crossing96/oncoscreening huggingface dataset:
Systemic control and evaluation of the response to neoadjuvant chemotherapy in resectable thoracic esophageal squamous cell carcinoma with ¹⁸F-fluorodeoxyglucose positron emission tomography-positive lymph nodes.	PURPOSE: (18)F-fluorodeoxyglucose positron emission tomography-positive lymph nodes (PET-N positive) in patients with resectable thoracic esophageal squamous cell carcinoma (TESCC) are associated with a high rate of postoperative distant recurrence. The purpose of this study was to evaluate the systemic control and survival benefit of neoadjuvant chemotherapy (NAC, cisplatin + doxorubicin + 5-fluorouracil) in these patients. METHODS: Of 77 patients with resectable TESCC who were PET-N positive, we evaluated 51 treated with NAC + surgery in this study and 26 who had undergone surgery alone (SA) in a previous study. Historical comparisons of the groups were made, and the response to treatment was evaluated in the NAC group. RESULTS: The NAC group had a higher rate of pN0-1 and a lower rate of postoperative recurrence (p < 0.0001 and p < 0.024, respectively) than the SA group; however, their relapse-free survival (RFS) rates were not significantly different. The NAC group had a significantly higher RFS in cT1/T2 cases, but showed similar survival in cT3 cases. On the other hand, post-treatment PET-N-negative patients had a higher RFS (p = 0.008) and a lower rate of distant recurrence (p = 0.021), even with cT3 disease. A multivariate analysis identified the post-treatment PET-N evaluation to be the only significant predictor of the RFS in cT3 cases. CONCLUSIONS: NAC significantly suppressed postoperative recurrence in TESCC PET-N-positive patients, but the survival benefit was unclear. However, post-treatment PET-N-negative patients were likely responders to NAC.	esophagus
Altered mitochondrial function and energy metabolism is associated with a radioresistant phenotype in oesophageal adenocarcinoma.	Neoadjuvant chemoradiation therapy (CRT) is increasingly the standard of care for locally advanced oesophageal cancer. A complete pathological response to CRT is associated with a favourable outcome. Radiation therapy is important for local tumour control, however, radioresistance remains a substantial clinical problem. We hypothesise that alterations in mitochondrial function and energy metabolism are involved in the radioresistance of oesophageal adenocarcinoma (OAC). To investigate this, we used an established isogenic cell line model of radioresistant OAC. Radioresistant cells (OE33 R) demonstrated significantly increased levels of random mitochondrial mutations, which were coupled with alterations in mitochondrial function, size, morphology and gene expression, supporting a role for mitochondrial dysfunction in the radioresistance of this model. OE33 R cells also demonstrated altered bioenergetics, demonstrating significantly increased intracellular ATP levels, which was attributed to enhanced mitochondrial respiration. Radioresistant cells also demonstrated metabolic plasticity, efficiently switching between the glycolysis and oxidative phosphorylation energy metabolism pathways, which were accompanied by enhanced clonogenic survival. This data was supported in vivo, in pre-treatment OAC tumour tissue. Tumour ATP5B expression, a marker of oxidative phosphorylation, was significantly increased in patients who subsequently had a poor pathological response to neoadjuvant CRT. This suggests for the first time, a role for specific mitochondrial alterations and metabolic remodelling in the radioresistance of OAC.	esophagus
Clinicopathology significance of podoplanin immunoreactivity in esophageal squamous cell carcinoma.	BACKGROUD AND AIM: Podoplanin (D2-40) is a specific marker for lymphatic endothelium. The vast majority of previous studies on podoplanin immunostaining in esophageal squamous cell carcinoma (ESCC) focused on identifying lymphatic vessel invasion (LVI) and counting lymphatic vessel density (LVD) and had contradictory results. Recent studies show podoplanin expression on cancer cells or tumor stroma in several cancers, which have specific significance; but the status in ESCC remains unclear. Therefore, the aim of this study was to further study and summarize the clinicopathological significance of podoplanin immunoreactivity in ESCC. MATERIALS AND METHODS: We examined podoplanin expression in tissue specimens from 107 patients with ESCC by immunohistochemistry. Podoplanin positive lymphatic vessels in intratumoral and peritumoral