crossing96/oncoscreening huggingface dataset:
Esophagectomy in elderly patients: which is the best prognostic score?	Our study aimed to identify the best prognostic score for fitness for surgery and postoperative morbidity in elderly patients. A prospectively collected database of a consecutive series of patients with esophageal cancer evaluated for possible esophagectomy at our unit was analyzed. Fitness for surgery and postoperative morbidity were used as measures of outcome. The performances of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) score, the Charlson Comorbidity Index, the age-related Charlson Comorbidity Index (ACCI), the American Society of Anesthesiologists scale and the prognostic nutritional index (PNI) were evaluated in elderly patients. Discrimination was measured with receiver operating characteristics curve analysis; calibration was assessed by the Hosmer-Lemeshow goodness-of-fit test. Age did not result a significant predictor for postoperative complications. In elderly patients, ACCI predicted the judgment of the multidisciplinary team about fitness for surgery with the best discrimination (C-index = 0.94). PNI had the best discrimination for postoperative complications (C-index = 0.71) in the elderly group. ACCI best predicted the fitness for surgery in elderly patients. In elderly patients, the most discriminative prognostic score for postoperative complication was PNI, which could be used at admission for surgery to correctly inform patients about their risk and, possibly, to take extra precaution in case of high risk.	esophagus
The epidemiology, diagnosis, and treatment of Barrett's carcinoma.	BACKGROUND: Roughly 3000 new cases of Barrett's carcinoma arise in Germany each year. In view of recent advances in the epidemiology, diagnosis, and treatment of this disease, an update of the clinical recommendations is in order. METHODS: This review is based on selected relevant publications, including current reviews, meta-analyses, and guidelines. RESULTS: The risk of progression of Barrett's esophagus to carcinoma lies between 0.10% and 0.15% per year. Risk factors for progression include male sex, age over 50 years, obesity, longstanding and frequent reflux symptoms, smoking, length of the Barrett's esophagus, and intraepithelial neoplasia. Well-differentiated carcinomas that are confined to the esophageal mucosa can be resected endoscopically with a cure rate above 90%. For more advanced, but still locally confined tumors, surgical resection is the treatment of choice. In stages cT3/4, the prognosis can be improved with neo-adjuvant chemo - therapy or combined radiotherapy and chemotherapy. Metastatic Barrett's carcinoma can be treated by endoscopic, chemotherapeutic, radiotherapeutic, and palliative methods. CONCLUSION: Early carcinoma can often be cured by endoscopic resection. Locally advanced carcinoma calls for multimodal treatment. Current research focuses on means of preventing the progression of Barrett's esophagus, the scope of applicability of endoscopic techniques, and the optimization of multimodal treatment strategies for advanced disease.	esophagus
Thoracoscopic and Laparoscopic Enucleation of Esophageal Leiomyomas.	Although infrequent, esophageal leiomyomas are the most common benign intramural tumors of the esophagus. As malignant potential is not a concern in these lesions, they represent ideal candidates for an organ-preserving approach. Due to their well-circumscribed growth, a minimally invasive approach should be pursued in almost all patients. We present our recent techniques and results associated with totally minimally invasive thoracoscopic and laparoscopic approaches to resection of esophageal leiomyomas. These approaches require technical expertise but can be accomplished with a short learning curve.	esophagus
MIC-1/GDF15 in Barrett's oesophagus and oesophageal adenocarcinoma.	BACKGROUND: Biomarkers are needed to improve current diagnosis and surveillance strategies for patients with Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC). Macrophage inhibitory cytokine 1/growth differentiation factor 15 (MIC-1/GDF15) tissue and plasma levels have been shown to predict disease progression in other cancer types and was therefore evaluated in BO/OAC. METHODS: One hundred thirty-eight patients were studied: 45 normal oesophagus (NE), 37 BO, 16 BO with low-grade dysplasia (LGD) and 40 OAC. RESULTS: Median tissue expression of MIC-1/GDF15 mRNA was ⩾25-fold higher in BO and LGD compared to NE (P<0.001); two-fold higher in OAC vs BO (P=0.039); and 47-fold higher in OAC vs NE (P<0.001). Relative MIC-1/GDF15 tissue expression >720 discriminated between the presence of either OAC or LGD vs NE with 94% sensitivity and 71% specificity (ROC AUC 0.86, 95% CI 0.73-0.96; P<0.001). Macrophage inhibitory cytokine 1/growth differentiation factor 15 plasma values were also elevated in patients with OAC vs NE (P<0.001) or BO (P=0.015).High MIC-1/GDF15 plasma levels (⩾1140 pg ml(-1)) were an independent predictor of poor survival for patients with OAC (HR 3.87, 95% CI 1.01-14.75; P=0.047). CONCLUSIONS: Plasma and tissue levels of MIC-1/GDF15 are significantly elevated in patients with BO, LGD and OAC. Plasma MIC-1/GDF15 may have value in diagnosis and monitoring of Barrett's disease.	esophagus
