crossing96/oncoscreening huggingface dataset:
Targeting cancer stem cells with a pan-BCL-2 inhibitor in preclinical and clinical settings in patients with gastroesophageal carcinoma.	OBJECTIVE: Gastro-oesophageal cancers (GEC) are resistant to therapy and lead to poor prognosis. The cancer stem cells (CSCs) and antiapoptotic pathways often confer therapy resistance. We sought to elucidate the antitumour action of a BCL-2 inhibitor, AT101 in GEC in vitro, in vivo and in a clinical trial. METHODS: Extensive preclinical studies in vitro and in vivo were carried out to establish the mechanism action of AT101 on targeting CSCs and antiapoptotic proteins. A pilot clinical trial in patients with GEC was completed with AT-101 added to standard chemoradiation. RESULTS: Overexpression of BCL-2 and MCL-1 was noted in gastric cancer tissues (GC). AT-101 induced apoptosis, reduced proliferation and tumour sphere formation in MCL-1/BCL-2 high GC cells. Interestingly, AT101 dramatically downregulated genes (YAP-1/Sox9) that control CSCs in GEC cell lines regardless of BCL-2/MCL-1 expression. Addition of docetaxel to AT-101 amplified its antiproliferation and induced apoptosis effects. In vivo studies confirmed the combination of AT101 and docetaxel demonstrated stronger antitumour activity accompanied with significant decrease of CSCs biomarkers (YAP1/SOX9). In a pilot clinical trial, 13 patients with oesophageal cancer (EC) received AT101 orally concurrently with chemoradiation. We observed dramatic clinical complete responses and encouraging overall survival in these patients. Clinical specimen analyses revealed that AT-101 dramatically reduced the expression of CSCs genes in treated EC specimens indicating antitumour activity of AT101 relies more on its anti-CSCs activity. CONCLUSIONS: Our preclinical and clinical data suggest that AT-101 overcomes resistance by targeting CSCs pathways suggesting a novel mechanism of action of AT101 in patients with GEC.	esophagus
The challenge of offering potentially curative treatment to patients with esophageal cancer and a history of liver transplantation: A literature review and case report.	BACKGROUND: With survival after liver transplantation continuing to improve, effective and evidence-based treatment of malignancies in this patient group is needed as a matter of urgency. Treatment outcomes for esophageal cancer, a challenging malignancy to treat in otherwise fit and well patients, after liver transplant are rarely reported. METHODS: A systematic literature review was performed according to the PRISMA guidance to identify studies reporting outcomes of radical esophageal cancer treatment in patients with liver transplant. Management strategies and oncological outcomes were compared with a case managed at our institution. RESULTS: Six studies were identified for review, and the outcomes of 13 patients were collated. The most common indication for liver transplant was alcohol-related liver disease (62%), and the most common tumor type was adenocarcinoma (54%). Neoadjuvant chemotherapy was delivered safely in 23% of cases in the literature and in the case managed at our institution. The median time from liver transplant to esophagectomy was 46 months, and the majority of patients underwent an Ivor-Lewis esophagectomy. The median follow-up from esophagectomy was 17 months, with a pooled 1-year survival of 77% and recurrence rate of 38%. This was comparable with corresponding rates reported for nontransplanted patients. CONCLUSION: This case report and systematic review demonstrates that radical treatment of esophageal cancer after liver transplantation is not only technically feasible when managed by expert multidisciplinary teams but that it also improves survival. Routine surveillance of liver transplant patients with evidence of Barrett's preoperatively should be considered and close involvement of appropriate specialists in individual treatment planning is vital to acceptable outcomes.	esophagus
