P=0*023). Interpretation: POEM can be safely and effectively performed in children with achalasia. In addition, it produces a better clinical response during long-term follow-up compared with that in adults. Funding: This study was supported by grants from the National Natural Science Foundation of China (81873552, 81470811, 81570595, and 81670483), Major Project of Shanghai Municipal Science and Technology Committee (18ZR1406700, 16411950400, 16DZ2280900), Chen Guang Program of Shanghai Municipal Education Commission (15CG04), and Outstanding Young Doctor Training Project of Shanghai Municipal Commission of Health and Family Planning (2017YQ026), and the Project of Shanghai Municipal Commission of Health and Family Planning (SHDC12016203). Declaration of Interest: All authors have none to declare. Ethical Approval: This retrospective study was approved by the local ethics committee. Written informed consent was obtained before POEM from patients or their caretakers if patients were

BACKGROUND AND AIMS: Making an optimal and lasting submucosal cushion is critical for endoscopic submucosal dissection. The thermo-sensitive binary hydrogels system composed of poloxamer 407 and poloxamer 188 might be an excellent submucosal injection solution considering the unique feature that it remains liquid at room temperature and becomes gelatinous after being injected in the submucosa of the digestive tract. The present study focuses on preparing the thermo-sensitive binary hydrogels system and testing its capacity in mucosal lifting and its role in the endoscopic submucosal dissection procedure. METHODS: Various concentrations of poloxamer 407 and poloxamer 188 were added to normal saline. The gelation temperature viscosity of the thermo-sensitive binary hydrogels system was measured to choose the best formula. The thermo-sensitive binary hydrogels system and normal saline were first compared in extracted porcine stomach. For in vivo study, the thermo-sensitive binary hydrogels system and normal saline were compared for facilitating the endoscopic submucosal dissection procedure. RESULTS: Among the 46 kinds of thermo-sensitive binary hydrogels system, gelation temperatures of the thermo-sensitive binary hydrogels system I (poloxamer 407/poloxamer 188, 17%/0.5%, w/w) and the thermo-sensitive binary hydrogels system II (poloxamer 407/poloxamer 188, 18%/2%, w/w) were among the ideal range of gelation temperature. The injecting pressure in vitro study of thermo-sensitive binary hydrogels system II was significantly higher than that of thermo-sensitive binary hydrogels system I and normal saline (p

The objective of this study is to evaluate the feasibility and efficacy of endoscopic full-thickness resection (EFTR) and fully covered retrievable self-expandable metal stents (SEMSs) placement for this kind of tumors.A total of six consecutive patients, presenting with esophageal and GE junction SMTs, received EFTR and SEMSs placement at the our endoscopic center between January 2015 and June 2015. Their medical records were thoroughly investigated.EFTR was performed successfully in all cases. The en bloc resection rate was 100%. The final pathological diagnoses were leiomyomas in all six cases. No patients developed delayed bleeding. SEMSs were placed immediately after EFTR during the same endoscopic session except patient #1. Complete healing of esophageal leakage after stent placement was achieved for 6/6 patients (100%) without the need for surgical interventions. Stent migration occurred in one patient. No residual tumor or tumor recurrence was observed during the follow-up period.EFTR combined with fully covered retrievable self-expandable metallic stents placement is a feasible and effective new method for providing radical treatments for SMTs from the deep MP layer of esophagus and GE junction. Standardization of the procedure should be studied further.

Background and study aims: Peroral endoscopic myotomy (POEM) is now a widely used treatment for esophageal achalasia, supported by several large cohort studies. Although major perioperative adverse events (mAE) are rare, in-depth investigations of related risks and preventive measures are lacking. The aim of this study was to systematically assess mAEs during POEM by analyzing their incidence, risks, prevention, and management. Patients and methods: This retrospective single-center analysis included all patients (n = 1680) undergoing POEM between August 2010 and July 2015 at Zhongshan Hospital. Major adverse events were defined as: vital-sign instability, intensive care unit (ICU) stay, hospital readmission, conversion to open surgery, invasive postoperative procedure, blood transfusion, or prolonged (> 5 days) hospitalization for functional impairment. Results: A total of 55 patients (3.3 %, 95 % confidence interval [CI] 2.5 % – 4.2 %) experienced mAEs: delayed mucosal barrier failure (n = 13, 0.8 %; 95 %CI 0.4 % – 1.3 %), delayed bleeding (n = 3, 0.2 %; 95 %CI 0.04 % – 0.5 %), hydrothorax (n = 8, 0.5 %; 95 %CI 0.2 % – 0.9 %), pneumothorax (n = 25, 1.5 %; 95 %CI 1.0 % – 2.2 %), and miscellaneous (n = 6, 0.4 %; 95 %CI 0.1 % – 0.8 %). Four patients (0.2 %) required ICU admission. No surgical conversion occurred, and 30-day mortality was zero. In stepwise multivariate regression, institution experience of Conclusion: In general, POEM appears to be a safe procedure. Major adverse events were rare and could usually be prevented or anticipated, and were all managed effectively.

