crossing96/oncoscreening huggingface dataset:
Transcription factor NFE2L3 promotes the proliferation of esophageal squamous cell carcinoma cells and causes radiotherapy resistance by regulating IL-6.	OBJECTIVE: To scrutinize the impact of overexpression and interference of NFE2L3 on radiosensitivity of esophageal squamous cell carcinoma cells (ESCC) and its downstream mechanism and to assess whether NFE2L3 expression alters in vivo radiosensitivity of ESCC by developing a subcutaneous tumor model in mice. METHODS: Through RNA-Seq, we compared the differentially expressed genes between the ECA-109R cell line and its parent ECA-109 cell line. The differentially expressed genes were selected and verified by qRT-PCR. Transfection of ESCC cell lines with NFE2L3 inhibitor or mimic lentivirus constructs was done to study the activity of NFE2L3. To assess the effect of NFE2L3 on cellular growth and proliferation, clonogenic survival assay, EdU incorporation assay, and CCK-8 assay were done after irradiation. To probe how many irradiated DNA double-strand breaks were produced, the corresponding intensity of γ-H2AX foci were detected by immunofluorescence. Apoptotic cells were assayed by flow cytometry assay after irradiation; To investigate the downstream genes of NFE2L3, we knocked NFE2L3, and RNA-Seq was used to find out the downstream genes. qRT-PCR and western blot ensued to score associated protein profiles. The in vivo ESCC cell radiosensitivity was scrutinized by nude mouse xenograft models. RESULTS: The differential genes between ECA-109R cells and its parent ECA-109 cells were compared by qRT-PCR to unveil a significant increase in NFE2L3 expression. Functional analysis indicated that NFE2L3 increased radioresistance in ESCC cells. Then, through high-throughput sequencing and bioinformatics analysis, IL-6 was found to be a hub gene that played a role downstream of NFE2L3 and was verified by qRT-PCR, western blot, and double luciferase reporter gene experiment. NFE2L3 could regulate ESCC cell radiosensitivity via the IL-6-STAT3 signaling pathway, and downregulation of IL-6 expression could reverse the effects of highly expressed NFE2L3. In vivo tumor xenograft experiments confirmed that NFE2L3 affects the sensitivity to radiation therapy. CONCLUSION: NFE2L3 can affect the radiosensitivity of ESCC cells through IL-6 transcription and IL-6/STAT3 signaling pathway. This makes NFE2L3 a putative target to regulate ESCC cell radiosensitivity.	esophagus
PET-directed combined modality therapy for gastroesophageal junction cancer: Results of the multicentre prospective MEMORI trial of the German Cancer Consortium (DKTK).	BACKGROUND: Positron emission tomography (PET) may differentiate responding and non-responding tumours early in the treatment of locally advanced gastroesophageal junction adenocarcinomas. Early PET non-responders (P-NR) after induction CTX might benefit from changing to chemoradiation (CRT). METHODS: Patients underwent baseline (18)F-FDG PET followed by 1 cycle of CTX. PET was repeated at day 14-21 and responders (P-R), defined as ≥35% decrease in SUV(mean) from baseline, continued with CTX. P-NR switched to CRT (CROSS). Patients underwent surgery 4-6 weeks post-CTX/CRT. The primary objective was an improvement in R0 resection rates in P-NR above a proportion of 70%. RESULTS: In total, 160 patients with resectable gastroesophageal junction adenocarcinomas were prospectively investigated by PET scanning. Eighty-five patients (53%) were excluded. Seventy-five eligible patients were enrolled in the study. Based on PET criteria, 50 (67.6%)/24 (32.4%) were P-R and P-NR, respectively. Resection was performed on 46 responders, including one patient who withdrew the ICF, and 22 non-responders (per-protocol population). R0 resection rates were 95.6% (43/45) for P-R and 86.4% (19/22) for P-NR. No treatment related deaths occurred. With a median follow-up time of 24.5 months, estimated 18 months DFS was 75.4%/64.2% for P-R/P-NR, respectively. The estimated 18 months OS was 95.5% for P-R and 68.2% for P-NR. CONCLUSION: The primary endpoint of the study to increase the R0 resection rate in metabolic NR was not met. PET response after induction CTX is prognostic for outcome with a prolonged OS and DFS in PET responders. TRIAL REGISTRATION: NCT00002014-000860-16.	esophagus