Postoperative intensive care unit stay after minimally invasive esophagectomy shows large hospital variation. Results from the Dutch Upper Gastrointestinal Cancer Audit.	INTRODUCTION: The value of routine intensive care unit (ICU) admission after minimally invasive esophagectomy (MIE) has been questioned. This study aimed to investigate Dutch hospital variation regarding length of direct postoperative ICU stay, and the impact of this hospital variation on short-term surgical outcomes. MATERIALS AND METHODS: Patients registered in the Dutch Upper Gastrointestinal Cancer Audit (DUCA) undergoing curative MIE were included. Length of direct postoperative ICU stay was dichotomized around the national median into short ICU stay ( ≤ 1 day) and long ICU stay ( > 1 day). A case-mix corrected funnel plot based on multivariable logistic regression analyses investigated hospital variation. The impact of this hospital variation on short-term surgical outcomes was investigated using multilevel multivariable logistic regression analyses. RESULTS: Between 2017 and 2019, 2110 patients from 16 hospitals were included. Median length of postoperative ICU stay was 1 day [hospital variation: 0-4]. The percentage of short ICU stay ranged from 0 to 91% among hospitals. Corrected for case-mix, 7 hospitals had statistically significantly higher short ICU stay rates and 6 hospitals had lower rates. ICU readmission, in-hospital/30-day mortality, failure to rescue, postoperative pneumonia, cardiac complications and anastomotic leakage were not associated with hospital variation in length of ICU stay. Total length of hospital stay was significantly shorter in hospitals with relatively short ICU stay. CONCLUSION: This study showed significant hospital variation in postoperative length of ICU stay after MIE. Short ICU stay was associated with shorter overall hospital admission and did not negatively impact short-term surgical outcomes. More selected use of ICU resources could result in a national significant cost reduction.	esophagus
Hypoxic tumour cell-derived exosomal miR-340-5p promotes radioresistance of oesophageal squamous cell carcinoma via KLF10.	BACKGROUND: Radiotherapy resistance is a major obstacle in the treatment of oesophageal squamous cell carcinoma (OSCC). Hypoxia is a critical cause of radioresistance. However, the communication between hypoxic cells and aerobic cells via exosomes during the transfer of radiation resistance remains unclear. METHODS: Exo-miR-340-5p levels were analysed by RNA-seq and qRT-PCR. We co-cultured OSCC cells with isolated normoxic and hypoxic exosomes to study their impact on radiosensitivity. We used a specific exo-miR-340-5p mimic and knock-down retrovirus to explore the role of this miRNA in the transfer of radioresistance from hypoxic to normoxic cells. Dual-luciferase reporter and RIP assays were used to verify KLF10 as a putative target of miR-340-5p. Several in vitro assays were conducted and xenograft models were established to investigate the effect of exo-miR-340-5p on OSCC radiosensitivity. The plasma exo-miR-340-5p levels in OSCC patients were analysed to study the clinical value of this parameter. RESULTS: Hypoxic exosomes alleviated radiation-induced apoptosis and accelerated DNA damage repair. miR-340-5p was highly expressed in hypoxic exosomes and was transferred into normoxic cells, where it induced radioresistance. Overexpression of miR-340-5p in normoxic OSCC cells mimicked the radioresistance of cells co-cultured with hypoxic exosomes. Knockdown of miR-340-5p in hypoxic exosomes reversed the radioresistance effect, indicating that exo-miR-340-5p is critical for hypoxic EV-transferred radioresistance. KLF10 was identified as the direct target of miR-340-5p. Moreover, metformin was found to increase the expression of KLF10 and enhance the radiosensitivity of OSCC. Higher levels of miR-340-5p in the plasma exosomes from OSCC patients are related to a poorer radiotherapy response and prognosis. CONCLUSIONS: Hypoxic tumour cell-derived exosomal miR-340-5p confers radioresistance in OSCC by targeting KLF10/UVRAG, suggesting that miR-340-5p could be a potential biomarker and therapeutic target for the enhancement of radiosensitivity in OSCC. Metformin can increase KLF10 expression, which ameliorates the radioresistance induced by exo-miR-340-5p transfer. Therefore, metformin could be further investigated as a therapeutic option for the treatment of OSCC.	esophagus
Total laparoscopic transabdominal-transdiaphragmatic approach for treating Siewert II tumors: a prospective analysis of a case series.	BACKGROUND: Although the morbidity of gastric cancer has decreased, the incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing. Furthermore, no consensus exists on which surgical approach should be applied for Siewert type II AEG. The purpose of our study was to evaluate the technical safety and feasibility of a new surgical approach. METHODS: Sixty patients with Siewert type II AEG underwent laparoscopic total gastrectomy with the total laparoscopic transabdominal-transdiaphragmatic (TLTT) approach, which needs an incision in the diaphragm. RESULTS: The median operative time, reconstruction time, and estimated blood loss were 214.8 ± 41.6 min, 29.40 ± 7.1 min, and 209.0 ± 110.3 ml, respectively. All of the patients had negative surgical margins. CONCLUSION: There were no intraoperative complications or conversions to open surgery. Our surgical procedure provides a unique option for the safe application of laparoscopic lower mediastinal lymph node dissection and gastrointestinal reconstruction. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800014336. Registered on 31 December 2017 - Prospectively registered, http://www.chictr.org.cn/edit.aspx?pid=23111&htm=4 .	esophagus
