Correlation between tumor budding and the long-term follow-up outcomes after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND: The effect of tumor budding (TB) on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after endoscopic submucosal dissection (ESD) remains unclear. We evaluated the long-term outcomes of patients with superficial ESCC after ESD and the risk factors of TB for the long-term prognosis. METHODS: We conducted a retrospective study in a Chinese hospital. All patients with ESCC treated by ESD and reported TB were included consecutively. Comparative analyses were conducted in three parts: specimen analysis, follow-up analyses of unmatched patients, and propensity score-matched (PSM) patients. Cox proportional hazard regression models were constructed to identify risk factors for overall survival and recurrence-free survival (RFS). RESULTS: A total of 437 patients were enrolled [154 TB and 283 no tumor budding (NTB)], and 258 patients (52 TB and 206 NTB) were included in the follow-up analysis. Results showed that the invasion depth, differentiation type, and positive vascular invasion (all p < 0.001) of the TB group were significantly different from the NTB group. The all-cause mortality and the median RFS time between the two groups were comparable. RFS rate at 5 years were 84.6% and 80.6%, respectively (p = 0.43). Cox analyses identified that having other cancers but not TB, as a risk factor independently associated with overall survival and RFS after ESD. CONCLUSION: TB tends to be associated with invasion depth, differentiation type, and positive vascular invasion. However, it might not affect the long-term outcomes of patients with superficial ESCC after ESD when other high-risk factors are negative.

BAP1-mediated MAFF deubiquitylation regulates tumor growth and is associated with adverse outcomes in colorectal cancer.

BACKGROUND: Despite improvements in colorectal cancer (CRC) treatment, the prognosis for advanced CRC patients remains poor. Disruption of protein stability is one of the important factors in cancer development and progression. In this study, we aim to identify and analyze novel dysregulated proteins in CRC, assessing their significance and the mechanisms. METHODS: Using quantitative proteomics, expression pattern analysis, and gain-of-function/loss-of-function experiments, we identify novel functional protein dysregulated by ubiquitin-proteasome axis in CRC. Prognostic significance was evaluated in a training cohort of 546 patients and externally validated in 794 patients. Mechanistic insights are gained through molecular biology experiments, deubiquitinating enzymes (DUBs) expression library screening, and RNA sequencing. RESULTS: MAFF protein emerged as the top novel candidate substrate regulated by ubiquitin-proteasome in CRC. MAFF protein was preferentially downregulated in CRC compared to adjacent normal tissues. More importantly, multicenter cohort study identified reduced MAFF protein expression as an independent predictor of overall and disease-free survival in CRC patients. The in vitro and vivo assays showed that MAFF overexpression inhibited CRC growth, while its knockdown had the opposite effect. Intriguingly, we found the abnormal expression of MAFF protein was predominantly regulated via ubiquitination of MAFF, with K48-ubiquitin being dominant. BAP1 as a nuclear deubiquitinating enzyme (DUB), bound to and deubiquitinated MAFF, thereby stabilizing it. Such stabilization upregulated DUSP5 expression, resulting in the inhibition of ERK phosphorylation. CONCLUSIONS: This study describes a novel BAP1-MAFF signaling axis which is crucial for CRC growth, potentially serving as a therapeutic target and a promising prognostic biomarker for CRC.

Developing a machine learning-based prognosis and immunotherapeutic response signature in colorectal cancer: insights from ferroptosis, fatty acid dynamics, and the tumor microenvironment.

