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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.

BACKGROUND Achalasia is an esophageal motility disorder with unknown etiology. Previous findings indicate that immune-mediated inflammatory process causes inhibitory neuronal degeneration. This study was designed to evaluate levels of serological cytokines and chemokines in patients with achalasia. METHODS We collected information from forty-seven patients with achalasia who underwent peroral endoscopic myotomy. Control samples were collected from forty-seven age- and sex-matched healthy people. The concentrations of serological cytokines and chemokines were analyzed by Luminex xMAP immunoassay. Serological and clinical data were compared between groups. KEY RESULTS Compared with healthy controls, achalasia patients had significantly increased concentrations of eleven cytokines and chemokines, namely, TGF-s1 (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.

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.

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.

Endoscopic full-thickness resection (EFTR) is a minimally invasive method for en bloc resection of gastrointestinal (GI) lesions originating from the muscularis propria layer. Successful closure of the wall defect is a critical step.The aim of this study was to evaluate the feasibility and efficacy of a novel and simplified endoscopic grasp-and-loop (GAL) closure method using an endo-loop assisted with grasping forceps for defect closure.From January 2015 to March 2016, 13 patients with submucosal tumors (SMTs) originating from the muscularis propria (MP) layer underwent EFTR and were enrolled in this study. After successful tumor resection, an endo-loop was anchored onto the circumferential margin of the gastric defect with grasping forceps assistance and tightened gently. Patient characteristics, tumor size, en bloc resection, and postoperative complications were evaluated.Of the 13 lesions in the stomach, two were located in the greater curvature of the mid-upper body, 11 were located in the fundus. The endoscopic GAL closure method was successfully performed after EFTR in all the 13 patients without laparoscopic assistance. The mean procedure time was 43.5 min (range 20-80 min), while the GAL closure procedure took a mean of 9.4 min (range 3-18 min). The mean resected lesion size was 1.5 cm (range 0.5-3.5 cm). Pathological diagnoses of these lesions were 11 gastrointestinal stromal tumors (GISTs) and two leiomyomas. No major adverse events occurred during or after the procedure. All the patients were discharged after a mean time of 2.4 days (range 1-4 days). No residual lesion or tumor recurrence was found during the follow-up period (median, 5 months; range, 1-15 months).The endoscopic GAL closure method is feasible, effective, and safe for closing the gastric defect after EFTR in patients.

The aim of this study is to evaluate the long-term outcomes of a large series of patients treated with submucosal tunneling endoscopic resection (STER).STER is a newly developed treatment for upper gastrointestinal submucosal tumors originating from the muscularis propria layer. Recently, reports about STER are increasing, but a large study with long-term follow-up is little known.In a retrospective study, a total of 180 patients with upper gastrointestinal submucosal tumors undergoing STER were included from June 2011 to May 2013. Clinicopathological, endoscopic, and follow-up data were collected and analyzed.The en bloc resection was achieved in 90.6% of patients and the complications rate was 8.3%. Based on statistical analysis, tumors with irregular shape and greater size were the significant contributors to piecemeal resection and long operative times. Besides tumor shape and size, tumor in deep muscularis propria and long operative time were also risk factors of complications. The median hospitalization time was 3.2 days. All of the complications were cured by conservative treatment. A median follow-up of 36 months was available and all patients were free from local recurrence or distant metastasis during the study period.STER is an effective and safe methodology for the resection of upper gastrointestinal submucosal tumors. Tumor size and shape impact on the piecemeal resection rate and procedural difficulty. STER for large tumors with irregular shape in the deep muscularis propria is also feasible but associated with relatively high risks of piecemeal resection and complications.

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.

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).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.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.This risk-scoring system demonstrated good performance in predicting clinical failure in patients who underwent POEM.

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.

Objective Our study aimed to compare the curative effect and immunoregulation between MSCs activated by Poly(I:C) for 24 hours and unactivated MSCs on lupus mice. Materials and methods MSCs were pretreated by Poly(I:C) at 50 μg/mL for 24 h. B6.MRL- Fas lpr mice were divided into UC-MSC treated group, FLS treated group, Poly(I:C) preconditioned MSC treated group (P-MSC) and untreated group randomly. All treated mice were infused with 1 × 10 6 MSCs or FLSs at the 24th week and were sacrificed 4 weeks later. The spleen weight, serum immunoglobulin G (IgG) levels, serum anti-double stranded DNA (anti-dsDNA) antibody levels, immune cell subsets, renal lesions and IgG deposition in the kidney were evaluated. The effects of two kinds of MSCs on the proliferation and apoptosis of CD4+ T cells were detected by flow cytometry. The TLR3 expression at protein level in MSCs was assessed with and without Poly(I:C) treatment. The expression of immunoregulatory factors were detected by qRT-PCR in different dose and duration of Poly(I:C). Result Poly(I:C) preconditioned MSCs had similar therapeutic effects in lupus mice compared with untreated MSCs in vivo. Furthermore, Poly(I:C) treated MSCs and untreated MSCs had comparable inhibitory effects on proliferation of T cells, and Poly(I:C) could enhance the expression of TLR3 at protein and mRNA level. Poly(I:C) could partly alter the mRNA levels of immunoregulatory factors, such as hepatocyte growth factor, transforming growth factor β1, vascular endothelial growth factor, but did not have significant changes in cyclooxygenase 2, interleukin 6, tumor necrosis factor α, indoleamine 2,3-dioxygenase, interferon γ and chemokine (C-C motif) ligand 2. Conclusion Our study did not find that Poly(I:C) treatment could enhance the therapeutic effect of MSCs in lupus mice in vivo.

Although endoscopic submucosal dissection (ESD) of colorectal carcinoids is increasing, little is known about long-term outcomes of patients. We investigated the efficacy and safety of ESD of colorectal carcinoids and evaluated long-term outcomes, including local recurrence and metastasis.We performed a retrospective analysis of data collected from 239 consecutive patients with colorectal carcinoids20 mm who underwent endoscopic ultrasonography (to evaluate the size of tumor and the depth of invasion), followed by ESD from January 2007 through October 2012 at the Zhongshan Hospital of Fudan University. Histology and patient data were collected during a median follow-up period of 52 months (range, 25-94 months) to determine tumor stage and type, completeness of resection, complications, tumor recurrence, and distant metastasis.En bloc resection was achieved for all of the 239 treated lesions; tumor tissues were completely resected for 216 of the lesions (90.38%). Eight patients had ESD-related complications (3.35%). As more ESDs were performed by endoscopists, the rate of complete tumor resection increased, and the rate of complications decreased. ESD of carcinoids in colon increased the risk of non-R0 resection and the rate of complications. During the follow-up period, all patients remained free from local recurrence. However, distant metastases were detected in 6 patients (2.51%); lymphovascular invasion was a risk factor for metastasis.ESD is effective for the resection of rectal carcinoids20 mm and causes complications in less than 4% of patients. ESD for colonic carcinoids is feasible but associated with a higher non-R0 resection rate and a trend toward higher complications risk. Tumor features and stage determine risk for distant metastasis, so long-term follow-up is essential.