Changes in hospital variation in the probability of receiving treatment with curative intent for esophageal and gastric cancer.	BACKGROUND: Previous studies describe a large variation in the proportion of patients undergoing treatment with curative intent for esophageal (EC) and gastric cancer (GC). Since centralization of surgical care was initiated and more awareness regarding hospital practice variation was potentially present, we hypothesized that hospital practice variation for potentially curable EC and GC patients changed over time. METHODS: Patients with potentially curable EC (n = 10,115) or GC (n = 3988) diagnosed between 2012-2017 were selected from the Netherlands Cancer Registry. Multilevel multivariable logistic regression was used to analyze the differences in the probability of treatment with curative intent between hospitals of diagnosis over time, comparing 2012-2014 with 2015-2017. Relative survival (RS) between hospitals with different probabilities of treatment with curative intent were compared. RESULTS: The range of proportions of patients undergoing treatment with curative intent per hospital of diagnosis for EC was 45-95 % in 2012-2014 and 54-89 % in 2015-2017, and for GC 52-100 % and 45-100 %. The adjusted variation declined for EC with Odds Ratios ranging from 0.50 to 1.72 between centers in the first period to 0.70-1.44 in the second period (p < 0.001) and did not change for GC (Odds Ratios ranging from 0.78 to 1.23 to 0.82-1.23, (p = 1.00)). A higher probability of treatment with curative intent was associated with a better survival for both malignancies. CONCLUSION: Although substantial variation between hospitals of diagnosis in the probability in receiving treatment with curative intent still exists for both malignancies, it has decreased for EC. A low probability of receiving curative treatment remained associated with worse survival.	esophagus
Esophageal metal stent for malignant obstruction after prior radiotherapy.	The association between severe adverse events (SAEs) and prior radiotherapy or stent type remains controversial. Patients with esophageal or esophagogastric junctional cancer who underwent stent placement (2005-2019) were enrolled in this retrospective study conducted at a tertiary cancer institute in Japan. The exclusion criteria were follow-up period of < 1 month and insufficient data on stent type or cancer characteristics. We used Mann-Whitney's U test for quantitative data and Fisher's exact test for categorical data. Multivariate analysis was performed using a logistic regression model. 107 stents were placed. Low radial-force stents (L group) were used in 51 procedures and high radial-force stents (H group) in 56 procedures. SAEs developed after nine procedures, the median interval from stent placement being 6 days (range, 1-141 days). SAEs occurred more frequently in the H (14%: 8/56) than in the L group (2%: 1/51) (P = 0.03). In patients who had undergone prior radiotherapy, SAEs were more frequent in the H (36%: 4/11) than in the L group (0%: 0/13) (P = 0.03). Re-obstruction and migration occurred after 16 and three procedures, respectively; these rates did not differ significantly between groups (P = 0.59, P = 1, respectively). Low radial-force stents may reduce the risk of SAEs after esophageal stenting.	esophagus
Immunohistochemical Staining With Neuroendocrine Markers is Essential in the Diagnosis of Neuroendocrine Neoplasms of the Esophagogastric Junction.	Neuroendocrine neoplasms (NENs) of the esophagogastric junction (EGJ) are uncommon and the classification of these tumors has been revised several times. Since 2016, at the Department of Pathology, Rigshospitalet, Denmark, all adenocarcinomas and poorly differentiated carcinomas of the EGJ have been stained routinely with the neuroendocrine markers, synaptophysin and chromogranin A, to detect a possible neuroendocrine component. This study aimed to determine if routine immunohistochemical staining is necessary to detect neuroendocrine differentiation of the EGJ tumors by evaluating how often a neuroendocrine component of the tumors was correctly identified or missed on routine hematoxylin and eosin-stained slides, and by evaluating the interobserver agreement among several pathologists. Of 262 cases a NEN was identified in 24 (9.2%). Up to 22.7% of all EGJ NENs would have been missed without routinely performed neuroendocrine staining in all EGJ tumors. The interobserver agreement between 3 pathologists was slight to moderate. In conclusion, immunohistochemical staining with neuroendocrine markers is essential for the diagnosis of NENs, and to detect all NENs, we recommend to perform this routinely on all resected tumors of the EGJ.	esophagus