Instruction: Colorectal cancer (CRC) poses a challenge to public health and is characterized by a high incidence rate. This study explored the relationship between ferroptosis and fatty acid metabolism in the tumor microenvironment (TME) of patients with CRC to identify how these interactions impact the prognosis and effectiveness of immunotherapy, focusing on patient outcomes and the potential for predicting treatment response. Methods: Using datasets from multiple cohorts, including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we conducted an in-depth multi-omics study to uncover the relationship between ferroptosis regulators and fatty acid metabolism in CRC. Through unsupervised clustering, we discovered unique patterns that link ferroptosis and fatty acid metabolism, and further investigated them in the context of immune cell infiltration and pathway analysis. We developed the FeFAMscore, a prognostic model created using a combination of machine learning algorithms, and assessed its predictive power for patient outcomes and responsiveness to treatment. The FeFAMscore signature expression level was confirmed using RT-PCR, and ACAA2 progression in cancer was further verified. Results: This study revealed significant correlations between ferroptosis regulators and fatty acid metabolism-related genes with respect to tumor progression. Three distinct patient clusters with varied prognoses and immune cell infiltration were identified. The FeFAMscore demonstrated superior prognostic accuracy over existing models, with a C-index of 0.689 in the training cohort and values ranging from 0.648 to 0.720 in four independent validation cohorts. It also responses to immunotherapy and chemotherapy, indicating a sensitive response of special therapies (e.g., anti-PD-1, anti-CTLA4, osimertinib) in high FeFAMscore patients. Conclusion: Ferroptosis regulators and fatty acid metabolism-related genes not only enhance immune activation, but also contribute to immune escape. Thus, the FeFAMscore, a novel prognostic tool, is promising for predicting both the prognosis and efficacy of immunotherapeutic strategies in patients with CRC.

A dynamic online nomogram predicting prostate cancer short-term prognosis based on 18F-PSMA-1007 PET/CT of periprostatic adipose tissue: a multicenter study.

BACKGROUND: Rising prostate-specific antigen (PSA) levels following radical prostatectomy are indicative of a poor prognosis, which may associate with periprostatic adipose tissue (PPAT). Accordingly, we aimed to construct a dynamic online nomogram to predict tumor short-term prognosis based on 18F-PSMA-1007 PET/CT of PPAT. METHODS: Data from 268 prostate cancer (PCa) patients who underwent 18F-PSMA-1007 PET/CT before prostatectomy were analyzed retrospectively for model construction and validation (training cohort: n = 156; internal validation cohort: n = 65; external validation cohort: n = 47). Radiomics features (RFs) from PET and CT were extracted. Then, the Rad-score was constructed using logistic regression analysis based on the 25 optimal RFs selected through maximal relevance and minimal redundancy, as well as the least absolute shrinkage and selection operator. A nomogram was constructed to predict short-term prognosis which determined by persistent PSA. RESULTS: The Rad-score consisting of 25 RFs showed good discrimination for classifying persistent PSA in all cohorts (all P < 0.05). Based on the logistic analysis, the radiomics-clinical combined model, which contained the optimal RFs and the predictive clinical variables, demonstrated optimal performance at an AUC of 0.85 (95% CI: 0.78-0.91), 0.77 (95% CI: 0.62-0.91) and 0.84 (95% CI: 0.70-0.93) in the training, internal validation and external validation cohorts. In all cohorts, the calibration curve was well-calibrated. Analysis of decision curves revealed greater clinical utility for the radiomics-clinical combined nomogram. CONCLUSION: The radiomics-clinical combined nomogram serves as a novel tool for preoperative individualized prediction of short-term prognosis among PCa patients.

Effect of vinegar supplementation on patients with esophageal lesions lightly stained with Lugol's iodine solution: Prospective single-centre trial.