Current endoscopic methods of radical therapy in early esophageal cancer.	During the last three decades, there has been an increasing incidence of the esophageal cancer at the global level, approx. 400,000 new esophageal cancers being currently diagnosed annually. This is the eighth leading cause of cancer incidence and the sixth leading cause of cancer death overall. If we refer to the countries of Western Europe and North America, we could see an increase in the esophageal adenocarcinoma in detriment of squamous cancer. As for the Asian region, referring in particular to China and Japan, 9 out of 10 esophageal cancers are squamous cell carcinomas. Considering that the incidence of gastric cancer in Japan is very high, the endoscopic screenings performed inevitably led to an increased rate of early detection of esophageal cancer, reaching approximately 20% of all esophageal cancers detected. This has led to the possibility of developing therapeutic endoscopic techniques with radical visa that we will describe while presenting comparative data from literature. Currently, however, there are not enough data on the effectiveness of these types of therapies, compared to surgery, in order to be transformed into standard therapeutic endoscopic treatment for early esophageal cancer. However, the combined therapy, resection/ endoscopic ablation + chemoradiotherapy, appears as an alternative to be taken into account. Abbreviations EEC = esophageal early cancer, BE = Barrett's esophagus, HGD = High-grade dysphagia, EUS = Ultra sound endoscopy, CT = Computer tomograph, UGE = Upper gastro endoscopy, PET-CT = Positron Emission Tomography, FNAB = Fine needle aspiration biopsy, EMR = Esophageal mucosal resection, ESD = Esophageal submucosal dissection, SCC = Squamous cellular cancer, PCT = Poli-chemotherapy, RT- Radio-therapy.	esophagus
Gastric pull-up reconstruction combined with free jejunal transfer (FJT) following total pharyngolaryngo-oesophagectomy (PLE).	INTRODUCTION: Reconstruction following total pharyngolaryngo-oesophagectomy (PLE) still challenges surgeons because of the extreme length of removed tissue. Gastric pull-up reconstruction, one of the most common reconstructive methods after PLE, has many complications such as anastomotic fistula and gastric necrosis caused by the high anastomotic tension. However, modifications of gastric pull-up reconstruction aiming to reducing the high anastomotic tension have been less reported compared with other aspects with this technique. Here we report a modified gastric pull-up reconstruction combined with free jejunal transfer (FTJ) to reduce the anastomosis tension, and thus to reduce the risk of complications after PLE. METHODS: Patients underwent a standard surgical procedure including total pharyngolaryngo-oesophagectomy and bilateral internal jugular lymph nodal clearance. A free jejunal graft about 10 cm was harvested and placed in the appropriate position between mobilized stomach and oropharynx. The anastomosis between the free jejunal graft and the gastric tube was created through a stapler. Vascular anastomosis was made between the jejunal artery and the transverse cervical artery, and between the jejunal vein and the internal jugular vein. Hand suturing technique was used in the anastomosis between jejunum and pharynx. RESULTS: None of the patients suffered from any complications such as anastomotic fistula. Both patients resumed early postoperative oral intake. So far, they remain free of tumor recurrence and are in good health for 46 and 18 months, respectively. CONCLUSION: Considering the tumor status and the patient condition, the gastric pull-up reconstruction combined with FJT after PLE could be a reliable choice.	esophagus
[Complicated gastroesophageal reflux disease in the presence of congenital esophageal shortening].	The paper presents a clinical case of complicated gastroesophageal reflux disease (GERD) and describes problems in the differential diagnosis of malignant esophageal lesion in patients with GERD and a treatment modality used in this clinical case.	esophagus
