crossing96/oncoscreening huggingface dataset:
Incidence, Morbidity, and Mortality of Achalasia: A Nationwide, Population-Based Cohort Study in South Korea.	BACKGROUND/AIMS: Although an association between achalasia and esophageal cancer has been reported, whether achalasia confers a substantial increase in mortality is unknown. Moreover, the causes of death related to achalasia have not been investigated. We performed this nationwide, population-based cohort study on achalasia because no such study has been performed since the introduction of high-resolution manometry in 2008. METHODS: This study was performed using data extracted from the Korean National Health Insurance Service database, covering a 9-year period from 2009 to 2017. Control participants without a diagnostic code for achalasia were randomly selected and matched by sex and birth year at a case-to-control ratio of 1:4. Data on the cause of death from Statistics Korea were also analyzed. RESULTS: The overall incidence of achalasia was 0.68 per 100,000 person-years, and the prevalence was 6.46 per 100,000 population. Patients with achalasia (n=3,063) had significantly higher adjusted hazard ratio (aHR) for esophageal cancer (aHR, 3.40; 95% confidence interval [CI], 1.25 to 9.22; p=0.017), pneumonia (aHR, 2.30; 95% CI, 1.89 to 2.81; p<0.001), aspiration pneumonia (aHR, 3.92; 95% CI, 2.38 to 6.48; p<0.001), and mortality (aHR, 1.68; 95% CI, 1.44 to 1.94; p<0.001). Esophageal cancer carried the highest mortality risk (aHR, 8.82; 95% CI, 2.35 to 33.16; p=0.001), while pneumonia had the highest non-cancer mortality risk (aHR, 2.28; 95% CI, 1.31 to 3.96; p=0.004). CONCLUSIONS: In this nationwide study, achalasia was associated with increased risk of mortality. Esophageal cancer and pneumonia were the most common comorbidities and the major causes of death in patients with achalasia.	esophagus
RIG-I Promotes Tumorigenesis and Confers Radioresistance of Esophageal Squamous Cell Carcinoma by Regulating DUSP6.	We investigated the expression and biological function of retinoic acid inducible gene I (RIG-I) in esophageal squamous cell carcinoma (ESCC). Materials and methods: An immunohistochemical analysis was performed on 86 pairs of tumor tissue and adjacent normal tissue samples of patients with ESCC. We generated RIG-I-overexpressing ESCC cell lines KYSE70 and KYSE450, and RIG-I- knockdown cell lines KYSE150 and KYSE510. Cell viability, migration and invasion, radioresistance, DNA damage, and cell cycle were evaluated using CCK-8, wound-healing and transwell assay, colony formation, immunofluorescence, and flow cytometry and Western blotting, respectively. RNA sequencing was performed to determine the differential gene expression between controls and RIG-I knockdown. Tumor growth and radioresistance were assessed in nude mice using xenograft models. RIG-I expression was higher in ESCC tissues compared with that in matched non-tumor tissues. RIG-I overexpressing cells had a higher proliferation rate than RIG-I knockdown cells. Moreover, the knockdown of RIG-I slowed migration and invasion rates, whereas the overexpression of RIG-I accelerated migration and invasion rates. RIG-I overexpression induced radioresistance and G2/M phase arrest and reduced DNA damage after exposure to ionizing radiations compared with controls; however, it silenced the RIG-I enhanced radiosensitivity and DNA damage, and reduced the G2/M phase arrest. RNA sequencing revealed that the downstream genes DUSP6 and RIG-I had the same biological function; silencing DUSP6 can reduce the radioresistance caused by the overexpression of RIG-I. RIG-I knockdown depleted tumor growth in vivo, and radiation exposure effectively delayed the growth of xenograft tumors compared with the control group. RIG-I enhances the progression and radioresistance of ESCC; therefore, it may be a new potential target for ESCC-targeted therapy.	esophagus
