Long-term outcomes of endoscopic resection for well-differentiated nonampullary duodenal neuroendocrine tumors.

BACKGROUND AND AIMS: Nonampullary duodenal neuroendocrine tumors (NAD-NETs) are rare, with limited evidence regarding endoscopic treatment. This study investigated the efficacy and safety of endoscopic resection of well-differentiated NAD-NETs and evaluated long-term outcomes, including local recurrence and metastasis. METHODS: Seventy-eight patients with NAD-NETs who underwent endoscopic resection between January 2011 and August 2022 were included. Clinicopathologic characteristics and treatment outcomes were collected and analyzed. RESULTS: En-bloc resection was achieved for 74 tumors (94.9%) and R0 resection for 68 tumors (87.2%). Univariate analysis identified tumors in the second part of the duodenum, tumor size ≥10 mm, and muscularis propria invasion as risk factors for noncurative resection. Two patients with R1 resection (vertical margin involvement) and 2 patients with lymphovascular invasion underwent additional surgery. Four patients experienced adverse events (5.1%), including 2 cases of delayed bleeding and 2 cases of perforation, all successfully managed conservatively. During a median follow-up period of 62.6 months, recurrence and lymph node metastasis were only detected in 1 patient with R1 resection 3 months after the original procedure. CONCLUSIONS: Endoscopic resection is safe and effective and provides a favorable long-term outcome for patients with well-differentiated NAD-NETs without regional lymph node or distant metastasis.

Identification and validation of UBE2B as a prognostic biomarker promoting the development of esophageal carcinomas.

Introduction: Ubiquitination is a crucial biological mechanism in humans, essential for regulating vital biological processes, and has been recognized as a promising focus for cancer therapy. Our objective in this research was to discover potential enzymes associated with ubiquitination that may serve as therapeutic targets for individuals with esophageal carcinoma (ESCA). Methods: To identify genes linked to the prognosis of ESCA, we examined mRNA sequencing data from patients with ESCA in the TCGA database. Further investigation into the role of the candidate gene in ESCA was conducted through bioinformatic analyses. Subsequently, we carried out biological assays to assess its impact on ESCA development. Results: Through univariate Cox regression analysis, we identified Ubiquitin Conjugating Enzyme E2 B (UBE2B) as a potential gene associated with the prognosis of ESCA. UBE2B exhibited significant upregulation and was found to be correlated with survival outcomes in ESCA as well as other cancer types. Additionally, UBE2B was observed to be involved in various biological pathways linked to the development of ESCA, including TNF-a signaling via NF-κB, epithelial-mesenchymal transition, inflammatory response, and hypoxia. Moreover, immune-related pathways like B cell activation (GO: 0042113), B cell receptor signaling pathway (GO: 0050853) and B cell mediated immunity (GO:0019724) were also involved. It was found that high expression of UBE2B was correlated with the increase of several kinds of T cells (CD8 T cells, Th1 cells) and macrophages, while effector memory T cell (Tem) and Th17 cells decreased. Furthermore, UBE2B showed potential as a prognostic biomarker for ESCA, displaying high sensitivity and specificity. Notably, proliferation and migration in ESCA cells were effectively suppressed when the expression of UBE2B was knocked down. Conclusions: To summarize, this study has made a discovery regarding the importance of gaining new insights into the role of UBE2B in ESCA. UBE2B might be an oncogene with good ability in predicting and diagnosing ESCA. Consequently, this discovery highlights the feasibility of targeting UBE2B as a viable approach for treating patients with ESCA.

Endoscopic resection for calcifying fibrous tumors of the gastrointestinal tract.

