crossing96/oncoscreening huggingface dataset:
Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer.	BACKGROUND: Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate consisting of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. The drug may have efficacy in patients with HER2-positive advanced gastric cancer. METHODS: In an open-label, randomized, phase 2 trial, we evaluated trastuzumab deruxtecan as compared with chemotherapy in patients with HER2-positive advanced gastric cancer. Patients with centrally confirmed HER2-positive gastric or gastroesophageal junction adenocarcinoma that had progressed while they were receiving at least two previous therapies, including trastuzumab, were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan (6.4 mg per kilogram of body weight every 3 weeks) or physician's choice of chemotherapy. The primary end point was the objective response, according to independent central review. Secondary end points included overall survival, response duration, progression-free survival, confirmed response (response persisting ≥4 weeks), and safety. RESULTS: Of 187 treated patients, 125 received trastuzumab deruxtecan and 62 chemotherapy (55 received irinotecan and 7 paclitaxel). An objective response was reported in 51% of the patients in the trastuzumab deruxtecan group, as compared with 14% of those in the physician's choice group (P<0.001). Overall survival was longer with trastuzumab deruxtecan than with chemotherapy (median, 12.5 vs. 8.4 months; hazard ratio for death, 0.59; 95% confidence interval, 0.39 to 0.88; P = 0.01, which crossed the prespecified O'Brien-Fleming boundary [0.0202 on the basis of number of deaths]). The most common adverse events of grade 3 or higher were a decreased neutrophil count (in 51% of the trastuzumab deruxtecan group and 24% of the physician's choice group), anemia (38% and 23%, respectively), and decreased white-cell count (21% and 11%). A total of 12 patients had trastuzumab deruxtecan-related interstitial lung disease or pneumonitis (grade 1 or 2 in 9 patients and grade 3 or 4 in 3), as adjudicated by an independent committee. One drug-related death (due to pneumonia) was noted in the trastuzumab deruxtecan group; no drug-related deaths occurred in the physician's choice group. CONCLUSIONS: Therapy with trastuzumab deruxtecan led to significant improvements in response and overall survival, as compared with standard therapies, among patients with HER2-positive gastric cancer. Myelosuppression and interstitial lung disease were the notable toxic effects. (Funded by Daiichi Sankyo; DESTINY-Gastric01 ClinicalTrials.gov number, NCT03329690.).	esophagus
Comparison of general anesthesia and conscious sedation in procedure-related complications during esophageal endoscopic submucosal dissection.	BACKGROUND: Endoscopic submucosal dissection (ESD) has a favorable outcome, compared to esophagectomy, for early esophageal neoplasia. Recent studies used general anesthesia for esophageal ESD to minimize complications due to insufficient sedation and patient movement. We aimed to evaluate the safety of general anesthesia in comparison with conscious sedation provided by anesthesiologists for esophageal ESD. METHODS: We retrospectively reviewed the electronic medical records of 158 patients who underwent esophageal ESD under general anesthesia or conscious sedation provided by anesthesiologists. We evaluated the incidence of procedure-related complications, including perforation, post-ESD bleeding, cardiopulmonary adverse events (arrhythmia, hypotension, and hypoxemia), procedure failure, stricture, and new lung consolidation after ESD. Cases of frank perforation, post-ESD bleeding requiring a vigorous diagnostic approach, and cardiopulmonary adverse events were regarded as acute complications of ESD. RESULTS: Acute complications occurred only in the conscious sedation group (8/83 [9.6%] vs. 0/75 [0.0%]; p value = 0.007). The numbers of patients with frank perforation, post-ESD bleeding, and cardiopulmonary adverse events were four, one, and three, respectively. Moreover, new lung consolidation after ESD developed only in the conscious sedation group (7/83 [8.4%] vs. 0/75 [0.0%]; p value = 0.014). ESD failed in four patients in the conscious sedation group. The incidences of stricture that required stent insertion and hospital stay after ESD were comparable between the two groups. CONCLUSION: General anesthesia is associated with a lower incidence of acute procedure-related complications in esophageal ESD compared to conscious sedation provided by anesthesiologists. Therefore, we recommend general anesthesia as a safer option for esophageal ESD.	esophagus