BACKGROUND Achalasia is a motility disorder of unknown etiology. Previous studies supported the hypothesis that autoimmune-mediated inflammatory responses produce inhibitory neuronal degeneration. This study was designed to explore the role of mast cells in achalasia. METHODS We collected information from 116 patients with achalasia who underwent peroral endoscopic myotomy between December 2016 and May 2017. Lower esophageal sphincter (LES) muscle biopsy was performed in all patients with achalasia, as well as 20 control subjects. The number of mast cells, interstitial cells of Cajal (ICCs), nNOS-positive cells, and S-100-positive cells in the LES were evaluated by immunohistochemistry. Pathological and clinical data were compared between groups. KEY RESULTS Compared with controls, the LES of patients with achalasia had significantly fewer ICCs, nNOS-positive cells, and S-100-positive cells and a higher number of mast cells (all P

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.

The endoscopic resection of gastrointestinal mesenchymal tumors (GIMTs) is widely accepted because of its minimal invasiveness. However, one major concern is the high rate of positive microscopic margins remaining following endoscopic resection, which was thought to be related to a higher risk of recurrence. This study aimed to determine whether positive margins affect the recurrence rate of gastric GIMTs and the factors associated with positive margins. Patients with gastric GIMTs were recruited retrospectively from January 2008 to December 2013. Clinical and pathological features, endoscopic procedure information, and follow-up data were collected and analyzed. The study included 777 patients. All tumors were removed along with the pseudocapsule without macroscopic residual (ER0), and the median tumor size was 15.2 mm (range 3–100 mm). Pathological evaluation revealed 371(47.7%) GISTs. The rate of microscopic R1 resection rate was 47.0% (443/777). In a stepwise multivariate analysis, a significantly increased incidence of R1 resection was recorded for the GISTs (OR 11.13, 95% CI 3.00–41.37). In a subgroup analysis of GISTs, a univariate analysis revealed that EFTR achieved a higher rate of R0 resection (OR 0.56, 95% CI 0.31–1.00), but it was proven insignificant in a stepwise multivariate analysis. Local recurrence occurred in two patients (0.3%) during a mean follow-up time of 34.2 months. Differences in the recurrence rates between the R0 and R1 groups were statistically insignificant (P = 0.841). R1 resection for gastric GIMTs is not related to a higher recurrence rate than R0 resection, and ER0 resection is sufficient for gastric GIMTs.

Although peroral endoscopic myotomy (POEM) is credited with high success rates in the treatment of achalasia, persistent/recurrent symptoms may occasionally develop afterwards. Our purpose was to evaluate the feasibility, safety, and efficacy of repeat peroral endoscopic myotomy (Re-POEM) as salvage therapy after initial POEM failure.Fifteen patients with persistence/recurrence of symptoms after previous POEM (Eckardt symptom score ≥ 4) were retrospectively selected from a prospectively maintained database housing a total of 1454 consecutive patients with achalasia. The primary endpoint was symptom relief during follow-up, defined by an Eckardt score of ≤ 3. Secondary outcome measures were procedure-related adverse events, change in manometric lower esophageal sphincter (LES) pressure, and reflux symptoms before and after Re-POEM.All patients underwent successful Re-POEM a mean of 13.5 months (range 4 - 37 months) after execution of their primary POEM procedures. Mean operative time was 41.5 minutes (range 28 - 62 minutes). One instance of submucosal tunnel infection was successfully managed with conservative treatment. During a mean follow-up period of 11.3 months (range 3 - 18 months), therapeutic success was achieved in all patients. The mean symptom score pretreatment was 5.6 (range 4 - 8), compared with a post-treatment mean of 1.2 (range 0 - 3; P 0.001). Mean LES pressure also declined from 25.0 mmHg to 9.5 mmHg after Re-POEM (P 0.001). The overall clinical reflux complication rate of Re-POEM was 33.3 %.Re-POEM appears safe and effective as a salvage option after initial POEM failure, conferring short-term symptom relief and being free of serious complications in all patients.

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.

Background Additional surgery is recommended when early colorectal cancer (ECRC) is resected by non-curative endoscopic submucosal dissection (ESD) and there is significant risk of lymph node metastasis (LNM). The aim of this study was to investigate the efficacy and safety of additional surgery after non-curative ESD for ECRC and evaluate long-term outcomes. Methods Patients with ECRC who underwent ESD and additional surgery between July 2007 and November 2013 were identified. Histology and patient data were collected during an average period of more than 5 years to determine tumor stage and type, resection status, complications, tumor recurrence, and distant metastasis. Results Fifty-one patients who underwent additional surgery were eligible for analysis. Overall, regional LNM was detected in 5 patients (9.8%) and presence of lymphovascular infiltration was a significant risk factor. Surgery-related complications occurred in 3 patients (5.9%). During a median follow-up period of 59 months, no metastasis or local recurrence was observed. Three patients died of other diseases and no CRC-related deaths took place. Conclusions Additional surgery after non-curative ESD for ECRC is effective and safe and should be encouraged to foster curative treatment and better long-term outcomes.