BACKGROUND: Calcifying fibrous tumors (CFTs) are rare mesenchymal lesions that can occur in various sites throughout the body, including the tubular gastrointestinal (GI) tract. AIM: To analyze the clinical findings of 36 patients with GI tract CFTs to provide guidance for diagnosis and treatment. METHODS: This retrospective study included 36 patients diagnosed with CFTs of the GI tract. We collected demographic and clinical information and conducted regular follow-ups to assess for local recurrence. RESULTS: The stomach was the most commonly involved site, accounting for 72.2% of the 36 CFTs. Endoscopic mucosal resection (n = 1, 2.8%), endoscopic submucosal dissection (n = 14, 38.9%), endoscopic full-thickness resection (n = 16, 44.4%), and submucosal tunneling endoscopic resection (n = 5, 13.9%) were used to resect calcifying fibrous tumors. Overall, 34 (94.4%) CFTs underwent complete endoscopic resections with a mean procedure time of 39.8 ± 29.8 min. The average maximum diameter of the tumors was 10.6 ± 4.3 cm. No complications, such as bleeding or perforation, occurred during an average hospital stay of 2.9 ± 1.2 d. In addition, two patients developed new growth of CFTs near the primary tumor sites, and none of the patients developed distant metastases during the follow-up period. CONCLUSION: GI tract CFTs are rare and typically benign tumors that can be effectively managed with endoscopic procedures.

Application of a nomogram model for the prediction of 90-day poor outcomes following mechanical thrombectomy in patients with acute anterior circulation large-vessel occlusion.

Background: The past decade has witnessed advancements in mechanical thrombectomy (MT) for acute large-vessel occlusions (LVOs). However, only approximately half of the patients with LVO undergoing MT show the best/independent 90-day favorable outcome. This study aimed to develop a nomogram for predicting 90-day poor outcomes in patients with LVO treated with MT. Methods: A total of 187 patients who received MT were retrospectively analyzed. Factors associated with 90-day poor outcomes (defined as mRS of 4-6) were determined by univariate and multivariate logistic regression analyzes. One best-fit nomogram was established to predict the risk of a 90-day poor outcome, and a concordance index was utilized to evaluate the performance of the model. Additionally, 145 patients from a single stroke center were retrospectively recruited as the validation cohort to test the newly established nomogram. Results: The overall incidence of 90-day poor outcomes was 45.16%, affecting 84 of 186 patients in the training set. Moreover, five variables, namely, age (odds ratio [OR]: 1.049, 95% CI [1.016-1.083]; p = 0.003), glucose level (OR: 1.163, 95% CI [1.038-1.303]; p = 0.009), baseline National Institute of Health Stroke Scale (NIHSS) score (OR: 1.066, 95% CI [0.995-1.142]; p = 0.069), unsuccessful recanalization (defined as a TICI grade of 0 to 2a) (OR: 3.730, 95% CI [1.688-8.245]; p = 0.001), and early neurological deterioration (END, defined as an increase of ≥4 points between the baseline NIHSS score and the NIHSS score at 24 h after MT) (OR: 3.383, 95% CI [1.411-8.106]; p = 0.006), were included in the nomogram to predict the potential risk of poor outcomes at 90 days following MT in LVO patients, with a C-index of 0.763 (0.693-0.832) in the training set and 0.804 (0.719-0.889) in the validation set. Conclusion: The proposed nomogram provided clinical evidence for the effective control of these risk factors before or during the process of MT surgery in LVO patients.

Endoscopic resection of giant esophageal subepithelial lesions: experience from a large tertiary center.