LINC00473 contributes to the radioresistance of esophageal squamous cell carcinoma by regulating microRNA‑497‑5p and cell division cycle 25A.	Long non‑coding RNA (lncRNA) LINC00473 plays a carcinogenic role in a variety of different tumor types. Nevertheless, the mechanisms through which LINC00473 regulates the radiosensitivity of esophageal squamous cell carcinoma (ESCC) cells remains elusive. In the present study, reverse transcription‑quantitative PCR was used to quantify the expression of LINC00473, microRNA (miRNA/miR)‑497‑5p and cell division cycle 25A (CDC25A) in ESCC tissues. The association between LINC00473 expression and the clinicopathological characteristics of patients with ESCC was also assessed. Furthermore, Cell Counting kit‑8 and colony formation assays were carried out to monitor the proliferation of ESCC cells exposed to X‑ray radiation. A dual‑luciferase reporter assay was also conducted to analyze the interaction between LINC00473 and miR‑497‑5p, as well as the interaction between CDC25A and miR‑497‑5p. The findings of the present study demonstrated that in ESCC tissues and cells, the expression levels of LINC00473 and CDC25A were significantly upregulated, while the expression of miR‑497‑5p was downregulated. The high expression level of LINC00473 was associated with a higher T stage, lymph node metastasis stage and a lower tumor differentiation grade in patients with ESCC. Following irradiation, transfection with miR‑497‑5p mimics reduced the promoting effect of LINC00473 overexpression on ESCC cell proliferation, and partially impeded the resistance of ESCC cells to X‑ray radiation induced by LINC00473 overexpression. Moreover, transfection with miR‑497‑5p inhibitors partially alleviated the inhibitory effects of LINC00473 knockdown on cellular proliferation, and partly reversed the sensitivity of cells to X‑ray irradiation induced by LINC00473 knockdown. Furthermore, it was confirmed that miR‑497‑5p was able to bind LINC00473 and the 3'‑untranslated region of CDC25A. On the whole, the findings of the present study demonstrate that LINC00473 reduces the radiosensitivity of ESCC cells by modulating the miR‑497‑5p/CDC25A axis.	esophagus
Characterization of super-enhancer-associated functional lncRNAs acting as ceRNAs in ESCC.	Long noncoding RNAs (lncRNAs) have important regulatory roles in cancer biology. Although some lncRNAs have well-characterized functions, the vast majority of this class of molecules remains functionally uncharacterized. To systematically pinpoint functional lncRNAs, a computational approach was proposed for identification of lncRNA-mediated competing endogenous RNAs (ceRNAs) through combining global and local regulatory direction consistency of expression. Using esophageal squamous cell carcinoma (ESCC) as model, we further identified many known and novel functional lncRNAs acting as ceRNAs (ce-lncRNAs). We found that most of them significantly regulated the expression of cancer-related hallmark genes. These ce-lncRNAs were significantly regulated by enhancers, especially super-enhancers (SEs). Landscape analyses for lncRNAs further identified SE-associated functional ce-lncRNAs in ESCC, such as HOTAIR, XIST, SNHG5, and LINC00094. THZ1, a specific CDK7 inhibitor, can result in global transcriptional downregulation of SE-associated ce-lncRNAs. We further demonstrate that a SE-associated ce-lncRNA, LINC00094 can be activated by transcription factors TCF3 and KLF5 through binding to SE regions and promoted ESCC cancer cell growth. THZ1 downregulated expression of LINC00094 through inhibiting TCF3 and KLF5. Our data demonstrated the important roles of SE-associated ce-lncRNAs in ESCC oncogenesis and might serve as targets for ESCC diagnosis and therapy.	esophagus
Limonoid compounds from Xylocarpus granatum and their anticancer activity against esophageal cancer cells.	BACKGROUND: To investigate the anticancer effects of limonoid compounds that were isolated and purified from Xylocarpus granatum fruits on human esophageal cancer (EC) cells. A structure-activity relationship experiment was designed to identify the functional moiety of limonoid compounds identified as being critical for its anticancer activity. METHODS: Eca109 cells were cultured in RPMI1640 medium and treated with limonoid compounds. Cell proliferation was determined by the MTT assay in vitro. Eca109 cells apoptosis was analyzed by by flow cytometry after being treated with xylogranatin C. The expression of p53, Bax, bcl-2, caspase-3 and GRP78 in Eca109 cells after xylogranatin C treatment was examined by western blot assay. RESULTS: Four linonoid compounds strongly inhibited the cellular proliferation of Eca109 cells. Xylogranatin C was the strongest inhibitor, whose inhibitory effect was comparable to that of the well-known chemotherapeutic agent, cisplatin. Furthermore, xylogranatin C might induce Eca109 cell apoptosis through joint effects on multiple pathways, including the death receptor and endoplasmic reticulum pathways. Additionally, xylogranatin C suppressed tumor cell proliferation by upregulating miR-203a expression in Eca109 cells. CONCLUSIONS: Xylogranatin C induced Eca109 cellular apoptosis and exerted antitumor activity. Xylogranatin C suppressed tumor cell proliferation by upregulating miR-203a expression in Eca109 cells.	esophagus
