Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies.

BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.

[New understanding about the concept of minimally invasive endoscopic surgery--ERBEC].

As a vital component of gastroenterology and endoscopology, minimally invasive endoscopic surgery has expanded its technology from surface to depth, from inside to outside, from intraluminal to extraluminal lesions, and from organic diseases to functional diseases. This paper summarizes the experience of minimally invasive endoscopic surgery in the recent two decades, and in combination with the current development trend, puts forward understanding about the concept of minimally invasive endoscopic surgery--ERBEC, namely elements, reservation-resection, bilateral-benefit, expansion, collaboration, in order to truly benefit patients through new methods and concepts.

[DNA methylation modification of BRMS1 in triple-negative breast cancer and its correlation with tumor metastasis].

Objective: To investigate the effect of methylation status of breast cancer metastasis suppressor gene 1 (BRMS1) on the expression of breast cancer and the biological behavior of cancer cells in triple-negative breast cancer (TNBC). Methods: The expression of BRMS1 in TNBC tissues and corresponding non-malignant tissues and its relationship with clinicopathological parameters were detected by immunohistochemistry. The mRNA and protein expression of BRMS1 in normal breast epithelial cells and TNBC cells were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The methylation specific polymerase chain reaction (MSP) was used to detect the methylation status of BRMS1 in each cell. These cells were treated with demethylated preparations (5-Aza-dC) to re-activate BRMS1 expression. Using tumor cell invasion assay to detect influence of BRMS1 demethylation on the invasion capacity of cancer cells. The data were statistically analyzed. Results: The positive expression rate of BRMS1 protein in TNBC tissues was significantly lower than that in corresponding non-malignant tissues (χ(2)= 6.635, P<0.05). The mRNA expression level of BRMS1 in patients with lymph node metastasis was significantly lower than those with no lymph node metastasis (P=0.018). The down-regulation of BRMS1 expression was related to the methylation of DNA promoter, which was statistically significant (χ(2)=14.68, P<0.05). The mRNA and protein expression of BRMS1 was also correlated with tumor size and TNM staging (P=0.000-0.003). After using 5-Aza-dC, the number of cells with invasive capacity was significantly lower than those of the control group (t=3.262-10.72, P<0.05). Conclusions: The decrease of BRMS1 expression in TNBC cells is related to the methylation of DNA. Demethylation can inhibit the invasion of breast cancer cells.

Lentivirus-mediated RASSF1A expression suppresses aggressive phenotypes of gastric cancer cells in vitro and in vivo.

Loss of Ras association domain family protein 1 isoform A (RASSF1A) expression is associated with the development of a variety of human cancers and the expression of carcinoembryonic antigen (CEA) frequently occurs in gastric cancer. This study investigated the effects of RASSF1A expression restoration using a hypoxia-inducible CEA promoter-driven vector on xenograft tumor growth in nude mice and on the in-vitro regulation of gastric cancer cell viability, cell cycle distribution, apoptosis, colony formation and invasion capacity. The data showed that the level of CEA mRNA and protein was much higher in gastric cancer SGC7901 cells than in a second gastric cancer cell line, MKN28, or in the MCF-10A normal epithelial breast cell line. RASSF1A expression was restored in SGC7901 cells compared with the negative control virus-infected SGC7910 cells. RASSF1A expression restoration significantly inhibited gastric cancer cell viability, colony formation and invasion capacity, but induced cell cycle arrest and apoptosis in vitro, especially under hypoxic culture conditions. At the gene level, restoration of RASSF1A expression under hypoxic culture conditions significantly suppressed matrix metalloproteinase-2 expression and prevented cyclinD1 expression. A nude mouse xenograft assay showed that the restoration of RASSF1A expression reduced gastric cancer xenograft formation and growth. In conclusion, the restoration of RASSF1A expression using a hypoxia-inducible and CEA promoter-driven vector suppressed aggressive phenotypes of gastric cancer cells in vitro and in vivo. These results suggest that LV-5HRE-CEAp-RASSF1A gene therapy may be a promising novel approach to treat advanced gastric cancer.