BACKGROUND AND AIMS: Increased reports on endoscopic resection (ER) of esophageal giant subepithelial lesions (g-SELs) have emerged in recent years. The aim of this study was to evaluate the efficacy, technical difficulty, and safety through our single-center experience. METHODS: Seventy-five patients with g-SELs undergoing endoscopic resection were included in the training set. Clinicopathologic features, procedure-related characteristics, postprocedural outcomes, and follow-up data were analyzed. A predictive nomogram model for procedural difficulty was proposed based on the multivariable logistic regression analysis. Internal and external validations were conducted to verify the model performance. RESULTS: The overall en bloc resection rate was 93.3%. Intraoperative and postoperative adverse events occurred in 7 (9.3%) and 13 (17.3%) patients, respectively. No recurrence or metastasis was observed. Thirty-two (42.7%) patients underwent a difficult procedure. Age (adjusted odds ratio [aOR], .915; P = .004), maximal tumor diameter ≥8 cm (aOR, 9.896; P = .009), irregular shape (aOR, 4.081; P = .053), extraluminal growth pattern (aOR, 5.419; P = .011), and submucosal tunneling endoscopic resection (aOR, .109; P = .042) were found to be statistically or clinically significant factors for predicting endoscopic resection difficulty, based on which a nomogram model was developed. Internal and external validations of the nomogram via receiver-operating characteristic curves and calibration curves achieved favorable results. CONCLUSIONS: Endoscopic resection serves as a promising therapeutic option for esophageal g-SELs. A younger patient age, large tumor size, irregular shape, and extraluminal growth may indicate increased endoscopic resection difficulty, whereas a submucosal tunneling endoscopic resection procedure tends to be of lower difficulty. Our nomogram model performs well for predicting endoscopic resection difficulty for esophageal g-SELs.

Feasibility and safety of endoscopic resection for the jejunoileal lesions.

BACKGROUND: Endoscopic resection (ER) for jejunoileal lesions (JILs) has been technically challenging. We aimed to characterize the clinicopathologic characteristics, feasibility, and safety of ER for JILs. METHOD: We retrospectively investigated 52 patients with JILs who underwent ER from January 2012 to February 2022. We collected and analyzed clinicopathological characteristics, procedure-related parameters, outcomes, and follow-up data. RESULTS: The mean age was 49.4 years. Of the 52 JILs, 33 ileal tumors within 20 cm from the ileocecal valve were resected with colonoscopy, while 19 tumors in the jejunum or the ileum over 20 cm from the ileocecal valve received enteroscopy resection. The mean procedure duration was 49.0 min. The en bloc resection and en bloc with R0 resection rates were 86.5% and 84.6%, respectively. Adverse events (AEs) included one (1.9%) major AE (delayed bleeding) and five (9.6%) minor AEs. During a median follow-up of 36.5 months, two patients had local recurrence (3.8%), while none had metastases. The 5-year recurrence-free survival (RFS) and disease-specific survival (DSS) were 92.9% and 94.1%, respectively. Compared with the enteroscopy group, overall AEs were significantly lower in the colonoscopy group (P < 0.05), but no statistical differences were observed in RFS (P = 0.412) and DSS (P = 0.579). There were no significant differences in AEs, RFS, and DSS between the endoscopic submucosal dissection (ESD) and the endoscopic mucosal resection (EMR) group. CONCLUSIONS: ER of JILs has favorable short-term and long-term outcomes. Both ESD and EMR can safely and effectively resect JILs in appropriately selected cases.

Management of delayed bleeding of upper gastrointestinal endoscopic submucosal tunneling procedures: a retrospective single-center analysis and brief meta-analysis.

OBJECTIVES: Delayed bleeding is a rare but important major adverse event (mAE) after endoscopic submucosal tunneling procedures (ESTP), which is scarcely reported. We aimed to characterize the clinical characteristics of delayed bleeding and provide better management of this mAE. METHOD: From August 2010 to October 2022, we reviewed 3852 patients with achalasia receiving peroral endoscopic myotomy (POEM) and 1937 patients with upper gastrointestinal tumors receiving submucosal tunneling endoscopic resection (STER). Among these, records of 22 patients (15 POEM, 7 STER) with delayed bleeding were collected. Clinical characteristics, treatment, and outcomes of delayed bleeding were analyzed. RESULTS: The mean age was 43.6 years. Ten patients (45.5%) were intratunnel bleeding, seven (31.8%) were intratunnel bleeding accompanied by mucosal bleeding, and five (22.7%) were mucosal bleeding. The most common accompanied symptoms were hematemesis, fever, and melena. The most common accompanied mAEs were fistula, pulmonary inflammation, and pleural effusion with atelectasis. The mean duration from ESTP to endoscopic intervention was 5.3 ± 4.9 days. Active bleeding was identified in 21 patients (95.5%). The bleeding was successfully controlled by electrocoagulation (19 cases), endoscopic clipping (six cases), and Sengstaken-Blakemore tube insertion (three cases), and no patient required surgical intervention. The mean hemostatic procedure duration was 61.8 ± 45.8 min. The mean post-bleeding hospital stay was 10.0 ± 6.2 days. A brief meta-analysis of previous studies showed the pooled estimate delayed bleeding rate after POEM, STER, and G-POEM was 0.4%. CONCLUSIONS: Delayed bleeding is uncommon and could be effectively managed by timely emergency endoscopic procedures without requiring subsequent surgical interventions.

