crossing96/oncoscreening huggingface dataset:
Consolidation Chemotherapy Rather than Induction Chemotherapy Can Prolong the Survival Rate of Inoperable Esophageal Cancer Patients Who Received Concurrent Chemoradiotherapy.	Concurrent chemoradiotherapy (CRT) is regarded as the standard treatment for inoperable esophageal cancers (EC). It is still controversial whether consolidation chemotherapy (CCT) or induction chemotherapy (IC) is beneficial for the patients who received CRT. Therefore, we carried out a retrospective analysis at our institution. A total of 186 inoperable EC patients from 20 October 2017 to 7 June 2021 who have previously received CRT were included in our study. The patients were divided into IC + CRT (n = 52), CCRT (n = 64), and CRT + CCT (n = 70) groups according to whether they received induction chemotherapy, consolidation chemotherapy, or not. We used Kaplan−Meier statistics to analyze their 1-, 2-, and 3-year OS. The median follow-up time for the whole group was 14.15 months. The 1-, 2-, 3- year overall survival (OS) for the CCRT group were 72.2%, 52.5%, and 29.5%, and 50.9%, 37.5%, and 25% for the IC + CRT group (p > 0.05). For the CRT + CCT group,1-, 2-, and 3-year OS were 89.8%, 59.0%, and 42.5% (p < 0.05). Adverse reactions in the three groups were mainly graded 0−3. The difference between the three groups was not statistically significant (p > 0.05). For non-surgical EC patients who received CRT, CCT after CRT but not IC before CRT can improve 1-, 2-, and 3-year OS with a low incidence of associated severe adverse effects. As a result, the addition of consolidation chemotherapy to chemoradiotherapy has significant prognostic advantages for inoperable EC patients.	esophagus
Predictive Model of Chemotherapy-Induced Myelosuppression for Patients with Esophageal Cancer.	BACKGROUND: The influential factors of chemotherapy-induced myelosuppression in esophageal cancer in central China are unclear. This study aimed to develop a model for prediction of incidence of myelosuppression during chemotherapy among patients with esophageal cancer. METHODS: In this retrospective study, a total of 1446 patients with esophageal cancer who underwent five different chemotherapy regimens between 2013 and 2020 at our institute were randomly assigned in a 7:3 ratio to training and validation data sets. Clinical and drug-related variables were used to develop the prediction model from the training data set by the machine learning method of random forest. Finally, this model were tested in the validation data set. RESULTS: The prediction model were established with 16 indispensable variables selected from 46 variables. The model obtained an area under the receiver-operating characteristic curve of .883 and accompanied by prediction accuracy of 80.0%, sensitivity of 77.8% and specificity of 81.8%. CONCLUSION: This new prediction model showed excellent predictive ability of incidence of myelosuppression in turn providing preventative measures for patients with esophageal cancer during chemotherapy.	esophagus
AI-assisted discovery of an ethnicity-influenced driver of cell transformation in esophageal and gastroesophageal junction adenocarcinomas.	Although Barrett's metaplasia of the esophagus (BE) is the only known precursor lesion to esophageal adenocarcinomas (EACs), drivers of cellular transformation in BE remain incompletely understood. We use an artificial intelligence-guided network approach to study EAC initiation and progression. Key predictions are subsequently validated in a human organoid model, in patient-derived biopsy specimens of BE, a case-control study of genomics of BE progression, and in a cross-sectional study of 113 patients with BE and EACs. Our model classified healthy esophagus from BE and BE from EACs in several publicly available gene expression data sets (n = 932 samples). The model confirmed that all EACs must originate from BE and pinpointed a CXCL8/IL8↔neutrophil immune microenvironment as a driver of cellular transformation in EACs and gastroesophageal junction adenocarcinomas. This driver is prominent in White individuals but is notably absent in African Americans (AAs). Network-derived gene signatures, independent signatures of neutrophil processes, CXCL8/IL8 expression, and an absolute neutrophil count (ANC) are associated with risk of progression. SNPs associated with changes in ANC by ethnicity (e.g., benign ethnic neutropenia [BEN]) modify that risk. Findings define a racially influenced immunological basis for cell transformation and suggest that BEN in AAs may be a deterrent to BE→EAC progression.	esophagus