Ligation-assisted endoscopic mucosal resection for esophageal granular cell tumors is safe and effective.	Given their malignant potential, resection of esophageal granular cell tumors (GCTs) is often undertaken, yet the optimal technique is unknown. We present a large series of dedicated endoscopic resection using band ligation (EMR-B) of esophageal GCTs. Patients diagnosed with esophageal GCTs between 2002 and 2019 were identified using a prospectively collected pathology database. Endoscopic reports were reviewed, and patients who underwent dedicated EMR-B of esophageal GCTs were included. Medical records were queried for demographics, findings, adverse events, and follow-up. We identified 21 patients who underwent dedicated EMR-B for previously identified esophageal GCT. Median age was 39 years; 16 (76%) were female. Eight (38%) had preceding signs or symptoms, potentially attributable to the GCT. Upon endoscopic evaluation, 12 (57%) were found in the distal esophagus. Endoscopic ultrasound was used in 15 cases (71%). Median lesion size was 7 mm, interquartile range 4 mm-8 mm. The largest lesion was 12 mm. A total of 20 (95%) had en bloc resection confirmed with pathologic examination. The only patient with tumor extending to the resection margin underwent surveillance endoscopy that showed no residual tumor. No patients experienced bleeding, perforation, or stricturing in our series. No patients have had known recurrence of their esophageal GCT. EMR-B of esophageal GCT achieves complete histopathologic resection with minimal adverse events. EMR-B is safe and effective and seems prudent compared with observation for what could be an aggressive and malignant tumor. EMR-B should be considered first-line therapy when resecting esophageal GCT up to 12 mm in diameter.	esophagus
[Clinical Practice Guideline for Endoscopic Resection of Early Gastrointestinal Cancer].	Although surgery was the standard treatment for early gastrointestinal cancers, endoscopic resection is now a standard treatment for early gastrointestinal cancers without regional lymph node metastasis. High-definition white light endoscopy, chromoendoscopy, and image-enhanced endoscopy such as narrow band imaging are performed to assess the edge and depth of early gastrointestinal cancers for delineation of resection boundaries and prediction of the possibility of lymph node metastasis before the decision of endoscopic resection. Endoscopic mucosal resection and/or endoscopic submucosal dissection can be performed to remove early gastrointestinal cancers completely by en bloc fashion. Histopathological evaluation should be carefully made to investigate the presence of risk factors for lymph node metastasis such as depth of cancer invasion and lymphovascular invasion. Additional treatment such as radical surgery with regional lymphadenectomy should be considered if the endoscopically resected specimen shows risk factors for lymph node metastasis. This is the first Korean clinical practice guideline for endoscopic resection of early gastrointestinal cancer. This guideline was developed by using mainly de novo methods and encompasses endoscopic management of superficial esophageal squamous cell carcinoma, early gastric cancer, and early colorectal cancer. This guideline will be revised as new data on early gastrointestinal cancer are collected.	esophagus
Usefulness of linked color imaging in the early detection of superficial esophageal squamous cell carcinomas.	BACKGROUND AND AIMS: Linked color imaging (LCI) improved the visibility of gastric cancer and colorectal flat lesions. This study aimed to investigate the usefulness of LCI in detecting superficial esophageal squamous cell carcinomas (SESCC). METHODS: We enrolled 37 consecutive SESCC patients (46 SESCCs) diagnosed using LCI and blue laser imaging bright mode (BLI-BRT) and treated in Hiroshima University Hospital between April 2018 and November 2018. Eight professional endoscopists compared images obtained on non-magnifying BLI-BRT and LCI versus conventional white light imaging (WLI). Identification and boundary diagnosis of SESCC with LCI and BLI-BRT were compared with WLI. Changes in lesion visibility were clarified. Interobserver agreement was assessed. Clinicopathological features of lesion that influence visibility with LCI were assessed. RESULTS: In LCI, 37% (17/46) of cases had improved visibility and 63% (29/46) had