crossing96/oncoscreening huggingface dataset:
Handling informative dropout in longitudinal analysis of health-related quality of life: application of three approaches to data from the esophageal cancer clinical trial PRODIGE 5/ACCORD 17.	BACKGROUND: Health-related quality of life (HRQoL) has become a major endpoint to assess the clinical benefit of new therapeutic strategies in oncology clinical trials. Typically, HRQoL outcomes are analyzed using linear mixed models (LMMs). However, longitudinal analysis of HRQoL in the presence of missing data remains complex and unstandardized. Our objective was to compare the modeling alternatives that account for informative dropout. METHODS: We investigated three alternative methods-the selection model (SM), pattern-mixture model (PMM), and shared-parameters model (SPM)-in relation to the LMM. We first compared them on the basis of methodological arguments highlighting their advantages and drawbacks. Then, we applied them to data from a randomized clinical trial that included 267 patients with advanced esophageal cancer for the analysis of four HRQoL dimensions evaluated using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. RESULTS: We highlighted differences in terms of outputs, interpretation, and underlying modeling assumptions; this methodological comparison could guide the choice of method according to the context. In the application, none of the four models detected a significant difference between the two treatment arms. The estimated effect of time on HRQoL varied according to the method: for all analyzed dimensions, the PMM estimated an effect that contrasted with those estimated by the SM and SPM; the LMM estimated effects were confirmed by the SM (on two of four HRQoL dimensions) and SPM (on three of four HRQoL dimensions). CONCLUSIONS: The PMM, SM, or SPM should be used to confirm or invalidate the results of LMM analysis when informative dropout is suspected. Of these three alternative methods, the SPM appears to be the most interesting from both theoretical and practical viewpoints. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov , number NCT00861094 .	esophagus
Curriculum for optical diagnosis training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.	This manuscript represents an official Position Statement of the European Society of Gastrointestinal Endoscopy (ESGE) aiming to guide general gastroenterologists to develop and maintain skills in optical diagnosis during endoscopy. In general, this requires additional training beyond the core curriculum currently provided in each country. In this context, ESGE have developed a European core curriculum for optical diagnosis practice across Europe for high quality optical diagnosis training. 1:  ESGE suggests that every endoscopist should have achieved general competence in upper and/or lower gastrointestinal (UGI/LGI) endoscopy before commencing training in optical diagnosis of the UGI/LGI tract, meaning personal experience of at least 300 UGI and/or 300 LGI endoscopies and meeting the ESGE quality measures for UGI/LGI endoscopy. ESGE suggests that every endoscopist should be able and competent to perform UGI/LGI endoscopy with high definition white light combined with virtual and/or dye-based chromoendoscopy before commencing training in optical diagnosis. 2:  ESGE suggests competency in optical diagnosis can be learned by attending a validated optical diagnosis training course based on a validated classification, and self-learning with a minimum number of lesions. If no validated training course is available, optical diagnosis can only be learned by attending a non-validated onsite training course and self-learning with a minimum number of lesions. 3:  ESGE suggests endoscopists are competent in optical diagnosis after meeting the pre-adoption and learning criteria, and meeting competence thresholds by assessing a minimum number of lesions prospectively during real-time endoscopy. ESGE suggests ongoing in vivo practice by endoscopists to maintain competence in optical diagnosis. If a competent endoscopist does not perform in vivo optical diagnosis on a regular basis, ESGE suggests repeating the learning and competence phases to maintain competence.Key areas of interest were optical diagnosis training in Barrett's esophagus, esophageal squamous cell carcinoma, early gastric cancer, diminutive colorectal lesions, early colorectal cancer, and neoplasia in inflammatory bowel disease. Condition-specific recommendations are provided in the main document.	esophagus
