crossing96/oncoscreening huggingface dataset:
Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy.	While cell fate determination and maintenance are important in establishing and preserving tissue identity and function during development, aberrant cell fate transition leads to cancer cell heterogeneity and resistance to treatment. Here, we report an unexpected role for the transcription factor p63 (Trp63/TP63) in the fate choice of the squamous versus neuroendocrine lineage in esophageal development and malignancy. Deletion of p63 results in extensive neuroendocrine differentiation in the developing mouse esophagus and esophageal progenitors derived from human embryonic stem cells. In human esophageal neuroendocrine carcinoma (eNEC) cells, p63 is transcriptionally silenced by EZH2-mediated H3K27 trimethylation (H3K27me3). Up-regulation of the major p63 isoform ΔNp63α, through either ectopic expression or EZH2 inhibition, promotes squamous transdifferentiation of eNEC cells. Together, these findings uncover p63 as a rheostat in coordinating the transition between squamous and neuroendocrine cell fates during esophageal development and tumor progression.	esophagus
Association of VEGFA polymorphisms with the risk of oesophageal cancer in Punjab, India: A case-control study.	Background & objectives Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors which stimulates tumour progression induction of endothelial cell migration and division, inhibition of the apoptosis of endothelial cells, induction of serine protease activity and enhancement of vascular permeability. This study aimed to investigate the correlation of VEGF+405G/C,-7C/T and+936C/T polymorphisms with oesophageal cancer risk. Methods DNA samples of 464 subjects (231 sporadic oesophageal cancer affected individuals and 233 controls) were genotyped forVEGF+936C/T,+405G/C and-7C/T polymorphisms. VEGF+936C/T and +405G/C polymorphisms were genotyped by PCR-RFLP method whereas VEGF-7C/T polymorphism was genotyped using Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Results CT genotype of VEGF-7C/T polymorphism was significantly associated with reduced risk of oesophageal cancer. VEGF-7C/T polymorphism was significantly associated with reduced risk of oesophageal cancer underdominant, co-dominant, over dominant and log-additive genetic models in total patients and in the female group. C+936G+405T-7 haplotype was significantly associated with decreased risk (P=0.01)of oesophageal cancer in total patients and also in the male group (P=0.02). Interpretation & conclusions In future, replication of the findings of the present study in a larger sample from different ethnic groups, along with functional analysis, may be insightful for the role of VEGFA polymorphisms in the pathogenesis of oesophageal cancer. Identification of the correlation of VEGF variants with specific therapy in oesophageal cancer may help in better selection of patients and monitoring treatment response in VEGF-therapy.	esophagus
Evaluation of patient satisfaction with an enhanced recovery protocol for esophageal resections: a concurrent quantitative and qualitative analysis.	Patient satisfaction during hospitalization for esophagectomy has been little studied. The aim of this study was to evaluate patients' satisfaction with a newly introduced enhanced recovery protocol (ERP) for esophagectomy. At hospital discharge, patients were invited to complete a questionnaire. This pseudonymized questionnaire contained 5-point Likert scales regarding items on multidisciplinary care (n = 7), information/communication (n = 7), length of stay (n = 1), and specific adaptations of care in the ERP (n = 11). One open question asked for patient experiences and suggestions for improving the ERP. Between May 2017 and December 2021, 521 patients were included in the ERP after esophagectomy. Of them, 327 patients (63%) completed the questionnaire. Response rates were evenly distributed between genders and slightly higher in younger patients (<60 years; 68%) as compared to elderly patients (>70 years; 60%). Quantitative analysis revealed high satisfaction rates for multidisciplinary care (86.8%), information/communication (84.9%), and ERP adaptations (82.2%), and length of stay was considered optimal in 80%. There were no significant differences in satisfaction observed between gender nor age groups. For the qualitative analysis, there were 108 open answers, resulting in 268 statements. Sentiments expressed in these statements were evaluated as negative, positive, or unspecified. Negative sentiments were attributable to alimentation, organizational factors, and communication. Positive sentiments were attributed to interpersonal relations, multidisciplinary care, and ERP. Overall, patients are very satisfied with the ERP for esophagectomy during hospitalization. By incorporating qualitative data, the results of this quantitative analysis are expanded and elucidated, showing areas where improvements to our ERP are possible to increase patient satisfaction.	esophagus