Long-term survival outcomes associated with robotic-assisted minimally invasive esophagectomy (RAMIE) for esophageal cancer.	BACKGROUND: Minimally Invasive esophagectomy for esophageal cancer is associated with less morbidity compared to open approach. Whether robotic-assisted minimally invasive esophagectomy (RAMIE) results in better long-term survival compared with open esophagectomy (OE) and minimally invasive esophagectomy (MIE) is unclear. METHODS: We analyzed data from the National Cancer Database (NCDB) for patients with primary esophageal cancers who underwent esophagectomy in 2010-2017. Those with unknown staging, distant metastasis, or diagnosed with another cancer were excluded. Patients were stratified by RAMIE, MIE, and OE operative techniques. The Kaplan-Meier method and associated log-rank test were employed to compare unadjusted survival outcomes by surgical technique, our primary outcome. Multivariable Cox proportional hazards regression model was employed to discern factors independently contributing to survival. RESULTS: A total of 5170 patients who underwent esophagectomy were included in the analysis; 428 underwent RAMIE, 1417 underwent MIE, and 3325 underwent OE. Overall median survival was 42 months. In comparison to RAMIE, there was an increased risk of death for those that underwent either MIE [Hazard Ratio (HR) = 1.19; 95% Confidence Interval (CI): > 1.00 to 1.41; P < 0.047)] or OE (HR = 1.22; 95% CI: 1.04 to 1.43; P < 0.017). Academic vs community program facility type was associated with decreased risk of death (HR = 0.84; 95% CI: 0.76 to 0.93; P < 0.001). In general, males from areas of lower income with advanced stages of cancer who received neoadjuvant chemotherapy or radiation were at increased risk of death. Factors that were not associated with survival included race and ethnicity, Charlson-Devo Score, type of health insurance, zipcode level education, and population density. CONCLUSIONS: Overall survival was significantly longer in patients with esophageal cancers that underwent RAMIE in comparison to either MIE or OE in a 7-year NCDB cohort study.	esophagus
Endoscopic resection in the treatment of intramural esophageal bronchogenic cysts: A retrospective analysis of 17 cases.	BACKGROUND: Intramural esophageal bronchogenic cysts (EBCs) are rare congenital malformations. Differences in reports on the clinical features of intramural EBCs and some controversies about the treatment strategy for intramural EBCs exist. OBJECTIVES: To investigate the clinical characteristics of intramural EBCs and evaluate the safety and efficacy of endoscopic resection. METHODS: The clinical and endoscopic features, endoscopic resection treatment, postoperative adverse events, and follow-up results of 17 patients with intramural EBCs were retrospectively studied. RESULTS: Intramural EBCs exhibited male predominance with a male/female ratio of 58.8% (10/7) and were predominantly found in the distal esophagus. Approximately 94.1% of patients presented with gastrointestinal symptoms. All lesions were protruding masses covered by intact mucosal epithelium. The morphologies of intramural EBCs were diverse under white light endoscopy. On endoscopic ultrasonography, intramural EBCs presented as homogeneous or inhomogeneous hypoechoic or anechoic lesions. Eleven lesions originated from the muscularis propria, which underwent submucosal tunnel endoscopic resection (STER), and six lesions were from the submucosa, which underwent endoscopic submucosal dissection (ESD). Approximately 88.2% of patients underwent complete endoscopic resection. No serious pneumothorax, bleeding, pleural effusion, esophagotracheal fistula, or other adverse events occurred in all patients after endoscopic resection, and no cyst recurrence, metastasis, or esophageal scar stenosis was observed during the follow-up period. CONCLUSIONS: Intramural EBCs can be treated by digestive endoscopic surgery. STER and ESD are safe, effective, and minimally invasive resection methods.	esophagus
Synergistic chemo-photothermal and ferroptosis therapy of polydopamine nanoparticles for esophageal cancer.	Aim: To develop synergistic chemo-photothermal and ferroptosis therapy nanoparticles to improve the efficacy of treatment for esophageal cancer. Materials & methods: Fe(3)O(4)@PDA-HCPT nanoparticles (NPs) were constructed and characterized. Their synergistic antitumor effects were evaluated in EC1 and EC109 esophageal cancer cells as well as in esophageal cancer-bearing mice. Results: In vitro and in vivo experiments showed that Fe(3)O(4)@PDA-HCPT NPs exhibited significant tumor inhibition and excellent diagnostic properties. The killing ability of tumor cells was significantly enhanced after irradiation. Conclusion: Synergistic application of the three therapies effectively inhibited tumor growth and exhibited potent antitumor effects, providing strong support for developing nanoparticles with synergistic antitumor effects of multiple therapies.	esophagus