Repurposing of KLF5 activates a cell cycle signature during the progression from a precursor state to oesophageal adenocarcinoma.	Oesophageal adenocarcinoma (OAC) is one of the most common causes of cancer deaths. Barrett's oesophagus (BO) is the only known precancerous precursor to OAC, but our understanding about the molecular events leading to OAC development is limited. Here, we have integrated gene expression and chromatin accessibility profiles of human biopsies and identified a strong cell cycle gene expression signature in OAC compared to BO. Through analysing associated chromatin accessibility changes, we have implicated the transcription factor KLF5 in the transition from BO to OAC. Importantly, we show that KLF5 expression is unchanged during this transition, but instead, KLF5 is redistributed across chromatin to directly regulate cell cycle genes specifically in OAC cells. This new KLF5 target gene programme has potential prognostic significance as high levels correlate with poorer patient survival. Thus, the repurposing of KLF5 for novel regulatory activity in OAC provides new insights into the mechanisms behind disease progression.	esophagus
Length of Barrett's esophagus in the presence of low-grade dysplasia, high-grade dysplasia, and adenocarcinoma.	INTRODUCTION: The identification and follow-up of ultra-short Barrett's esophagus (BE) is controversial. BE surveillance guidelines emphasize mainly on long-segment BE. However, in practice a substantial proportion of esophageal adenocarcinoma (EAC) are found close to the gastro-esophageal junction (GEJ). Our study aims to chart the length of BE when low-grade dysplasia (LGD), high-grade dysplasia (HGD) and EAC arise in BE. METHODS: Endoscopic findings from all cases with a diagnosis of LGD and HGD in BE between June 2014 and June 2019, and 100 consecutive cases of EAC diagnosed between June 2018 and August 2019, were reviewed. Additionally, 438 consecutive gastroscopies were reviewed to identify 100 cases of non-dysplastic BE. RESULTS: 99 cases of LGD and 61 cases of HGD were reviewed. LGD and HGD when diagnosed, was located in BE ≤ 1 cm in 20% and 18% cases, respectively. LGD and HGD when diagnosed, was located in BE ≤ 3 cm in 48.5% and 40.9% cases, respectively. LGD and HGD when diagnosed in BE ≤ 3 cm was found at index endoscopy in 67% and 42% cases, respectively. Of the 100 cases of EAC, only 23 had concurrent visible BE, with BE higher than the level of EAC in seven. EAC when found, had its proximal extent ≤ 1 cm from GEJ in 22% and ≤ 3 cm from GEJ in 40% cases. Of the 100 non-dysplastic BE, 53% were ≤ 1 cm and 78% were ≤ 3 cm long. CONCLUSION: Almost 20% of all dysplasia in BE occurs in BE < 1 cm. Over 40% occurs in BE < 3 cm. Similarly, 20% of EAC occurs within 1 cm of GEJ and 40% occur within 3 cm. A majority of dysplasia diagnosed within 3 cm of the GEJ is found on index endoscopy. We propose that all lengths of columnar lined epithelium above the GEJ are recognized as BE and subjected to a thorough biopsy protocol.	esophagus
The Negative Impact of Preoperative Chemotherapy on Survival After Esophagectomy for Vulnerable Elderly Patients with Esophageal Cancer.	BACKGROUND: The standard treatment for patients 75 years of age or younger with cStage 2 or 3 esophageal cancer is preoperative chemotherapy followed by esophagectomy. The optimal treatment for elderly patients, especially those considered vulnerable, remains unclear. METHODS: This study retrospectively reviewed the data for 42 patients ages 75-80 years with cStage 2 or 3 esophageal cancer who underwent esophagectomy between October 2002 and February 2019. The patients who received preoperative chemotherapy were compared with those who did not. The study also examined short- and long-term outcomes and the impact of preoperative chemotherapy on overall survival (OS) stratified by performance status (PS). RESULTS: Of the 42 patients, 18 underwent esophagectomy without preoperative chemotherapy and 24 underwent esophagectomy after preoperative chemotherapy. A significantly greater proportion of the patients with PS 0 received preoperative chemotherapy than the patients with PS 1 (P =0.007). The multivariate analysis showed preoperative chemotherapy to be an independent negative prognostic factor for OS (hazard ratio [HR], 5.025; 95% confidence interval [CI] 1.136-22.222; P = 0.033). Subgroup analysis showed that preoperative chemotherapy had a significant negative impact on the OS of the patients with PS 1 (P < 0.001). CONCLUSION: Preoperative chemotherapy was ineffective for the patients with PS 0 and had a significantly negative impact on the OS of the patients with PS 1. Preoperative chemotherapy should not be administered to patients 75 years of age or older with cStage 2 or 3 esophageal cancer.	esophagus
