crossing96/oncoscreening huggingface dataset:
Surgically Managed Signet Ring Cell Esophageal Carcinomas in the National Cancer Database.	BACKGROUND: Signet ring cell adenocarcinoma (SRC) is a less common histologic variant of esophageal adenocarcinoma (ACA). The low frequency of SRC limits the ability to make data-driven clinical recommendations for these patients. METHODS: The National Cancer Database was queried for adult patients with clinical stage I, II, or III adenocarcinoma of the noncervical esophagus diagnosed between 2004 and 2015 and stratified by SRC versus all other ACA variants. Cox proportional hazard regression models were adjusted for patient, tumor, and treatment characteristics. The role of surgery in SRC was evaluated among patients treated with chemoradiation alone versus chemoradiation with esophagectomy. RESULTS: Of the 681 SRC and 13,543 ACA patients who underwent esophagectomy, no significant differences in age, sex, race, or comorbidities were identified. Patients with SRC were more likely to have high-grade tumors (84% vs 41%, P < .001) and stage III tumors (47% vs 39%, P < .001) compared with patients with ACA. Complete (R0) resection was less common in SRC (81% vs 90%, P < .001). Adjusted 5-year mortality risk from surgery was higher for SRC patients compared with ACA patients (hazard ratio, 1.242; 95% confidence interval, 1.126-1.369; P < .001). Among SRC tumors, chemoradiation with esophagectomy was associated with superior survival (hazard ratio, 0.429; 95% confidence interval, 0.339-0.546; P < .001) compared with chemoradiation alone. CONCLUSIONS: Among surgically managed patients SRC appears to have a worse prognosis than ACA, which may reflect the tendency of SRC tumors to be higher grade and more locally advanced. However SRC histology does not appear to diminish the role of esophagectomy in the management of locoregionally confined esophageal cancer.	esophagus
Three-field versus two-field lymphadenectomy in transthoracic oesophagectomy for oesophageal squamous cell carcinoma: short-term outcomes of a randomized clinical trial.	BACKGROUND: The benefit and harm of three-field lymphadenectomy for oesophageal cancer are still unknown. The aim of this study was to compare overall survival and morbidity and mortality between three- and two-field lymphadenectomy in patients with oesophageal squamous cell carcinoma. METHODS: Between March 2013 and November 2016, patients with squamous cell carcinoma of the middle or distal oesophagus were assigned randomly to open oesophagectomy with three-field (cervical-thoracic-abdominal) or two-field (thoracic-abdominal) lymphadenectomy. No chemo(radio) therapy was given before surgery. This paper reports on the secondary outcomes of the study: pathology and surgical complications. RESULTS: Some 400 patients were randomized, 200 in each group. A median of 37 (i.q.r. 30-49) lymph nodes were dissected in the three-field group, compared with 24 (18-30) in the two-field group (P < 0·001). Some 43 of 200 patients (21·5 per cent) in the three-field group had cervical lymph node metastasis. More patients in the three-field group had pN3 disease: 21 of 200 (10·5 per cent) versus 10 of 200 (5·0 per cent) (P = 0·040). The rate and severity of postoperative complications were comparable between the two groups, except that six patients in the three-field arm needed reintubation compared with none in the two-field group (3·0 versus 0 per cent; P = 0·030). The 90-day mortality rate was 0 per cent in the three-field group and 0·5 per cent (1 patient) in the two-field group (P = 1·000). CONCLUSION: Oesophagectomy with three-field lymphadenectomy increased the number of lymph nodes dissected and led to stage migration owing to a 21·5 per cent rate of cervical lymph node metastasis. Postoperative complications were largely comparable between two- and three-field lymphadenectomy. Registration number: NCT01807936 ( https://www.clinicaltrials.gov).	esophagus