Efficient induction of anti-tumor immune response in esophageal squamous cell carcinoma via dendritic cells expressing MAGE-A3 and CALR antigens.	Despite advances in the various treatment options for esophageal squamous cell carcinoma (ESCC), its prognosis is still very poor with a 5-year survival rate of only 14-22%. Recently, among the various therapeutic approaches, the focus has shifted to immunotherapy, specifically immunotherapy involving dendritic cells (DCs), which depends on their maturation and antigen presentation to effector immune cells. Recent studies have suggested that melanoma-associated antigen 3 (MAGE-A3) is a potential immunotherapeutic target and also a candidate for the development of an anti-tumor vaccine. Calreticulin (CALR) has been shown to support induction of DC maturation. Therefore, in this study, we overexpressed MAGE-A3 and CALR on DCs and studied their potential to generate anti-tumor immune responses. We observed that adenovirus (Ad)-infected DCs overexpressing CALR and MAGE-A3 showed enhanced expression of CD80, CD83, CD86, and HLA-DR markers. Also, these DCs secreted higher levels of interleukin (IL)-12, which induces the T helper type 1 cell (Th1) response, and a lower level of IL-10, a negative regulator of the Th1 response. Furthermore, CALR/MAGE-A3-infected DCs stimulated CD8(+) cytotoxic T lymphocytes, which in turn secreted higher levels of interferon-γ, which induced cytotoxic effects on ESCC cells expressing MAGE-A3. In conclusion, our results revealed the potential of CALR/MAGE-A3-infected DCs to elicit a MAGE-A3-specific anti-tumor immunogenic response in ESCC. This proof-of-principle study may promote the future design and development of DC-based effective immunotherapy against ESCC.	esophagus
Esophageal adenocarcinoma and obesity: peritumoral adipose tissue plays a role in lymph node invasion.	Obesity is associated with cancer risk in esophageal adenocarcinoma (EAC). Adipose tissue directly stimulates tumor progression independently from body mass index (BMI), but the mechanisms are not fully understood. We studied the morphological, histological and molecular characteristics of peritumoral and distal adipose tissue of 60 patients with EAC, to investigate whether depot-specific differences affect tumor behavior. We observed that increased adipocyte size (a hallmark of obesity) was directly associated with leptin expression, angiogenesis (CD31) and lymphangiogenesis (podoplanin); however, these parameters were associated with nodal metastasis only in peritumoral but not distal adipose tissue of patients. We treated OE33 cells with conditioned media (CM) collected from cultured biopsies of adipose tissue and we observed increased mRNA levels of leptin and adiponectin receptors, as well as two key regulator genes of epithelial-to-mesenchymal transition (EMT): alpha-smooth muscle actin (α-SMA) and E-cadherin. This effect was greater in cells treated with CM from peritumoral adipose tissue of patients with nodal metastasis and was partially blunted by a leptin antagonist. Therefore, peritumoral adipose tissue may exert a direct effect on the progression of EAC by secreting depot-specific paracrine factors, and leptin is a key player in this crosstalk.	esophagus
The role of biological markers of epithelial to mesenchymal transition in oesophageal adenocarcinoma, an immunohistochemical study.	BACKGROUND: E-cadherin, β-catenin, epidermal growth factor receptor (EGFR), neuronal cadherin (N-cadherin) and Cyclin D1 are involved in epithelial to mesenchymal transition (EMT). However, the prognostic significance of EMT markers in oesophageal adenocarcinoma (OAC) is unknown. Aim of this study was to evaluate the prognostic value of, and the association between different EMT markers in OAC. METHODS: Tumour cores of 154 patients with OAC were included in a tissue microarray. Scoring criteria was based on immunohistochemical staining intensity. RESULTS: EMT-associated markers were expressed in OAC: reduced membranous E-cadherin and β-catenin were seen in 11.4% and 51.7%, nuclear β-catenin in 19.1% and EGFR and Cyclin D1 overexpression in 56.5% and 27.4% of tumours. Mesenchymal marker N-cadherin was not expressed in OAC. A positive correlation was seen between membranous β-catenin and E-cadherin expression (R=0.209, p=0.001) and between EGFR and Cyclin D1 (R=0.257, p=0.002). In univariate analysis, EGFR overexpression and membranous β-catenin staining were significantly associated with a poor survival (HR 2.145; 95% CI 1.429 to 3.218, p<0.001 and HR 1.665; 95% CI 1.114 to 2.488; p=0.013). However, Cyclin D1 (HR 1.092; 95% CI 0.702 to 1.698; p=0.697), nuclear β-catenin (HR 1.322; 95% CI 0.799 to 2.189; p=0.277) and E-cadherin (HR 1.012; 95% CI 0.554 to 1.851; p=0.968) were not associated with survival. In multivariate analysis, EGFR overexpression was an independent prognostic factor for poor survival (HR 1.678; 95% CI 1.055 to 2.668; p=0.029) together with T stage (HR 2.759; 95% CI 1.356 to 5.576; p=0.005). CONCLUSIONS: This study supports the presence of EMT in OAC. Moreover, EGFR overexpression was independently associated with a poor survival.	esophagus