unchanged visibility (interobserver agreement = 0.74). Among cases with multiple lugol voiding lesions (LVLs), ΔE between the lesion and background mucosa was significantly higher in LCI than in WLI (20.8 ± 7.9 vs 9.2 ± 6.1, P < 0.05). No significant differences were found in tumor size, morphological type, color, depth, and smoking or drinking history. However, multiple LVLs were significantly higher among cases with improved versus unchanged visibility. On BLI-BRT, 39% (18/46) of cases had improved visibility and 61% (28/46) had unchanged visibility (interobserver agreement = 0.60). CONCLUSION: Almost the same as BLI-BRT, LCI improves SESCC visibility compared with WLI. This is useful for cases with multiple LVLs. In cases without background coloration (BGC), LCI may make SESCC more visible than BLI-BRT.	esophagus
The paratumoral immune cell signature reveals the potential for the implementation of immunotherapy in esophageal carcinoma patients.	PURPOSE: Esophageal cancer (EC) is one of the most lethal gastrointestinal malignancies. Immunotherapy is a promising treatment modality for this disease. However, broader implementation of EC immunotherapy has been discouraged because of insufficient understanding of tumor interactions with the immune system. As with other malignancies, the current research on EC focuses on deciphering the immune cell signatures within the tumor microenvironment. However, the disease-elicited immune cell profiles in the paratumoral compartments are largely unknown. METHODS: We examined the immune cell signatures in 62 tissue samples from 16 EC patients in different esophageal tissue compartments: tumor tissue, peritumoral tissue, healthy esophageal tissue, and adjacent lymph nodes. We analyzed the proportions and distribution patterns of NK cells and CD4(+) and CD8(+) T cells as well as their death receptor (FasR, FasR/DR3)-expressing subpopulations. The analyzed data were then compared and correlated with the patients' clinicopathological data. RESULTS: We found that the FasR(+) NK cells, CD4(+) and CD8(+) T cells infiltrated lymph nodes at the lowest levels and that the FasR(+)DR3(+) CD4(+) T cells were enhanced in tumors. The comparisons with the clinicopathological data revealed a major impact of active smoking on the reduction in paratumoral NK cells and the upregulation of FasR in tumor-infiltrating NK and CD8(+) T cells. The lymph node metastatic stage, tumor stage, and Mandard grade correlated with the compartmental proportions of the evaluated immune cells. CONCLUSION: The novel association of the disease state with tumoral and paratumoral immune cell signatures suggests new possibilities for personalized immunotherapy for EC patients.	esophagus
Esophageal brachytherapy: Institut Gustave Roussy's experience.	PURPOSE: Esophageal cancer is characterized by its propension to local evolution, which conditions prognosis and quality of life. Brachytherapy may be a therapeutic option for all stages of esophageal cancer. METHODS AND MATERIALS: This retrospective unicentric study included all consecutive patients treated for an esophageal high-dose-rate brachytherapy in our institution from 1992 to 2018. RESULTS: Ninety patients were included. They were treated in four distinct indications: exclusive (7 patients), boost after external beam radiotherapy (41), reirradiation (36), or palliative aim (6). Most frequently prescribed schemes were 3 × 5 Gy (boost) or 6 × 5 Gy (exclusive treatment and reirradiation) at applicator's surface or at 5 mm. At the end of follow-up, 50% of patients had presented with local recurrence. Seventeen percent of patients had a metastatic relapse. Median overall survival was 15 months in the whole cohort: 22 months in the boost setting, 25 months for exclusive brachytherapy, 15 months for reirradiation, and only 2 months for palliative treatment. Tumor length at brachytherapy, brachytherapy dose, and interfraction response were significantly associated to overall survival. 40% of patients presented with grade 2+ toxicity, mostly esophagitis, including three toxic deaths. CONCLUSIONS: Although local control outcomes are still poor, one must remember that patients are unfit for any curative therapeutic option and that palliative chemotherapy offers mediocre results. The most promising setting probably is reirradiation because brachytherapy offers a remarkable dose gradient allowing best organ at risk sparing, with an encouraging rate of long survivors (19% at 2 years). Esophageal brachytherapy deserves to be further investigated because some patients, even unfit, may benefit from it, with acceptable toxicity.	esophagus