tissues and podoplanin positive expression in cancer cells and tumor stroma were analyzed, and correlated with clinicopathologic parameters and three-year overall and free-disease survival. RESULTS: 34 (31.8%) and 28 (26.2%) of 107 specimens had podoplanin positive expression in cancer cells and tumor stroma, respectively. Logistic regression analysis showed high intratumoral lymphatic vessel density (I-LVD) and podoplanin positivity in cancer cells were increased risks of lymph node metastasis (LNM) (OR=2.45, P=0.03; OR=0.35, P=0.01, respectively). Survival analysis showed that I-LVD was a significant factor related to poor three-year overall and free-disease survival (P=0.04, P=0.03, respectively). CONCLUSIONS: Previous data and our results show that podoplanin seems to be a useful marker to predict LNM, recurrence, and worse prognosis in ESCC; in particular, LVI, high I-LVD, and podoplanin positivity in cancer cells are associated with LNM, recurrence and overall survival.	esophagus
Autoantibodies response to MDM2 and p53 in the immunodiagnosis of esophageal squamous cell carcinoma.	The human homologue of the mouse double minute 2 (MDM2) is known to be overexpressed in a variety of human malignancies. As one of E3 ubiquitin-protein ligases, MDM2 interacts with the tumour suppressor p53 by mediating ubiquitination and degradation of p53. Since abnormally expressed proteins can induce autoimmune response, to further examine whether sera from patients with esophageal squamous cell carcinoma (ESCC) exhibited immunoreactivity against MDM2 and p53, autoantibody responses to MDM2 and p53 were evaluated by enzyme-linked immunosorbent assay (ELISA) in sera from patients with ESCC and normal individuals. Positive results were also confirmed by Western blotting and indirect immunofluorescence assay. The results demonstrated that the positive rate of autoantibody against p53 and MDM2 in ESCC sera was 22.9% (36/157) and 14.0% (22/157), whereas this rate was 0% (0/85) and 1.2% (1/85), respectively, in normal individuals. Some of the sera with antibodies specific for MDM2 also contained antibodies against p53. And there was an increase of positive antibody reactions reaching a frequency of 35% (55/157) combination with MDM2 and p53. This was significantly higher than the frequency of antibodies in normal individuals (P < 0.01). Our preliminary results suggest that autoantibodies against MDM2 and p53 may be useful serum biomarkers in the immunodiagnosis of ESCC.	esophagus
Application of sequential (18)F-FDG PET/CT scans for concurrent chemoradiotherapy of non-surgical squamous cell esophageal carcinoma.	PURPOSE: To explore the values of sequential (18)F-FDG PET/CT scanning in patients with non-surgical esophageal squamous cell carcinoma (ESCC) who received concurrent chemoradiotherapy (CCRT). METHODS: Twenty-eight patients with pathologically confirmed stage I-IV ESCC and who received definitive CCRT were prospectively enrolled into this trial. The (18)F-FDG PET/CT scans were performed four times. The maximum standardized uptake values (SUVmax) of each scanning were named as SUVmaxpet1, SUVmaxpet2, SUVmaxpet3, and SUVmaxpet4, respectively. The tumor volume with SUV greater than 40% of SUVmax was named as metabolic tumor volume (MTV). Follow-up investigation of patients was performed to record progression-free survival (PFS), relapse-free survival (RFS), and overall survival time (OS). RESULTS: The average value of MTV before treatment is 19.3 ml. The average value of SUVmax at four time points was 13.0 ± 7.4, 6.4 ± 3.2, 4.7 ± 1.9, and 3.4 ±1.8, respectively. Median follow-up time was 18.5 months (range 5-40). There was statistically significant difference in ΔR14 ((SUVmaxpet1- SUVmaxpet4) / SUVmaxpet1). Multivariate Cox regression survival analysis indicated that the MTV was an independent prognostic factor for PFS and RFS (HR = 1.13 and 1.14, respectively) before treatment. CONCLUSION: In CCRT of non-surgical ESCC, MTV before treatment could independently predict OS survival. SUVmaxpet2, SUVmaxpet3, and SUVmaxpet4 could predict RFS. Patients with reductions of SUVmaxpet4 less than 75% had a poor PFS, RFS, and OS.	esophagus