Influence of patient position in thoracoscopic esophagectomy on postoperative pneumonia: a comparative analysis from the National Clinical Database in Japan.	BACKGROUND: Two prominent patient positions during thoracoscopic esophagectomy are the left lateral decubitus position (LP) and the prone position (PP). However, whether the patient position during thoracoscopic esophagectomy influences short-term outcomes, especially postoperative pneumonia, remains unclear. We aimed to elucidate the impact of patient position on the occurrence of postoperative pneumonia. METHODS: We analyzed 9850 patients who underwent oncologic thoracoscopic esophagectomies between 2016 and 2019 from the National Clinical Database. We compared the short-term outcomes between the LP and PP groups, and the primary outcome measure was the incidence of postoperative pneumonia. RESULTS: This study included 2637 (26.8%) and 7213 (73.2%) patients in the LP and the PP groups, respectively. The baseline characteristics of the two groups were well-balanced. Compared with the LP group, the PP group had a longer operative time and less blood loss. There were no significant differences in the incidences of postoperative pneumonia, recurrent laryngeal nerve palsy, anastomotic leakage, severe complications, and reoperation between the groups. Meanwhile, prolonged ventilation and surgery-related mortality occurred more frequently in the LP than in the PP group (P < 0.001 and 0.046, respectively). After multivariable adjustment, the patient position did not significantly influence the incidence of postoperative pneumonia (odds ratio 0.91, 95% confidence interval 0.80-1.04). CONCLUSIONS: Although prolonged ventilation and surgery-related mortality occurred more frequently in the LP group than in the PP group, the patient position did not significantly influence the occurrence of postoperative pneumonia.	esophagus
Single-center experience in implementation of endoscopic surveillance protocol after esophagectomy.	Esophageal cancer has a notably high recurrence rate with a paucity of robust evidence in defining the optimal surveillance strategy. The surveillance protocol at our institution comprises of annual esophagogastroduodenoscopy (OGD) from years 1 to 5 postoperatively. This study aims to evaluate the implementation of the endoscopic surveillance at our center and ascertain the value of endoscopy in detecting local recurrence after esophagectomy. A retrospective cohort review of all patients (320 patients) who underwent esophagectomy between 2013 and 2018 was conducted. The local esophageal cancer database and corresponding OGD reports were accessed to obtain data on demographics, operation details, local recurrence, and endoscopy performed. 1086 OGDs were performed between 2014 and 2020, broadly categorized to surveillance and symptomatic OGDs; 555 and 531, respectively. Surveillance OGDs detected four asymptomatic local recurrences, of which only one was treated with curative intent. Symptomatic OGDs resulted in a higher yield for the detection of local recurrence compared with surveillance endoscopy; 5% versus 0.7%, with overall median time-to-recurrence of 11.5 months (95% confidence interval 9-17). Of local recurrences, 85.7% occurred within the first 2 years postoperatively. The proportion of endoscopic findings differed between intensive and ad hoc surveillance cohorts for strictures, esophagitis, Barrett's esophagus, and sloughing. Thirteen patients were diagnosed with histologically confirmed Barrett's with no subsequent local recurrences. Surveillance endoscopy had a low positive yield rate with subsequent minimal survival benefits. Therefore, it is prudent to consider an alternative protocol that focuses on the period with the highest risk of recurrence and symptom presentation.	esophagus
An anti-alcoholism drug, disulfiram and copper complex improves radio-resistance of tumor-initiating cells in esophageal squamous cell carcinoma.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a malignant cancer with a poor prognosis. Chemoradiotherapy is one of the most important strategies for patients with locally advanced unresectable ESCC; however, its therapeutic effect is unsatisfactory. Tumor-initiating cells (TICs) have been reported to be resistant to conventional chemotherapy and radiotherapy so far. Therefore, we aimed to develop a treatment strategy targeting TICs in ESCC to improve radiosensitivity. METHODS: First, we validated aldehyde dehydrogenase 1 (ALDH1) as a TIC marker and investigated its ability to mediate resistance in human ESCC cell lines using flow cytometry, Western blotting, and functional analyses. Then, we focused on disulfiram (DSF), an aldehyde dehydrogenase inhibitor, used to treat alcohol use disorder. We investigated the effect of DSF and copper (II) D-gluconate (Cu) on the radiosensitivity of ESCC in xenograft mouse models. RESULTS: ALDH1-positive cells showed an upregulation of SOX2 and