BAALC-AS1/G3BP2/c-Myc feedback loop promotes cell proliferation in esophageal squamous cell carcinoma.	BACKGROUND: Long non-coding RNAs (lncRNAs) have been found to be involved in the development of many cancers. In this study, we aimed to identify the molecular mechanisms of lncRNA BAALC antisense RNA 1 (BAALC-AS1) in regulating the malignancy of esophageal squamous cell carcinoma (ESCC). METHODS: The expression of BAALC-AS1 in cancer patients was analyzed using a tissue microarray. The protein and RNA levels of BAALC-AS1 were determined by Western blotting analysis and quantitative reverse transcription-PCR (RT-qPCR), respectively. The cell proliferation was determined by cell viability assays, bromodeoxyuridine incorporation, and flow cytometry. The relationships among BAALC-AS1, RasGAPSH3 domain-binding protein 2 (G3BP2), and c-Myc were determined using RNA immunoprecipitation, RNA pull-down assays, and luciferase assays. RESULTS: The expression of BAALC-AS1 was highly up-regulated and associated with malignant phenotypes in ESCC tissues and cell lines. In vivo and in vitro assays showed that BAALC-AS1 promoted ESCC cell proliferation, migration, and invasion. BAALC-AS1 directly interacted with G3BP2, and thereby inhibited the degradation of c-Myc RNA 3'-UTR by G3BP2, thus leading to the accumulation of c-Myc expression. Additionally, c-Myc acted as a transcription factor that can induce the expression of BAALC-AS1 by directly binding to its promoter region. CONCLUSIONS: BAALC-AS1/G3BP2/c-Myc feedback loop plays a critical role in the development of ESCC, which might provide a novel therapeutic target and facilitate the development of new therapeutic strategies for the treatment of ESCC.	esophagus
Supplemental enteral tube feeding nutrition after hospital discharge of esophageal cancer patients who have undergone esophagectomy.	BACKGROUND: After undergoing esophagectomy to treat esophageal cancer, there are changes in the normal intake patterns in most patients, with more than half found to have an inadequate oral intake at the time of their hospital discharge. However, the use of home supplemental enteral tube feeding nutrition after hospital discharge in esophagectomy patients has yet to be established. The aim of this study was to evaluate the feasibility of 90-day home supplemental enteral tube feeding nutrition in esophagectomy patients. METHODS: This single-center, prospective, and single-arm study evaluated the feasibility of using supplemental tube feeding nutrition intervention for 90 days in esophageal cancer patients who have undergone esophagectomy. RESULTS: This study enrolled 24 post-esophagectomy patients between February 2015 and September 2016. Twenty patients were administered 70% or more of the planned nutrient, with 83% of the patients completing the nutritional intervention procedure. There were no grade 3/4 adverse events observed, with a mean body weight change of - 7.6 ± 6.0%. CONCLUSIONS: Our results showed that routine use of 90-day home supplemental enteral tube feeding nutrition after hospital discharge for esophagectomy patients was both feasible and acceptable. TRIAL REGISTRATION: UMIN000016286.	esophagus
Factors influencing health-related quality of life in patients with Barrett's esophagus: a qualitative focus group study.	INTRODUCTION: Barrett's esophagus is a premalignant condition in the lower part of the esophagus, caused by gastroesophageal reflux disease. Previous studies found that having a Barrett's esophagus is associated with a significant decrease of health-related quality of life (HRQOL). Over the past decade, a considerable amount of literature has been published on the development of endoscopic treatment for (early) neoplasia in Barrett's esophagus. Though, currently very little is known about the impact of those endoscopic treatments on HRQOL from the perspective of patients. In this study, we aim to assess the factors influencing HRQOL according to Barrett's esophagus patients. METHODS: By using a qualitative focus group design, patients with nondysplastic Barrett's esophagus and patients with a history of endoscopic