Roles of adrenomedullin and hypoxia-inducible factor 1 alpha in patients with varicocele.

This study aimed to assess any changes in the plasma concentrations of adrenomedullin (ADM) and hypoxia-inducible factor 1 alpha (HIF 1a) in patients with varicocele (VC). Plasma concentrations of ADM and HIF 1a were measured in brachial vein (BV) and internal spermatic vein (ISV) of 30 fertile VC subjects and 35 untreated infertile VC patients. The results demonstrated that plasma levels of ADM and HIF 1a were significantly higher in ISV than those in BV in the fertile or infertile group respectively. The values of ADM and HIF 1a in BV or ISV of the infertile group were significantly higher than in BV or ISV of the fertile group respectively. Similar changes in values of reactive oxygen metabolites (ROM) were observed. Plasma HIF 1a concentration positively correlated with ROM levels. Plasma ADM concentration positively correlated with ROM values and HIF 1a levels in the two groups. Moreover, remarkable improvement in clinical sperm parameters was observed 3 months after surgery for the infertile patients. It is concluded that ADM may participate, along with HIF 1a, in mechanisms that aid spermatogenic cells in adapting to hypoxia. These predictors may have potential in infertility development in VC patients. Furthermore, early surgical repair is extremely important for infertile VC patients with poor semen quality.

[Endoscopic full-thickness resection in near clinical complete response rectal cancer after neoadjuvant therapy].

Objective: To investigate the safety and feasibility of endoscopic full-thickness resection (EFTR) in the treatment of near-clinical complete response (near-cCR) rectal cancer after neoadjuvant therapy. Methods: A 74-year-old female patient with cT3N0M0 stage rectal adenocarcinoma who refused radical surgery for rectal cancer underwent neoadjuvant chemoradiotherapy (5 cycles of CapeOx chemotherapy and concurrent radiotherapy for 25 sessions) after multidisciplinary team discussion. One month after completing neoadjuvant treatment, reassessment including digital rectal examination, colonoscopy, and pelvic enhanced magnetic resonance imaging suggested near-cCR. Despite this, the patient requested rectal-preserving therapy. Subsequently, EFTR was performed five weeks after completion of neoadjuvant treatment. Postoperatively, supportive care including fasting, antimicrobial therapy, and nutritional support was provided. The patient started a liquid diet on the 6th day postoperatively and was discharged on the 13th day. Results: Pathological analysis revealed tubular adenoma with low-grade epithelial dysplasia, with negative margins and negative involvement of the base. During one-year follow-up, there were no signs of local regrowth or distant metastasis, and satisfactory anal function was observed. Conclusion: EFTR is safe and feasible in patients with near-cCR rectal cancer after neoadjuvant therapy. This approach should be considered after thorough evaluation of the patient's condition.

Complete closure of large gastric defects after endoscopic full-thickness resection, using endoloop and metallic clip interrupted suture.

BACKGROUND AND STUDY AIM: Successful closure of wall defects is the key procedure following endoscopic full-thickness resection (EFTR). In this report we describe a new method similar to interrupted suture to repair gastric defects by means of endoloops and metallic clips. PATIENTS AND METHODS: We retrospectively analyzed 20 patients who presented at our institute between March 2011 and February 2012 with gastric submucosal tumors and who consequently underwent EFTR, with the resulting large gastric defects being closed using endoloops and metallic clips. Tumor characteristics, en bloc resection rates, and postoperative complications were evaluated in all the patients. RESULTS: The median age of the 20 patients was 47 years. The mean maximum size of lesions was 1.47 ± 0.72 cm (range 0.4 - 3 cm). All lesions were diagnosed by endoscopic ultrasound as tumors in the muscularis propria layer. The en bloc resection rate was 100 %. Five patients developed fever and complained of slight abdominal pain in the first day after treatment. No patient had severe complications such as peritonitis or abdominal abscess. In all cases, wounds healed after 1 month. We observed the persistence of the clips for over 3 months in 6 out of 19 cases without any clinical manifestations or large injury to the intestine. CONCLUSIONS: Our study provides evidence that the use of metallic clips and endoloops is a relatively safe, easy, and feasible method for repairing gastric defects resulting from EFTR.