An unexpected complication of prophylactic esophageal stenting: esophageal stent impaction after thread dislocation.	A 47-year-old woman was referred to our department with opportunistic endoscopic findings of two submucosal esophageal bulges, approximately half the circumference of the esophagus, both nearly 2.0 cm in size, and 24-27 cm from the incisors. Ultrasound endoscopy diagnosed smooth muscle tumors originating from the muscularis propria layer and she next underwent submucosal tunneling endoscopic resection. Intraoperatively, part of the tumor could not be separated from the muscularis propria layer and a U-shaped tumor was finally resected. A fully covered self-expanding esophageal nitinol stent was then inserted, covering the full circumference esophageal mucosa. The stent was fixed by ears with knotted thread and proton pump inhibitors were given for 1 week.	esophagus
HA-ADT suppresses esophageal squamous cell carcinoma progression via apoptosis promotion and autophagy inhibition.	Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer-related deaths. We have previously connected a non-sulfated glycosaminoglycan, hyaluronic acid (HA), with a common hydrogen sulfide (H(2)S) donor, 5-(4-hydroxyphenyl)-3H-1,2-dithiol-3-thione (ADT-OH), to reconstruct a novel conjugate, HA-ADT. In this study, we determined the effect of HA-ADT on the growth of ESCC. Our data suggested that HA-ADT exerted more potent effects than sodium hydrosulfide (NaHS, a fast H(2)S-releasing donor) and morpholin-4-ium (4-methoxyphenyl)-morpholin-4-ylsulfanylidenesulfido-λ5-phosphane (GYY4137, a slow H(2)S-releasing donor) on inhibiting the viability, proliferation, migration, and invasion of human ESCC cells. HA-ADT increased apoptosis by suppressing the protein expressions of phospho (p)-Ser473-protein kinase B (PKB/AKT), p-Tyr199/Tyr458-phosphatidylinositol 3-kinase (PI3K), and p-Ser2448-mammalian target of rapamycin (mTOR), but suppressed autophagy through the inhibition of the protein levels of p-Ser552-β-catenin, p-Ser9-glycogen synthase kinase-3β (GSK-3β), and Wnt3a in human ESCC cells. In addition, HA-ADT was more effective in terms of the growth inhibition of human ESCC xenograft tumor than NaHS and GYY4137. In conclusion, HA-ADT can suppress ESCC progression via apoptosis promotion and autophagy inhibition. HA-ADT might be efficacious for the treatment of cancer.	esophagus
Omission of intraoperative pyloric procedures in minimally invasive esophagectomy: assessing the impact on patients.	Pyloroplasty or pyloromyotomy is often undertaken during esophagectomy to aid gastric emptying postoperatively. Minimally invasive esophagectomy (MIE) frequently omits a pyloric procedure. The impact on perioperative outcomes and the need for subsequent interventions is unclear. This study assesses the requirements for endoscopic balloon dilation of the pylorus (EPD) following MIE. Patients undergoing MIE from 2016 to 2020 were reviewed. Patients undergoing open resection, or an intraoperative pyloric procedure were excluded. Demographic, clinical and pathological data were reviewed. Univariable and multivariable analysis were performed as appropriate. In total, 171 patients underwent MIE. There were no differences in age (median 65 vs. 65 years, P = 0.6), pathological stage (P = 0.10) or ASA status (P = 0.52) between those requiring and not requiring endoscopic pyloric dilation (EPD). Forty-three patients (25%) required EPD, with a total of 71 procedures. Twenty-seven patients (16%) had EPD on their index admission. Seventy-five patients (43%) had a postoperative complication. Higher ASA status was associated with increased requirement for EPD (odds ratio 10.8, P = 0.03). On multivariable analysis, there was no association between the need for a pyloric procedure and overall survival (P = 0.14). Eight patients (5%) required insertion of a feeding jejunostomy in the postoperative period, with no difference between those with or without EPD (P = 0.11). Two patients required subsequent surgical pyloromyotomy for delayed gastric emptying. Although pyloroplasty or pyloromyotomy can safely be excluded during MIE, a quarter of patients will require postoperative EPD procedures. The impact of excluding pyloric procedures on gastric emptying requires further study.	esophagus