BACKGROUND: Esophageal chromoendoscopy with iodine solution is important for detecting early esophageal cancer. The effect of routine treatment for lesions lightly stained with Lugol's iodine solution is limited, and the addition of natural substances to a regular diet is becoming increasingly common. Vinegar has antitumor effects as reported in previous studies. AIM: To evaluate whether vinegar supplementation could improve the prognosis of patients with lightly stained esophageal lesions. METHODS: This prospective single-centre trial included consecutive patients with lightly stained lesions between June 2020 and April 2022. Patients in the experimental group received increased amounts of vinegar for 6 months. The primary outcome of the study was the clinical therapeutic effect. Complications related to vinegar ingestion and adverse events were also recorded in detail. RESULTS: A total of 166 patients were included in the final analysis. There was no significant difference in the baseline data between the two groups. Intention-to-treat (ITT) analysis demonstrated that the rates at which endoscopic characteristics improved were 33.72% in the experimental group and 20.00% in the conventional group (P = 0.007); and the rates at which biopsy pathology improved were 19.77% and 8.75%, respectively (P = 0.011). Additional vinegar consumption had a statistically protective effect on the rate at which endoscopic characteristics improved [hazard ratio (HR) ITT = 2.183, 95%CI: 1.183-4.028; HRper-protocol (PP) = 2.307, 95%CI: 1.202-4.426] and biopsy pathology improved (HRITT = 2.931, 95%CI: 1.212-7.089; HRPP = 3.320, 95%CI: 1.295-8.507). No statistically significant effect of increased vinegar consumption on preventing high-grade intraepithelial neoplasia or early cancer was observed (HRITT = 0.382, 95%CI: 0.079-1.846; HRPP = 0.382, 95%CI: 0.079-1.846). The subgroup analyses indicated that the overall therapeutic improvement of endoscopic characteristics and biopsy pathology seemed more obvious in older (age > 60) male patients with small lesions (lesion size ≤ 0.5 cm). Three patients in the experimental group reported acid regurgitation and heartburn. No adverse event during gastroscopy were recorded during follow-up. CONCLUSION: A moderately increased ingestion of vinegar could not directly reduce the risk of esophageal cancer in the mucosa dysplasia population, but it improved the endoscopic characteristics and ameliorated the biopsy pathology to a certain extent. Further research is needed to verify the effect of nutritional intervention on precancerous esophageal lesions.

Primary epithelioid trophoblastic tumor of the lung: A case report.

ABSTRACT: Primary epithelioid trophoblastic tumor (ETT) of the lung is exceedingly rare. Only about three cases have been reported in Pubmed and worldwide literature. We presented a case of multiple primary ETT of the lung occurring in a 33-year-old Chinese female patient. Comprehensive physical examinations revealed no evidence of a primary lesion on the uterus or cervix uteri. Microscopic examination of the tumor demonstrated ETT of the lung, which was confirmed by immunohistochemical staining and declining level of beta-human choriogonadotropin ( ß -HCG) after the operation. Our case revealed that the ETT can occur in the lung and should be considered when a female had a tumor of lung with increasing ß -HCG.

Exploring a novel HE image segmentation technique for glioblastoma: A hybrid slime mould and differential evolution approach.

Glioblastoma is a primary brain tumor with high incidence and mortality rates, posing a significant threat to human health. It is crucial to provide necessary diagnostic assistance for its management. Among them, Multi-threshold Image Segmentation (MIS) is considered the most efficient and intuitive method in image processing. In recent years, many scholars have combined different metaheuristic algorithms with MIS to improve the quality of Image Segmentation (IS). Slime Mould Algorithm (SMA) is a metaheuristic approach inspired by the foraging behavior of slime mould populations in nature. In this investigation, we introduce a hybridized variant named BDSMA, aimed at overcoming the inherent limitations of the original algorithm. These limitations encompass inadequate exploitation capacity and a tendency to converge prematurely towards local optima when dealing with complex multidimensional problems. To bolster the algorithm's optimization prowess, we integrate the original algorithm with a robust exploitative operator called Differential Evolution (DE). Additionally, we introduce a strategy for handling solutions that surpass boundaries. The incorporation of an advanced cooperative mixing model accelerates the convergence of BDSMA, refining its precision and preventing it from becoming trapped in local optima. To substantiate the effectiveness of our proposed approach, we conduct a comprehensive series of comparative experiments involving 30 benchmark functions. The results of these experiments demonstrate the superiority of our method in terms of both convergence speed and precision. Moreover, within this study, we propose a MIS technique. This technique is subsequently employed to conduct experiments on IS at both low and high threshold levels. The effectiveness of the BDSMA-based MIS technique is further showcased through its successful application to the medical image of brain glioblastoma. The evaluation of these experimental outcomes, utilizing image quality metrics, conclusively underscores the exceptional efficacy of the algorithm we have put forth.