Peroral endoscopic remyotomy for failed Heller myotomy: a prospective single-center study.

BACKGROUND AND STUDY AIMS: Recurrence/persistence of symptoms occurs in approximately 20 % of patients after Heller myotomy for achalasia. Controversy exists regarding the therapy for patients in whom Heller myotomy has failed. The aim of the current study was to evaluate the efficacy and feasibility of peroral endoscopic myotomy (POEM), a new endoscopic myotomy technique, for patients with failed Heller myotomy. PATIENTS AND METHODS: A total of 12 patients with recurrence/persistence of symptoms after Heller myotomy, as diagnosed by established methods and an Eckardt score of ≥ 4, were prospectively included. The primary outcome was symptom relief during follow-up, defined as an Eckardt score of ≤ 3. Secondary outcomes were procedure-related adverse events, lower esophageal sphincter (LES) pressure on manometry, reflux symptoms, and medication use before and after POEM. RESULTS: All 12 patients underwent successful POEM after a mean of 11.9 years (range 2 - 38 years) from the time of the primary Heller myotomy. No serious complications related to POEM were encountered. During a mean follow-up period of 10.4 months (range 5 - 14 months), treatment success was achieved in 11/12 patients (91.7 %; mean score pre- vs. post-treatment 9.2 vs. 1.3; P < 0.001). Mean LES pressure was 29.4 mmHg pre-treatment and 13.5 mmHg post-treatment (P < 0.001). One patient developed mild reflux symptoms and required intermittent medication with proton pump inhibitors. CONCLUSIONS: POEM seems to be a promising new treatment for failed Heller myotomy resulting in short-term symptom relief in > 90 % of cases. Previous Heller myotomy may make subsequent endoscopic remyotomy more challenging, but does not prevent successful POEM.

Endoscopic management of impacted esophageal foreign bodies.

There are many reports on the endoscopic management of ingested foreign bodies in the upper gastrointestinal tract, however, little is known about the management of a specific subset of esophageal foreign bodies - impacted esophageal foreign bodies (IEFBs), especially perforating esophageal foreign bodies (PEFBs). The aim of this retrospective study on 78 cases was to report experience and outcome in the endoscopic management of the IEFBs in Chinese patients. From January 2006 to July 2011, a total of 750 patients with suspected upper gastrointestinal foreign bodies were admitted to the endoscopy center. Among these 750 patients, 78 cases that met the defined criteria of IEFBs were retrospectively enrolled in the present study, including 12 cases (12/78, 15.4%) with PEFBs. The major types of IEFBs were poultry bones (35.9%) and fish bones (17.9%). Most of the IEFBs (80.8%) were located in the upper esophagus, as were two thirds (66.7%) of the PEFBs. Foreign-body retrieval forceps were the most frequently used accessory devices. Extraction of IEFBs failed in eight patients (10.3%) during the endoscopic procedure. The difficult points in endoscopic management were PEFBs, IEFBs with sharp points, and those with impaction for more than 24 hours. IEFBs should be treated as early as possible, and their endoscopic management is safe and effective. Endoscopic management is the first choice for PEFBs when the duration of impaction is less than 24 hours and there are no abscesses outside of the esophageal tract as determined by a computed tomography scan.

[Epidemiological characteristics of imported COVID-19 cases in Tianjin].