Elucidation of PLK1 Linked Biomarkers in Oesophageal Cancer Cell Lines: A Step Towards Novel Signaling Pathways by p53 and PLK1-Linked Functions Crosstalk.	BACKGROUND: Oesophgeal adenocarcinoma (OAC) is the most frequent cause of cancer death. POLO-like kinase 1 (PLK1) is overexpressed in broad spectrum of tumors and has prognostic value in many cancers including esophageal cancer, suggesting its potential as a therapeutic target. p53, the guardian of genome is the most important tumor suppressors that represses the promoter of PLK1, whereas tumor cells with inactive p53 are arrested in mitosis due to DNA damage. PLK1 expression has been linked to the elevated p53 expression and has been shown to act as a biomarker that predicts poor prognosis in OAC. OBJECTIVES: The aim of the present study was identification of PLK1 associated phosphorylation targets in p53 mutant and p53 normal cells to explore the downstream signaling evets. METHODS: Here we develop a proof-of-concept phospho-proteomics approach to identify possible biomarkers that can be used to identify mutant p53 or wild-type p53 pathways. We treated PLK1 asynchronously followed by mass spectrometry data analysis. Protein networking and motif analysis tools were used to identify the significant clusters and potential biomarkers. RESULTS: We investigated approximately 1300 potential PLK1-dependent phosphopeptides by LCMS/ MS. In total, 2216 and 1155 high confidence phosphosites were identified in CP-A (p53+) and OE33 (p53-) cell lines owing to PLK1 inhibition. Further clustering and motif assessment uncovered many significant biomarkers with known and novel link to PLK1. CONCLUSION: Taken together, our study suggests that PLK1 may serve as a potential therapeutic target in human OAC. The data highlight the efficacy and specificity of small molecule PLK1 kinase inhibitors to identify novel signaling pathways in vivo.	esophagus
Long non-coding RNA CASC8 polymorphisms are associated with the risk of esophageal cancer in a Chinese population.	BACKGROUND: Esophageal cancer (EC) is an important disease that threatens public health and safety. Although there are numerous treatment options for esophageal cancer including surgery, radiation therapy, and chemotherapy, these treatments have limited effects. Its morbidity and mortality vary widely among countries and regions. Esophageal cancer is classified into squamous cell carcinoma (ESCC) and esopheageal adenocarcinoma (EADC). Here, we examined the genetic susceptibility to ESCC in relation to functional single nucleotide polymorphisms (SNPs) in the long non-coding RNA (lncRNA) CASC8. METHODS: To detect the susceptibility to ESCC in relation to functional polymorphisms in CASC8, a hypothesis-driven study was performed to identify CASC8 SNPs in 949 patients with ESCC and 1369 control subjects. RESULTS: The CASC8 rs1562430 GG genotype was significantly associated with increased ESCC risk in men, patients younger than 63 years, non-smokers, and nondrinkers. CONCLUSIONS: CASC8 rs1562430 A > G may cause susceptibility to ESCC and CASC8 SNPs may play a vital role in ESCC risk, thereby serving as a potential biomarker for diagnosing ESCC. A larger sample size and multifactor information are needed to confirm these results.	esophagus
Pathologic assessment of endoscopic resection specimens with superficial carcinoma of the esophagus: current practice and practical issues.	Endoscopic resection (ER) has become the first-line therapy for early esophageal cancer and offers a treatment alternative to surgery, owing to less morbidity and better quality of life. ER techniques include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). EMR is faster, simpler, and cheaper than ESD, but limited by its ability to resect lesions larger than 1.5 centimeters. Piecemeal EMR has limitations, including a high local recurrence rate and a suboptimal specimen for an accurate pathologic assessment. ESD, on the other hand, allows en bloc resections with negative (R0) margins, irrespective of lesion size, providing an excellent pathologic specimen, however, is technically challenging with a higher risk of complications. The evaluation of ER specimens in pathology varies slightly from institution to institution. Our review summarizes the current practices and issues in the pathologic assessment of esophageal ER specimens, which highlights the necessity of a systematic approach and standardization of both macroscopic and microscopic evaluation. There is a need for a comprehensive and standardized pathology report that will allow for uniform terminology for endoscopists, surgeons, and pathologists, which, in turn, will result in better treatment guidance.	esophagus
