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Purpose: Esophageal squamous cell carcinoma (ESCC) is an aggressive disease with a poor prognosis, caused by the inactivation of critical cell growth regulators that lead to uncontrolled proliferation and increased malignancy. Although Serine/Threonine Kinase 3 (STK3), also known as Mammalian STE20-like protein kinase 2 (MST2), is a highly conserved kinase of the Hippo pathway, plays a critical role in immunomodulation, organ development, cellular differentiation, and cancer suppression, its phenotype and function in ESCC require further investigation. In this study, we report for the first time on the role of STK3 kinase and its activation condition in ESCC, as well as the mechanism and mediators of kinase activation. Methods: In this study, we investigated the expression and clinical significance of STK3 in ESCC. We first used bioinformatics databases and immunohistochemistry to analyze STK3 expression in the ESCC patient cohort and conducted survival analysis. In vivo, we conducted a tumorigenicity assay using nude mouse models to demonstrate the phenotypes of STK3 kinase. In vitro, we conducted Western blot analysis, qPCR analysis, CO-IP, and immunofluorescence (IF) staining analysis to detect molecule expression, interaction, and distribution. We measured proliferation, migration, and apoptosis abilities in ESCC cells in the experimental groups using CCK-8 and transwell assays, flow cytometry, and EdU staining. We used RNA-seq to identify genes that were differentially expressed in ESCC cells with silenced STK3 or FOXO1. We demonstrated the regulatory relationship of the TP53INP1/P21 gene medicated by the STK3-FOXO1 axis using Western blotting and ChIP in vitro. Results: We demonstrate high STK3 expression in ESCC tissue and cell lines compared to esophageal epithelium. Cellular ROS induces STK3 autophosphorylation in ESCC cells, resulting in upregulated p-STK3/4. STK3 activation inhibits ESCC cell proliferation and migration by triggering apoptosis and suppressing the cell cycle. STK3 kinase activation phosphorylates FOXO1Ser212, promoting nuclear translocation, enhancing transcriptional activity, and upregulating TP53INP1 and P21. We also investigated TP53INP1 and P21's phenotypic effects in ESCC, finding that their knockdown significantly increases tumor proliferation, highlighting their crucial role in ESCC tumorigenesis. Conclusion: STK3 kinase has a high expression level in ESCC and can be activated by cellular ROS, inhibiting cell proliferation and migration. Additionally, STK3 activation-mediated FOXO1 regulates ESCC cell apoptosis and cell cycle arrest by targeting TP53INP1/P21. Our research underscores the anti-tumor function of STK3 in ESCC and elucidates the mechanism underlying its anti-tumor effect on ESCC. [ABSTRACT FROM AUTHOR]

The proline synthesis is importantly involved in tumor growth under hypoxia, while the underlying mechanism remains to be further investigated. Here we show that pyrroline-5-carpoxylate reductase-1 (PYCR1), displaying a constant nuclear localization, is phosphorylated by nuclear IGF1R at Tyrosine 135 under hypoxia; this phosphorylation promotes the binding of PYCR1 to ELK4 and thus PYCR1 recruitment to ELK4-targeted genes promoter. Under hypoxia, ELK4-binding ability and enzymatic activity of PYCR1 are both required for ELK4-Sirt7-mediated transcriptional repression and cell growth maintenance, in which PYCR1-catalyzed NAD+ production stimulates the deacetylation activity of Sirt7 on H3K18ac that restrains genes transcription. Functionally, PYCR1 Tyr-135 phosphorylation exerts supportive effect on tumor growth under hypoxia, and the level of PYCR1 Tyr-135 phosphorylation is associated with malignancy of colorectal cancer (CRC). These data uncover the relationship between the compartmentally metabolic activity of PYCR1 and genes transcription regulation, and highlight the oncogenic role of PYCR1 during CRC development. Additional roles of metabolic enzymes in cancer remain to be explored. Here, the authors show nuclear localized PYCR1 undergoes IGF1R-mediated phosphorylation under hypoxia, binds with ELK4 and recruits SIRT7 to modulate transcription of target genes to promote colorectal cancer progression. [ABSTRACT FROM AUTHOR]