treatment for Barrett's dysplasia were included. Data were analysed following the conventional content analyses approach. RESULTS: A total of 34 patients participated in the four focus group sessions. Experiencing symptoms was valued as the most important factor in both groups. Other factors identified as important HRQOL influencers were: use of medication, fear of cancer and trust in physicians and endoscopic procedures. CONCLUSIONS: In general, Barrett's esophagus patients experienced a good HRQOL, with a minimal emotional burden from the diagnosis of Barrett's esophagus. Most influencing factor on HRQOL was: experiencing reflux and dyspepsia symptoms. This study underlines the importance of adequate gastroesophageal reflux treatment and providing information to Barrett's esophagus patients, tailored to their personal needs.	esophagus
[Improvement of QOL by Surgery in Two Patients for Brain Metastasis from Esophageal Carcinoma with Paralysis-A Report of Two Cases].	Brain metastasis from esophageal cancer is rare. Symptoms such as paralysis caused a decline in quality of life(QOL)and activity of daily life(ADL)and required emergency treatment. We report 2 cases in which QOL was improved by emergency resection for brain metastasis from esophageal carcinoma with paralysis. Case 1: A 50's male was diagnosed esophageal carcinoma and underwent esophagectomy(pT3N2M0, Stage Ⅲ). Brain metastasis was detected owing to development of left hemiparesis. Craniotomy and tumorectomy were performed, left hemiparesis was improved. He died 10 months after diagnosis of brain metastasis due to progression of other metastatic lesions. Case 2: A 61-year-old female was diagnosed esophageal carcinoma and underwent esophagectomy(pT3N1M0, Stage Ⅲ). She developed right hemiparesis 5 months after esophagectomy, admitted to our hospital. Brain and lung metastases were detected, craniotomy and tumorectomy and were performed, right hemiparesis was improved. Although systemic chemotherapy was administered, she died 10 months after diagnosis of brain metastasis due to progression of lung metastasis. Conclusion: Aggressive surgical treatments for brain metastasis were one good treatment option to maintain QOL and ADL.	esophagus
[Recurrent Esophageal Cancer with Metastatic Lymph Node Penetrating in the Reconstructed Gastric Tube-A Case Report].	A 60-year-old man underwent thoracoscopic subtotal esophagectomy and posterior mediastinal gastric tube reconstruction after neoadjuvant chemotherapy. One year and 8 months postoperatively, recurrence was observed in the abdominal lymph nodes around the celiac artery and abdominal aorta. Chemoradiotherapy was initiated, followed by chemotherapy. Two months after the completion of chemoradiotherapy, the patient developed epigastric pain and anorexia because of the necrotic lymph node penetrating the gastric tube with cavity formation. Upper gastrointestinal endoscopy revealed a 25- mm-sized ulcer with central necrotic slough on the posterior wall of the stomach. Abdominal symptoms alleviated after conservative treatment with fasting and administration of antibiotics, and the inflammatory reaction improved. Oral nutritional supplements were started on hospitalization day 7, and abdominal symptoms or inflammatory reactions did not recur after resuming diet. The patient was discharged on hospitalization day 39 when the general condition stabilized. Subsequently, chemotherapy was restarted, and no regrowth of metastatic lesions was observed on endoscopy or CT examination 4 months later. Three years and 8 months after the recurrence, the recurrent disease has been controlled.	esophagus
[Outcomes of Salvage Thoracoscopic Esophagectomy after Definitive Radiochemotherapy for Clinical Stage Ⅳa Esophageal Cancer].	We investigated the clinical outcomes of salvage thoracoscopic esophagectomy for residual or recurrent cases after radical radiochemotherapy for cStage Ⅳa esophageal cancer. Thoracic procedure was started thoracoscopically in all cases, but converted to thoracotomy in 2 cases. The operation time was 315 minutes and the blood loss was 300 mL. Lymph node metastasis was diagnosed in 5 cases, and 2 cases were finished in R1or 2. Nine cases died of recurrence and 1 case died of pneumonia. The 2-year and 5-year survival rates(OS)of all cases were 46.1% and 28.3%, respectively. R1,2 cases and pN+ cases had significantly poor prognosis. Surgical treatment after radical radiochemotherapy for cStage Ⅳa esophageal cancer can be safely performed thoracoscopically. If R0 is not obtained, the long-term prognosis cannot be expected, and selection of R0 resectable cases is important.	esophagus