Receptor interactive protein kinase 3 promotes Cisplatin-triggered necrosis in apoptosis-resistant esophageal squamous cell carcinoma cells.	Cisplatin-based chemotherapy is currently the standard treatment for locally advanced esophageal cancer. Cisplatin has been shown to induce both apoptosis and necrosis in cancer cells, but the mechanism by which programmed necrosis is induced remains unknown. In this study, we provide evidence that cisplatin induces necrotic cell death in apoptosis-resistant esophageal cancer cells. This cell death is dependent on RIPK3 and on necrosome formation via autocrine production of TNFα. More importantly, we demonstrate that RIPK3 is necessary for cisplatin-induced killing of esophageal cancer cells because inhibition of RIPK1 activity by necrostatin or knockdown of RIPK3 significantly attenuates necrosis and leads to cisplatin resistance. Moreover, microarray analysis confirmed an anti-apoptotic molecular expression pattern in esophageal cancer cells in response to cisplatin. Taken together, our data indicate that RIPK3 and autocrine production of TNFα contribute to cisplatin sensitivity by initiating necrosis when the apoptotic pathway is suppressed or absent in esophageal cancer cells. These data provide new insight into the molecular mechanisms underlying cisplatin-induced necrosis and suggest that RIPK3 is a potential marker for predicting cisplatin sensitivity in apoptosis-resistant and advanced esophageal cancer.	esophagus
Predicting the invasion depth of esophageal squamous cell carcinoma: comparison of endoscopic ultrasonography and magnifying endoscopy.	OBJECTIVE: Predicting the invasion depth of superficial esophageal squamous cell carcinoma (SESCC) is important when selecting among therapeutic strategies. The aim of this study was to compare magnifying endoscopy with narrow-band imaging (ME-NBI) with endoscopic ultrasonography (EUS) for predicting the depth of tumor invasion in patients with SESCC. METHODS: This study enrolled 51 patients with SESCC (52 SESCC lesions) who underwent both ME-NBI and EUS at Pusan National University Hospital during 2010-2013. We reviewed the patients' medical records and compared ME-NBI and EUS findings with histopathological results according to clinicopathological factors. RESULTS: A total of 46 lesions in 45 patients were included in the final analysis. ME-NBI and EUS had overall accuracies of 76.1% and 84.8%, respectively, in distinguishing mucosal from non-mucosal cancers. There were no differences between ME-NBI and EUS in terms of sensitivities and specificities in distinguishing mucosal from non-mucosal cancers (p = 0.500 and p = 0.688, respectively). When both ME-NBI and EUS suggested a mucosal depth of lesion invasion, the frequency of mucosal cancer in the final histopathology was 94%. However, if either ME-NBI or EUS suggested a non-mucosal depth of invasion, the frequency of mucosal cancer was only 21%. CONCLUSION: ME-NBI and EUS are accurate predictors of SESCC invasion depth. If both methods suggest a mucosal depth of lesion invasion, the accuracy of the prediction is increased. Therefore, when possible, it would be better to evaluate the invasion depth of SESCC using both ME-NBI and EUS before deciding to perform endoscopic resection.	esophagus
Radiofrequency ablation for Barrett's-associated intramucosal carcinoma: a multi-center follow-up study.	BACKGROUND: Radiofrequency ablation (RFA), with or without endoscopic mucosal resection (EMR), has been validated as a safe, effective and durable treatment option for dysplastic Barrett's esophagus. Its durability in eradicating Barrett's-associated intramucosal carcinoma (IMC), however, is unclear. We set out to assess the long-term safety and efficacy of RFA for IMC. METHODS: Retrospective review of two tertiary care facility records for patients undergoing RFA, with or without EMR, for biopsy-proven IMC. Our primary outcome of interest was to quantify the rate of durable complete eradication for intestinal metaplasia and for IMC and associated dysplasia. A multi-variate regression analysis was performed to identify features which correlate with durable eradication of IMC/dysplasia. Our secondary outcome of interest was treatment-related complications. RESULTS: 36 patients (26 male; mean age 64 ± 12 years), with a mean Barrett's length of 3.5 ± 2.5 cm, underwent RFA for biopsy-proven IMC. EMR was performed in 31 (86%) prior to or during RFA. Complete eradication of IMC/dysplasia was achieved in 32/36 (89%) and patients required a mean of 1 ± 1 EMR and 2 ± 1 RFA sessions to achieve eradication. During a mean follow-up period of 24 ± 19 months, durable complete eradication of IMC/dysplasia was achieved in 29/36 (81%) patients. On multi-variate regression analysis, undergoing an EMR prior to RFA was associated with an increased likelihood of maintaining durable eradication of IMC/dysplasia (p = 0.03). Treatment-related complications included: bleeding (3%) and stricture formation (19%). CONCLUSION: RFA is an effective and durable treatment option for Barrett's-associated IMC. Greater than 80% of patients will achieve and maintain complete eradication of IMC at a mean of 2 years follow-up.	esophagus