Objective The aim of this study was to evaluate the outcomes of endoscopic submucosal dissection (ESD) for superficial proximal esophageal neoplasia. Summary of background data The surgery for a tumor located in proximal esophagus is relatively difficult and leads to a high morbidity and mortality. ESD is a minimally invasive endoscopic treatment of superficial neoplasia of the gastrointestinal tract allowing en block resection with low recurrence rates; however, ESD for superficial proximal esophageal neoplasia is little known. Methods We retrospectively analyzed 102 consecutive patients who fit the inclusion criteria with 106 lesions who underwent ESD from February 2009 to July 2015 at the Zhongshan Hospital, Fudan University in Shanghai, China. During the study, the en bloc and pathologically complete resection rates, complication rate, incidence of esophageal stricture after ESD, disease-specific, and overall survival rates were evaluated. Results The mean age was 62 (45-84) years with 100% en bloc resection rate. The mean operation time was 48 (10-144) minutes. The mean diameter of the resected tumors was 2.9 (1.2-6.5) cm. The pathological diagnoses were high-grade intraepithelial dysplasia in 45 (42.5%) lesions, and the rest were squamous cell carcinoma with staging of intraepithelial in 18 (17.0%), lamina propria in 13 (12.3%), muscularis mucosa in 16 (15.1%), SM1 in 10 (9.4%), and SM2 or deeper in 4 (3.8%) of the lesions. The R0 resection rates were 94.3% (100/106). There was no delayed bleeding. Two small perforations observed were closed successfully with clips. Symptomatic esophageal strictures in 17 (16.7%) patients were treated by endoscopic balloon dilation with a mean of 4 (1-14) times and 88.2% (15/17) success. Additional treatments of esophagectomy or chemoradiotherapy were recommended to patients with SM1 or deeper neoplasia or incomplete resection. Local recurrence was observed in 3 (2.9%) cases. Fifteen patients were lost to follow-up. Five-year overall survival rate was 98% and disease-specific survival rate was 100%. The mean follow-up time was 33.6 months. Conclusions ESD for the superficial proximal esophageal neoplasia is a safe and a very effective treatment method with a 100% 5-year disease-specific survival rate.

The colorectal endoscopic submucosal dissection (ESD) remains technically challenging, especially for older patients who frequently encounter complex chronic diseases and have a loose colon. However, only limited number of studies are available for the safety of ESD in older patients with especially large laterally spreading tumors. Therefore, in this retrospective study, we compared the outcomes of ESD for laterally spreading tumors (LST) ≥3cm(cm) in older patients to that in younger patients.Consecutive patients with LSTs 3cm or larger were enrolled for from May 2010-2016. These patients were divided into two groups: the younger group (65years) and the older group (≥65years). The clinicopathologic findings and the outcomes of ESD procedures were compared between the two groups.A total of 70 patients in the younger group and 73 patients in the older group were treated by ESD for colorectal LSTs larger than 3cm. No significant differences were observed in the gender ratio, tumor morphological type, tumor location, and tumor size between the two groups. The en bloc resection rates were 85.7 and 89.0%, respectively, without a significant difference. The procedural time was similar between the younger and older patients (71.8±34.7min vs. 70.6±29.5min). The duration of hospital stay was not significantly different between the two groups (4.1±2.2days vs. 4.4±2.5days). No significant differences were observed between the two groups with respect to ESD-related complications including delayed bleeding, perforation, and stricture.ESD appears to be an effective and safe method for LSTs larger than 3cm in older patients.

Background & Aims Peroral endoscopic myotomy (POEM) is a minimally invasive endoscopic surgical procedure that is effective in treatment for spastic esophageal motility disorders. However, little is known about the learning curve for endoscopists. We aimed to evaluate the effects of various factors on the POEM learning curve. Methods We performed a retrospective study of 1346 patients who underwent POEM for achalasia at Shanghai Zhongshan Hospital in China from August 2010 through July 2015. We used risk-adjusted cumulative sum and moving average methods to evaluate outcomes. The primary outcome was a composite of technical failure and adverse events. Secondary outcomes included procedure time and the composite outcome of technical failure, adverse events, and clinical failure of the first 192 cases performed by only the original, training surgeon. Results The primary composite outcome occurred in 54 (4%) of the 1346 patients: 10 technical failures and 44 adverse events. This composite outcome was independently associated with the case number ( P = .010), full-thickness myotomy ( P = .002), and procedure time ( P = .001). After we adjusted for these risk factors, cumulative sum analysis showed that the primary composite outcome decreased gradually after 100 cases. The procedure time was high during the first few cases and decreased after endoscopists performed 70 cases. The secondary composite outcome of technical failure, adverse events, and clinical failure for the 192 cases performed by only the original surgeon gradually decreased after 90–100 cases. Conclusions In a retrospective analysis of POEM procedures, we found that 100 cases were required to decrease the risk of technical failure, adverse events, and clinical failure (the learning curve). Seventy cases can be considered the threshold for decreasing procedure time.

Background Submucosal tunneling endoscopic resection (STER) is regarded as a promising method for resection of submucosal tumors (SMTs); however, little is known about a comprehensive comparison of STER and thoracoscopic enucleation (TE). The aim of this study was to compare the clinical outcomes of STER and TE for large symptomatic SMTs in the esophagus and esophagogastric junction, as well as to analyze the factors that affect the feasibility and safety of STER. Study Design We enrolled 166 patients with large symptomatic SMTs in the esophagus and esophagogastric junction from September 2011 to March 2016 in this retrospective study. The clinicopathologic features and treatment results were collected and analyzed. Results En bloc resection was achieved in 84.6% of the patients in the STER group and 86.7% of the patients in the TE group (p = 0.708). Notably, the procedure time and hospital stay in the STER group were considerably shorter than those in the TE group. Tumor transverse diameter is a significant risk factor for piecemeal resection, adverse events, and technical difficulties. No recurrence or metastasis was found during a mean follow-up period of more than 2 years. Conclusions Submucosal tunneling endoscopic resection is effective and safe for large SMTs in the esophagus and esophagogastric junction. This procedure has the advantage of being more minimally invasive with a shorter procedure time and hospital stay compared with TE. Submucosal tunneling endoscopic resection for tumors with a transverse diameter ≥3.5 cm and an irregular shape is associated with relatively high risk for piecemeal resection, adverse events, and technical difficulties.

Background Colorectal carcinomas (CRCs) arise from premalignant precursors in an adenoma-carcinoma sequence, in which adenoma with high-grade dysplasia (HGD) and early-stage carcinoma are defined as advanced neoplasia. A limited number of studies have evaluated the long-term outcomes of endoscopic submucosal dissection (ESD) for advanced colorectal neoplasia. This study aimed to assess the efficacy and safety of ESD for advanced colorectal neoplasia as well as the long-term outcomes, including local recurrence and metastasis. Methods We analyzed data collected from 610 consecutive patients with 616 advanced colorectal neoplasia lesions treated with ESD between January 2007 and December 2013. Clinical, endoscopic, and histological data were collected over a median follow-up period of 58 months to determine tumor stage and type, resection status, complications, tumor recurrence, and distant metastasis. Results The overall rates of en bloc resection, histological complete resection, and major complications were 94.3%, 89.4%, and 2.3%, respectively. Hybrid ESD was an independent factor of piecemeal resection. Tumor location in the colon was associated with increased risk of ESD-related complications. During the follow-up period, all patients remained free of metastasis. However, local recurrence occurred in 4 patients (0.8%); piecemeal resection was a risk factor. Conclusions ESD is effective and safe for resection of advanced colorectal neoplasia, with a high en bloc resection rate and favorable long-term outcomes. ESD is indicated for the treatment of HGD and early-stage CRC to obtain curative resection and reduce local recurrence rate.