Targeting IGF1R signaling enhances the sensitivity of cisplatin by inhibiting proline and arginine metabolism in oesophageal squamous cell carcinoma under hypoxia.	BACKGROUND: Cisplatin (DDP)-based chemotherapy is commonly adopted as the first-line treatment for patients with oesophageal squamous cell carcinoma (OSCC), but the high rate of drug resistance limits its clinical application and the underlying mechanisms at play remain unclear. The aims of this study were to elucidate the role of abnormal signal transmission and metabolism in the chemoresistance of OSCC under hypoxia and to identify targeted drugs that enhance the sensitivity of DDP chemotherapy. METHODS: Upregulated genes in OSCC were determined by RNA sequencing (RNA-seq), the Cancer Genome Atlas (TCGA) database, immunohistochemistry (IHC), real-time quantitative PCR (RT-qPCR), and western blotting (WB). The clinicopathological significance of insulin-like growth factor-I receptor (IGF1R), argininosuccinate synthetase 1 (ASS1), and pyrroline-5-carboxylate reductase 1 (PYCR1) in OSCC was analysed using tissue micriarray (TMA). Metabolic abnormalities were determined by untargeted metabolomics analysis. The DDP-resistance role of IGF1R, ASS1, and PYCR1 in OSCC was investigated in vitro and in vivo. RESULTS: Generally, tumour cells exist in a hypoxic microenvironment. By genomic profiling, we determined that IGF1R, as a receptor tyrosine kinase (RTK), was upregulated in OSCC under low-oxygen conditions. Clinically, enhanced IGF1R expression was associated with higher tumour stages and a poorer prognosis in OSCC patients, and its inhibitor, linsitinib, showed synergistic effects with DDP therapy in vivo and in vitro. Since oxygen-deprivation frequently lead to metabolic reprogramming, we further learned via metabolomics analysis that abnormal IGF1R pathways promoted the expression of metabolic enzymes ASS1 and PYCR1 by the transcriptional activity of c-MYC. In detail, enhanced expression of ASS1 promotes arginine metabolism for biological anabolism, whereas PYCR1 activates proline metabolism for redox balance, which maintains the proliferation ability of OSCC cells during DDP treatment under hypoxic conditions. CONCLUSION: Enhanced expression of ASS1 and PYCR1 via IGF1R pathways rewired arginine and proline metabolism, promoting DDP resistance in OSCC under hypoxia. Linsitinib targeting IGF1R signaling may lead to promising combination therapy options for OSCC patients with DDP resistance.	esophagus
Patterns and prognostic values of programmed cell death-ligand 1 expression and CD8 + T-cell infiltration in small cell carcinoma of the esophagus: a retrospective analysis of 34 years of National Cancer Center data in China.	BACKGROUND: Small cell carcinoma of the esophagus (SCCE) is an extremely rare and highly aggressive neuroendocrine malignancy with a strikingly poor prognosis. Given the great clinical successes of checkpoint immunotherapies, we explored the expression profile and clinical significance of programmed cell death-ligand 1 (PD-L1) and CD8 + T cell in SCCE for the first time. MATERIALS AND METHODS: Tumor-infiltrating immune cells (TIICs) and tumor cells in postoperative, whole tumor sections from 147 SCCE patients were stained for PD-LI expression. We also evaluated each patient's Combined Positive Score (CPS). Multiplex immunofluorescence staining (CD3, CD20, CD68, and PD-L1) was introduced to clarify the location of PD-L1. CD8 density was analyzed by digital imaging and analysis of entire slides. Clinical outcomes were tested for correlations with both PD-L1 expression and CD8 density. RESULTS: No patients had PD-L1 expressed in their tumor cells. PD-L1 + expression in TIICs was detected in 65 patients (44.2%) and 42 (28.6%) exhibited CPS positivity. Multiplex immunofluorescence staining demonstrated that most of the PD-L1 was expressed on the CD68 + monocytes/macrophages. PD-L1 expression in the TIICs and CPS was found to be correlated with paraffin block age, tumor length, macroscopic type, T stage, and increased overall survival (OS). Expression of PD-L1 in TIICs showed significantly prolonged relapse-free survival (RFS). Increasing CD8 densities were associated with increased PD-L1 expression ( Ptrend <0.0001). Multivariate regression confirmed that PD-L1 in TIICs and CD8 states were independent predictors of OS, and CD8 status were found to be independently predictive of RFS. A stratification based on PD-L1 and CD8 status was also significantly associated with both OS and RFS. CONCLUSION: Expression of PD-L1 was only detected in TIICs from approximately half of the patients with SCCEs. In SCCEs, PD-L1 and CD8 status are novel prognostic biomarkers and may inform the implementation of risk-related therapeutic strategies. SCCEs with higher CD8 infiltration also had higher expression of PD-L1, suggesting the development of resistance against adaptive immunity. These findings support the assertion that PD-L1/programmed cell death 1 inhibitors should be investigated in this rare malignancy.	esophagus