GR, Sgk1, and NDRG1 in esophageal squamous cell carcinoma: their correlation with therapeutic outcome of neoadjuvant chemotherapy.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly malignant neoplasm. The glucocorticoid (GC)-glucocorticoid receptor (GR) pathway plays pivotal roles in cellular response to various stresses of tumor cells, including chemotherapy. However, the status of the GC-GR pathway in ESCC, including its correlation with chemotherapeutic responses, is largely unknown. METHODS: GR, serum-and glucocorticoid-regulated kinase 1 (Sgk1), and N-myc down regulation gene 1 (NDRG1) were immunolocalized in 98 patients with ESCC who had undergone esophagectomy following neoadjuvant chemotherapy (NAC) with 2 courses of 5-fluorouracil + cisplatin. We also examined biopsy specimens before NAC in 42 cases and compared the results between those before and after NAC. RESULTS: Overall survival (OS) of the patients treated with surgery following NAC was significantly shorter in the group with high GR than that with low GR status (P = 0.0473). Both OS and disease-free survival (DFS) were significantly shorter in both Sgk1- and NDRG1-high groups than in the low groups (OS: Sgk1, P = 0.0055; NDRG1, P = 0.0021; DFS: Sgk1, P = 0.0240; NDRG1, P = 0.0086). Biopsy specimens before NAC showed significantly shorter DFS in the high Sgk1 group (P = 0.0095), while both OS and DFS were shorter in the high NDRG1 group (OS, P = 0.0233; DFS, P = 0.0006) than in the respective low groups. In the high NDRG1 group of biopsy specimens before NAC, the tumor reduction rate by NAC was significantly attenuated (P = 0.021). CONCLUSIONS: High GR, Sgk1, and NDRG1 statuses in ESCC after NAC was significantly associated with an overall worse prognosis, with no significant changes in their expression levels before and after NAC. Therefore, increased activity of the GC-GR pathway with enhanced induction of Sgk1 and NDRG1 in carcinoma cells play pivotal roles in tumor progression and development of chemo-resistance in patients with ESCC undergoing NAC.	esophagus
Pericardial effusion after definitive concurrent chemotherapy and intensity modulated radiotherapy for esophageal cancer.	BACKGROUND: The literature regarding pericardial effusion after definitive concurrent chemotherapy and intensity modulated radiotherapy (IMRT) for esophageal cancer was lacking. This study aimed to investigate the risk factors of pericardial effusion in esophageal cancer patients undergoing definitive concurrent chemotherapy and IMRT. METHODS: A total of 126 consecutive esophageal cancer patients treated with definitive concurrent chemotherapy and IMRT between 2008 and 2018 were reviewed. The pericardial effusion was determined on computed tomography scan of the chest and graded by the Common Terminology Criteria for Adverse Events, version 4.0. The cumulative incidence of pericardial effusion was estimated by the Kaplan-Meier method and compared between groups by the log-rank test. The risk factors of pericardial effusion were determined with multivariate Cox proportional hazards regression analysis. RESULTS: The median follow-up time was 14.0 months. Thirty-seven (29.4%) patients had pericardial effusion after a median interval of 6.6 months since the end of IMRT. The cumulative incidence of pericardial effusion of any grade was higher in patients with mean heart dose > 23.45 Gy (p = 0.00018), heart V30 > 33.55% (p = 0.00015), mean pericardium dose > 20.33 Gy (p = 0.00027), and pericardium V20 > 42.55% (p = 0.00018). Furthermore, eight (6.3%) patients had symptoms related to pericardial effusion and were considered as cases with pericardial effusion ≥ grade 3. The cumulative incidence of pericardial effusion ≥ grade 3 was higher in patients with pericardium V30 > 65.80% (p = 0.00028), V40 > 55.35% (p < 0.0001), and V60 > 24.70% (p = 0.0021). Multivariate analyses showed the above dose-volume parameters predicted the risk of pericardial effusion in esophageal cancer. CONCLUSIONS: Dose-volume parameters predicting the risk of pericardial effusion were identified in esophageal cancer treated with definitive concurrent chemotherapy and IMRT. They could be applied as constraints of IMRT for esophageal cancer.	esophagus
CCL2-CCR2 axis recruits tumor associated macrophages to induce immune evasion through PD-1 signaling in esophageal carcinogenesis.	BACKGROUND: The poor prognosis of esophageal squamous cell carcinoma (ESCC) highlights the need for novel strategies against this disease. Our previous study suggested the involvement of CCL2 and tumor associated macrophages (TAMs) in esophageal carcinogenesis. Despite the recognition of TAMs as a promising target for cancer treatment, mechanisms underlying its infiltration, activation and tumor-promotive function in ESCC remain unknown. METHODS: Human esophageal tissue array and TCGA database were used to evaluate the clinical relevance of CCL2 and TAMs in ESCC. F344 rats and C57BL/6 mice were treated with N-nitrosomethylbenzylamine (NMBA) to establish orthotopic models of esophageal carcinogenesis. CCL2/CCR2 gene knockout mice and macrophage-specific PPARG gene knockout mice were respectively used to investigate the role of