ChK1 activation induces reactive astrogliosis through CIP2A/PP2A/STAT3 pathway in Alzheimer's disease.

Cancerous Inhibitor of PP2A (CIP2A), an endogenous PP2A inhibitor, is upregulated and causes reactive astrogliosis, synaptic degeneration, and cognitive deficits in Alzheimer's disease (AD). However, the mechanism underlying the increased CIP2A expression in AD brains remains unclear. We here demonstrated that the DNA damage-related Checkpoint kinase 1 (ChK1) is activated in AD human brains and 3xTg-AD mice. ChK1-mediated CIP2A overexpression drives inhibition of PP2A and activates STAT3, then leads to reactive astrogliosis and neurodegeneration in vitro. Infection of mouse brain with GFAP-ChK1-AAV induced AD-like cognitive deficits and exacerbated AD pathologies in vivo. In conclusion, we showed that ChK1 activation induces reactive astrogliosis, degeneration of neurons, and exacerbation of AD through the CIP2A-PP2A-STAT3 pathway, and inhibiting ChK1 may be a potential therapeutic approach for AD treatment.

Long non-coding RNA ZFAS1 regulates cell proliferation and invasion in cervical cancer via the miR-190a-3p/KLF6 axis.

Long non-coding RNA (lncRNA) ZFAS1 (zinc finger antisense 1) was demonstrated to play critical roles in various cancer progression. However, the functions of ZFAS in cervical cancers (CC) are unclear. Human CC cell lines were used for in vitro experiments. RT-qPCR (Real Time Quantitative PCR) was performed to detect the expression of ZFAS1, microRNA-190a-3p (miR-190a-3p) and Kruppel-like factor 6 (KLF6). Cell proliferation, invasion and migration assays were used to investigate biological behaviors of CC cells related to CC progression. The relationship of KLF6 to ZFAS1 and miR-190a-3p was analyzed by circRIP and luciferase reporter assay. In addition, in vivo experiment was carried out to explore the function of ZFAS1 in tumor growth of CC. The expression levels of ZFAS1 and KLF6 were both significantly elevated, while the expression of miR-190a-3p was inhibited in CC tumor tissues. In addition, ZFAS1 influenced CC tumor growth through miR-190a-3p. KLF6 was a target of miR-190a-3p and inhibited miR-190a-3p-induced CC tumor growth. Furthermore, KLF6 was negatively regulated by miR-190a-3p, but positively regulated by ZFAS1. Overexpression of ZFAS1 and inhibition of miR-190a-3p significantly increased the expression levels of KLF6. Finally, in vitro assays demonstrated that inhibition of ZFAS1 reduced CC tumor growth and the expression levels of KLF6, but increased the expression levels of miR-190a-3p. ZFAS1 could regulate CC pathogenesis via regulating the miR-190a-3p/KLF6 axis, which might be considered as new CC therapeutic targets.

Successful cholangioscopic electrocoagulation for biliary papillomatosis: Report covering six cases (with video) / Electrocoagulación colangioscópica exitosa para la papilomatosis biliar: Informe de 6 casos (con vídeo)

Background: Biliary papillomatosis is a rare type of papillomatosis. Depending on the location of the disease, radical surgical resection or liver transplants are the treatment of choice. These radical surgical options may be unrealistic in patients who are not surgical candidates or who are unwilling to consider surgery. Aims: To evaluate the effectiveness of endoscopic electrocoagulation for the biliary papillomatosis. Methods: In this case series, we report six patients with unresectable biliary papillomatosis who underwent cholangioscopic electrocoagulation using needle knife and their clinic follow up information. Results: After patients received cholangioscopy with electrocoagulation of the residual biliary papilloma, the daily T-tube drainage volume increased to 200–400ml with improvement in the drainage content and significant relief of clinical symptoms, such as jaundice and abdominal pain. Conclusion: This method of using electrocoagulation to directly target and destroy tumor tissue is a safe and effective alternative for those with unresectable disease, and this method has shown to enhance T-tube drainage volume and improve patients’ overall clinical symptoms.(AU)