miR-942 promotes cancer stem cell-like traits in esophageal squamous cell carcinoma through activation of Wnt/β-catenin signalling pathway.	The Wnt/β-catenin signalling pathway is known to play a vital role in the maintenance of cancer stem cells (CSCs), which are reported to be the origin of malignant cancers, and result in poor prognosis of multiple kinds of cancer. Therefore, it is of great importance to illuminate the mechanism by which the Wnt/β-catenin pathway regulates the cancer stem cell-like traits in cancers. Here, we report that miR-942 is significantly upregulated in esophageal squamous cell carcinoma (ESCC), and miR-942 levels are associated with poor prognosis in ESCC patients. Overexpression of miR-942 promotes, whereas inhibition of miR-942 decreases, the tumor sphere formation, the CD90+ subpopulation cells and the expression of pluripotency associated markers. Moreover, in vivo assay shows that miR-942 overexpressing cells form larger tumors and display higher tumourigenesis. Furthermore, we demonstrate that miR-942 upregulates the Wnt/β-catenin signaling activity via directly targeting sFRP4, GSK3β and TLE1, which are multiple level negative regulators of the Wnt/β-catenin signaling cascade. In addition, our results indicate that c-myc directly binds to the miR-942 promoter and promotes its expression. Taken together, our findings establish an oncogenic role of miR-942 in ESCC and indicate that miR-942 might be an effective therapeutic target for ESCC.	esophagus
Toll-like receptor 9 expression in the natural history of Barrett mucosa.	Increased expression of TLR9 in esophageal adenocarcinoma and squamous cell carcinoma correlates with poor prognosis. We have explored the expression and suspected that TLR9 activation might contribute to pathogenesis in esophageal columnar metaplasia-dysplasia-neoplasia sequence, and hence, we have studied the usefulness of TLR9 as a marker for dysplasia. We have determined the expression of TLR9 in specimens with normal esophagus (n = 89), gastric (n = 71), or intestinal metaplasia (n = 56) without dysplasia, and low-grade (n = 51) or high-grade dysplasia (n = 40), and esophageal adenocarcinoma (n = 88). We observed linearly increasing TLR9 expression in specimens to be associated with change from normal epithelium to columnar metaplasia and further to dysplasia. ROC curve analysis showed clinically irrelevant sensitivity of 71% and specificity of 67% for TLR9 intensity in detection of low-grade dysplasia. Membrane-associated TLR9 expression detected by immunohistochemistry and immunofluorescence was predominantly associated with foveolar-type dysplasia as detected by HE staining (p = 0.015). TLR9 is expressed in Barrett's esophagus, and dissolution of TLR9 staining increases from nondysplastic epithelium to dysplastic. TLR9 may serve as a new way of recognizing the histopathological origin of dysplasia (adenomatous vs foveolar) with observed subcellular pattern of TLR9.	esophagus
[Expression of sphingomyelin synthase 1 (SGMS1) gene varies in human lung and oesophagus cancer].	The investigation of molecular mechanisms contributing to cancer progression is the burning problem ofcurrent research. Considerable attention has been given to the study of gene expression in cancer cells. Sphingomyelin synthase 1 gene (SGMS1) is one of the genes whose expression can be altered in cancer. SMS1 enzyme, encoded by this gene, catalyzes the synthesis of sphingomyelin and diacylglycerol from phosphatidylcholine and ceramide. SMS1 may maintain the balance between cell death and survival by regulating the formation of the pro-apoptotic mediator ceramide and anti-apoptotic mediator diacylglycerol. In addition, the changes in sphingomyelin level and sphingomyelin synthase activity have been observed in cancers of many tissues. However the peculiarities of SGMS1 gene transcription have been insufficiently explored. In this work the expression of transcripts of SGMS1 has been investigated by the method of Real Time PCR in matched pairs of samples of human lung and oesophagus cancer and adjacent tissues without pathology. A significant decrease in SMS1 transcripts expression has been found in samples of human lung cancer. At the same time, in the samples of human oesophagus cancer and adjacent tissue, expression of SMS1 transcripts varies insignificantly: it is increased in 7 and decreased in 5 of 15 samples. The obtained results indicate that SGMS1 gene is differently expressed in cancers of different genesis.	esophagus