infiltration and polarization of TAMs in ESCC. CCL2-mediated monocyte chemotaxis was estimated in malignantly transformed Het-1A cells. THP-1 cells were used to simulate TAMs polarization in vitro. RNA-sequencing was performed to uncover the mechanism. RESULTS: Increasing expression of CCL2 correlated with TAMs accumulation in esophageal carcinogenesis, and they both predicts poor prognosis in ESCC cohort. Animal studies show blockade of CCL2-CCR2 axis strongly reduces tumor incidence by hindering TAMs recruitment and thereby potentiates the antitumor efficacy of CD8(+) T cells in the tumor microenvironment. More importantly, M2 polarization increases PD-L2 expression in TAMs, resulting in immune evasion and tumor promotion through PD-1 signaling pathway. CONCLUSION: This study highlights the role of CCL2-CCR2 axis in esophageal carcinogenesis. Our findings provide new insight into the mechanism of immune evasion mediated by TAMs in ESCC, suggesting the potential of TAMs-targeted strategies for ESCC prevention and immunotherapy.	esophagus
Vasculogenic Mimicry: A Promising Prognosticator in Head and Neck Squamous Cell Carcinoma and Esophageal Cancer? A Systematic Review and Meta-Analysis.	Vasculogenic mimicry (VM) is an intratumoral microcirculation pattern formed by aggressive cancer cells, which mediates tumor growth. In this study, we compiled the evidence from studies evaluating whether positive VM status can serve as a prognostic factor to patients with squamous cell carcinoma of the head and neck (HNSCC) or esophagus (ESCC). Comprehensive systematic searches were conducted using Cochrane Library, Ovid Medline, PubMed, and Scopus databases. We appraised the quality of studies and the potential for bias, and performed random-effect meta-analysis to assess the prognostic impact of VM on the overall survival (OS). Seven studies with 990 patients were eligible, where VM was detected in 34.24% of patients. Positive-VM was strongly associated with poor OS (hazard ratio = 0.50; 95% confidence interval: 0.38-0.64), which remained consistent following the subgroup analysis of the studies. Furthermore, VM was associated with more metastasis to local lymph nodes and more advanced stages of HNSCC and ESCC. In conclusion, this study provides clear evidence showing that VM could serve as a promising prognosticator for patients with either HNSCC or ESCC. Further studies are warranted to assess how VM can be implemented as a reliable staging element in clinical practice and whether it could provide a new target for therapeutic intervention.	esophagus
Influence of body composition and muscle strength on outcomes after multimodal oesophageal cancer treatment.	BACKGROUND: Influence of sarcopenia in combination with other body composition parameters and muscle strength on outcomes after oesophageal surgery for oesophageal cancer remains unclear. The objectives were (i) to describe the incidence of sarcopenia in relation to adipose tissue quantity and distribution and muscle strength; (ii) to evaluate if neoadjuvant chemoradiation (nCRTx) influences body composition and muscle strength; and (iii) to evaluate the influence of body composition and muscle strength on post-operative morbidity and long-term survival. METHODS: This retrospective study included patients with oesophageal cancer who received nCRTx followed by surgery between January 2011 and 2016. Skeletal muscle, visceral, and subcutaneous adipose tissue cross-sectional areas were calculated based on computed tomography scans, and muscle strength was measured using hand grip tests, 30 seconds chair stand tests, and maximal inspiratory and expiratory pressure tests prior to nCRTx and after nCRTx. RESULTS: A total of 322 patients were included in this study. Sarcopenia was present in 55.6% of the patients prior to nCRTx and in 58.2% after nCRTx (P = 0.082). Patients with sarcopenia had a significantly lower muscle strength and higher fat percentage. The muscle strength and incidence of sarcopenia increased while the mean body mass index and fat percentage decreased during nCRTx. A body mass index above 25 kg/m(2) was associated with anastomotic leakage (P = 0.032). Other body composition parameters were not associated with post-operative morbidity. A lower handgrip strength prior to nCRTx was associated with pulmonary and cardiac complications (P = 0.023 and P = 0.009, respectively). In multivariable analysis, a lower number of stands during the 30 seconds chair stand test prior to nCRTx (hazard ratio 0.93, 95% confidence interval 0.87-0.99, P = 0.017) and visceral adipose