Causal association between metabolites and upper gastrointestinal tumors: A Mendelian randomization study.	Upper gastrointestinal (UGI) tumors, notably gastric cancer (GC) and esophageal cancer (EC), are significant global health concerns due to their high morbidity and mortality rates. However, only a limited number of metabolites have been identified as biomarkers for these cancers. To explore the association between metabolites and UGI tumors, the present study conducted a comprehensive two‑sample Mendelian randomization (MR) analysis using publicly available genetic data. In the present study, the causal relationships were examined between 1,400 metabolites and UGI cancer using methods such as inverse variance weighting and weighted medians, along with sensitivity analyses for heterogeneity and pleiotropy. Functional experiments were conducted to validate the MR results. The analysis identified 57 metabolites associated with EC and 58 with GC. Key metabolites included fructosyllysine [EC: Odds ratio (OR)=1.450, 95% confidence interval (CI)=1.087‑1.934, P=0.011; GC: OR=1.728, 95% CI=1.202‑2.483, P=0.003], 2'‑deoxyuridine to cytidine ratio (EC: OR=1.464, 95% CI=1.111‑1.929, P=0.007; GC: OR=1.464, 95% CI=1.094‑1.957, P=0.010) and carnitine to protonylcarnitine (C3) ratio (EC: OR=0.655, 95% CI=0.499‑0.861, P=0.002; GC: OR=0.664, 95% CI=0.486‑0.906, P=0.010). Notably, fructosyllysine levels and the 2'‑deoxyuridine to cytidine ratio were identified as risk factors for both EC and GC, while the C3 ratio served as a protective factor. Functional experiments demonstrated that fructosyllysine and the 2'‑deoxyuridine to cytidine ratio promoted the proliferation of EC and GC cells, whereas carnitine inhibited their proliferation. In conclusion, the present findings provide insights into the causal factors and biomarkers associated with UGI tumors, which may be instrumental in guiding targeted dietary and pharmacological interventions, thereby contributing to the prevention and treatment of UGI cancer.	esophagus
Neoplastic Progression Risk in Females With Barrett's Esophagus: A Systematic Review and Meta-Analysis of Individual Patient Data.	BACKGROUND AND AIMS: Females with Barrett's esophagus (BE) have a lower risk of neoplastic progression than males, but sufficiently powered risk analyses are lacking. This systematic review and meta-analysis of individual patient data (IPD) aimed to provide more robust evidence on neoplastic progression risk in females. METHODS: We conducted a systematic literature search of 3 electronic databases (Medline, Embase, Google Scholar) from inception until August 2023. Eligible studies (1) reported original data on progression from nondysplastic BE, indefinite for dysplasia, or low-grade dysplasia to high-grade dysplasia or esophageal adenocarcinoma; and (2) included female and male patients. IPD were quality controlled by 2 independent reviewers. The primary outcome was the association between sex and neoplastic progression risk, adjusted for risk factors using multivariable Cox regression analysis. Secondary outcomes were sex differences in time to progression and annual progression rate. RESULTS: IPD were obtained from 11 of 66 eligible studies, including 2196 (31%) females. Neoplastic progression risk was lower in females (hazard ratio for males vs females, 1.44; 95% confidence interval, 1.13-1.82) after adjusting for age, smoking, medication use, hiatal hernia, BE length, and baseline pathology. The annual progression rate was 0.88% in females vs 1.29% in males. Time to progression was similar in both sexes: 3.7 years (interquartile range, 2.1-7.7 years) in females and 4.2 years (interquartile range, 2.0-8.1 years) in males. CONCLUSION: Although females had a lower neoplastic progression risk, sex differences were smaller than previously reported, and time to progression was similar for both sexes. Future research should focus on other factors than sex to identify low- and high-risk BE patients.	esophagus