Anti-cancer treatment within two weeks serves as a risk factor for clinical outcomes among cancer patients with COVID-19.

Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in infections among patients with cancer. Our study aimed to investigate the potential adverse impact of anti-cancer treatments within 2 weeks of COVID-19 infection on clinical outcomes in patients with cancer. Methods: This retrospective cohort study analyzed 70 cancer patients with COVID-19 infection from the First Hospital of Jilin University in Changchun City, Jilin Province, between March and June 2022. Data on demographic characteristics, vaccination status, COVID-19 clinical classification, symptoms, complications, tumor-related characteristics, laboratory examinations and medical interventions were extracted from electronic medical record. The primary outcome of our study was Intensive Care Unit (ICU) admission. Logistic regression model was performed to investigate the association between anti-cancer treatments within 2 weeks after COVID-19 infection and the risk of ICU admission. Results: Of the 70 patients enrolled in this study, 37 received anti-cancer treatments within 2 weeks after COVID-19 infection. Patients receiving anti-cancer treatment were more likely to experience non-mild COVID-19, require oxygen therapy, develop acute respiratory distress syndrome (ARDS) and exhibit elevated inflammatory levels. The risk of ICU admission (P<0.001) and 30-day mortality after reverse transcriptase polymerase chain reaction (RT-PCR) negative conversion (P=0.007) was significantly higher in patients receiving anti-cancer treatments. In multivariate Logistic regression analysis, non-mild classification of COVID-19, anti-cancer treatments within 2 weeks and ECOG > 1were all independently associated with ICU admission after adjusting for confounder factors. The risk of ICU admission rose to 43.63 times (95% confidence interval=1.31-1452.94, P=0.035) in patients receiving anti-cancer treatments within 2 weeks. Conclusion: Anti-cancer treatments within 2 weeks of COVID-19 infection increase the risk of ICU admission and 30-day mortality after RT-PCR negative conversion in patients with cancer. It may be recommended to postpone cancer-related treatments for more than 2 weeks in cancer patients with COVID-19 infection.

Landscape of Psychological Profiles in Patients With Esophageal Achalasia.

INTRODUCTION: Esophageal achalasia (EA) is a chronic esophageal dysmotility disease, of which psychological distress was poorly understood. This study aims to assess the status of psychosocial characteristics in EA and to determine the relationship between psychological distress and EA. METHODS: Seventy pairs of age and gender-matched patients with EA and healthy control individuals were prospectively enrolled from December 2019 to April 2020 at our hospital. Demographic, psychosocial, and clinical data were obtained. Psychosocial assessments contained psychological distress (Symptom Checklist-90 Revised), perceived stress (Perceived Stress Scale-14), and stressful life events (Life Events Scale). Comparison for psychological parameters was made between patients with EA and controls as well as for EA before/after per oral endoscopic myotomy (POEM). Spearman rank correlation coefficients were used to testify the association between psychological distress and achalasia symptoms. RESULTS: The mean course and Eckardt score of patients with EA were 4.26 ± 5.11 years and 6.63 ± 2.21, respectively. There was a significant difference between patients with EA and healthy individuals in Global Severity Index ( P = 0.039) and Positive Symptoms Total ( P = 0.041) for Symptom Checklist-90 Revised as well as positive intensity ( P = 0.011) for the Life Events Scale. Somatization ( P < 0.001), anxiety ( P = 0.021), anger-hostility ( P = 0.009), and others (appetite and sleep, P = 0.010) accounted for the most difference. Somatization was positively associated with chest pain ( P = 0.045). Two patients with EA developed recurrence and showed no relationship with psychological status. Psychological status was significantly improved after POEM. DISCUSSION: Psychological distress, especially somatization, was more prevalent in patients with EA than healthy controls. POEM seemed able to improve psychological distress.