tissue of >128 cm(2) after nCRTx (hazard ratio 1.81, 95% confidence interval 1.30-2.53, P = 0.001) were associated with worse overall survival. CONCLUSIONS: Sarcopenia occurs frequently in patients with oesophageal cancer and is associated with less muscle strength and a higher fat percentage. Body composition changes during nCRTx did not influence survival. Impaired muscle strength and a high amount of visceral adipose tissue are associated with worse survival. Therefore, patients with poor fitness might benefit from preoperative nutritional and muscle strengthening guidance, aiming to increase muscle strength and decrease visceral adipose tissue. However, this should be confirmed in a large prospective study.	esophagus
Expression of the microRNA-200 Family, microRNA-205, and Markers of Epithelial-Mesenchymal Transition as Predictors for Endoscopic Submucosal Dissection over Esophagectomy in Esophageal Adenocarcinoma: A Single-Center Experience.	Endoscopic submucosal dissection (ESD) is an effective treatment of early esophageal adenocarcinomas (EACs). The decision of ESD over esophagectomy is based on clinical evaluation of tumor depth and invasion. On a molecular level, tumor invasion is strongly associated with epithelial-to-mesenchymal transition (EMT). Here, we investigated whether localized ESD-resected and surgically resected EAC samples displayed different expression profiles of EMT protein and microRNA markers and whether these different expression profiles were able to retrospectively discriminate localized and surgically resected samples. By doing this, we aimed to evaluate whether preoperative measurement of EMT marker expression might support the decision regarding ESD over surgery. The results showed that ESD-resected samples displayed an epithelial expression profile, i.e., high expression of epithelial protein markers, whereas surgically resected samples displayed high expression of mesenchymal markers. In addition, the anti-EMT microRNA-205 was significantly more expressed in ESD-resected samples, whereas we found no significant differences in the expression levels of microRNA-200 family members. Furthermore, in our retrospective approach, we have demonstrated that measurement of selected EMT markers and microRNA-205 has significant discrimination power to distinguish ESD-resected and surgically resected samples. We suggest that the assessment of EMT status of EAC samples on a molecular level may support clinical evaluation regarding the applicability of ESD.	esophagus
19q13 KRAB zinc-finger protein ZNF471 activates MAPK10/JNK3 signaling but is frequently silenced by promoter CpG methylation in esophageal cancer.	Zinc-finger proteins (ZFPs) are the largest transcription factor family in mammals, involved in the regulation of multiple physiologic processes including cell differentiation, proliferation, apoptosis and neoplastic transformation. Approximately one-third of ZFPs are Krüppel-associated box domain (KRAB)-ZFPs. Methods: ZNF471 expression and methylation were detected by reverse-transcription PCR and methylation-specific PCR. The impact and mechanism of ectopic ZNF471 expression in esophageal squamous cell carcinoma (ESCC) cells was evaluated in vitro and in vivo. Results: We identified a 19q13 KRAB-ZFP, ZNF471, as a methylated target in ESCC. We further found that ZNF471 is significantly downregulated in ESCC tissues compared with adjacent non-cancer tissues, due to its aberrant promoter CpG methylation, and further confirmed by methylation analysis and treatment with demethylation agent. Restoration of ZNF471 expression in silenced ESCC cells significantly altered cell morphology, induced apoptosis and G0/G1 arrest, and inhibited tumor cell colony formation, viability, migration and invasion. Importantly, ZNF471 was found to activate the expression of MAPK10/JNK3 and PCDH family genes, and further enhance MAPK10 signaling and downstream gene expression through binding to the MAPK10/JNK3 promoter. Conclusion: Our results demonstrate that ZNF471 is an important tumor suppressor and loss of ZNF471 functions hampers MAPK10/JNK3 signaling during esophageal carcinogenesis.	esophagus
