The activation of asparagine synthetase by the transcription factor FOXM1 plays a pivotal role in the initiation and progression of ESCC.

This study explores the role of the transcription factor FOXM1 in the initiation and progression of oesophageal squamous cell carcinoma (ESCC). Our findings reveal that FOXM1 is highly expressed in ESCC and correlates with the prognosis of the disease. The relationship between FOXM1 and asparagine synthetase (ASNS) is investigated, and the study demonstrates that FOXM1 activates ASNS, impacting the tumour stemness of ESCC. In this study, we reveal the association between FOXM1 and ESCC development, as well as FOXM1's promotion of migration and proliferation in ESCC cells. The study also highlights FOXM1's regulation of ASNS transcription and the functional role of ASNS in ESCC metastasis and growth. Furthermore, the study explores the impact of FOXM1 and ASNS on ESCC stemness and their potential implications for chemotherapy resistance.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Microscopic positive tumor margin does not increase the rate of recurrence in endoscopic resected gastric mesenchymal tumors compared to negative tumor margin.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: R1 resection for gastric GIMTs is not related to a higher recurrence rate than R0 resection, and ER0 resection is sufficient for gastric GIMTs.

Outcomes of Endoscopic Submucosal Dissection vs Esophagectomy for T1 Esophageal Squamous Cell Carcinoma in a Real-World Cohort.

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.

Application of convolutional neural network in the diagnosis of the invasion depth of gastric cancer based on conventional endoscopy.

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.

Clinical and endoscopic predictors for intraprocedural mucosal injury during per-oral endoscopic myotomy.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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 experience >1 year was a protective factor for MI (OR, .614; P = .042) and type II MI (OR, .297; P = .042). CONCLUSIONS: 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 effect of prior treatment on clinical outcomes in patients with achalasia undergoing peroral endoscopic myotomy.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a treatment option for patients with previous surgical or endoscopic treatment. We aimed to evaluate the influence of prior treatment on perioperative and follow-up outcomes in patients undergoing POEM. METHODS: From August 2010 to December 2014, a total of 1384 patients with achalasia underwent POEM at our center. We retrospectively reviewed 849 patients who completed follow-up. Patients with an Eckardt score ≥ 4 after POEM were considered to have a clinical failure. We compared variables between patients with and without prior treatment. We analyzed risk factors for perioperative major adverse events, and clinical reflux and failure during follow-up.  RESULTS: 245 patients (28.9 %) had undergone prior treatment, and 34 patients (4.0 %) experienced a major adverse event associated with the POEM procedure. During a median follow-up of 23 months (range 1 - 71), clinical reflux occurred in 203 patients (23.9 %) and clinical failure was recorded for 94 patients (11.1 %). Patients with prior treatment had a longer procedure duration (P = 0.001) and longer hospital stay after POEM (P = 0.001). Prior treatment was not an independent risk factor for major adverse events or clinical reflux (odds ratio [OR] 1.19, P = 0.65; OR 1.26, P = 0.19; logistic regression), but it did increase the rate of clinical failure during follow-up (hazard ratio 1.90, P = 0.002; Cox regression). CONCLUSIONS: POEM was performed safely with a low rate of major adverse events in patients with achalasia who had undergone prior surgical or endoscopic treatment. However, prior treatment increased the risk of clinical failure after POEM.