Objective: To understand the epidemiological characteristics of imported COVID-19 cases in Tianjin, and provide references for risk assessment and control of imported COVID-19 cases. Methods: The information of imported COVID-19 cases were obtained from National Notifiable Disease Report System of China CDC. The data of imported COVID-19 cases reported from Tianjin airport and epidemiological surveys by CDCs at all levels from March 15, 2020 to August 31, 2021 were collected and analyzed by using software Excel 2010, SPSS 25.0 and R. Results: From March 15, 2020 to August 31, 2021, a total of 606 imported cases of COVID-19 were reported in Tianjin, in which 552 cases were finally included in the analysis. The male to female ratio of the cases was 1.8∶1, the age of the cases ranged from 3 to 77 years, and the cases were mainly reported in age group 20-39 years (59.8%). The areas where the imported case sojourned within 14 days included Europe (242 cases, 43.8%), Africa (139 cases, 25.2%), Americas (85 cases, 15.4%) and Asia (86 cases, 15.6%). The proportion of confirmed cases in autumn and winter was relatively high. During the study period, the proportion of infected persons found in custom entry quarantine decreased, and the proportion of persons with personal health declaration and under medical isolation observation increased. The interval between entry and diagnosis of infected persons tended to increase. Conclusion: The proportion of imported COVID-19 cases detected on the first day of entry at Tianjin airport decreased, and the interval to detect the infected persons trended to increase, to which close attention must be paid.

Correlated electrons step by step: itinerant-to-localized transition of fe impurities in free-electron metal hosts.

High-resolution photoemission spectroscopy and ab initio calculations have been employed to analyze the onset and progression of d-sp hybridization in Fe impurities deposited on alkali metal films. The interplay between delocalization, mediated by the free-electron environment, and Coulomb interaction among d electrons gives rise to complex electronic configurations. The multiplet structure of a single Fe atom evolves and gradually dissolves into a quasiparticle peak near the Fermi level with increasing host electron density. The effective multiorbital impurity problem within the exact diagonalization scheme describes the whole range of hybridizations.

[Analysis of selective endoscopy results during the epidemic of coronavirus disease 2019 (COVID-19)].

Objective: To explore the necessity and safety of selective endoscopy to detect gastrointestinal (GI) malignancy during the outbreak of coronavirus disease 2019 (COVID-19). Methods: A retrospective cohort study was carried out to analyze the clinical data of selective endoscopy performed at the Endoscopic Center, Zhongshan Hospital of Fudan University from February 20 to March 6, 2020. Clinical data included epidemiological questionnaire, chief complaints, endoscopic findings and biopsy pathology results, etc. All medical staff had blood test for IgM/IgG antibodies of COVID-19. Patients and their families were followed up by phone to determine whether they were infected with COVID-19. Meanwhile, the clinical data of selective endoscopy during the same period from February 20 to March 6, 2019 were collected as the control group to compare the overall results of endoscopy examinations during the epidemic and the detection rate of GI malignancy. Results: A total of 911 patients underwent endoscopy in the epidemic period group, and a total of 5746 cases in the control group, which was 6.3 times over the epidemic period group. In the epidemic period group, 544 cases received gastroscopy and 367 cases received colonoscopy, while 3433 cases received gastroscopy and 2313 cases received colonoscopy in the control group, which were both 6.3 times of epidemic period group. Gastroscopy revealed that 39 patients (7.2%) were diagnosed with upper GI malignancies in the epidemic period group and 77 patients (2.2%) in the control group with significant difference (χ(2)=40.243, P<0.001). The detection rate of gastric cancer in these two groups was 3.3% (n=18) and 1.7% (n=59) respectively with significant difference (χ(2)=6.254,P=0.012). The detection rate of esophageal cancer was 3.7% (n=20) and 0.5% (n=18) respectively with significant difference (χ(2)=49.303,P<0.001). Colonoscopy revealed that colorectal cancer was found in 32 cases (8.7%) of the epidemic period group and 88 cases (3.8%) of the control group with significant difference (χ(2)=17.888, P<0.001). During the epidemic period, no infection of medical staff was found through the blood test of IgM/IgG antibodies on COVID-19. No patient and family members were infected with COVID-19 by phone follow-up. Conclusion: Compared with the same period in 2019, the number of selective endoscopy decreases sharply during the epidemic period, while the detection rate of various GI malignant tumors increases significantly, which indicates that patients with high-risk symptoms of GI malignancies should still receive endoscopy as soon as possible. Provided strict adherence to the epidemic prevention standards formulated by the state and professional societies, it is necessary to carry out clinical diagnosis and treatment as soon as possible.