Chemoradiotherapy and radiotherapy alone in patients with esophageal cancer aged 80 years or older based on the Comprehensive Registry of Esophageal Cancer in Japan.	BACKGROUND: There has been no definitive evidence of chemoradiotherapy being superior to radiotherapy alone in patients aged 80 years or older. The purpose of the present study was to evaluate the results of radiotherapy and chemoradiotherapy in patients aged 80 years or older with esophageal cancer in the Japanese Nationwide Cancer Database. METHODS: A total of 358 patients aged 80 years or older who were treated with radiotherapy alone or with chemoradiotherapy for esophageal cancer between 2009 and 2011 were enrolled. RESULTS: The 5-year overall survival (OS) rates in patients with cStages 0-I, II, III and IV were 40.9%, 24.7%, 12.2% and 4.9%, respectively. The 5-year cause-specific survival (CSS) rates in patients aged 80 years or older with cStages 0-I, cStage II, cStage III and cStage IV were 73.5%, 41.4%, 25.3% and 7.4%, respectively. In patients treated with radiotherapy alone, the 5-year OS rates for patients with cStages 0-I, II, III and IV were 36.5%, 12.0%, 5.4% and 0%, respectively. In patients treated with chemoradiotherapy, the 5-year OS rates for patients with cStages 0-I, II, III and IV were 45.0%, 36.1%, 16.4% and 7.1%, respectively. In multivariate analysis, chemoradiotherapy, early stage and squamous cell carcinoma were significantly favorable prognostic factors for OS in patients aged 80 years or older (p < 0.001, p < 0.001 and p = 0.0323, respectively). We were unable to evaluate toxicities, because of lack of information in the registry. CONCLUSION: Concurrent chemotherapy with radiotherapy for esophageal cancer in patients aged 80 years or older is a significantly favorable prognostic factor for OS. However, chemoradiotherapy should be carefully selected in elderly patients.	esophagus
Postoperative recurrent laryngeal nerve palsy is associated with pneumonia in minimally invasive esophagectomy for esophageal cancer.	BACKGROUND: During the past decade, minimally invasive esophagectomy (MIE) for esophageal cancer has been adopted worldwide with expectations of lower invasiveness. However, the rate of postoperative pneumonia, which is an independent risk factor for oncological prognosis in esophageal cancer, remains high. The aim of this retrospective follow-up study is to clarify whether there is a strong correlation between recurrent laryngeal nerve (RLN) palsy and postoperative pneumonia in MIE. METHODS: This retrospective follow-up study included 209 patients with esophageal cancer who underwent thoracoscopic esophagectomy in the prone position (TEP) at Kobe University between 2011 and 2018. Inclusion criteria included age 18-85 years; cT1-3, cN0-3 disease; upper mediastinal lymphadenectomy; and ability to undergo simultaneous esophagectomy and reconstruction of the gastric conduit or pedicled jejunum. Univariate and multivariate logistic regression were conducted to identify independent risk factors for pneumonia. RESULTS: Among 209 TEPs, pneumonia of Clavien-Dindo classification grade > II occurred in 44 patients (21%). In the pneumonia positive and negative groups, there were significant differences in age (67.9 ± 7.5 vs. 64.9 ± 8.6 years), 3-field lymph node dissection [27 (61%) vs. 67 (41%)], transfusion [20 (45%) vs. 41 (25%)], left RLN palsy [19 (43%) vs. 18 (11%)], and any RLN palsy [20 (45%) vs. 18 (11%)]. In multivariate analysis, any RLN palsy was associated with a higher incidence of pneumonia [odds ratio (OR), 6.210; 95% confidence interval (CI), 2.728-14.480; P < 0.0001]. In addition, age was associated with a higher incidence of pneumonia (OR, 1.049; 95% CI, 1.001-1.103; P = 0.046). Changes in the rate of any RLN palsy over time were quite similar to changes in the incidence of pneumonia. CONCLUSION: There is a strong correlation between RLN palsy and pneumonia in MIE for esophageal cancer. Prevention of RLN palsy may reduce the incidence of pneumonia, leading to better oncological prognosis.	esophagus
A Review on Sources and Pharmacological Aspects of Sakuranetin.	Sakuranetin belongs to the group of methoxylated flavanones. It is widely distributed in Polyomnia fruticosa and rice, where it acts as a phytoalexin. Other natural sources of this compound are, among others, grass trees, shrubs, flowering plants, cheery, and some herbal drugs, where it has been found in the form of glycosides (mainly sakuranin). Sakuranetin has antiproliferative activity against human cell lines typical for B16BL6 melanoma, esophageal squamous cell carcinoma (ESCC) and colon cancer (Colo 320). Moreover, sakuranetin shows antiviral activity towards human rhinovirus 3 and influenza B virus and was reported to have antioxidant, antimicrobial, antiinflammatory, antiparasitic, antimutagenic, and antiallergic properties. The aim of this review is to present the current status of knowledge of pro-health properties of sakuranetin.	esophagus