Appropriateness of using patient-derived xenograft models for pharmacologic evaluation of novel therapies for esophageal/gastro-esophageal junction cancers.	The high morbidity and mortality of patients with esophageal (E) and gastro-esophageal junction (GEJ) cancers, warrants new pre-clinical models for drug testing. The utility of primary tumor xenografts (PTXGs) as pre-clinical models was assessed. Clinicopathological, immunohistochemical markers (p53, p16, Ki-67, Her-2/neu and EGFR), and global mRNA abundance profiles were evaluated to determine selection biases of samples implanted or engrafted, compared with the underlying population. Nine primary E/GEJ adenocarcinoma xenograft lines were further characterized for the spectrum and stability of gene/protein expression over passages. Seven primary esophageal adenocarcinoma xenograft lines were treated with individual or combination chemotherapy. Tumors that were implanted (n=55) in NOD/SCID mice had features suggestive of more aggressive biology than tumors that were never implanted (n=32). Of those implanted, 21/55 engrafted; engraftment was associated with poorly differentiated tumors (p=0.04) and older patients (p=0.01). Expression of immunohistochemical markers were similar between patient sample and corresponding xenograft. mRNA differences observed between patient tumors and first passage xenografts were largely due to loss of human stroma in xenografts. mRNA patterns of early vs late passage xenografts and of small vs large tumors of the same passage were similar. Complete resistance was present in 2/7 xenografts while the remaining tumors showed varying degrees of sensitivity, that remained constant across passages. Because of their ability to recapitulate primary tumor characteristics during engraftment and across serial passaging, PTXGs can be useful clinical systems for assessment of drug sensitivity of human E/GEJ cancers.	esophagus
Safety and efficacy of carbon dioxide cryotherapy for treatment of neoplastic Barrett's esophagus.	BACKGROUND AND STUDY AIMS: Endoscopic cryotherapy has been used successfully for the ablation of Barrett's esophagus but outcome data are limited. The aim of this study was to assess the long-term safety and efficacy of carbon dioxide (CO2) cryotherapy as primary or rescue treatment for Barrett's esophagus with high grade dysplasia (HGD) or neoplasia. PATIENTS AND METHODS: This was a retrospective, single-center, nonrandomized study carried out in an academic, tertiary care center and affiliated community hospital. A total of 78 patients with neoplastic Barrett's esophagus who had not undergone previous ablation (treatment-naïve group) or who had persistent or recurrent neoplasia despite previous treatment (rescue treatment group) were enrolled. Visible Barrett's lesions, when present, were removed by endoscopic mucosal resection, which was followed by CO2 cryotherapy until neoplasia had been eradicated, or intervening therapy was necessary, or treatment was considered to have failed. Surveillance biopsies were obtained at standard intervals. Rates of complete response for cancer, HGD, and intestinal metaplasia were calculated. Treatment failure, recurrence, adverse events, progression, and mortality were also recorded. RESULTS: Between 2006 and 2013, 64 evaluable patients (20 treatment naïve, 44 rescue treatment) were treated and followed up (median time 4.2 years). At 1 year, the overall complete response rates were 77 % for cancer (10/13), 89 % for dysplasia 57/64), 94 % for HGD (60/64; 100 % for treatment naïve, 91 % for rescue treatment), and 55 % for intestinal metaplasia (35/64). Long-term complete response for neoplasia with rescue therapy was 87 % (56/64). Disease-specific mortality was 1/68 (2 %). Treatment failed to eradicate neoplasia in four patients (6 %) (all in the rescue group). Recurrent or new intestinal metaplasia was detected in 20/64 (31 %) after two negative follow-up procedures. Serious adverse events were noted in two patients (3 %). Post-cryotherapy pain occurred in four patients (6 %; only two needed analgesics). No bleeding or new strictures were noted. Buried Barrett's was detected in 5/68 patients (7 %). CONCLUSIONS: CO2 cryotherapy was a safe and effective primary curative or rescue therapy for Barrett's neoplasia.	esophagus