[Analysis on cluster cases of COVID-19 in Tianjin].

Objective: To understand the characteristics of clusters of COVID-19 cases in Tianjin, and provide epidemiological evidence for the prevention and control of COVID-19. Methods: The data of all the COVID-19 cluster cases in Tianjin, reported by 22 February 2020, were collected to analyze the characteristics of different types of the clusters. Results: A total of 115 COVID-19 cases were reported in 33 clusters in Tianjin included 28 family clusters (71 cases), 1 work place cluster (10 cases), 3 transport vehicle clusters (8 cases) and 1 public place cluster (26 cases). Family clusters were caused by the cases from the working place or public place clusters. Numbers of secondary cases of family clusters was between 1 to 7, the median number was 2. The interval from onset to diagnosis for the first case was longer than those of other cases in the familial clusters (Z=-2.406, P=0.016). The median of incubation period of the public place clusters was 2 days. The intervals from onset to diagnosis were significant different among the family, working place and public place clusters (H=8.843, P=0.012), and also significant differences in onset time among the secondary cases (H=16.607, P=0.000). Conclusions: In the surveillance of COVID-19 epidemic, special attention should be paid to places where clustering are prone to occur, and the epidemiological investigation should be carried out timely to confirm the cluster. To prevent the transmission of COVID-19, the close contacts of the patients should be transferred to an assigned observation place on time for single room isolation. The awareness of COVID-19 prevention is low in some rural areas, reflected by many mass gathering activities and delayed medical care seeking after onset. It is necessary to strengthen the health education and take control measures in early period of epidemic.

[Epidemiological characteristics of confirmed COVID-19 cases in Tianjin].

Objective: To investigate the clinical and epidemiological characteristics of 135 confirmed cases of COVID-19 in Tianjin. Methods: The clinical and epidemiological data of 135 cases of COVID-19 in Tianjin were collected, and the data were analyzed with descriptive method. The factors influencing the severity of the illness were analyzed. Results: Among the 135 COVID-19 cases, 72 were males and 63 were females, the age of the cases was (48.62±16.83) years, and the case fatality rate was 2.22%. Local transmission caused 74.81% of the cases. A total of 33 clusters occurred, involving 85.92% of all COVID-19 cases. The median of the incubation period of COVID-19 was 6.50 days, the average generation interval was 5 days, and the household secondary transmission rate was 20.46%. Fever was the main symptom (78.63%), followed by cough (56.48%). Multivariate regression analysis indicated that age (OR=1.038, 95%CI: 1.010-1.167) and the number of chronic underlying diseases (OR=1.709, 95%CI: 1.052-2.777) were the risk factors of severe illness. Conclusions: Fever was the main symptom at the early phase of COVID-19 in Tianjin, and the local cluster cases accounted for high proportion in confirmed COVID-19 cases reported in Tianjin. Severe illness was prone to occur in people with old age and multi underlying diseases. Strict isolation of close contacts and intensive care of high-risk groups are the main measures to reduce the morbidity and case fatality of COVID-19.

[A novel and simplified closure method for defect closure after endoscopic full-thickness resection of gastric submucosal tumors: short-term outcomes of "Shao-Mai" closure method].