Nanog, exhibiting much stronger tumor-initiating properties than ALDH1-negative cells. Furthermore, inhibition of ALDH1 attenuated the tumor-initiating properties of ESCC cell lines. Our results also showed that ALDH1-positive cells were resistant to chemotherapy and radiotherapy, and the inhibition of ALDH1 led to the mitigation of therapeutic resistance. Our in vitro and in vivo studies revealed that the DSF/Cu complex could radiosensitize ALDH1-positive ESCC cells and downregulate the phosphoinositide 3-kinase/Akt pathway. CONCLUSION: ALDH1 inhibition by the DSF/Cu complex enhances the radiosensitivity of TICs in ESCC. The drug repositioning approach using disulfiram is a potential treatment option to overcome radioresistance in patients with locally advanced ESCC.	esophagus
Early detection of radiation-induced myocardial damage by [(18)F]AlF-NOTA-FAPI-04 PET/CT imaging.	PURPOSE: Retrospective analysis revealed increased [(18)F]AlF-NOTA-FAPI-04 uptake in the myocardium of patients with esophageal squamous cell cancer (ESCC) treated with concurrent chemoradiotherapy (CCRT). This study investigated and verified the feasibility of [(18)F]AlF-NOTA-FAPI-04 PET/CT for detecting radiation-induced myocardial damage (RIMD). METHODS: Myocardial FAPI uptake was analyzed before and during radiotherapy in thirteen ESCC patients treated with CCRT. In the animal study, a single dose of 50 Gy was delivered to the cardiac apex of Wistar rats (24 rats, including 16 RIMD model rats and 8 control model rats). RIMD model rats were scanned with [(18)F]AlF-NOTA-FAPI-04 PET/CT weekly for 12 weeks, and left ventricular ejection fraction (LVEF) was measured by magnetic resonance imaging. Dynamic, blocking, and [(18)F]FDG PET/CT studies (4 rats/group) were performed on RIMD rats at 5 weeks post-radiation, and histopathological analyses were conducted. RESULTS: Increased FAPI uptake in the myocardium was found after CCRT (1.53 ± 0.53 vs 1.88 ± 0.70, P = 0.015). In RIMD rats, significantly increased FAPI uptake in the damaged myocardium was observed from the 2nd week post-radiation exposure and peaked in the 5th week. Significantly more intense tracer accumulation was observed in the damaged myocardium than in the remote myocardium, as identified by decreased [(18)F]FDG uptake and confirmed by autoradiography, hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining. The LVEF remained unchanged at the 3rd week post-radiation exposure but was remarkably decreased compared with that in the control group at the 8th week. CONCLUSION: Through clinical phenomena and animal experimental studies, this study indicated that [(18)F]AlF-NOTA-FAPI-04 PET/CT imaging can detect RIMD noninvasively and before a decrease in LVEF, indicating the clinical potential of [(18)F]AlF-NOTA-FAPI-04 as a PET/CT tracer for early monitoring of RIMD.	esophagus
[Occurrence of gastric cancer after laparoscopic Roux-en-Y gastric bypass: a systematic review].	Laparoscopic Roux-en-Y gastric bypass (RYGB) is an important obesity surgery. The risk of remnant gastric cancer after RYGB for obesity is gaining growing attention from bariatric surgeons and patients with obesity. This systematic review included articles from major databases internationally and domestically that specifically described the remnant gastric cancer after RYGB intervention, a total of 21 cases was subsequently analyzed. The average median time from post-operative RYGB to diagnosis of gastric cancer was 11 years (1-28 years), the duration of gastric cancer symptoms lasted 7 days to 6 years, abdominal pain is the most common (71.4%), especially in the upper abdomen (33.3%), followed by nausea and vomiting (33.3%), over-weight loss (33.3%), and abdominal bloating (28.6%), etc. Neoplasm location was reported to occur in the antrum or the pre-pyloric region (71.4%), with adenocarcinoma being the most common tumor histology observed (71.4%), tumor stage III-IV as the most diagnosed, 38.1% of tumor were deemed to be unresectable, 52.4% of the patients performed subtotal gastrectomy and lymphadenectomy. In addition, a global article investigating the occurrence of esophageal gastric cancer after RYGB in 64 cases revealed the common preoperative medical history include smoking habits (37.5%), alcohol issues (14.0%), GERD (86.0%), presence with Barret esophagus (10.9%), patients that has other malignant tumor medical history (6.3%), first-degree relatives (6.3%), or other family members with gastric esophagus cancer family history. Although the incidence of gastric cancer after RYGB is rare, the increasing prevalence of gastric cancer development is one of great concern. A rise in clinical cases of patients treated with RYGB presents a target for future studies. Risk of gastric cancer after RYGB should be evaluated and considered in high-risk cases.	esophagus