Long-term variation in psoas muscle mass index is affected by short-term loss after esophagectomy in survivors of esophageal cancer.	Changes in muscle mass may be an objective approach toward measuring the quality of life after surgery, but long-term changes due to surgery without the effect of cachexia remain unclear. Patients with esophageal cancer who underwent esophagectomy and did not experience cancer recurrence for 3 years were analyzed. The psoas muscle mass index (PMI) was assessed before surgery and 7 days, 1 year, and 3 years after surgery. Patients with no change or increased PMI within 7 days after surgery were categorized into the Nondecreasing-PMI group, whereas those with decreased PMI were categorized into the Decreasing-PMI group. Eighty-four and 51 patients were categorized into the Nondecreasing- and Decreasing-PMI groups, respectively. The Decreasing-PMI group had a higher incidence rate of anastomotic leakage than the Nondecreasing-PMI group (25% vs. 12%, respectively; P = 0.042). Moreover, the Decreasing-PMI group showed a significantly greater decrease in the PMI 1 year after surgery than the Nondecreasing-PMI group (-9.2% vs. -4.0%, respectively; P = 0.048). However, although the Decreasing-PMI group had a greater decrease in the PMI than the Nondecreasing-PMI group, no significant difference was observed 3 years after surgery (-9.8% vs. -5.3%, respectively; P = 0.115). A decrease in PMI in the acute phase after esophagectomy may contribute to a long-term decrease in the PMI. Intensive interventions may be beneficial for these patients to improve their long-term quality of life.	esophagus
[Submucosal tunneling endoscopic resection for large esophageal leiomyoma: technical aspects and risk of complications].	We analyzed the technical aspects and risk of possible complications after submucosal tunneling endoscopic resection for large esophageal leiomyoma. A patient with a 4-cm non-epithelial esophageal tumor underwent STER procedure in June 2018. Surgery time was 130 min. There were no intraoperative complications. Postoperative period was complicated with mediastinitis with reactive pneumonia and pleural effusion accompanied by episodes of hyperthermia up to 38°C for 5 days. The patient was discharged in 12 days after complete resolution of pneumonia confirmed by chest X-ray. Contrast-enhanced examination after 3 postoperative days revealed no contrast agent leakage outside the esophagus. The previously applied clips were visualized. Endoscopic examination in 3 months after surgery visualized postoperative scar without signs of deformation and narrowing of the esophagus. No complaints were observed throughout 3.5-year follow-up period. CONCLUSION: This report demonstrates the advantages of tunnel dissection ensuring organ-sparing procedure with the best functional result. However, intra- and postoperative complications are possible after STER. The risk of complications and complexity of surgery depend on transverse size (>3.5 cm), shape and localization of tumor. Larger neoplasm is accompanied by more difficult surgery and higher risk of complications. Therefore, adequate selection of patients for STER is essential.	esophagus
The course of pain and dysphagia after radiofrequency ablation for Barrett's esophagus-related neoplasia.	BACKGROUND: Radiofrequency ablation (RFA) is effective for eradication of Barrett's esophagus (BE) neoplasia, but little is known on the course of pain and dysphagia after RFA. We aimed to describe the course of post-RFA symptoms and to identify possible associated risk factors. METHODS: In this multicenter, observational cohort study, all RFA procedures registered in a prospective database were included. Patient and treatment characteristics were collected from medical records and patients self-registered post-procedural symptoms in electronic symptom diaries for 14 days. Mixed model regression was used for the analyses. RESULTS: In total, 255 diaries were completed. Post-RFA pain was reported for 95 % (95 %CI 93-98) of procedures (median duration 14 days; 25th-75th percentiles [p25-p75] 11-14) and major pain for 64 % (95 %CI 58-69; median duration 8 days, p25-p75 3-13). Post-procedural pain significantly increased with BE length, younger age, and no prior ablation. Dysphagia was present after 83 % (95 %CI 79-88) of procedures (median duration 13 days, p25-p75 9-14). The risk of dysphagia decreased with age and increased when patients experienced more pain. CONCLUSIONS: RFA treatment for BE-related neoplasia seems a significant burden for patients, and post-procedural symptoms should be taken into account when counseling patients before starting endoscopic eradication therapy.	esophagus
Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial.	BACKGROUND: Dual-targeted anti-HER2 therapy significantly improves outcomes in HER2-positive breast cancer and could be beneficial in other HER2-positive cancers. JACOB's end-of study analyses aimed to evaluate the long-term efficacy and safety of pertuzumab plus trastuzumab and chemotherapy for previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer. METHODS: Eligible patients were randomized 1:1 to pertuzumab/placebo plus trastuzumab and chemotherapy every 3 weeks. PRIMARY ENDPOINT: overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety. RESULTS: The intention-to-treat population comprised 388 patients in the pertuzumab arm and 392 in the placebo arm. The safety population comprised 385 and 388 patients, respectively. Median follow-up was ≥ 44.4 months. Median OS was increased by 3.9 months (hazard ratio 0.85 [95% confidence intervals, 0.72-0.99]) and median PFS by 1.3 months (hazard ratio 0.73 [95% confidence intervals, 0.62-0.85]) in the pertuzumab vs. the placebo arm. ORR was numerically higher (57.0% vs. 48.6%) and median DoR 1.8 months longer with pertuzumab treatment. There was a trend for more favorable hazard ratios in certain subgroups related to HER2 amplification/overexpression. Safety was comparable between arms, except for serious and grade 3-5 adverse events, and any-grade diarrhea, which were more frequent with pertuzumab. CONCLUSIONS: JACOB did not meet its primary endpoint. Nonetheless, the study continues to demonstrate some, albeit limited, evidence of treatment activity and an acceptable safety profile for pertuzumab plus trastuzumab and chemotherapy in previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer after long-term follow-up. Trial registration NCT01774786; https://clinicaltrials.gov/ct2/show/NCT01774786 .	esophagus
[Effect of splenic hilar lymphadenectomy on locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction with a tumor diameter ≥4 cm: a five-year survival analysis].	Objective: To examine the long term outcome of splenic hilar lymphadenectomy (SHL) for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG) with a tumor diameter ≥4 cm. Methods: A total of 489 locally advanced Siewert type Ⅱ and Ⅲ AEG patients with a tumor diameter ≥4 cm who underwent radical resection from January 2010 to April 2016 were included. There were 383 males and 106 females. There were 225 patients aged≥65 years and 264 patients aged <65 years. SHL was conducted in 270 patients(SHL group). Wilcoxon rank-sum test or χ(2) test were conducted for inter-group comparison. Cox proportional hazard regression was used to analyze the long term outcome of SHL and the prognosis factors of overall survival. Kaplan-Meier curve was drawn finally. The results of survival analysis were verified by Log-rank test. Results: Followed-up to April 2021,the median follow-up time was 78.0 months (range: 74.0 to 85.0 months), the follow-up rate was 95.5%(467/489). The splenic hilar lymphnode metastasis rate of the SHL group was 12.6% (34/270). Younger patients (<65 years old), less complications, higher proportion of patients received adjuvant chemotherapy were demonstrated in the SHL group (χ(2): 5.644 to 6.744, all P<0.05). Multivariate analysis showed that SHL was the independent prognosis factor of overall survival for patients with Siewert type Ⅱ and Ⅲ AEG and a tumor diameter≥4 cm (HR=0.68, 95%CI: 0.52 to 0.88, P=0.004) along with preoperative CA19-9, pathological T stage, pathological N stage, adjuvant chemotherapy and postoperative complication. Further subgroup analysis demonstrated that the SHL group had better 5-year overall survival than non-SHL group (62.4% vs. 39.2%, χ(2)=17.983, P=0.006) in Siewert type Ⅲ AEG rather than in Siewert type Ⅱ AEG(57.3% vs. 53.7%, χ(2)=3.031, P=0.805). Conclusion: In experienced center, splenic hilar lymphadenectomy can improve the prognosis of Siewert type Ⅲ AEG with a tumor diameter ≥4 cm.	esophagus