Comprehensive Analysis Identifies the PPAR-Targeted Genes Associated with Ovarian Cancer Prognosis and Tumor Microenvironment.

Background: There is a significant role for peroxisome proliferator-activated receptors (PPARs) in the development of cancer. Nevertheless, the role of PPARs-related genes in ovarian cancer (OC) remains unclear. Methods: The open-accessed data used for analysis were downloaded from The Cancer Genome Atlas database, which was analyzed using the R software. Results: In our study, we comprehensively investigated the PPAR target genes in OC, including their biological role. Meanwhile, a prognosis signature consisting of eight PPAR target genes was established, including apolipoprotein A-V, UDP glucuronosyltransferase 2 family, polypeptide B4, TSC22 domain family, member 1, growth hormone inducible transmembrane protein, renin, dedicator of cytokinesis 4, enoyl CoA hydratase 1, peroxisomal (ECH1), and angiopoietin-like 4, which showed a good prediction efficiency. A nomogram was constructed by combining the clinical feature and risk score. Immune infiltration and biological enrichment analysis were applied to investigate the difference between high- and low-risk patients. Immunotherapy analysis indicated that low-risk patients might respond better to immunotherapy. Drug sensitivity analysis indicated that high-risk patients might respond better to bleomycin, nilotinib, pazopanib, pyrimethamine, and vinorelbine, yet worse to cisplatin and gefitinib. Furthermore, the gene ECH1 was selected for further analysis. Conclusions: Our study identified a prognosis signature that could effectively indicates patients survival. Meanwhile, our study can provide the direction for future studies focused on the PPARs in OC.

Salvage peroral endoscopic myotomy is a promising treatment for achalasia after myotomy failure.

BACKGROUND AND AIMS: Reintervention modalities after myotomy failure in achalasia patients have yet to be established. The efficacy and safety of salvage peroral endoscopic myotomy (POEM) for treatment of achalasia after myotomy failure were evaluated in the study. METHODS: Between August 2011 and August 2021 at the Endoscopy Center of Zhongshan Hospital, 219 achalasia patients who had previously undergone a myotomy underwent a salvage POEM and were thus retrospectively enrolled in this study. After propensity score matching (PSM), operation-related parameters were compared between the salvage POEM group and the naïve POEM group. Subgroup analysis was performed between patients with previous Heller myotomy (HM) and patients with previous POEM. RESULTS: With similar baseline characteristics between both groups after PSM, the salvage POEM group presented with shorter tunnel length (11.8 ± 2.2 cm vs 12.8 ± .9 cm, P < .0001) and myotomy length (9.8 ± 2.0 cm vs 10.4 ± 1.0 cm, P < .0001) than the naïve POEM group. No significant differences were found in procedure-related adverse events between patients of salvage POEM and naïve POEM. The primary outcome of treatment success occurred in 175 of 193 patients (90.7%) in the salvage POEM group versus 362 of 374 patients (96.8%) in the naïve POEM group (P = .0046). At a 2- and 5-year follow-up, significantly higher rates of clinical failures were observed in the previous HM subgroup than in the previous POEM subgroup (P = .0433 and P = .0230, respectively). CONCLUSIONS: Salvage POEM after a previous myotomy failure, especially after a POEM failure, is a promising treatment option because it has a durable clinical relief rate.

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.

Endoscopic resection and suturing methods for non-ampullary duodenal submucosal tumors: "mini-invasive" treatments that should never be underestimated.