Per-oral endoscopic myotomy (POEM) has received wide acceptance as a highly effective and safe treatment for esophageal achalasia. Short-term and small-scale studies are ample, but long-term large-scale studies are few. The aim of the study was to systematically analyze our long-term results of POEM, with particular emphasis on POEM failures and associated risk factors.In this single-center study, consecutive patients treated with POEM between August 2010 and December 2012 were included. The Kaplan-Meier survival function was used to estimate clinical success rate at each year. The Cox proportional hazards model was used to analyze risk factors related to recurrence.A total of 564 patients were included. Major perioperative adverse events occurred in 36 patients (6.4%). After a median follow-up of 49 months (range, 3-68), the Eckardt score and lower esophageal sphincter (LES) pressure were significantly decreased (median Eckardt score, 8 to 2 [P .05]; median LES pressure, 29.7 mm Hg to 11.9 mm Hg [P .05]). Fifteen failures occurred within 3 months, 23 between 3 months and 3 years, and 10 after 3 years. The estimated clinical success rates at 1, 2, 3, 4, and 5 years were 94.2%, 92.2%, 91.1%, 88.6%, and 87.1%, respectively. Multivariate Cox regression revealed long disease duration (≥10 years) and history of prior interventions to be risk factors for recurrence. Clinical reflux occurred in 37.3% of patients (155/ 416).POEM is a highly safe and effective treatment for esophageal achalasia with favorable long-term outcomes.

Background and Aims Endoscopic submucosal dissection (ESD) of colorectal submucosal tumors (SMTs) is becoming increasingly common; however, there have been few large consecutive studies analyzing its therapeutic efficacy and safety. The aim of this study was to evaluate the efficacy, safety, and long-term outcomes of ESD for colorectal SMTs. Methods This retrospective study included 412 consecutive patients with colorectal SMTs who underwent ESD at the Zhongshan Hospital of Fudan University from January 2008 to July 2014. Tumor histopathology, completeness of resection, adverse events, tumor recurrence, and distant metastasis were analyzed. Results Complete resection was achieved for 358 lesions (86.9%). Thirteen patients had serious adverse events (3.2%) including bleeding and perforation, and 28 patients (6.8%) had post-ESD electrocoagulation syndrome (PEECS). Because more ESDs for colorectal SMTs were performed by endoscopists, the rate of complete resection increased (78.5% vs 88.5%), and the rate of serious adverse events decreased (9.2% vs 2.0%). SMTs in the colon increased the risk of incomplete resection (19.6% vs 11.3%), serious adverse events (8.7% vs 1.6%), and PEECS (16.3% vs 4.1%). SMTs originating from the muscularis propria and sized ≥20 mm increased the rate of PEECS (22.7% vs 5.9% and 31.3% vs 5.8%, respectively). Conclusion ESD is effective for resection of colorectal SMTs and rarely causes serious adverse events. Tumor location and the experience of endoscopists influence the complete resection rate and the development of serious adverse events. ESD is feasible for large tumors and tumors in the muscularis propria, but this is associated with relatively high risks of adverse events.

The sigmoid-shaped esophagus is considered to be the advanced stage of achalasia, in which the esophageal lumen is significantly dilated, swerved, and rotated. In consideration of the efficacy of peroral endoscopic myotomy (POEM) for early achalasia, it may also offer another option for the treatment of advanced achalasia with sigmoid-shaped esophagus. Our purpose was to evaluate the feasibility and long-term efficacy of POEM for patients with sigmoid-type achalasia. 32 consecutive patients with sigmoid-type achalasia (S1 type in 29 patients and S2 type in 3 patients) were prospectively included. Primary outcome was symptom relief during follow-up, defined as an Eckardt score ≤3. Secondary outcomes were procedure-related adverse events, the resting lower esophageal sphincter (LES) pressure, clinical reflux complications, and procedure-related parameters. All cases received POEM successfully. The mean operation time was 63.7 min (range 22–130 min). No serious complications related to POEM were encountered. During a mean follow-up period of 30.0 months (range 24–44 months), treatment success was achieved e in 96.8 % of cases (mean score pre- vs. post-treatment 7.8 vs. 1.4; P

The esophagogastric junction (EGJ) is a difficult location for endoscopic resection due to its narrow lumen and sharp angle. Potential increased risks of perforation and mediastinal infection exist, especially for submucosal tumors (SMTs) originating from the muscularis propria (MP) layer. We previously demonstrated the safety and efficacy of submucosal tunneling endoscopic resection (STER) for upper gastrointestinal SMTs, but the feasibility of STER for the removal of SMTs at the EGJ requires systematic investigation. The aim of the investigation was to evaluate the clinical impact of STER on the removal of SMTs at the EGJ.A prospective study was carried out which included a consecutive cohort of 57 patients who underwent STER for 57 SMTs of the EGJ originating from the MP layer between July 2010 and August 2012 in a single academic medical center. Adverse events, en bloc resection rate, and local recurrence were evaluated.The average maximum diameter of the lesions was 21.5 mm (range 6-35 mm). The en bloc resection rate was 100 % (57/57). No delayed hemorrhage or severe adverse events occurred in any of the 57 patients following STER. No local recurrence and distant metastasis occurred during 24 months' follow-up. Less subcutaneous emphysema and pneumomediastinum absorption time (p = 0.005) occurred with CO2 versus air insufflations.Our study showed that STER was safe and effective, provided accurate histopathologic evaluation, and was curative for SMTs of the deep MP layers at the EGJ. CO2 gas insufflation is recommended.