Esophageal carcinoma: Evaluation with q-space diffusion-weighted MR imaging ex vivo.	PURPOSE: To determine the usefulness of q-space MR imaging as means of evaluating the depth of mural invasion, the histologic grades, and lymph node metastasis in esophageal carcinomas. METHODS: Twenty esophageal specimens each containing a carcinoma were studied with a 7.0 Tesla MR imaging system. q-Space MR images were obtained with a 50-60 mm × 25-30 mm field of view, 256 × 128 matrix, 2 mm section thickness, 10 b values ranging from 0 to 7163 s/mm(2) , and a motion-probing gradient in the y-direction, and the MR images were compared with the histopathologic findings. RESULTS: The mean displacement maps, probability for zero displacement maps, and kurtosis maps in all 20 carcinomas (100%) made it possible to identify the depth of tumor invasion of the esophageal wall. These q-space MR imaging parameters were significantly correlated with the histologic grades of the esophageal carcinomas (P < 0.01), and also significantly correlated with their nuclear-cytoplasmic ratios (P < 0.01 or P < 0.001) and tumor cellularity (cell density) (P < 0.01 or P < 0.001). The q-space MR imaging parameters were also capable of differentiating between the metastatic lymph nodes and nonmetastatic lymph nodes (P < 0.01). CONCLUSION: q-Space MR imaging ex vivo provides excellent diagnostic accuracy for evaluating mural invasion by esophageal carcinomas, the histologic grades of esophageal carcinomas, and lymph node metastasis by esophageal carcinomas.	esophagus
The prognostic significance of cancer-associated fibroblasts in esophageal squamous cell carcinoma.	BACKGROUND: Cancer-associated fibroblasts (CAF) are activated fibroblasts in the cancer stroma and play an important role in cancer progression. Some reports have indicated the correlation between the expression of CAF markers and adverse prognosis in several cancers. However, no reports have studied CAF phenotype and its clinical relevance in esophageal squamous cell carcinoma (ESCC). METHODS: We investigated CAF phenotype of ESCC based on histology and immunohistochemical expressions of five CAF markers such as fibroblast activation protein (FAP), smooth muscle actin (SMA), fibroblast-specific protein-1 (FSP1), platelet-derived growth factor receptor (PDGFRα), and PDGFRβ in 116 ESCC tissue samples. Besides, we also examined the correlation of the CAF phenotype with clinical relevance as well as other cancer-microenvironment related factors. RESULTS: Histologically immature CAF phenotype was correlated with poor prognosis (p<0.001) and associated with increased microvessel density, increased tumor associated macrophages, and epithelial to mesenchymal transition. CAF markers were characteristically expressed in stromal fibroblast close to tumor cells and the expression pattern of 5 CAF markers was highly heterogeneous in every individual cases. Of five CAF markers, SMA, FSP1, and PDGFRα were unfavorable prognostic indicators of ESCC. The number of positive CAF markers was greater in ESCC with immature CAFs than in those with mature ones. CONCLUSIONS: Our results demonstrate that histologic classification of CAF phenotype is a reliable and significant prognostic predictor in ESCC. CAF markers have the potential to be diagnostic and therapeutic targets in ESCC.	esophagus
Negative surveillance endoscopy occurs frequently in patients with short-segment non-dysplastic Barrett's esophagus.	Surveillance endoscopy of non-dysplastic Barrett's esophagus (NDBE) that fails to detect intestinal metaplasia (IM), or negative surveillance, is known to occur in clinical practice, although the frequency and possible outcomes in a large cohort in clinical practice is not well described. The goals of this study were to define frequency in which negative surveillance occurs and endoscopic outcomes in a screening cohort of short segment NDBE. A retrospective cohort (n = 184) of patients newly diagnosed with short segment NDBE at an outpatient academic tertiary care center between 2003 and 2011 were reviewed. Only those with one or more surveillance endoscopies were included to define a frequency of negative surveillance. Included patients were further assessed if they had two or more surveillance endoscopies and were classified into groups as