Histopathological Spectrum of the Upper Gastrointestinal Tract Endoscopic Biopsies at a Tertiary Hospital: A Descriptive Cross-sectional Study.	INTRODUCTION: Upper gastrointestinal tract disorders are prevalent worldwide, encompassing neoplastic and non-neoplastic lesions like infections and inflammation. Endoscopic biopsies play a crucial role in diagnosis, treatment monitoring, and complication detection. Despite their routine use, comprehensive data on their histopathological spectrum is sparse. This study aimed to delineate this spectrum and assess the prevalence of non-neoplastic and neoplastic lesions in upper gastrointestinal tract endoscopic biopsies. METHODS: This descriptive cross-sectional study at a tertiary care center analyzed upper gastrointestinal endoscopic biopsies from August 1, 2019, to July 31, 2021. After obtaining ethical clearance (reference number: 039-078/079), we collected all upper gastrointestinal endoscopic biopsies received during the two-year study period, excluding inadequate biopsies, resection specimens, therapeutic cases, and specific lesions.Histopathological examination was conducted using H&E, Giemsa, and Periodic acid-Schiff stains. Diagnoses were categorized into non-neoplastic and neoplastic lesions following WHO guidelines. Data were analyzed using SPSS 16.0 to determine the frequency of neoplastic and non-neoplastic cases. RESULTS: Among 155 upper gastrointestinal biopsies, 124 (80%) were non-neoplastic (95% CI: 73.71-86.29%) and 31 (20%) were neoplastic (95% CI: 13.71-26.29%). Non-neoplastic lesions were predominantly chronic gastritis, with chronic active gastritis being the most frequent 34 (27.41%). Neoplastic lesions were mainly adenocarcinomas in the stomach 20 (64.51%) and squamous cell carcinomas in the esophagus 7 (22.58%). CONCLUSIONS: The prevalence of neoplastic lesions were found to lower compared to the published literature and showed predominance of adenocarcinoma in upper gastrointestinal neoplastic lesions.	esophagus
Effect of pyloroplasty on clinical outcomes following esophagectomy.	INTRODUCTION: The role of concurrent pyloroplasty with esophagectomy is unclear. Available literature on the impact of pyloroplasty during esophagectomy on complications and weight loss is varied. Data on the need for further pyloric intervention are scarce. Our study compares the clinical outcomes after esophagectomy with or without pyloroplasty and investigates the role of post-operative pyloric dilatation. METHODS: Consecutive patients (n = 207) undergoing Ivor Lewis esophagectomy performed by two surgeons at our institution were included. Data on patient demographics, mortality rate, anastomotic leak, respiratory complications (Clavien-Dindo grade ≥ 3), anastomotic stricture rate, and percentage weight loss at 1 and 2 year post-operatively were evaluated. For weight analysis at 1 and 2 year post-operatively, patients were excluded if they had been diagnosed with recurrence or died prior to the 1 or 2 year timepoints. RESULTS: Ninety-two patients did not have a pyloroplasty, and 115 patients had a pyloroplasty. There were no complications resulting from pyloroplasty. There was no significant demographic difference between the groups except for age. Mortality rate, anastomotic leak, respiratory complications, anastomotic stricture rate, and percentage weight loss at 1 and 2 years were statistically similar between the two groups. However, 14.1% of patients without pyloroplasty required post-operative endoscopic pyloric balloon dilatation to treat respiratory complications or gastroparesis. Subgroup analysis of patients without pyloroplasty indicated that patients requiring dilatation had greater weight loss at 1 year (15.8% vs 9.4%, p = 0.02) and higher respiratory complications rate (27.3% vs 4.7%, p = 0.038). CONCLUSIONS: Overall results from our study that pyloroplasty during Ivor Lewis esophagectomy is safe and useful to prevent the need for post-operative pyloric dilatation.	esophagus
Oxygen Saturation Endoscopic Imaging as a Novel Alternative to Assess Tissue Perfusion During Esophagectomy.	BACKGROUND: Assessment of gastric conduit perfusion during esophagectomy is crucial to determine its viability and identify the optimal site for anastomosis. Indocyanine green (ICG) fluorescence imaging is commonly used for this purpose, but it is contraindicated in patients with hypersensitivity to ICG, iodine, or shellfish. Oxygen saturation endoscopic imaging (OXEI) is a newer, non-pharmacologic technique for assessing perfusion. We report our experience with OXEI in 3 esophagectomy patients who had contraindications to ICG. METHODS: All 3 patients underwent robot-assisted esophagectomies. None of the conduits had ischemic areas identified by white light. Using a 5 mm laparoscopic specialized camera (ELUXEO Vision, FUJIFILM Healthcare Americas Corp., USA), OXEI was deployed for intracorporeal assessment of gastric conduit perfusion after pull-up into the chest. Postoperative outcomes including anastomotic leaks and complications were recorded. RESULTS: In two patients, OXEI revealed ischemic zones, which were resected to ensure optimal conduit viability. In the remaining patient, OXEI indicated robust vascularity throughout the conduit. All three patients experienced uneventful postoperative courses and were discharged within 10 days. There were no instances of anastomotic leaks or other major complications. CONCLUSION: In our experience, OXEI is a viable method for intraoperative assessment of gastric conduit perfusion in patients with contraindications to ICG. Prospective studies are needed to validate its efficacy in preventing anastomotic complications and to compare it with other methods of perfusion assessment including gross visual and ICG dye in a larger patient population.	esophagus