Background and Aims According to guidelines, endoscopic resection should only be performed for patients whose early gastric cancer invasion depth is within the mucosa or submucosa of the stomach regardless of lymph node involvement. The accurate prediction of invasion depth based on endoscopic images is crucial for screening patients for endoscopic resection. We constructed a convolutional neural network computer-aided detection (CNN-CAD) system based on endoscopic images to determine invasion depth and screen patients for endoscopic resection. Methods Endoscopic images of gastric cancer tumors were obtained from the Endoscopy Center of Zhongshan Hospital. An artificial intelligence–based CNN-CAD system was developed through transfer learning leveraging a state-of-the-art pretrained CNN architecture, ResNet50. A total of 790 images served as a development dataset and another 203 images as a test dataset. We used the CNN-CAD system to determine the invasion depth of gastric cancer and evaluated the system's classification accuracy by calculating its sensitivity, specificity, and area under the receiver operating characteristic curve. Results The area under the receiver operating characteristic curve for the CNN-CAD system was .94 (95% confidence interval [CI], .90-.97). At a threshold value of .5, sensitivity was 76.47%, and specificity 95.56%. Overall accuracy was 89.16%. Positive and negative predictive values were 89.66% and 88.97%, respectively. The CNN-CAD system achieved significantly higher accuracy (by 17.25%; 95% CI, 11.63-22.59) and specificity (by 32.21%; 95% CI, 26.78-37.44) than human endoscopists. Conclusions We constructed a CNN-CAD system to determine the invasion depth of gastric cancer with high accuracy and specificity. This system distinguished early gastric cancer from deeper submucosal invasion and minimized overestimation of invasion depth, which could reduce unnecessary gastrectomy.

Background & Aims Esophagectomy is the standard treatment for early-stage esophageal squamous cell carcinoma (EESCC), but patients who undergo this procedure have high morbidity and mortality. Endoscopic submucosal dissection (ESD) is a less-invasive procedure for treatment of EESCC, but is considered risky because this tumor frequently metastasizes to the lymph nodes. We aimed to directly compare outcomes of patients with EESCC treated with ESD vs esophagectomy. Methods We performed a retrospective cohort study of patients with T1a-m2/m3, or T1b EESCCs who underwent ESD (n = 322) or esophagectomy (n = 274) from October 1, 2011 through September 31, 2016 at Zhongshan Hospital in Shanghai, China. The primary outcome was all-cause mortality at the end of follow up (minimum of 6 months). Secondary outcomes included operation time, hospital stay, cost, perioperative mortalities/severe non-fatal adverse events, requirement for adjuvant therapies, and disease-specific mortality and cancer recurrence or metastasis at the end of the follow up period. Results Patients who underwent ESD were older (mean 63.5 years vs 62.3 years for patients receiving esophagectomy; P = .006) and a greater proportion was male (80.1% vs 70.4%; P = .006) and had a T1a tumor (74.5% vs 27%; P = .001). A lower proportion of patients who underwent ESD had perioperative mortality (0.3% vs 1.5% of patients receiving esophagectomy; P = .186) and non-fatal severe adverse events (15.2% vs 27.7%; P = .001)—specifically lower proportions of esophageal fistula (0.3% of patients receiving ESD vs 16.4% for patients receiving esophagectomy; P = .001) and pulmonary complications (0.3% vs 3.6%; P = .004). After a median follow-up time of 21 months (range, 6–73 months), there were no significant differences between treatments in all-cause mortality (7.4% for ESD vs 10.9%; P = .209) or rate of cancer recurrence or metastasis (9.1% for ESD vs 8.9%; P = .948). Disease-specific mortality was lower among patients who received ESD (3.4%) vs patients who patients who received esophagectomy (7.4%) (P = .049). In Cox regression analysis, depth of tumor invasion was the only factor associated with all-cause mortality (T1a–m3 or deeper vs T1a–m2: hazard ration, 3.54; P = .04). Conclusion In a retrospective study of patients with T1am2/m3 or T1b EESCCs treated with ESD (n = 322) or esophagectomy (n = 274), we found lower proportions of patients receiving ESD to have perioperative adverse events or disease specific mortality after a median follow up time of 21 months. We found no difference in overall survival or cancer recurrence or metastasis in patients with T1a or T1b ESCCs treated with ESD vs esophagectomy.

Peroral endoscopic myotomy (POEM) has recently been introduced as a promising alternative to laparoscopic Heller myotomy for idiopathic achalasia. Several proposed technical modifications are yet to be tested in randomized trials. The objective of our study was to evaluate efficacy and safety of water-jet (WJ) assisted POEM versus the conventional (C) technique. The clinical trial registration number is NCT01742494. A prospective randomized trial was carried out in Zhongshan Hospital, Fudan University (Shanghai, China), in 100 consenting achalasia patients between August 2011 and April 2012. Patients eligible for POEM were randomized to use of either the HybridKnife (WJ group) or the conventional technique using injection and triangle tip knife interchangeably (C group). A total of 100 patients with comparable characteristics between groups were included. Procedure time was significantly shorter for the WJ group (22.9 ± 6.7 vs. 35.9 ± 11.7 min; p

A circular muscle myotomy preserving the longitudinal outer esophageal muscular layer is often recommended during peroral endoscopic myotomy (POEM) for achalasia. However, because the longitudinal muscle fibers of the esophagus are extremely thin and fragile, and completeness of myotomy is the basis for the excellent results of conventional surgical myotomy, this modification needs to be further debated. Here, we retrospectively analyzed our prospectively maintained POEM database to compare the outcomes of endoscopic full-thickness and circular muscle myotomy.According to the myotomy depth, 103 patients with full-thickness myotomy were assigned to group A, while 131 patients with circular muscle myotomy were assigned to group B. Symptom relief, procedure-related parameters and adverse events, manometry outcomes, and reflux complications were compared between groups.The mean operation times were significantly shorter in group A compared with group B (p = 0.02). There was no increase in any procedure-related adverse event after full-thickness myotomy (all p0.05). During follow-up, treatment success (Eckardt score ≤ 3) persisted for 96.0% (95 of 99) of patients in group A and for 95.0% (115 of 121) of patients in group B (p = 0.75). There were no statistically significant differences in pre- and post-treatment D-value of symptom scores and lower esophageal sphincter pressures between groups (both p0.05). The overall clinical reflux complication rates were also similar (21.2% vs 16.5%, p = 0.38).Short-term symptom relief and manometry outcomes of each method were comparable. Full-thickness myotomy significantly reduced the procedure time but did not increase the procedure-related adverse events or clinical reflux complications.