The measurement of NRF2 and TP53 in blood expects radiotherapeutic sensitivity in patients with esophageal cancer.	OBJECTIVE: This study investigates the relationship between the mRNA expression of nuclear factor erythroid 2-related factor 2 (NRF2) and Tumor protein p53 (TP53) in circulating tumor cells (CTC) and sensitivity to radiotherapy in patients with esophageal cancer. To investigate the relationship between cytokines IL-6, CD8(+), and NRF2 during patient treatment and their predictive role for treatment. METHODS: Radiosensitivity was assessed by measuring a morphological or functional change in the tumor in response to ionizing radiation. Fasting venous anticoagulated blood (EDTA anticoagulation) was drawn from patients, and the Trizol-chloroform two-step method was used for RNA extraction. Data were collected from 45 patients admitted with radiotherapy alone from January 2018 to December 2021. The expression levels of NRF2mRNA (Messenger Ribose Nucleic Acid) and TP53mRNA in CTCs were detected by reverse transcription-polymerase chain reaction (RT-PCR). Pre- and post-treatment changes in IL-6 and CD8(+) were recorded. The correlation between their expression level and the clinical stage, radiotherapy sensitivity, and efficacy of patients was analyzed. RESULTS: Twenty-six cases were sensitive to radiotherapy, and 19 were resistant, for a radiotherapy sensitivity rate of 58.8%. NRF2mRNA and TP53mRNA values increased in 19 radiotherapy-resistant patients and decreased in 26 radiotherapy-sensitive patients compared with those before radiotherapy (P = 0.001, P＜0.05). The ΔCT values of NRF2mRNA and TP53mRNA before treatment were moderately correlated with prognosis (P < 0.002). Inflammatory cytokine IL-6 was elevated in 22 of 45 patients after radiation, P = 0.04. NRF2 mRNA level was consistently elevated with CD8(+) in 10 patients, P = 0.02. CONCLUSIONS: The expression of NRF2mRNA and TP53mRNA in the CTCs found in the peripheral blood of patients with esophageal squamous carcinoma was significantly associated with the sensitivity to radiotherapy. NRF2 mRNA level was consistently elevated with CD8(+) and IL-6 in patients.	esophagus
Selective Elimination of NRF2-Activated Cells by Competition With Neighboring Cells in the Esophageal Epithelium.	BACKGROUND & AIMS: NF-E2-related factor 2 (NRF2) is a transcription factor that regulates cytoprotective gene expression in response to oxidative and electrophilic stresses. NRF2 activity is mainly controlled by Kelch-like ECH-associated protein 1 (KEAP1). Constitutive NRF2 activation by NRF2 mutations or KEAP1 dysfunction results in a poor prognosis for esophageal squamous cell carcinoma (ESCC) through the activation of cytoprotective functions. However, the detailed contributions of NRF2 to ESCC initiation or promotion have not been clarified. Here, we investigated the fate of NRF2-activated cells in the esophageal epithelium. METHODS: We generated tamoxifen-inducible, squamous epithelium-specific Keap1 conditional knockout (Keap1-cKO) mice in which NRF2 was inducibly activated in a subset of cells at the adult stage. Histologic, quantitative reverse-transcription polymerase chain reaction, single-cell RNA-sequencing, and carcinogen experiments were conducted to analyze the Keap1-cKO esophagus. RESULTS: KEAP1-deleted/NRF2-activated cells and cells with normal NRF2 expression (KEAP1-normal cells) coexisted in the Keap1-cKO esophageal epithelium in approximately equal numbers, and NRF2-activated cells formed dysplastic lesions. NRF2-activated cells exhibited weaker attachment to the basement membrane and gradually disappeared from the epithelium. In contrast, neighboring KEAP1-normal cells exhibited accelerated proliferation and started dominating the epithelium but accumulated DNA damage that triggered carcinogenesis upon carcinogen exposure. CONCLUSIONS: Constitutive NRF2 activation promotes the selective elimination of epithelial cells via cell competition, but this competition induces DNA damage in neighboring KEAP1-normal cells, which predisposes them to chemical-induced ESCC.	esophagus