Antecedentes: La papilomatosis biliar es un tipo raro de papilomatosis. Dependiendo de la localización de la enfermedad, la resección quirúrgica radical o los trasplantes de hígado son el tratamiento de elección. Estas opciones quirúrgicas radicales pueden ser poco realistas en pacientes que no son candidatos a la cirugía o que no están dispuestos a considerarla. Objetivos: Evaluar la eficacia de la electrocoagulación endoscópica para la papilomatosis biliar. Métodos: En esta serie de casos, informamos de 6 pacientes con papilomatosis biliar irresecable que fueron sometidos a electrocoagulación colangioscópica mediante bisturí de aguja, y de su información de seguimiento clínico. Resultados: Después de que los pacientes recibieran la colangioscopia con electrocoagulación del papiloma biliar residual, el volumen de drenaje diario del tubo en T aumentó a 200-400ml con mejora del contenido del drenaje y alivio significativo de los síntomas clínicos, como la ictericia y el dolor abdominal. Conclusión: Este método de uso de la electrocoagulación para apuntar directamente y destruir el tejido tumoral es una alternativa segura y eficaz para aquellos con enfermedad no resecable, y este método ha demostrado mejorar el volumen de drenaje del tubo T y mejorar los síntomas clínicos generales de los pacientes.(AU)

Prophylactic transcatheter angiographic embolization reduces Forrest IIa ulcer rebleeding: A retrospective study.

ABSTRACT: The application of transcatheter angiographic embolization (TAE) is controversial in the treatment of ulcer bleeding. This study aims to determine rebleeding risk factors and evaluate the efficacy of prophylactic TAE (p-TAE) following endoscopic hemostasis in rebleeding prevention of Forrest lla ulcers.The medical records of Forrest lla ulcer patients who underwent endoscopic hemostasis (E group) and endoscopic hemostasis plus p-TAE (E + p-TAE group) in West China Hospital from May 2009 to May 2018 were retrospectively reviewed. Baseline characteristics, clinical efficacy, and rebleeding risk factors were analyzed.As a result, a total of 102 patients were included, with 75 and 27 patients in E and E + p-TAE group, respectively. Most of the baseline data in E and E + p-TAE group were similar except for the proportion of protruded non-bleeding visible vessel (NBVV) (E group vs E + p-TAE group, 50.7% vs 74.1%, P = .035). The rebleeding rate of E + p-TAE group (3.7%) was significantly lower than E group (24.0%) (P = .02). The protruded NBVV (OR: 6.896, 95% confidence interval [CI]: 1.532-30.642, P = .01) and employment of p-TAE (OR: 0.038, 95% CI: 0.003-0.448, P = .009) were identified as independent risk factors for Forrest IIa ulcer rebleeding. Additionally, log-rank test indicated the rebleeding occurrence was greatly reduced by p-TAE in patients with protruded NBVVs (P = .006).In conclusion, the protruded NBVV and employment of p-TAE were the independent risk factors tightly associated with rebleeding of Forrest IIa ulcer. P-TAE following endoscopic hemostasis could effectively prevent Forrest IIa ulcer from rebleeding.

Successful cholangioscopic electrocoagulation for biliary papillomatosis: Report covering six cases (with video).

BACKGROUND: Biliary papillomatosis is a rare type of papillomatosis. Depending on the location of the disease, radical surgical resection or liver transplants are the treatment of choice. These radical surgical options may be unrealistic in patients who are not surgical candidates or who are unwilling to consider surgery. AIMS: To evaluate the effectiveness of endoscopic electrocoagulation for the biliary papillomatosis. METHODS: In this case series, we report six patients with unresectable biliary papillomatosis who underwent cholangioscopic electrocoagulation using needle knife and their clinic follow up information. RESULTS: After patients received cholangioscopy with electrocoagulation of the residual biliary papilloma, the daily T-tube drainage volume increased to 200-400ml with improvement in the drainage content and significant relief of clinical symptoms, such as jaundice and abdominal pain. CONCLUSION: This method of using electrocoagulation to directly target and destroy tumor tissue is a safe and effective alternative for those with unresectable disease, and this method has shown to enhance T-tube drainage volume and improve patients' overall clinical symptoms.