Objectives: Post-ESD esophageal stricture especially after wholly circumferential ESD remains an unresolved issue without ideal strategies. Our initiative novel self-control stricture-preventing water balloon may be an alternative. Methods: Patients with esophageal neoplastic lesions expected to result in a whole circular mucosa defect after esophageal ESD from February 2018 to August 2020 were included in the study. We used a novel self-control stricture-preventing water balloon combined with oral prednisolone as preventive strategy for the enrolled patients. Results: Thirty-seven patients (9 females and 28 males, patients aged 52 to 82 years) finished the 12-week treatment including steroid treatment and balloon placement. The median size of longitudinal diameter was 7 cm (range from 4 to 14 cm). All the lesions achieved curative resection and the median procedure time was 110 min (range 50 to 180 min). Balloons were found migration in 4 patients. As a result, there were 3 patients (8.1%) experienced stricture. Generally, patients could tolerate to balloons, only with mild uncomfortableness, such as occasional sore throat, cough, and retrosternal pain. In addition, during the follow-up period, no significant adverse events associated to oral steroid administration were observed and no recurrence was found. Conclusions: Our novel self-control stricture-preventing water balloon based on the oral steroid therapy is effective and safe. This strategy well prevents esophageal stricture after complete circumferential ESD. [ABSTRACT FROM AUTHOR]

Aim: To investigate the risk factors for delayed bleeding following endoscopic submucosal dissection (ESD) for colorectal neoplasms. Methods: We retrospectively reviewed the medical records of 991 consecutive patients who underwent ESD for colorectal neoplasms at our hospital from January 2007 to November 2016. Delayed post-ESD bleeding was defined as bleeding within 6 h to 30 days after ESD that resulted in either of the three situations: overt hematochezia, bleeding spots confirmed by repeat colonoscopy, or the requirement of a blood transfusion. Delayed bleeding was furtherly separated into early and late delayed bleeding by the end of post-ESD day 2. We analyzed the relationship between delayed bleeding and candidate factors including patient-, lesion-, and treatment-related details. Results: Delayed post-ESD bleeding was found in 47 patients (4.7%), of which 18 cases were late delayed bleeding. Among all patients, 14 patients required a second colonoscopy, and 2 other patients were transferred to surgery. Univariate analysis revealed that patients with hypertension (p = 0.017) and using hot biopsy forceps for wound management (p = 0.028) were significantly associated with late delayed bleeding. Both risk factors remained significant after multivariate analysis: hypertension (OR 2.829, 95% CI 1.101–7.265, p = 0.031), hot biopsy forceps (OR 2.873, 95% CI 1.013–8.147, p = 0.047). Using hot biopsy forceps was also the significant risk factor for late delayed bleeding compared with early delayed bleeding. Conclusion: Patient with hypertension and using hot biopsy forceps for wound management during procedure call for attention on high risk of delayed post-ESD bleeding. Therefore, additional perioperative treatment is recommended in patients with these risk factors. [ABSTRACT FROM AUTHOR]