Robotic versus open Ivor-Lewis esophagectomy: A more accurate lymph node dissection without burdening the leak rate.	BACKGROUND: Robotic-assisted minimally invasive esophagectomy (RAMIE) combines the beneficial effects of minimally invasive surgery on postoperative complications, especially on pulmonary ones, with the safety of the anastomosis performed in open surgery. Moreover, RAMIE could allow a more accurate lymphadenectomy. METHODS: We reviewed our database to identify all patients with adenocarcinoma of the esophagus treated by Ivor-Lewis esophagectomy in the period January 2014 to June 2022. Patients were divided according to the thoracic approach into RAMIE and open esophagectomy (OE) groups. We compared the groups for early surgical outcomes, 90-day mortality as well as R0 rate, and the number of lymph nodes harvested. RESULTS: We identified 47 patients in RAMIE and 159 patients in the OE group. Baseline characteristics were comparable. Operative time was significantly longer for RAMIE procedures (p < 0.01); however, we did not observe the difference in overall (RAMIE 55.5% vs. OE 61%, p = 0.76) and severe complications rate (RAMIE 17% vs. OE 22.6%, p = 0.4). The anastomotic leak rate was 2.1% after RAMIE and 6.9% after OE (p = 0.56). We did not report the difference in 90-day mortality (RAMIE 2.1% vs. OE 1.9%, p = 0.65). In the RAMIE group, we observed a significantly higher number of thoracic lymph nodes harvested, with a median of 10 lymph nodes in the RAMIE group versus 8 in the OE group (p < 0.01). CONCLUSIONS: In our experience, RAMIE has morbimortality rates comparable to OE. Moreover, it allows a more accurate thoracic lymphadenectomy which results in a higher thoracic lymph nodes retrieval rate.	esophagus
Prognostic impact of endoscopic response evaluation after neoadjuvant chemotherapy for esophageal squamous cell carcinoma: a nationwide validation study.	BACKGROUND: Our previous study reported the prognostic significance of endoscopic response (ER) evaluation, defined ER, and revealed ER as an independent prognostic factor of overall survival (OS) and recurrence-free survival (RFS) for esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemotherapy (NAC) and surgery. The present study aimed to validate the prognostic impact of ER using a nationwide database from the authorized institute for board-certified esophageal surgeons by the Japan Esophageal Society. METHODS: This study retrospectively reviewed patients with ESCC who underwent subtotal esophagectomy at 85 authorized institutes for esophageal cancer from 2010 to 2015. Patients were classified as ER when the tumor size was markedly reduced post-NAC compared to pre-NAC. The correlation between OS and RFS was investigated. RESULTS: Of 4781 patients initially enrolled, 3636 were selected for subsequent analysis. Of them, 642 (17.7%) patients were classified as the ER group. Patients with ER showed significantly better OS and RFS. Subgroup analysis revealed the statistical difference in OS and RFS in cStage II and III, while the magnitude of survival difference between ER and non-ER was not evident in cStage I and IV. The percentage of ER varied from 46 to 87% among groups when institutions were classified into 3 subgroups based on the hospital volume, which would indicate the interinstitutional inconsistency. CONCLUSIONS: The prognostic impact of ER was validated using a nationwide database. Standardization of ER evaluation is required to improve the interinstitutional consistency and clinical validity of the ER evaluation.	esophagus
Real-world upper endoscopy utilization patterns among patients with gastroesophageal reflux disease, Barrett esophagus, and Barrett esophagus-related esophageal neoplasia in the United States.	This study fills a gap in literature by providing contemporary real-world evidence on the prevalence of patients with gastroesophageal reflux disease (GERD), Barrett esophagus (BE), and Barrett esophagus-related neoplasia (BERN) and their upper endoscopy utilization patterns in the United States. A retrospective cohort study design was used: adults with GERD, nondysplastic Barrett esophagus (NDBE), and BERN (indefinite for dysplasia [IND], low-grade dysplasia [LGD], high-grade dysplasia [HGD], or esophageal adenocarcinoma [EAC]) were identified from the MarketScan databases (January 01, 2015-December 31, 2019). For each disease stage, prevalence of adults in commercial claims by