Negative-Pressure Isolation Mask for Endoscopic Examination During the Coronavirus Disease 2019 Pandemic: A Randomized Controlled Trial.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, endoscopists have high risks of exposure to exhaled air from patients during gastroscopy. To minimize this risk, we transformed the oxygen mask into a fully closed negative-pressure gastroscope isolation mask. This study aimed to evaluate the effectiveness, safety, and feasibility of use of this mask during gastroscopy. METHODS: From February 28, 2020, to March 10, 2020, 320 patients undergoing gastroscopy were randomly assigned into the mask group (n = 160) or conventional group (n = 160). Patients in the mask group wore the isolation mask during gastroscopy, whereas patients in the conventional group did not wear the mask. The adenosine triphosphate fluorescence and carbon dioxide (CO2) concentration in patients' exhaled air were measured to reflect the degree of environmental pollution by exhaled air. Patients' vital signs, operation time, and adverse events during endoscopy were also evaluated. RESULTS: Four patients were excluded because of noncooperation or incomplete data. A total of 316 patients were included in the final analysis. The difference between the highest CO2 concentration around patients' mouth and CO2 concentration in the environment was significantly decreased in the mask group compared with the conventional group. There was no significant difference in the adenosine triphosphate fluorescence, vital signs, and operation time between the 2 groups. No severe adverse events related to the isolation mask, endoscopy failure, or new coronavirus infection during follow-up were recorded. DISCUSSION: This new isolation mask showed excellent feasibility of use and safety compared with routine gastroscopy during the COVID-19 pandemic.

Detection of multiple lesions of gastrointestinal tract for endoscopy using artificial intelligence model: a pilot study.

BACKGROUND: This study was aimed to develop a computer-aided diagnosis (CAD) system with deep-learning technique and to validate its efficiency on detecting the four categories of lesions such as polyps, advanced cancer, erosion/ulcer and varices at endoscopy. METHODS: A deep convolutional neural network (CNN) that consists of more than 50 layers were trained with a big dataset containing 327,121 white light images (WLI) of endoscopy from 117,005 cases collected from 2012 to 2017. Two CAD models were developed using images with or without annotation of the training dataset. The efficiency of the CAD system detecting the four categories of lesions was validated by another dataset containing consecutive cases from 2018 to 2019. RESULTS: A total of 1734 cases with 33,959 images were included in the validation datasets which containing lesions of polyps 1265, advanced cancer 500, erosion/ulcer 486, and varices 248. The CAD system developed in this study may detect polyps, advanced cancer, erosion/ulcer and varices as abnormality with the sensitivity of 88.3% and specificity of 90.3%, respectively, in 0.05 s. The training datasets with annotation may enhance either sensitivity or specificity about 20%, p = 0.000. The sensitivities and specificities for polyps, advanced cancer, erosion/ulcer and varices reached about 90%, respectively. The detect efficiency for the four categories of lesions reached to 89.7%. CONCLUSION: The CAD model for detection of multiple lesions in gastrointestinal lumen would be potentially developed into a double check along with real-time assessment and interpretation of the findings encountered by the endoscopists and may be a benefit to reduce the events of missing lesions.

Management of an endoscopy center during the outbreak of COVID-19: Experience from West China Hospital.

Since the outbreak of the coronavirus disease 2019 (COVID-19), various measures have been taken to protect against the infection. As droplet and contact transmission are the main routes of COVID-19 infection, endoscopy centers are considered to be high-risk areas for exposure to COVID-19. We have undertaken several countermeasures in our endoscopic center during the pandemic, and have gained significant experience in terms of prevention and control of COVID-19. We here present our experience and strategies adopted for preventing hospital infection in our endoscopy center during the COVID-19 pandemic. We describe our management of the environment, endoscope, patients, and medical staff, and our self-made masks.