Objective: To evaluate the feasibility and short-term efficacy of a novel and simplified closure method developed by our team for the defect closure after endoscopic full-thickness resection (EFTR) for gastric submucosal tumors (SMT) in the gastric wall. Methods: A prospective single-arm clinical study was used. Inclusion criteria: (1) the lesion was located in the fundus or the greater curvature of the stomach, and was confirmed to originate from the muscularis propria layer; (2) the diameter of the tumor was ≤3.5 cm, and the tumor had no extensive adhesion to the peritoneal tissues and organs in extraperitoneal cavity; (3) the tumor had no malignant features under ultrasound endoscopy; (4) the patient agreed to participate in the study; (5) patients with severe complications were excluded. Based on the above criteria, 20 patients with gastric SMT at the Endoscopy Center of Zhongshan Hospital of Fudan University from January 2015 to March 2018 were enrolled in this study, including 5 males and 15 females with mean age of 61.1 (38 to 70) years. Grasping forceps-assisted endo-loop snare ligation device which is called "Shao-Mai" method was used to close the defect site. All the patients underwent EFTR and "Shao-Mai" method to perform defect closure. After successful tumor resection by EFTR, an endo-loop was anchored onto the edge of the gastric defect with grasping forceps assistance and closed tightly. The observation indicators included tumor size, en bloc resection, operation time, postoperative complications and hospital stay. The follow-up indicators included tumor residual, local recurrence, and metachronous lesions. Results: All the 20 lesions were located in the muscularis propria with a size of 0.5-3.5 (mean 1.4) cm. Three of them were located in the greater curvature of the mid-upper gastric body, 17 were located in the fundus. The endoscopic "Shao-Mai" closure was successfully performed after EFTR in all the 20 cases. Endoscope was used uniquely through the entire process, without laparoscopic assistance. The operative time was 20-100 (mean 43.8) minutes, while the "Shao-Mai" closure procedure took a range of 3-30 (mean 10.1) minutes. The en bloc resection rate was 100%. The pathological diagnosis included 17 gastrointestinal stromal tumors and 3 leiomyomas. No major complications occurred during or after surgery. All the patients were discharged 1-11 (mean 3.1) days after operation. The wounds of all the cases were healed completely six months after operation and only scar was observed without ulcer. No residual lesion, tumor recurrence or metastasis, leakage or fistula of digestive tract were found during the follow-up period of 15-54 (median 41) months. Conclusion: The endoscopic "Shao-Mai" closure method is a simplified novel way, which is feasible, effective, and safe for closing the gastric defect after EFTR.

[Investigation and analysis on characteristics of a cluster of COVID-19 associated with exposure in a department store in Tianjin].

Objective: To describe the epidemiological characteristics of a cluster of COVID-19 cases reported in Baodi district of Tianjin as of 18 February, 2020, which might be associated with the exposure in a local department store, and provide suggestions for prevention and control strategy development. Methods: The basic characteristics, time and area distributions, clinical manifestations, epidemiological history and transmission mode of the COVID-19 cases associated with the department store exposure were analyzed. Results: A total of 40 COVID-19 cases were associated with the department store exposure, accounting for 75.47% of the total confirmed cases (53 cases) reported in Baodi district. The cases were mainly at the age of 60 years or older (35.00%) and farmers (40.00%). The main clinical manifestations included fever (95.00%), cough (35.00%), and diarrhea (15.00%). The proportion of confirmed severe cases was 32.50%. The incidence curve showed that the incidence peak occurred on 31 January, 2020. Among the 40 cases, 6(15.00%) were department store employees, 19 (47.50%) were customers and 15 (37.50%) were close contacts (secondary cases). The first case occurred on 21 January, 2020, this case was a department store employee who had a purchasing history at whole sale markets in other provinces and cities before the onset, and 3 employees were still on duty after symptom onsets. The median of the incubation period of customer cases was 6 days, and the median of the interval between onset and medical treatment of customer cases was 7 days. Conclusion: This was a cluster epidemic of COVID-19, which might be associated with the exposure in the department store. By now, the current prevention and control measures have achieved satisfied effects.

[Endoscopic minimally invasive treatment--from inside the lumen to outside the lumen, from the superficial layer to the deep layer].