Metabolomic transition trajectory and potential mechanisms of N-nitrosomethylbenzylamine induced esophageal squamous cell carcinoma in rats.	Esophageal squamous cell carcinoma (ESCC) is an environment-relevant malignancy with a high mortality. Nitrosamines, a class of nitrogen-containing environmental carcinogens, are widely suggested as a risk factor for ESCC. However, how nitrosamines affect metabolic regulation to promote ESCC tumorigenesis is largely unknown. In this study, the transition trajectory of serum metabolism in the course of ESCC induced by N-nitrosomethylbenzylamine (NMBA) in rats was depicted by an untargeted metabolomic analysis, and the potential molecular mechanisms were revealed. The results showed that the metabolic alteration in rats was slight at the basal cell hyperplasia (BCH) stage, while it became apparent when the esophageal lesion developed into dysplasia (DYS) or more serious conditions. Moreover, serum metabolism of severe dysplasia (S-DYS) showed more similar characteristics to that of carcinoma in situ (CIS) and invasive cancer (IC). Aberrant nicotinate (NA) and nicotinamide (NAM) metabolism, tryptophan (TRP) metabolism, and sphingolipid metabolism could be the key players favoring the malignant transformation of esophageal epithelium induced by NMBA. More particularly, NA and NAM metabolism in the precancerous stages and TRP metabolism in the cancerous stages were demonstrated to replenish NAD(+) in different patterns. Furthermore, both the IDO1-KYN-AHR axis mediated by TRP metabolism and the SPHK1-S1P-S1PR1 axis by sphingolipid metabolism provided an impetus to create the pro-inflammatory yet immune-suppressive microenvironment to facilitate the esophageal tumorigenesis and progression. Together, these suggested that NMBA exerted its carcinogenicity via more than one pathway, which may act together to produce combination effects. Targeting these pathways may open up the possibility to attenuate NMBA-induced esophageal carcinogenesis. However, the interconnection between different metabolic pathways needs to be specified further. And the integrative and multi-level systematic research will be conducive to fully understanding the mechanisms of NMBA-induced ESCC.	esophagus
Verbascoside represses malignant phenotypes of esophageal squamous cell carcinoma cells by inhibiting CDC42 via the HMGB1/RAGE axis.	BACKGROUND: As an aggressive human malignancy, esophageal squamous cell carcinoma (ESCC) is prevalent globally, especially in China. Verbascoside (VE) exerts anti-cancer effects in several human cancers. This work was to investigate the effects of VE on ESCC cells. METHODS: Esophageal squamous cell carcinoma cell proliferation, apoptosis, migration, and invasion were assessed by CCK-8, TUNEL, and Transwell assays. Gene and protein levels were detected by RT-qPCR and western blotting. CDC42 activity was evaluated by G-lisa assay. RESULTS: Verbascoside significantly inhibited cell proliferation, migration, and invasion and induced cell apoptosis in ESCC cells. Furthermore, it was found that VE markedly inhibited HMGB1 and RAGE expression in a dose-dependent manner. Besides, HMGB1/RAGE upregulation partially reversed the anti-cancer effects of VE on ESCC cells. VE repressed HMGB1/RAGE-induced CDC42 activation in ESCC cells. In addition, ML141-mediated CDC42 inactivation further enhanced the effect of VE on ESCC cell proliferation, apoptosis, migration, and invasion. CONCLUSIONS: Our findings indicated that VE has significant anti-tumor potential in ESCC by suppressing HMGB1/RAGE-dependent CDC42 activation.	esophagus
Effect of Health Disparities on Refusal of Trimodality Therapy in Localized Esophageal Adenocarcinoma: A Propensity Score Matched Analysis of the National Cancer Database.	BACKGROUND: Factors associated with refusal of multimodality therapy in patients with localized esophageal adenocarcinoma (EA) remain unknown. We hypothesized that sociodemographic disparities affect decision to pursue optimal trimodally therapy for patients with EA. METHODS: NCDB for esophageal cancer (2004-2017) was utilized. Included were patients diagnosed with cT3-T4 cN0 or cTany N1-3 EA of the mid-lower esophagus. Annual institutional esophagectomy volumes were categorized as low (<20/year) and high (≥20/year). Conditional logistic regression was used to identify predictors of refusal of offered treatment. Kaplan Meier method was used to compare survival. RESULTS: 13 091 patients met selection criteria, mean age was 62.4 ± 9.6 years and 11 581 (88.5%) were males. 633 (4.8%) patients refused at least one component of recommended treatment (chemotherapy, radiation, and esophagectomy), most commonly refusal of surgery (N = 554, 4.2%). On multivariable analysis, factors predictive of treatment refusal included older age, female gender, black race, no insurance, low income (below poverty), mid-esophageal tumors, and treatment at low-volume centers. Patients who were recommended treatment but refused had significantly worse survival than those who adhered to treatment (median 23.1 ± 1.1 vs. 32.1 ± 1.2 months; P < .001). CONCLUSIONS: In this study, sociodemographic disparities and center volume were among factors predictive of therapy refusal in patients with localized esophageal adenocarcinoma. While understanding potential reasons for treatment refusal is critical, this data suggests that socioeconomic variables may drive patient decisions.	esophagus