OBJECTIVE: To evaluate the effectiveness and safety of endoscopic resection and various suturing methods to treat non-ampullary duodenal submucosal tumors (NAD-SMTs). DESIGN: We performed a retrospective observational study of patients with NAD-SMTs who underwent endoscopic resection at Zhongshan Hospital, Fudan University, China, between June 2017 and December 2020. Data on patient characteristics, treatments and follow-up results were collected. The association between clinicopathologic characteristics and different suturing methods or adverse events were analyzed. RESULTS: Of 128 patients analyzed, 26 underwent endoscopic mucosal resection (EMR), 64 underwent endoscopic submucosal excavation (ESE), and 38 underwent endoscopic full-thickness resection (EFTR). EMR and ESR are both appropriate for non-full-thickness lesions, whereas ESE is more appropriate for tumors located in the bulb or descending duodenum. Gastric tube drainage is more strongly recommended after ESE. Satisfactory suturing is also vital endoscopic resection of NAD-SMTs. Metallic clips are often used in EMR or ESE of non-full-thickness lesions. The pathological findings revealed that the full-thickness lesions were predominantly gastrointestinal stromal tumors (GIST), Brunner's tumor or lipoma, and the surgeons usually used purse-string sutures to close the wounds. The operation time was longer for purse-string suture closure than metallic clip closure. Eleven patients had complications. Risk factors for adverse events included large-diameter tumor (≥ 2 cm), location in the descending part of the duodenum, involvement of the fourth layer of the duodenal wall, EFTR, and GIST. CONCLUSIONS: Endoscopic resection of NAD-SMTs is effective but is associated with a high incidence of complications due to their anatomical peculiarities. Preoperative diagnosis is quite important. Careful selection of treatment and suturing methods are necessary to reduce the risk of adverse effects. Given the increased frequency of severe complications during or following duodenal endoscopic resection, this procedure should be performed by experienced endoscopists.

Clinical outcomes of endoscopic resection for the treatment of esophageal gastrointestinal stromal tumors: a ten-year experience from a large tertiary center in China.

BACKGROUNDS: Esophageal gastrointestinal stromal tumors (E-GISTs) are extremely rare and surgical resection is the recommended approach. However, surgical resection usually causes severe trauma that may result in significant postoperative morbidity. Endoscopic resection (ER) has developed rapidly in recent years and has been widely used in gastrointestinal lesions. Nevertheless, the feasibility and efficacy of ER in the management of E-GISTs are unknown. METHODS: Retrospective data were collected from January 2011 to December 2020 in a large tertiary center of China. Twenty-eight patients with E-GISTs treated by ER were included in the study. RESULTS: Of the 28 patients, there were 21 males and 7 females, with a median age of 55 years (40-70 years). The median tumor size was 15 mm (5-80 mm). The technical success rate was 100% (28/28), while the en bloc resection rate was 96.4% (27/28). The median operation time was 35 min (10-410 min). Sixteen (57.2%) tumors were categorized into very low risk group, six (21.4%) into low risk group, and six (21.4%) into high risk group. Pathologists carefully examined margins of each lesion. There were 11 lesions (39.3%) determined as R0 resection and 17 lesions (60.7%) as R1 resection with positive margins. The median hospital stay was 2 days (range, 1-8 days). One patient suffered from hydrothorax and required drainage, leading to a major adverse event rate of 3.6% (1/28). There was no conversion to surgery, and no death occurred within 30 days after the procedure. Imatinib was given to two patients after ER under multidisciplinary team surveillance. During follow-up (median of 54 months, 9-122 months), no recurrences or metastasis were observed. CONCLUSION: ER is safe and effective for E-GISTs and might become an optional choice in the future. Multicenter, prospective, large samples with long-term follow-up studies are still needed.

Single-cell transcriptomic analysis deciphers key transitional signatures associated with oncogenic evolution in human intramucosal oesophageal squamous cell carcinoma.