Since the introduction of endoscopic submucosal dissection (ESD) in China in 2006, endoscopic minimally invasive treatment has experienced a booming development for more than 10 years, and its indications are gradually being expanded from inside the lumen to outside the lumen, from the superficial layer to the deep layer, from organic diseases to functional diseases. This article summaries the development of endoscopic minimally invasive resection in the past 10 years, from the perspective of mucosa, submucosa, muscularis, serosal and even extraluminal lesions, respectively, to introduce the role of endoscopic minimally invasive treatment. For mucosal lesions, ESD has become a first-line treatment for early gastric cancer; endoscopic treatment of colorectal lesions is still controversial in Europe and the United States, but is gradually being accepted. For submucosal tumors(SMT), the Expert Consensus for Endoscopic Diagnosis and Treatment of Submucosal Tumors in China (version 2018) was published in 2018, and the principles and related technical rules for gastrointestinal SMT have been highlighted. For serosal and even extraluminal lesions, natural orifice transluminal endoscopic surgery (NOTES) and tunnel endoscopic surgery, mainly including endoscopic myotomy (POEM) and endoscopic transmucosal tunneling tumor resection (STER), showed potential for development in preliminary studies, and showed good results in cholecystectomy, appendectomy, achalasia, gastroparesis and even extra-gastrointestinal tumor resection. This article describes the various endoscopic treatment techniques, and looks into their application prospects and future challenges.

[Practice guideline of peroral endoscopic myotomy of achalasia: Zhongshan experience].

Peroral endoscopic myotomy (POEM) is a novel clinical technique developed in 2010, and has been widely accepted for treating achalasia and esophageal motility disorders, because of its minimal invasiveness and good efficacy. Zhongshan Hospital has published the practice guideline (the "Zhongshan experience") of peroral endoscopic myotomy of achalasia (v1.2018) based on experience combined with literatures. (1) Preoperative evaluation includes clinical symptom assessment, gastroscopy, high-resolution manometry and upper gastrointestinal radiography. (2) Absolute indication is idiopathic achalasia, and age is no longer a contraindication. (3) The criteria include the medical centers with legal qualifications and the operators with over 5 years of clinical experience in gastroenterological surgery or gastroenterology and more than 30 cases of esophageal endoscopic submucosal dissection (ESD). (4) The length of the myotomy is 8 to 10 cm. The recommended location of the myotomy is the anterior or posterior wall. Whether a full-thickness or circular muscle myotomy is chosen is based on patient's condition. (5) If pleural effusion, atelectasis or pneumothorax occurs, CT examination is recommended during the postoperative period. If patients presents with symptoms such as vomiting and high fever, endoscopic examination and upper gastrointestinal radiography should be performed. (6) Major adverse events include mucosal injury, perforation, bleeding, pneumothorax and pleural effusion. (7) The Eckardt score system and endoscopic examination are used for evaluating the effectiveness after POEM.

[Interpretation of the Chinese Consensus on Endoscopic Diagnosis and Management of Gastrointestinal Submucosal Tumors (version 2018)].

In August 2018, The Chinese Consensus on Endoscopic Diagnosis and Management of Gastrointestinal Submucosal Tumors, which was formulated by the Surgical Group of Chinese Society of Digestive Endoscopology, the Chinese Physicians Association Endoscopy Branch Digestive Endoscopy Professional Committee, the Gastrointestinal Surgery Group of Chinese Society of Surgery, was published in Chinese Journal of Gastrointestinal Surgery. This consensus is the first guideline in the area of gastrointestinal submucosal tumors (SMTs) in China, and it proposed the diagnosis and management procedure of SMTs from the endoscopists' viewpoint. This consensus presents case selection principles and technical principles of endoscopic treatment of SMTs. For and the indication and contraindication of endoscopic treatment of SMTs, it is suggested that clinician choose optimal procedure according to disease's characteristics and techniques of the clinician. In this review, the key contents of consensus are interpreted in detail. The application of endoscopic snare resection, endoscopic submucosal excavation, endoscopic full-thickness resection and submucosal tunneling endoscopic resection at different SMTs was summarized. At the same time, the controversies in endoscopic diagnosis and management of the SMTs, such as biopsy, indication of endoscopic treatment and new techniques of endoscopic therapy, were analyzed.