Paravertebral Versus EPidural Analgesia in Minimally Invasive Esophageal ResectioN (PEPMEN): A Randomized Controlled Multicenter Trial.	OBJECTIVE: To compare the quality of recovery in patients receiving epidural or paravertebral analgesia for minimally invasive esophagectomy (MIE). BACKGROUND: Paravertebral analgesia may be a promising alternative to epidural analgesia, avoiding potential side effects and improving postoperative recovery. METHODS: This randomized controlled superiority trial was conducted across 4 Dutch centers with esophageal cancer patients scheduled for transthoracic MIE with intrathoracic anastomosis, randomizing patients to receive either epidural or paravertebral analgesia. The primary outcome was Quality of Recovery (QoR-40) on the third postoperative day (POD). Secondary outcomes included quality of life, postoperative pain, opioid consumption, inotropic/vasopressor medication use, hospital stay, complications, readmission, and mortality. RESULTS: From December 2019 to February 2023, 192 patients were included: 94 received epidural and 98 paravertebral analgesia. QoR-40 score on POD3 was not different between groups (mean difference: 3.7, 95% CI: -2.3 to 9.7; P =0.268). Epidural patients had significantly higher QoR-40 scores on POD1 and 2 (mean difference: 7.7, 95% CI: 2.3-13.1; P =0.018 and mean difference: 7.3, 95% CI: 1.9-12.7; P =0.020) and lower pain scores (median 1 vs 2; P <0.001 and median 1 vs 2; P =0.033). More epidural patients required vasopressor medication on POD1 (38.3% vs 13.3%; P <0.001). Urinary catheters were removed earlier in the paravertebral group (median POD3 vs 4; P <0.001). No significant differences were found in postoperative complications or hospital/intensive care unit stay. CONCLUSIONS: This randomized controlled trial did not demonstrate the superiority of paravertebral over epidural analgesia regarding the quality of recovery on POD3 after MIE. Both techniques are effective and can be offered in clinical practice.	esophagus
The cellular signaling and regulatory role of protein phosphatase in tumor diagnosis: Upstream miRNAs of PTEN.	Protein phosphatases have demonstrated considerable promise in the realm of early tumor diagnosis across various malignancies. These enzymes play a critical role in modulating the PI3K-Akt signaling pathway, which is integral to cellular processes such as proliferation, survival, and migration. When the activity of protein phosphatases becomes abnormal, it can disrupt these essential signaling pathways, potentially leading to the initiation and progression of tumors. Consequently, monitoring for abnormal expression and activity levels of protein phosphatases could serve as a vital biomarker for early cancer detection. By identifying these alterations, clinicians may be better equipped to diagnose tumors at an earlier stage, significantly improving patient outcomes.In summary, our study highlights the multifaceted and significant role of PTEN in various forms of cancer, including esophageal squamous cell carcinoma (ESCA). Further analysis showed that the expression levels of protein phosphatase and PTEN protein were significantly associated with the early diagnosis of tumors, especially in the early stage of tumors, and their detection sensitivity and specificity were high. Therefore, by detecting the expression of protein phosphatase and PTEN protein, the early diagnosis of tumor can be achieved, and the therapeutic effect and prognosis of patients can be improved.	esophagus