Radial incision and cutting for dilation before endoscopic submucosal dissection in patients with esophageal cancer on the distal side of severe benign esophageal strictures.	We investigated the efficacy and safety of radial incision and cutting as a novel dilation method for strictures just before endoscopic submucosal dissection in patients with metachronous esophageal cancer localized on the distal side of strictures and determined the optimal dilation method. Consecutive patients who underwent endoscopic submucosal dissection for superficial esophageal squamous cell carcinomas localized on the distal side of severe strictures were investigated retrospectively and assigned to a radial incision and cutting (19 patients; 23 lesions) or an endoscopic balloon dilation (20 patients; 20 lesions) group. We evaluated the passage success rates of cap-wearing endoscopes with diameters ≥8.9 mm, the procedural success, en bloc resection, complete resection, major adverse event rates, and total procedure times. Compared to the endoscopic balloon dilation group, the passage success rate of a conventional endoscope with a transparent cap (87% vs. 50%) and procedural success rate (96% vs. 63%) were significantly higher in the radial incision and cutting group. The mean procedure time of 'dilation and ESD' was significantly shorter in the radial incision and cutting group than in the endoscopic balloon dilation group. Neither group experienced any serious adverse events. Radial incision and cutting followed by endoscopic submucosal dissection was effective and safe in patients with superficial esophageal squamous cell carcinomas localized on the distal side of severe benign esophageal strictures. Endoscopic submucosal dissection using a cap-wearing endoscope was possible with radial incision and cutting, and the procedure time was shorter than that for endoscopic balloon dilation.	esophagus
A MXI1-NUTM1 fusion protein with MYC-like activity suggests a novel oncogenic mechanism in a subset of NUTM1-rearranged tumors.	Most NUTM1-rearranged neoplasms (NRNs) have fusions between NUTM1 and BRD (bromodomain-containing) family members and are termed NUT carcinomas (NCs) because they show some squamous differentiation. However, some NRNs are associated with fusions between NUTM1 and members of the MAD (MAX dimerization) gene family of MYC antagonists. Here we describe a small round cell malignancy from the gastro-esophageal junction with a previously unreported fusion between NUTM1 and the MAD family member MXI1. In contrast to NCs, the MXI1-NUTM1 tumor did not show squamous differentiation and did not express MYC, TP63 or SOX2, genes known to be targets of BRD-NUTM1 proteins and critical for NC oncogenesis. Transcriptome analysis showed paradoxical enrichment of MYC target genes in the MXI1-NUTM1 tumor despite the lack of MYC expression. When expressed in vitro MXI1-NUTM1 partially phenocopied MYC, enhancing cell proliferation and cooperating with oncogenic HRAS to produce anchorage-independent cell growth. These data provide evidence that MAD family members, which are normally repressors of MYC activity, can be converted into MYC-like mimics by fusion to NUTM1. The pathological features and novel oncogenic mechanism of the MXI1-NUTM1 tumor show that identification of NUTM1 fusion partners can be important for accurate diagnostic classification of some NRN subtypes, and potentially may guide therapeutic options.	esophagus
Efficacy of immune-checkpoint inhibitors in metastatic gastric or gastroesophageal junction adenocarcinoma by patient subgroups: A systematic review and meta-analysis.	