Gastric schwannoma is not so recognized by clinicians as its counterparts. The efficacy of endoscopic resection has not been described yet. Our aim was to assess the efficacy and safety of endoscopic resection in the management of gastric schwannoma. Retrospective data were reviewed from January 2008 to December 2013 in our center. Fourteen patients who had endoscopic resection with the final pathology result of gastric schwannoma were included in the study. Of the 14 patients, there were 12 females and two males. The median age was 59 years (range 32–83). Thirteen tumors (92.9 %) were from the muscularis propria and one located in the submucosa. Endoscopic en bloc resection was achieved in 12 patients (12/14, 85.7 %), including seven cases of endoscopic full-thickness resection (EFTR). The mean resected tumor size was 1.73 ± 1.10 cm (range 0.3–4.0 cm). In one case, endoscopic resection was suspended due to the limited experience of EFTR during the early period of the study. In another case, due to the difficult tumor location (gastric angle) and extraluminal growth pattern, the patient was referred to laparoscopic surgery. In the 12 successful endoscopic resection cases, during the median follow-up time of 4 years (range 17–77 months, one patient lost), no tumor residue, recurrence or metastasis was found. Endoscopic resection is safe and effective in treating gastric schwannoma with excellent long-term outcomes. However, it should be performed with caution because schwannoma is mainly located in the deep muscular layer, which leads to the full-thickness resection of gastric wall.

Mucosal injury (MI) is one of the most common perioperative adverse events of per-oral endoscopic myotomy (POEM). Severe undertreated MI may lead to contamination of the tunnel and even mediastinitis. This study explored the characteristics, predictors, and management approaches of intraoperative MI.A retrospective review of the prospectively collected database at a large tertiary referral endoscopy unit was conducted for all patients undergoing POEM between August 2010 and March 2016. MI was graded according to the difficulty of repair (I, easy to repair; II, difficult to repair). The primary outcomes were the incidence and predictors of intraoperative MI. Secondary outcomes were MI details and the corresponding treatment.POEM was successfully performed in 1912 patients. A total of 338 patients experienced 387 MIs, for an overall frequency of 17.7% (338/1912). Type II MI was rare, with a frequency of 1.7% (39/1912). Major adverse events were more common in patients with MI than in those without MI (6.2% vs 2.5%, P .001). On multivariable analysis, MI was independently associated with previous Heller myotomy (odds ratio [OR], 2.094; P = .026), previous POEM (OR, 2.441; P = .033), submucosal fibrosis (OR, 4.530; P .001), mucosal edema (OR, 1.834; P = .001), and tunnel length ≥13 cm (OR, 2.699; P .001). Previous POEM (OR, 5.005; P = .030) and submucosal fibrosis (OR, 12.074; P .001) were significant predictors of type II MI. POEM experience1 year was a protective factor for MI (OR, .614; P = .042) and type II MI (OR, .297; P = .042).MI during POEM is common, but type II injury is rare. Previous POEM and submucosal fibrosis were significant predictors of type II mucosal injury. POEM experience after the learning curve reduces the risk of MI.

Endoscopic full-thickness resection (EFTR) is a "changing-concept" endoscopic resection technique, which safely allows resecting deep submucosal tumors (SMTs) in the gastrointestinal (GI) wall. It's a highly promising endoscopic procedure that allows full-thickness excision of a small piece of the complete GI wall by using only a flexible endoscope. EFTR is a meeting point between surgery and endoscopy and probably the onset of many prospective combined minimally invasive therapeutic techniques that science will explore. In this review, use of the EFTR technique for gastrointestinal SMTs is highlighted, focusing on some technical aspects, indications, contraindications and outcomes.

Peroral endoscopic myotomy (POEM) has been developed to provide a less-invasive myotomy for achalasia in adults but seldom has been used in pediatric patients.To evaluate the feasibility, safety, and efficacy of POEM for pediatric patients with achalasia.Single-center, prospective study.Academic medical center.A total of 27 pediatric patients (mean age 13.8 years, range 6-17 years) with achalasia.The primary outcome was symptom relief during follow-up, defined as an Eckardt score of ≤3. Secondary outcomes were procedure-related adverse events, clinical reflux adverse events, and lower esophageal sphincter (LES) pressure on manometry before and after POEM.A total of 26 cases (96.3%) underwent successful POEM. A submucosal tunnelling attempt failed in 1 case because of serious inflammation and adhesion. No serious adverse events related to POEM were encountered. During a mean follow-up period of 24.6 months (range 15-38 months), treatment success was achieved in all patients (mean score before vs after treatment 8.3 vs 0.7; P .001). Mean LES pressure also decreased from a mean of 31.6 mm Hg to 12.9 mm Hg after POEM (P .001). Five patients developed clinical reflux adverse events (19.2%).Single center and lack of some objective evaluations.This relatively long-term follow-up study adds to the evidence that POEM seems to be a promising new treatment for pediatric patients with achalasia, resulting in long-term symptom relief in all cases and without serious adverse events.