calendar year, annual number of upper endoscopies per patient and time between upper endoscopies were reported. In 2019, in commercial claims (N = 12,363,227), the annual prevalence rate of GERD was 13.7% and 0.70% for BE/BERN, among which, 87.1% had NDBE, 6.8% had IND, 2.3% had LGD, 1.0% had HGD, and 2.8% had EAC. From 2015-2019, the study included 3,310,385 patients with GERD, 172,481 with NDBE, 11,516 with IND, 4332 with LGD, 1549 with HGD, and 11,676 with EAC. Annual mean number of upper endoscopies was 0.20 per patient for GERD, 0.37 per patient for NDBE, 0.43 for IND, 0.58 for LGD, and 0.87 for HGD. Median time (months) to second upper endoscopy was 38.10 for NDBE, 36.63 for IND, 22.63 for LGD, and 11.90 for HGD. Upper endoscopy utilization increased from GERD to BE to BERN, and time between upper endoscopies decreased as the disease stage progressed from BE to BERN, with less frequent utilization in BERN than what would be expected from guideline recommendations for surveillance.	esophagus
Multidisciplinary nutritional management improves nutritional and hospitalized outcomes of patients with esophageal cancer undergoing chemoradiotherapy: A randomized control trial.	BACKGROUND: This study aimed to investigate the effects of multidisciplinary whole-course nutrition management on the nutritional status and complications during the course of treatment in patients with esophageal cancer (EC) undergoing chemoradiotherapy. METHODS: A total of 36 EC patients undergoing chemoradiotherapy were divided into a control group (n = 18) and an intervention group (n = 18). Participants in the control group were given routine nutritional support, whereas those in the intervention group were provided whole-course nutrition management from the nutrition support team. Nutrition-related indicators, that is, serum albumin level (ALB), hemoglobin (Hb), and C reactive protein were assessed before, during, and after treatment in both groups. The incidence of complications (e.g., lymphocytopenia, radiation esophagitis, and myelosuppression), clinical outcomes, length of hospital stay, and hospital costs were also recorded. Differences between the 2 groups were tested using the Mann-Whitney U and chi-square tests. RESULTS: The ALB and Hb levels of the patients in the control group decreased significantly [ALB: -2.6 (-5.6, 0), P = .01; Hb: -12.0 (-27.0, -2.0), P = .04] and C reactive protein increased [8.9 (2.9, 14.9), P = .02] compared to those before treatment, while the indicators of participants in the intervention group did not change (P > .05). The incidence of grade ≥ II lymphocytopenia was higher in the control group than that in the intervention group (33.3% vs 61.1%, P = .03). Moreover, compared with the control group, the average length of hospital stay decreased by 12 days [47 (40, 50) vs 35 (23, 40), P = .001], and in-patient expenses decreased by 20,504 CNY in the intervention group (P = .004). CONCLUSION: Multidisciplinary whole-course nutrition management can maintain the nutritional status of patients with EC undergoing chemoradiotherapy. This may lower the incidence of complications, shorten hospital stays, and reduce in-patient expenses.	esophagus
PES1 reduces CD8(+) T cell infiltration and immunotherapy sensitivity via interrupting ILF3-IL15 complex in esophageal squamous cell carcinoma.	BACKGROUND: Although immune checkpoint blockade (ICB) therapy has brought survival benefits to patients with specific cancer types, most of cancer patients remain refractory to the ICB therapy, which is largely attributed to the immunosuppressive tumor microenvironment. Thereby, it is urgent to profile key molecules and signal pathways responsible for modification of tumor microenvironment. METHODS: Multiple databases of esophageal squamous cell carcinoma (ESCC) were integratively analyzed to screen candidate genes responsible for infiltration of CD8(+) T cells. Expression of pescadillo ribosomal biogenesis factor 1 (PES1) in clinical ESCC samples was examined by qRT-PCR, western blotting, and immunohistochemistry. The mechanisms of PES1 were investigated via RNA sequencing and mass spectrometry followed by immunoprecipitation and proximity ligation assay. The clinical and therapeutic significance of PES1 in ESCC was comprehensively investigated using ESCC cells and mouse model. RESULTS: PES1 was significantly upregulated and correlated with poor prognosis in ESCC patients. PES1 knockdown decreased ESCC cell growth