Peroral endoscopic myotomy (POEM) has recently been described as a scar-free and less-invasive surgical myotomy option for treating achalasia. This procedure incorporates concepts of natural orifice transluminal endoscopic surgery and achieves endoscopic myotomy by using a submucosal tunnel as the operating space. Initial published experience in humans is more than encouraging despite a relatively short follow-up. Common complications of POEM include mucosal injury, subcutaneous emphysema, mediastinal emphysema, pneumothorax, pneumoperitoneum, and pleural effusion. Postoperative delayed bleeding in the submucosal tunnel is a rare complication after POEM, and only 1 patient with delayed bleeding has been reported in the literature to date. Despite its low incidence, delayed bleeding can result in serious conditions, such as massive bleeding, hemorrhagic shock, and death. Thus, early

Endoscopic resection of colonic submucosal tumors (SMTs) is challenging and carries a high risk of perforation. In this prospective pilot study we aimed to evaluate the feasibility, safety, and efficacy of endoscopic full-thickness resection of colonic SMTs. The study enrolled 19 consecutive patients with colonic SMTs 3 cm in size or smaller. In 18 of the 19 patients full-thickness resection was carried out endoscopically with the entire tumor capsule intact. In 16 of these18 patients, full-thickness resection was carried out and the colonic wall defect closed all endoscopically; in the other 2 patients, laparoscopic closure was needed. Two cases of local peritonitis were managed with conservative treatment. No deaths occurred within 30 days, and no recurrence was detected after a median of 18 months' follow-up. Endoscopic full-thickness resection is a novel method enabling resection of colonic SMTs. The colonic wall mucosal defect can be closed endoscopically in the majority of cases. It appears to be a safe and effective endoscopic technique for managing these tumors, which traditionally are managed by colonic resection.

Colorectal cancer is a common malignancy and one of the major causes of cancer-related deaths worldwide. Similar to other human cancers, tumor metastasis is the biggest obstacle in the clinical treatment of colorectal cancer. In this study, we explored the functional role of SLIT2 in colon tumor metastasis and the relevant molecular mechanisms.Immunohistochemistry, Western blotting, and quantitative reverse transcription-polymerase chain reaction were used to measure SLIT2 expression in colorectal tumor tissues in the presence or absence of metastasis. Wound-healing assays, Transwell assays, Western blotting, and immunofluorescence assays were used to examine the effects of SLIT2 on SW480 and NCM460 cell migration and the epithelial-to-mesenchymal transition (EMT). An AKT inhibitor was introduced to examine the mechanism underlying SLIT2-mediated suppression of NCM460 cell migration.Higher SLIT2 expression was detected in metastasis-positive tumor tissues, and this upregulation was beneficial for the overall survival of patients with colorectal cancer. Either the addition of purified SLIT2 or overexpression of SLIT2 inhibited SW480 cell migration, whereas the depletion of SLIT2 with shRNA enhanced the migratory ability of NCM460 cells. Meanwhile, SLIT2 depletion also induced β-catenin accumulation and altered the expression levels of several molecules related to EMT in NCM460 cells. AKT inhibition abrogated the effects of SLIT2 depletion on EMT and migration in NCM460 cells.SLIT2 suppresses colon tumor metastasis, and it exerts its suppressive activity against colorectal cancer metastasis by restraining AKT signaling and EMT, thus making it a potential clinical prognosis marker in colorectal cancer.

Background/aims To improve the understanding of esophageal leakage after peroral endoscopic myotomy (POEM). Materials and methods From August 2010 to April 2013, patients with postoperative esophageal leakage were identified from the database of cases with achalasia who had undergone POEM and their medical records were reviewed. Results Three patients (0.4%, 3/679) developed esophageal leakage after POEM. All three patients had non-severe chest or upper abdominal pain within 3 days after the procedure. Infections were observed, and computed tomography scans showed pleural effusion in all three patients. Pneumonia occurred in two of the three patients. Esophageal leakage was confirmed by gastroscopy. Incision rupture due to an early breaking-off of the clips at the tunnel entry was revealed in two cases. When detected, the entry was immediately closed using metal clips. A thoracic drain was placed in all cases. An enteric feeding tube was also placed to help correct nutrition deficiencies. Successful leakage closure was achieved in all three cases and no surgical intervention was needed. Conclusion Early diagnosis and treatment can improve the status of patients with esophageal leakage after POEM and can shorten the recovery time.

Background Given the high morbidity and mortality rates for surgery and the diminishment of quality of life caused by operative resection of the gastric cardia, a minor invasive treatment without loss of curability is desirable for submucosal tumors (SMTs) of the esophagogastric junction (EGJ). Endoscopic submucosal dissection (ESD) has been used successfully for the removal of esophageal or gastric SMTs; however, the EGJ has been regarded as a difficult location for ESD because of its narrow lumen and sharp angle. Objective To evaluate the clinical impact of ESD for SMTs of the EGJ arising from the muscularis propria layer. Design Single-center, prospective study. Setting Academic medical center. Patients 143 patients with 143 SMTs of the EGJ originating from the muscularis propria layer. Interventions ESD. Main Outcome Measurements Complications, en bloc resection rate, local recurrence, and distant metastases. Results The average maximum diameter of the lesions was 17.6 mm (range 5 - 50 mm). The en bloc resection rate was 94.4% (135/143). All en bloc resection lesions showed both lateral and deep tumor-free margins, including 20 GI stromal tumors. Perforations occurred in 6 patients (4.2%, 6/143), and metal clips were used to occlude the defect. Four pneumoperitoneum and 2 pneumothorax caused by perforations were resolved with nonsurgical treatment. Local recurrence and distant metastasis have not occurred during a 2-year follow-up. Limitations Single-center, short follow-up. Conclusions ESD appears to be a safe, feasible, and effective procedure for providing accurate histopathologic evaluations, as well as curative treatments for SMTs of the EGJ originating from the muscularis propria layer.

This study was designed to evaluate the clinical efficacy, safety, and feasibility of endoscopic full-thickness resection (EFR) for gastric submucosal tumors (SMTs) originated from the muscularis propria. Twenty-six patients with gastric SMTs originated from the muscularis propria were treated by EFR between July 2007 and January 2009. EFR technique consists of five major procedures: (1) injecting normal saline into the submucosa and precutting the mucosal and submucosal layer around the lesion; (2) a circumferential incision as deep as muscularis propria around the lesion by the endoscopic submucosal dissection (ESD) technique; (3) incision into serosal layer around the lesion with Hook knife; (4) completion of full-thickness incision to the tumor including the serosal layer with Hook, IT, or snare by gastroscopy without laparoscopic assistance; (5) closure of the gastric-wall defect with metallic clips. EFR was successfully performed in all 26 patients without laparoscopic assistance. The complete resection rate was 100%, and the mean operation time was 105 (range, 60–145) min. The mean resected lesion size was 2.8 (range, 1.2–4.5) cm. Pathological diagnosis of these lesions included gastrointestinal stromal tumors (GISTs) (16/26), leiomyomas (6/26), glomus tumors (3/26), and Schwannoma (1/26). No gastric bleeding, peritonitis sign, or abdominal abscess occurred after EFR. No lesion residual or recurrence was found during the follow-up period (mean, 8 months; range, 6–24 months). EFR seems to be an efficacious, safe, and minimally invasive treatment for patients with gastric SMT, which makes it possible to resect deep gastric lesion and provide precise pathological diagnosis of it. With the development of EFR, the indication of endoscopic resection may be expanded.