Prognostic value of sarcopenia in patients treated by Radiochemotherapy for locally advanced oesophageal cancer.	BACKGROUND: Sarcopenia is defined by a loss of skeletal muscle mass with or without loss of fat mass. Sarcopenia has been associated to reduced tolerance to treatment and worse prognosis in cancer patients, including patients undergoing surgery for limited oesophageal cancer. Concomitant chemo-radiotherapy is the standard treatment for locally-advanced tumour, not accessible to surgical resection. Using automated delineation of the skeletal muscle, we have investigated the prognostic value of sarcopenia in locally advanced oesophageal cancer (LAOC) patients treated by curative-intent chemo-radiotherapy. METHODS: The clinical, nutritional, anthropometric, and functional-imaging ((18)FDG-PET/CT) data were collected in 97 patients treated between 2006 and 2012 in our institution. The skeletal muscle area was automatically delineated on cross-sectional CT images acquired at the 3rd. lumbar vertebra level and divided by the patient's squared height (SML3/h(2)) to obtain the Skeletal Muscle Index (SMI). The primary endpoint was overall survival probability. RESULTS: Seventy-six deaths were reported. The median survival time was 27 [95% Confidence Interval 23-40] months for the whole population. Univariate analyses (Cox Proportional Hazard Model) showed decreased survival probabilities in patients with reduced SMI, WHO > 0, Body Mass Index ≤21, and Nutritional Risk Index ≤97.5. Multivariate analyses showed that sarcopenia was the only significant prognostic factor (HR 2.32 [1.24-4.34], p = 0.008). Using Receiver Operating Characteristics curves, the Area Under the Curve (AUC) was 0.73 in males (p = 0.0002], the optimal threshold being 51.5 cm(2)/m(2). In women, the AUC was 0.65 (p = 0.19). CONCLUSION: Sarcopenia is a powerful independent prognostic factor, associated with a rise of the overall mortality in patients treated exclusively by radiochemotherapy for a locally advanced oesophageal cancer. L3 CT images are easily gathered from (18)FDG-PET/CT acquisitions.	esophagus
Surgery versus radical endotherapies for early cancer and high-grade dysplasia in Barrett's oesophagus.	BACKGROUND: Barrett's oesophagus is one of the most common pre-malignant lesions in the world. Currently the mainstay of therapy is surgical management of advanced cancer but this has improved the five-year survival very little since the 1980s. As a consequence, improved survival relies on early detection through endoscopic surveillance programmes. Success of this strategy relies on the fact that late-stage pre-malignant lesions or very early cancers can be cured by intervention. Currently there is considerable controversy over which method is best: that is conventional open surgery or endotherapy (techniques involving endoscopy). OBJECTIVES: We used data from randomised controlled trials (RCTs) to examine the effectiveness of endotherapies compared with surgery in people with Barrett's oesophagus, those with early neoplasias (defined as high-grade dysplasia (HGD) and those with early cancer (defined as carcinoma in-situ, superficially invasive, early cancer or superficial cancer T-1m (T1-a) and T-1sm (T1-b)). SEARCH METHODS: We used the Cochrane highly sensitive search strategy to identify RCTs in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, EBMR, Controlled Trials mRCT and ISRCTN, and LILACS, in July and August 2008. The searches were updated in 2009 and again in April 2012. SELECTION CRITERIA: Types of studies: RCTs comparing endotherapies with surgery in the treatment of high-grade dysplasia or early cancer. All cellular types of cancer were included (i.e. adenocarcinomas, squamous cell carcinomas and more unusual types) but will be discussed separately. TYPES OF PARTICIPANTS: patients of any age and either gender with a histologically confirmed diagnosis of early neoplasia (HGD and early cancer) in Barrett's or squamous lined oesophagus. Types of interventions; endotherapies (the intervention) compared with surgery (the control), all with curative intent. DATA COLLECTION AND ANALYSIS: Reports of studies that meet the inclusion criteria for this review would have been analysed using the methods detailed in Appendix 9. MAIN RESULTS: We did not identify any studies that met the inclusion criteria. In total we excluded 13 studies that were not RCTs but that compared surgery and endotherapies. AUTHORS' CONCLUSIONS: This Cochrane review has indicated that there are no RCTs to compare management options in this vital area, therefore trials should be undertaken as a matter of urgency. The problems with such randomised methods are standardising surgery and endotherapies in all sites, standardising histopathology in all centres, assessing which patients are fit or unfit for surgery and making sure there are relevant outcomes for the study (i.e. long-term survival (over five or more years)) and no progression of HGD.	esophagus