BACKGROUND AND AIMS: The early diagnosis and intervention of oesophageal squamous cell carcinoma (ESCC) are particularly important because of the lack of effective therapies and poor prognosis. Comprehensive research on early ESCC at the single-cell level is rare due to the need for fresh and high-quality specimens obtained from ESD. This study aims to systematically describe the cellular atlas of human intramucosal ESCC. METHODS: Five paired samples of intramucosal ESCC, para-ESCC oesophageal tissues from endoscopically resected specimens and peripheral blood mononuclear cells were adopted for scRNA-seq analysis. Computational pipeline scMetabolism was applied to quantify the metabolic diversity of single cells. RESULTS: A total of 164 715 cells were profiled. Epithelial cells exhibited high intra-tumoural heterogeneity and two evolutionary trajectories during ESCC tumorigenesis initiated from proliferative cells, and then through an intermediate state, to two different terminal states of normally differentiated epithelial cells or malignant cells, respectively. The abundance of CD8+ TEX s, Tregs and PD1+ CD4+ T cells suggested an exhausted and suppressive immune microenvironment. Several genes in immune cells, such as CXCL13, CXCR5 and PADI4, were identified as new biomarkers for poor prognosis. A new subcluster of malignant cells associated with metastasis and angiogenesis that appeared at an early stage compared with progressive ESCC was also identified in this study. Intercellular interaction analysis based on ligand-receptor pairs revealed the subcluster of malignant cells interacting with CAFs via the MDK-NCL pathway, which was verified by cell proliferation assay and IHC. This indicates that the interaction may be an important hallmark in the early change of tumour microenvironment and serves as a sign of CAF activation to stimulate downstream pathways for facilitating tumour invasion. CONCLUSION: This study demonstrates the changes of cell subsets and transcriptional levels in human intramucosal ESCC, which may provide unique insights into the development of novel biomarkers and potential intervention strategies.

Comparison of specimen quality among the standard suction, slow-pull, and wet suction techniques for EUS-FNA: A multicenter, prospective, randomized controlled trial.

Background and Objectives: Standard suction technique (SST), slow-pull technique (SPT), and wet suction technique (WEST) of EUS-FNA are designed to improve the diagnostic yields of solid and solid-cystic lesions. We conducted a multicenter, prospective, randomized crossover trial to compare SST, SPT, and WEST on specimen quality and diagnostic accuracy using a 22G needle. Methods: Patients with solid or solid-cystic lesions referred for EUS-FNA at four tertiary hospitals from December 2017 to August 2019 were considered eligible. All lesions were sampled using a 22G needle by the three techniques performed consecutively in a randomized order. The primary outcome was quality of the specimen acquired by each technique regarding blood contamination, tissue integrity and cellularity for diagnosis, graded on a predefined scale. The secondary outcomes were the diagnostic yield of EUS-FNA and the incidence of adverse events. ClinicalTrial. gov registration number: NCT03567863. Results: A total of 300 patients (mean age, 60.6 years, 188 men) were enrolled. WEST was superior (mean score 4.02 ± 1.51) over SST (3.67 ± 1.57, P = 0.018), but comparable to SPT (3.83 ± 1.55, P = 0.370) in overall specimen quality evaluation. WEST produced better tissue integrity (1.42 ± 0.74) and higher cellularity (1.32 ± 0.80) than SST and SPT. SPT (1.43 ± 0.69) was superior to SST (1.27 ± 0.72, P = 0.004) and WEST (1.28 ± 0.71, P = 0.006) in avoiding blood contamination. WEST achieved a diagnostic accuracy of 74.7%, higher than SST (64.4%, P = 0.007) and SPT (65.0%, P = 0.012). One bleeding event occurred with a pancreatic lesion. Conclusions: WEST was comparable to SPT and superior to SST in the overall quality of the specimen and achieved highest diagnostic yield.

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.

Erratum: A scoring system to support surgical decision-making for cardial submucosal tumors.

[This corrects the article DOI: 10.1055/a-1775-7976.].

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.