Background Although gastric glomus tumors are usually benign lesions, occasional malignant transformation has been reported. Thus, complete resection of the gastric glomus tumor is necessary. Objective To provide a better understanding of the endoscopic features of this rare entity with an emphasis on its diagnosis and treatment. Design Retrospective case series. Setting Academic medical center. Patients Six patients (2 men, 4 women; median age 48 years) received a diagnosis of gastric glomus tumor and were treated. Interventions Endoscopic diagnosis and resection. Main Outcome Measurements Endoscopic features, resection success, adverse events, and follow-up endoscopy. Results Gastric glomus tumors do not exhibit specific features on gastroscopy and EUS that distinguish them from other gastric submucosal tumors. Endoscopic submucosal enucleation was successful in 5 patients. In one patient, the operation had to be discontinued because of significant bleeding during the procedure. The mean tumor size was 19.8 ± 6.2 mm (range 12-30 mm). Perforation occurred in 1 patient and was successfully managed with hemoclips. No local recurrence was observed during follow-up (mean duration 9 ± 5.1 months, range 3-17 months). Limitations Small number of patients (N = 6), limited follow-up, retrospective study. Conclusions Diagnosis of gastric glomus tumors is difficult when based only on features derived from gastroscopy and EUS. Endoscopic submucosal enucleation is a feasible and safe procedure with which to diagnose and treat this lesion. However, further investigation and comparative studies are required to confirm the safety and efficacy of this method.

The objective of this study was to determine the efficacy and safety of endoscopic submucosal dissection for locally recurrent colorectal cancer after previous endoscopic mucosal resection.A total of 16 patients with locally recurrent colorectal lesions were enrolled. A needle knife, an insulated-tip knife and a hook knife were used to resect the lesion along the submucosa. The rate of the curative resection, procedure time, and incidence of complications were evaluated.Of 16 lesions, 15 were completely resected with endoscopic submucosal dissection, yielding an en bloc resection rate of 93.8 percent. Histologic examination confirmed that lateral and basal margins were cancer-free in 14 patients (87.5 percent). The average procedure time was 87.2 +/- 60.7 minutes. None of the patients had immediate or delayed bleeding during or after endoscopic submucosal dissection. Perforation in one patient (6.3 percent) was the only complication and was managed conservatively. The mean follow-up period was 15.5 +/- 6.8 months; none of the patients experienced lesion residue or recurrence.Endoscopic submucosal dissection appears to be effective for locally recurrent colorectal cancer after previous endoscopic mucosal resection, making it possible to resect whole lesions and provide precise histologic information.

Increasing evidence indicates the immunosuppressive nature of the local environment in tumor. The present study was focused on analyzing the immune status within hepatocellular carcinoma. In contrast to the increasing number of CD4(+) T cells, CD8(+), CD3(-)CD56(+), CD3(+)CD56(+), and gammadeltaT cells were all found to be under-represented in tumor infiltrating lymphocytes. Notably, the relative abundance of CD3(+)CD56(+) cells appeared to be correlated with patient survival. Functional analysis demonstrated that CD4(+) cells in the tumor tended to produce more IL-10 but less IFN-gamma, whereas CD8(+) cells showed impaired capacity for the production of both IFN-gamma and perforin. Consistent with previous reports, we observed a significant increase of Foxp3(+) cells in the tumor tissue. Intriguingly, although over 90% of CD4(+)CD25(high) cells were found to be Foxp3(+), the majority of Foxp3(+) cells were identified in the CD4(+)CD25(medium) and CD4(+)CD25(-) subsets. In support of its role as a negative regulator, CD4(+)CD25(high) cells suppressed the proliferation of CD4(+)CD25(-) cells isolated from the same tissues in an APC dependent manner. In conclusion, the tumor microenvironment of hepatocellular carcinoma is featured by the presence of multiple immunosuppressive factors.

Background and study aims: Submucosal tunneling endoscopic resection (STER) has become a potential option for the endoscopic treatment of a selected group of patients with submucosal tumors (SMTs) originating from the muscularis propria layer in the upper gastrointestinal tract. The aim of this retrospective study was to analyze the incidence and management of STER-related complications. Patients and methods: From January 2011 to August 2013, 290 patients with upper gastrointestinal SMTs treated by STER were included in the study. Clinicopathological characteristics and complication data were collected and analyzed retrospectively. Results: Mucosal injury occurred in three cases (1.0 %) and major bleeding occurred in five cases (1.7 %). The gas-related complications were very common; however, only nine cases of major pneumothorax (> 30 % lung collapse) needed therapeutic intervention (3.1 %). Thoracic effusion occurred in 49 patients, 11 of whom had low grade fever or segmental atelectasis that required thoracentesis and drainage (3.8 %). Thus, although the overall incidence of complications was 23.4 % (68/290), only 10.0 % of procedures (29/290) required intervention for complications. Based on the statistical analysis, irregular shape, tumor in the deep muscularis propria layer, long procedure time, and air insufflation were risk factors of STER-related major complications. Conclusion: Although the incidence of STER-related complications was relatively high, most of these complications were minor and did not require therapeutic intervention. STER is a safe technique for the treatment of upper gastrointestinal SMTs.