Comparison between AJCC 8th edition gastric and esophageal ypTNM classification system in Siewert II esophagogastric junction adenocarcinomas: A retrospective study based on Eastern and Western Data.	INTRODUCTION: Multimodal therapy has become the standard treatment for curable upper gastrointestinal cancers. However, it remains unclear which 8th edition AJCC post-neoadjuvant therapy pathological classification system, esophageal (ypTNM-EC) or gastric (ypTNM-GC), can predict the overall survival (OS) of patients with Siewert II adenocarcinomas better. METHODS: Patients diagnosed with Siewert II adenocarcinomas receiving neoadjuvant therapy plus curative resection at the University Medical Center Utrecht (UMC Utrecht) and the Peking University Cancer Hospital (PUCH) between the 2001 and 2022 were included in this study. The patients from two institutions were analyzed separately. Predictive univariable and multivariable Cox models based on ypTNM-EC and ypTNM-GC were constructed. The C-index and calibration curves were used to compare the predictive abilities of ypTNM-EC and ypTNM-GC Cox models. RESULTS: A total of 125 patients from UMCU and 145 from PUCH were included. There was no significant difference in the C-index between the ypTNM-EC and the ypTNM-GC univariable and multivariable Cox models in the UMC Utrecht (p-value = 0.883; p-value=0.681) and PUCH (p-value = 0.808; p-value=0.548) cohorts, and no significant difference was observed between their calibration curves in the two cohorts. CONCLUSION: The AJCC 8th edition ypTNM prognostic classification systems for esophageal and gastric cancer demonstrated no difference in predicting OS for patients with Siewert II adenocarcinomas both in the Western and Eastern data. The ypTNM-GC, with fewer stage groups, may offer greater convenience for clinical application.	esophagus
Gram-Negative Microflora Dysbiosis Facilitates Tumor Progression and Immune Evasion by Activating the CCL3/CCL5-CCR1-MAPK-PD-L1 Pathway in Esophageal Squamous Cell Carcinoma.	Gram-negative (G-) microflora dysbiosis occurs in multiple digestive tumors and is found to be the dominant microflora in the esophageal squamous cell carcinoma (ESCC) microenvironment. The continuous stimulation of G- bacterium metabolites may cause tumorigenesis and reshape the microimmune environment in ESCC. However, the mechanism of G- bacilli causing immune evasion in ESCC remains underexplored. We identified CC chemokine receptor 1 (CCR1) as a tumor-indicating gene in ESCC. Interestingly, expression levels of CCR1 and PD-L1 were mutually upregulated after G- bacilli metabolite lipopolysaccharide stimulation. First, we found that CCR1 high expression levels were associated with poor overall survival in ESCC. Importantly, we found that high levels of CCR1 expression upregulated PD-L1 expression by activating MAPK phosphorylation in ESCC and induced tumor malignant behavior. Finally, we found that T-cell exhaustion and cytotoxicity suppression were associated with CCR1 expression in ESCC, which were decreased after CCR1 inhibiting. Our work identifies CCR1 as a potential immune check point regulator of PD-L1 and may cause T-cell exhaustion and cytotoxicity suppression in ESCC microenvironment and highlights the potential value of CCR1 as a therapeutic target of immunotherapy. Implications: The esophageal microbial environment and its metabolites significantly affect the outcome of immunotherapy for ESCC.	esophagus
Relationship between hospital surgical volume and the perioperative esophagectomy costs for esophageal cancer: a nationwide administrative claims database study.	BACKGROUND: Numerous studies have described positive relationships between hospital volume (HV) and clinical outcomes in highly complex procedures, including esophagectomies. Although the centralization of surgery has been considered a possible solution for improving clinical outcomes, the HV impact on perioperative healthcare costs is unknown. This study aimed to determine the relationship between HV and perioperative healthcare costs for patients undergoing esophagectomy for esophageal cancer. METHODS: This retrospective, nationwide cohort study used Japanese Administrative Claims Database data. Data on esophagectomies performed nationwide in 2015 were extracted. The outcome measure was perioperative healthcare costs per person from the perspective of the insurer. The healthcare costs in outpatient or inpatient settings of any hospital and clinic where patients received treatment were summed up from the month the surgery was performed to 3 months after. Linear regression analyses were conducted to assess the risk-adjusted effects of the HV category (1-4/5-9/10-14/15-) on perioperative costs. RESULTS: A total of 5232 patients underwent an esophagectomy at 584 hospitals. The overall perioperative cost was 20.834 billion Japanese yen (JPY). The median perioperative costs per person for each HV category (1-4/5-9/10-14/15-) were 3.728 (709 patients), 3.740 (658 patients), 3.760 (512 patients), and 3.760 (3253 patients) million JPY, respectively (P = 0.676). Multivariate analyses revealed that each HV category had no significant impact on perioperative costs. CONCLUSIONS: There were no significant differences in the perioperative costs between high- and low-volume centers. Esophageal cancer surgery centralization may be achievable without increasing healthcare costs.	esophagus