in vitro and in vivo and enhanced the efficacy of ICB therapy in mouse model, which was established through subcutaneous inoculation with ESCC cells. Analyses on RNA sequencing and mass spectrometry suggested that PES1 expression was negatively correlated with IL15 and ILF3 was one of the PES1-associated proteins. It has been known that ILF3 interacts with and stabilizes IL15 mRNA to increase IL15 protein level. Our data further indicated that PES1 interfered with the interaction between ILF3 and IL15 mRNA and impaired ILF3-mediated stabilization of IL15 mRNA, which eventually reduced the protein level of IL15. Interestingly, the inhibitory effect of ICB therapy boosted by PES1 knockdown dramatically antagonized by knockdown of IL15, which suppressed the tumor-infiltrated CD8(+) T cells in ESCC. Finally, we confirmed the relationships among PES1, IL15, and CD8(+) T cell infiltration in 10 locally advanced ESCC patients receiving ICB neoadjuvant therapy and demonstrated that ICB therapy would be more effective in those with low expression of PES1. CONCLUSIONS: Altogether, our findings herein provided novel insights on biological function and clinical significance of PES1 and suggested that high expression of PES1 could suppress ILF3-IL15 axis-mediated immunosurveillance and promote resistance to ICB through restraining tumor-infiltrated CD8(+) T cells.	esophagus
Feasibility and Safety of Tailored Lymphadenectomy Using Sentinel Node-Navigated Surgery in Patients with High-Risk T1 Esophageal Adenocarcinoma.	BACKGROUND: Selective lymphadenectomy using sentinel node-navigated surgery (SNNS) might offer a less invasive alternative to esophagectomy in patients with high-risk T1 esophageal adenocarcinoma (EAC). The aim of this study was to evaluate the feasibility and safety of a new treatment strategy, consisting of radical endoscopic resection of the tumor followed by SNNS. METHODS: In this multicenter pilot study, ten patients with a radically resected high-risk pT1cN0 EAC underwent SNNS. A hybrid tracer of technetium-99m nanocolloid and indocyanine green was injected endoscopically around the resection scar the day before surgery, followed by preoperative imaging. During surgery, sentinel nodes (SNs) were identified using a thoracolaparoscopic gammaprobe and fluorescence-based detection, and subsequently resected. Endpoints were surgical morbidity and number of detected and resected (tumor-positive) SNs. RESULTS: Localization and dissection of SNs was feasible in all ten patients (median 3 SNs per patient, range 1-6). The concordance between preoperative imaging and intraoperative detection was high. In one patient (10%), dissection was considered incomplete after two SNs were not identified intraoperatively. Additional peritumoral SNs were resected in four patients (40%) after fluorescence-based detection. In two patients (20%), a (micro)metastasis was found in one of the resected SNs. One patient experienced neuropathic thoracic pain related to surgery, while none of the patients developed functional gastroesophageal disorders. CONCLUSIONS: SNNS appears to be a feasible and safe instrument to tailor lymphadenectomy in patients with high-risk T1 EAC. Future research with long-term follow-up is warranted to determine whether this esophageal preserving strategy is justified for high-risk T1 EAC.	esophagus
Right thoracoscopic resection in the supine position for recurrent pretracheal lymph nodes after esophagectomy.	Mediastinal lymph node recurrence is often observed following esophageal cancer surgery; however, no treatment has been established for the same. Surgical resection is often considered for cases of recurrence in a single lymph node region, although the procedures and approaches vary depending on the recurrence site. Right thoracoscopic resection is rarely opted for owing to its high surgical difficulty. Herein, we report a successful case of right thoracoscopic resection in the supine position for recurrent pretracheal lymph nodes following esophagectomy. The intraoperative findings revealed few adhesions around the recurrent lymph nodes due to the initial surgery, and the recurrent lymph nodes were safely resected within a short period. The patient was discharged on postoperative day 4 without any complications, and there was no recurrence after 20 months. Thus, right thoracoscopic resection may be a promising treatment option for recurrent pretracheal lymph nodes after esophagectomy.	esophagus