BACKGROUND: Efficacy of immune checkpoint inhibitors (ICIs) in metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma is inconsistent. Whether the efficacy of ICIs is comparable across different subgroups remains unknown. METHODS: We identified randomized controlled trials (RCTs) that compared standard treatment for metastatic gastric/GEJ adenocarcinoma to ICIs. Hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival (OS) were extracted and pooled in a meta-analysis. Prespecified subgroups were included as follows: age at randomization (</≤65 vs ≥/>65 years), gender (female vs male), ethnicity (Asians vs non-Asians), performance-status (0 vs 1), tumor location (gastric vs GEJ), and histological subtype (diffuse vs others). OS in patients with programmed death ligand (PD-L1) positive and with microsatellite instability-high (MSI-H) were also extracted and pooled in a meta-analysis. RESULTS: Five RCTs comprising 2,264 patients were analyzed. Compared to standard therapy, ICIs did not improve OS (HR = 0.86, 95% CI 0.71-1.03, P = .10) and the effect of ICIs on OS was similar in all subgroups. Nonsignificantly greater effect sizes were seen in older patients (HR = 0.85 vs 0.88, P = .81), male (HR = 0.82 vs 0.99, P = .16), Asians (HR = 0.86 vs 0.96, P = .55), performance-status 0 (HR = 0.84 vs 0.88, P = .81), GEJ tumors (HR = 0.78 vs 0.90, P = .37), and nondiffuse subtype (HR = 0.71 vs 0.79, P = .62). ICIs were associated with significantly improved OS in patients with MSI-H (HR = 0.33, P = .001), but not in PD-L1 positive disease (HR = 0.86, P = .06). CONCLUSIONS: Compared to standard treatment, ICIs in metastatic gastric/GEJ adenocarcinoma did not improve OS. None of the evaluated subgroups has shown increased magnitude of effect to ICIs, aside of the small group with MSI-H tumors.	esophagus
Genetic variants in GHR and PLCE1 genes are associated with susceptibility to esophageal cancer.	"BACKGROUND: Esophageal cancer (EC) is the leading cause of cancer-related mortality worldwide. The underlying genetic risk factors remain unclear. The association between gene growth hormone receptor (GHR) and phospholipase C epsilon 1 (PLCE1) polymorphisms and the EC risk were identified in this study. METHODS: A total of 506 EC cases and 507 controls were included in this research. Two SNPs (rs6898743 of GHR and rs2274223 of PLCE1) were selected and genotyped. The associations between gene polymorphisms and the EC risk were assessed by logistic regression analysis. The databases RegulomeDB, GTEx, and UALCAN were used for functional annotations. RESULTS: In the allelic frequencies analysis, the rs6898743 of GHR was associated with decreased susceptibility of EC (OR = 0.83, 95% CI: 0.70-1.00, p = 0.049), while rs2274223 of PLCE1 was associated with increased 0.25-fold EC risk (OR = 1.25, 95% CI: 1.02-1.53, p = 0.037). The ""GC"" genotype of rs6898743 was associated with a 0.24-fold decreased risk of EC under co-dominant model (OR = 0.76, 95% CI: 0.58-0.99, p = 0.046), and the ""GA"" genotype of rs2274223 was associated with increased EC risk under co-dominant model (OR = 1.36, 95% CI: 1.04-1.77, p = 0.023). Using GTEx database, rs2274223 was found to be significant associated with increased PLCE1 expression (p = 4.1 × 10(-7) ) in esophagus muscularis. The UALCAN database demonstrated that the GHR gene was under-expressed in esophageal cancer tissues (p = 0.017). CONCLUSION: The gene GHR and PLCE1 polymorphisms are associated with EC in the general population and the results need to be verified in future."	esophagus
Long noncoding RNA TTTY15 promotes growth and metastasis of esophageal squamous cell carcinoma by sponging microRNA-337-3p to upregulate the expression of JAK2.	Long noncoding RNA (lncRNA) testis-specific transcript, Y-linked 15 (TTTY15) plays an important regulatory role in prostate cancer, but its role in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aimed to explore the expression pattern, biological function and underlying mechanism of TTTY15 in ESCC. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of TTTY15 and microRNA (miR)-337-3p in ESCC tissues and cell lines. Cell counting kit-8 method was used to detect the proliferation of ESCC cells. Transwell method was used to determine the migration and invasion of ESCC cells. Luciferase reporter assay was used to verify the interaction between TTTY15 and miR-337-3p. Western blot was used to analyze the effects of TTTY15 and miR-337-3p on Janus kinase 2 (JAK2) expression. In the present study, we demonstrated that the expression level of TTTY15 was significantly upregulated in ESCC tissues, while the expression of miR-337-3p was downregulated. In ESCC samples, the expression levels of TTTY15 and miR-337-3p were negatively correlated. TTTY15 knockdown could significantly reduce the proliferation, migration and invasion of ESCC cells, and miR-337-3p mimics had similar effects. In addition, overexpression of TTTY15 inhibited miR-337-3p by binding with it. TTTY15 could indirectly modulate JAK2, and overexpression of TTTY15 could reverse the inhibitory effects of miR-337-3p on malignant phenotypes of ESCC cells. In conclusion, TTTY15 plays an oncogenic role in ESCC by targeting miR-337-3p/JAK2 axis.	esophagus