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

Background: Endoscopic submucosal dissection (ESD) has been widely accepted as the treatment for early-stage esophageal epithelial neoplasms. However, stricture is a common complication after large-circumference ESD. This retrospective study is conducted to evaluate the efficacy and safety of intralesional steroid injection plus oral steroid administration in preventing esophageal stricture.Methods: 70 patients with a mucosal defect extending over more than two-thirds of the circumference after esophageal ESD for epithelial neoplasms were enrolled in this study. Those who received intralesional triamcinolone injection combined with oral prednisolone administration were assigned to the treatment group, while those who were treated without any prophylaxis of esophageal stricture were assigned to the control group. The primary observation result was the frequency of stricture. The secondary observation results were the number of endoscopic balloon dilation (EBD) sessions and rate of complications.Results: Compared with the control group, the frequency of stricture (14.7% 5/34 patients vs. 51.5% 19/36 patients) and number of EBD sessions (mean 0.2 vs. 3.3) were significantly lower in the treatment group. One patient suffered from perforation in the treatment group and recovered with conservative treatment. None steroid-related complications were found during a long-term follow-up.Conclusions: Intralesional steroid injection plus oral steroid administration is safe and effective in preventing stricture following esophageal ESD for esophageal epithelial neoplasms with a mucosal defect extending no less than two-thirds of the circumference in a long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: Anorectal malignant melanoma (ARMM) is a rare disease accounting for less than 1% of primary anorectal malignancies. Here we first present a case of early primary anorectal malignant melanoma completely resected by endoscopic submucosal dissection (ESD). Methods and results: A 43-year-old woman visited our hospital because of suspected anal melanoma found by routine colonoscopy in her local hospital. Following series of tests including CT, MRI, and whole-body PET-CT did not show any evidence of metastasis. The lesion was removed by the method of ESD in en bloc and no delayed bleeding or perforation occurred. The result of histopathologic examinations confirmed to be malignant melanoma. No recurrence or distant metastases were found during follow-up time (the latest follow-up was 2 years after ESD). Conclusion: The present case showed endoscopic submucosal dissection that can be an effective and safe alternative treating early primary anorectal malignant melanoma. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the management and treatment for complications during and after peroral endoscopic myotomy (POEM) for patients suffering from esophageal achalasia (EA). Methods: The data of 119 cases of EA patients who underwent POEM from October 2010 to July 2011 and the complications that arose during the operation, after the operation, and during follow-up were analyzed. Results: Complications that occurred during the operation included cutaneous emphysema (22.7 %, 27/119) and pneumothorax (2.5 %, 3/119). Postoperative complications included pneumothorax (25.2 %, 30/119), subcutaneous emphysema (55.5 %, 66/119), mediastinal emphysema (29.4 %, 35/119), delayed hemorrhage (0.8 %, 1/119), pleural effusion (48.7 %, 58/119), minor inflammation or segmental atelectasis of the lungs (49.6 %, 59/119), and gas under diaphragm or aeroperitoneum (39.5 %, 47/119). Complications that occurred during follow-up included one case of difficulty eating caused by the stricture of mucosa and one case of dehiscence at the mouth of the tunnel created during surgery, with food retention. No deaths occurred. All complications were resolved through traditional treatment. No additional surgery was needed. Conclusion: Complications arising during and after POEM should be treated quickly and can be resolved by using traditional treatment. POEM can be expected to become the preferred treatment for EA. [ABSTRACT FROM AUTHOR]

Capsule endoscopy (CE) is non-invasive and painless during gastrointestinal examination. However, capsule endoscopy can increase the workload of image reviewing for clinicians, making it prone to missed and misdiagnosed diagnoses. Current researches primarily concentrated on binary classifiers, multiple classifiers targeting fewer than four abnormality types and detectors within a specific segment of the digestive tract, and segmenters for a single type of anomaly. Due to intra-class variations, the task of creating a unified scheme for detecting multiple gastrointestinal diseases is particularly challenging. A cascade neural network designed in this study, Cascade-EC, can automatically identify and localize four types of gastrointestinal lesions in CE images: angiectasis, bleeding, erosion, and polyp. Cascade-EC consists of EfficientNet for image classification and CA&#95;stm&#95;Retinanet for lesion detection and location. As the first layer of Cascade-EC, the EfficientNet network classifies CE images. CA&#95;stm&#95;Retinanet, as the second layer, performs the target detection and location task on the classified image. CA&#95;stm&#95;Retinanet adopts the general architecture of Retinanet. Its feature extraction module is the CA&#95;stm&#95;Backbone from the stack of CA&#95;stm Block. CA&#95;stm Block adopts the split-transform-merge strategy and introduces the coordinate attention. The dataset in this study is from Shanghai East Hospital, collected by PillCam SB3 and AnKon capsule endoscopes, which contains a total of 7936 images of 317 patients from the years 2017 to 2021. In the testing set, the average precision of Cascade-EC in the multi-lesions classification task was 94.55%, the average recall was 90.60%, and the average F1 score was 92.26%. The mean mAP@ 0.5 of Cascade-EC for detecting the four types of diseases is 85.88%. The experimental results show that compared with a single target detection network, Cascade-EC has better performance and can effectively assist clinicians to classify and detect multiple lesions in CE images., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)