sampling error or negative IM on consecutive surveillances based on the results of their surveillance endoscopies. The frequency of a negative surveillance endoscopy in all short-segment NDBE patients was 19.66% (92 endoscopic exams were negative for IM of 468 total surveillance exams). A negative surveillance endoscopy occurred in 40.76% (n = 75) patients. Sampling error occurred in 44.12% and negative IM on consecutive surveillance endoscopies in 55.88% of those with ≥ 2 surveillance endoscopies and an initially negative surveillance exam. The frequency of negative IM on consecutive surveillances was 19.00% of all patients who had two surveillance endoscopies. When the index diagnostic Barrett's esophagus segment length was < 1 cm, 32.14% (18/56) of all patients (with ≥ 2 surveillance endoscopies) had negative IM on consecutive surveillance endoscopies. Negative surveillance occurs frequently in short-segment NDBE. When an initial negative surveillance endoscopy occurs, it may be due to either a sampling error or lack of detectable IM on surveillance exam. When a <1 cm segment of NDBE is diagnosed, a significant proportion of patients may go on to have continuously undetected IM on consecutive surveillance endoscopic exams without intervention.	esophagus
Phospholipase C epsilon 1 (PLCE1 rs2274223A>G, rs3765524C>T and rs7922612C>T) polymorphisms and esophageal cancer risk in the Kashmir Valley.	BACKGROUND: Phospholipase C epsilon 1 (PLCE1) encodes a member of the phospholipase family of proteins that play crucial roles in carcinogenesis and progression of several cancers including esophageal cancer (EC). In two large scale genome-wide association studies (GWAS) single nucleotide polymorphisms (SNP, rs2274223A>G, rs3765524C>T) in PLCE1 were identified as novel susceptibility loci of esophageal cancer (EC) in China. The aim of the present study was to investigate this finding in Kashmir Valley, a high risk area. MATERIALS AND METHODS: We determined genotypes of three potentially functional SNPs (rs2274223A>G, rs3765524C>T and rs7922612C>T) of PLCE1 in 135 EC patients, and 195 age and gender matched controls in Kashmiri valley by PCR RFLP method. Risk for developing EC was estimated by binary logistic regression using SPSS. RESULTS: The selected PLCE1 polymorphisms did not show independent association with EC. However, the G2274223T3765524T7922612 haplotype was significantly associated with increased risk of EC (OR=2.92; 95% CI=1.30-6.54; p=0.009). Smoking and salted tea proved to be independent risk factors for EC. CONCLUSIONS: Genetic variations in PLCE1 modulate risk of EC in the high risk Kashmiri population.	esophagus
Feasibility of esophageal reconstruction using a pedicled jejunum with intrathoracic esophagojejunostomy in the upper mediastinum for esophageal cancer.	OBJECTIVE: An alternative conduit is needed when the gastric tube cannot be used as an esophageal substitute for reconstruction after esophagectomy. We adopted pedicle jejunal reconstruction with intrathoracic anastomosis in the upper mediastinum under such circumstances. The aim of this study was to evaluate the feasibility of this technique. METHODS: Two hundred and ten patients with esophageal cancer underwent esophagectomy and reconstruction from 1998 to 2013. Among them, 6 patients underwent colon interposition (colon group) and 13 underwent jejunum reconstruction (jejunum group) including 8 thoracoscopic anastomosis. The operative results of both groups were compared with those of 191 gastric tube reconstructions (stomach group). RESULTS: The operative times in the colon and jejunum groups were significantly longer than that in the stomach group (P = 0.001 and P = 0.018, respectively). The colon group showed more operative blood loss and more frequent anastomotic leakage and ischemic stenosis of the conduit than did the stomach group (1605 vs. 530 g, P = 0.007; 50 vs. 12.6 %, P = 0.035; 16.7 vs. 0 %, P = 0.03, respectively). There was no anastomotic leakage, conduit necrosis and mortality in the jejunum group. Ischemic stenosis of the conduit occurred more frequently in jejunum group than in the stomach group (23.1 vs. 0 %, P < 0.001). However, the stenosis could be managed safely with endoscopic treatment. Patient survival in the colon and jejunum groups was consistent with that in the stomach group. CONCLUSIONS: Pedicle jejunal reconstruction with intrathoracic anastomosis can be performed safely under thoracotomy or thoracoscopic surgery when stomach cannot be used as an esophageal substitute after esophagectomy.	esophagus