To investigate the effect of herb-partitioned moxibustion combined with acupuncture on the expression of intestinal epithelial tight junction (TJ) proteins.Sixty patients diagnosed with mild to moderate Crohn's disease (CD) were allocated into the herb-partitioned moxibustion combined with acupuncture (HMA) group (n = 30) or the mesalazine (MESA) group (n = 30) using a parallel control method. There were 2 sets of acupoints used alternately for HMA treatment. The following points were included in Set A: ST25 (Tianshu), RN6 (Qihai), and RN9 (Shuifen) for herb-partitioned moxibustion and ST36 (Zusanli), ST37 (Shangjuxu), LI11 (Quchi), and LI4 (Hegu) for acupuncture. The points for Set B included BL23 (Shenshu) and BL25 (Dachangshu) for herb-partitioned moxibustion and EX-B2 of T6-T1 (Jiajixue) for acupuncture. The patients received the same treatment 6 times a week for 12 consecutive weeks. The MESA group received 1 g of mesalazine enteric coated tablets 4 times daily for 12 consecutive weeks. Intestinal tissues were stained and examined to compare the morphological and ultrastructural changes before and after the treatment session. Immunohistochemistry and in situ hybridization assays were used to detect the expression of intestinal epithelial TJ proteins zonula occludens-1 (ZO-1), occludin, and claudin-1. The mRNA levels were also evaluated.After the treatment, both herb-partitioned moxibustion combined with acupuncture and mesalazine improved intestinal morphology and ultrastructure of CD patients; the patients treated with HMA showed better improvement. HMA significantly increased the expression of ZO-1 (P = 0.000), occludin (P = 0.021), and claudin-1 (P = 0.016). MESA significantly increased the expression of ZO-1 (P = 0.016) and occludin (P = 0.026). However, there was no significant increase in the expression of claudin-1 (P = 0.935). There was no statistically significant difference between the two groups for the expression of occludin and claudin-1 (P0.05). The HMA group showed a significant improvement in ZO-1 expression compared to the MESA group (2333.34 ± 352.51 vs 2160.38 ± 307.08, P = 0.047). HMA significantly increased the expression of ZO-1 mRNA (P = 0.000), occludin mRNA (P = 0.017), and claudin-1 mRNA (P = 0.017). MESA significantly increased the expression of ZO-1 mRNA (P = 0.000), occludin mRNA (P = 0.042), and claudin-1 mRNA (P = 0.041). There was no statistically significant difference between the two groups in the expression of occludin and claudin-1 mRNA (P0.05). However, the HMA group showed a significant improvement in ZO-1 mRNA expression compared with the MESA group (2378.17 ± 308.77 vs 2200.56 ± 281.88, P = 0.023).HMA can repair intestinal epithelial barrier lesions and relieve inflammation by upregulating the expression of TJ proteins and their mRNAs.

A novel HLA-A allele, HLA-A*0279, was identified using PCR-SSP and PCR-SBT methods. It is inheritable. HLA-A*0279 differs from HLA-A*020601 by a single nucleotide at position 497 in exon 3, leading to an amino acid change from Threonine to Isoleucine at the alpha2 helix of HLA molecule. To investigate whether the altered amino acid residue could affect its peptide-binding repertoire, we compared the predicted crystal structure of HLA-A*020601 and HLA-A*0279 by Swiss-PdbViewer software analysis. We found that the crystal structure of the two molecules is very similar except for a difference in the number of hydrogen bonds they can possibly form, which in turn could affect their structural stability. To test whether HLA-A*0279 has the ability to cross-present A*0201 - restricted peptides to T cells, the full lenght cDNA of HLA-A*0201, -A* 020601 and -A*0279 were respectively transfected into COS-7 cells, which were then used as targets in IFN-gamma release Elispot assay. A*2079 was found to be able to present A*0201- restricted peptides to and induce the response of CTL, thus it can be classified as member of the HLA-A2 functional supertype family. This finding would benefit the design of peptide vaccines to be applied in broader populations.

In the absence of efficient systemic chemotherapy, immunotherapy is considered a hopeful treatment for controlling recurrence of hepatocellular carcinoma (HCC). The identification of proper antigenic peptides presented by MHC class I molecules is a critical step for the development of therapeutic vaccines against tumors. Currently, the "reverse immunology" approach is the most commonly used technique in the identification of the tumor-associated T cell epitopes. However, it is based on T cell dependent approach and cannot fully reflect the actual presentation of epitope in tumor in vivo. In the present study, we managed to identify the naturally presented MAGE epitopes of HCC directly by epitope prediction, HPLC differential analysis and MS detection. We successfully detected a naturally processed peptide FLWGPRALV (MAGE-3(271-279), HLA-A2-restricted) with an estimated number of 38-39 copies/cell in HCC. To our knowledge, this is the first evidence that the naturally processed MAGE-3(271-279) can be isolated and identified from the tumor tissue of HCC patient. Furthermore, specific CD8(+) T cell responses to this epitope were also found after tumor relapse by IFN-gamma release Cytospot and tetramer assay indicating that MAGE-3(271-279) was indeed presented by HCC cells in vivo. In addition, another new antigen peptide was found, which may be derived from MAGE-1. Our findings demonstrate the potential of the direct approach for identification of tumor-associated epitopes. This approach may become a useful tool for the development of vaccine against cancer in the future.

Recombinant fragments of S proteins from the Severe Acute Respiratory Syndrome (SARS) coronavirus (SARA-CoV) were generated and used in a Western blot (WB) assay that was compared to a commercial SARS ELISA method. In 85% of confirmed SARS cases ( n = 20), the S2 recombinant fragment based WB was positive and this was comparable to the commercial ELISA using heat killed SARS-CoV. WB using the other four recombinant fragments in confirmed SARS cases generated lower rates of detection (S1—75%, S1-N—25%, S1-C—55%). Evaluation of sera from healthy controls ( n = 60) resulted in two weakly positive ELISA results with the remainder being negative while the S2 protein WB demonstrated three positive results from the 20 controls with a history of SARS contact and no positive results in 40 noncontact controls. A discrepancy between the ELISA and S2 WB arose when evaluating per-2003 sera from individuals ( n = 10) with SARS-like symptoms (ELISA—100% positive, S2 WB—30% positive). These data suggest that the S2 WB assay may be particularly useful in ELISA-negative SARS cases and in some ELISA-positive non-SARS cases.

To extend the search for hepatocellular carcinoma (HCC) associated antigens with immunogenicity for clinical applications, we constructed a cDNA expression library using resected human HCC tissue sample and screened it by serological analysis of recombinant cDNA expression library (SEREX) with autologous and allogeneic sera. A total of 24 distinct antigens were isolated and kinectin was the antigen most frequently identified. We found that kinectin was alternatively spliced at four sites and obtained all eight theoretical forms of variant, six by SEREX and two by RT-PCR, from the different splicing combinations of the last three sites. In addition, the splicing patterns of four sites were analyzed. Variant containing D2 was overexpressed in cancerous tissues and this alteration may be tumor associated. The four splicing sites, the variants generated by alternative splicing, and the humoral immune response in HCC patients, may help to analyze the role of kinectin in human HCC cell biology.Key words: alternative splicing, antibody response, hepatocellular carcinoma, kinectin, serological analysis of recombinant cDNA expression library (SEREX).