Esophageal Squamous Cell Cancer Patients Research Articles

ASO Visual Abstract: Utility of Initial Tumor Reduction as a Prognostic Factor in Esophageal Squamous Cell Cancer Patients Undergoing Neoadjuvant Chemotherapy Followed by Surgery: A Retrospective Cohort Study.

ASO Visual Abstract: Utility of Initial Tumor Reduction as a Prognostic Factor in Esophageal Squamous Cell Cancer Patients Undergoing Neoadjuvant Chemotherapy Followed by Surgery: A Retrospective Cohort Study.

Utility of Initial Tumor Reduction as a Prognostic Factor in Esophageal Squamous Cell Cancer Patients Undergoing Neoadjuvant Chemotherapy Followed by Surgery : A Retrospective Cohort Study.

While a neoadjuvant chemotherapy regimen using docetaxel, cisplatin, and 5-fluorouracil (NAC-DCF) is considered the standard treatment for locally advanced esophageal cancer (EC) in Japan, a reliable marker for early prediction of treatment efficacy remains unclear. We investigated the utility of the tumor response after a first course of NAC-DCF as a post-surgery survival predictor in patients with EC. We enrolled 150 consecutive patients who underwent NAC-DCF followed by surgery for EC between September 2009 and January 2019. The initial tumor reduction (ITR), defined as the percentage decrease in the shorter diameter of the tumor after the first course of NAC-DCF, was evaluated using computed tomography. We analyzed the relationship between ITR, clinicopathological parameters, and survival. The median ITR was 21.07% (range -11.45 to 50.13%). The optimal cut-off value for ITR for predicting prognosis was 10% (hazard ratio [HR] 3.30, 95% confidence interval [CI] 1.98-5.51), based on univariate logistic regression analyses for recurrence-free survival (RFS). Compared with patients with ITR <10%, patients with ITR ≥10% showed a significantly higher proportion of ypM0 (80.0% vs. 92.5%) and responders in terms of overall clinical response (50.0% vs. 80.8%). Multivariate analysis for RFS revealed that ypN2-3 (HR 2.78, 95% CI 1.67-4.62), non-response in terms of overall clinical response (HR 1.87, 95% CI 1.10-3.18), and ITR <10% (HR 2.48, 95% CI 1.42-4.32) were independent prognostic factors. Tumor response after the first course of NAC-DCF may be a good predictor of survival in patients with EC who underwent NAC-DCF plus surgery.

Effect of longitudinal changes of cachexia on the efficacy and toxicity of immune checkpoint inhibitors in esophageal squamous cell cancer (ESCC) patients

PurposeImmune checkpoint inhibitors (ICIs) have enhanced survival in advanced esophageal squamous cell cancer (ESCC) patients, but their efficacy varies. Cachexia, characterized by muscle loss and significant weight loss, might influence ICI response. This study examines the relationship between cachexia's longitudinal changes and ICI outcomes in ESCC patients. MethodsESCC patients undergoing at least two ICI cycles from 2017 to 2021 were studied. Cachexia's baseline and evolving patterns during ICI treatment were observed. Kaplan-Meier and Cox regression analyses were used to assess cachexia's effect on ICI efficacy. Chi-square tests were used to determine cachexia's link to immune-related adverse effects (irAEs). ResultsTwo hundred seventy-eight ICI-treated patients had a median progression-free survival (PFS) of 5.78 months and overall survival (OS) of 8.3 months. Pretreatment cachexia led to worse outcomes: PFS 7.87 versus 5.3 months, time to progression (TTP) 10.9 versus 6.1 months, and OS 14.3 versus 9.2 months. Irreversible cachexia showed the poorest results. Cachexia's changes weren't associated with irAEs. ConclusionBaseline and evolving cachexia significantly impact ICI efficacy in ESCC patients. Continuous cachexia monitoring during ICI therapy is crucial for optimal ESCC management.

From pixels to patient care: deep learning-enabled pathomics signature offers precise outcome predictions for immunotherapy in esophageal squamous cell cancer.

Immunotherapy has significantly improved survival of esophageal squamous cell cancer (ESCC) patients, however the clinical benefit was limited to only a small portion of patients. This study aimed to perform a deep learning signature based on H&E-stained pathological specimens to accurately predict the clinical benefit of PD-1 inhibitors in ESCC patients. ESCC patients receiving PD-1 inhibitors from Shandong Cancer Hospital were included. WSI images of H&E-stained histological specimens of included patients were collected, and randomly divided into training (70%) and validation (30%) sets. The labels of images were defined by the progression-free survival (PFS) with the interval of 4months. The pretrained ViT model was used for patch-level model training, and all patches were projected into probabilities after linear classifier. Then the most predictive patches were passed to RNN for final patient-level prediction to construct ESCC-pathomics signature (ESCC-PS). Accuracy rate and survival analysis were performed to evaluate the performance of ViT-RNN survival model in validation cohort. 163 ESCC patients receiving PD-1 inhibitors were included for model training. There were 486,188 patches of 1024*1024 pixels from 324 WSI images of H&E-stained histological specimens after image pre-processing. There were 120 patients with 227 images in training cohort and 43 patients with 97 images in validation cohort, with balanced baseline characteristics between two groups. The ESCC-PS achieved an accuracy of 84.5% in the validation cohort, and could distinguish patients into three risk groups with the median PFS of 2.6, 4.5 and 12.9months (P < 0.001). The multivariate cox analysis revealed ESCC-PS could act as an independent predictor of survival from PD-1 inhibitors (P < 0.001). A combined signature incorporating ESCC-PS and expression of PD-L1 shows significantly improved accuracy in outcome prediction of PD-1 inhibitors compared to ESCC-PS and PD-L1 anlone, with the area under curve value of 0.904, 0.924, 0.610 for 6-month PFS and C-index of 0.814, 0.806, 0.601, respectively. The outcome supervised pathomics signature based on deep learning has the potential to enable superior prognostic stratification of ESCC patients receiving PD-1 inhibitors, which convert the images pixels to an effective and labour-saving tool to optimize clinical management of ESCC patients.

MR radiomics predicts pathological complete response of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy: a multicenter study

BackgroundMore than 40% of patients with resectable esophageal squamous cell cancer (ESCC) achieve pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT), who have favorable prognosis and may benefit from an organ-preservation strategy. Our study aims to develop and validate a machine learning model based on MR radiomics to accurately predict the pCR of ESCC patients after nCRT.MethodsIn this retrospective multicenter study, eligible patients with ESCC who underwent baseline MR (T2-weighted imaging) and nCRT plus surgery were enrolled between September 2014 and September 2022 at institution 1 (training set) and between December 2017 and August 2021 at institution 2 (testing set). Models were constructed using machine learning algorithms based on clinical factors and MR radiomics to predict pCR after nCRT. The area under the curve (AUC) and cutoff analysis were used to evaluate model performance.ResultsA total of 155 patients were enrolled in this study, 82 in the training set and 73 in the testing set. The radiomics model was constructed based on two radiomics features, achieving AUCs of 0.968 (95%CI 0.933–0.992) in the training set and 0.885 (95%CI 0.800-0.958) in the testing set. The cutoff analysis resulted in an accuracy of 82.2% (95%CI 72.6-90.4%), a sensitivity of 75.0% (95%CI 58.3-91.7%), and a specificity of 85.7% (95%CI 75.5-96.0%) in the testing set.ConclusionA machine learning model based on MR radiomics was developed and validated to accurately predict pCR after nCRT in patients with ESCC.

Cone-beam computed-tomography-based delta-radiomic analysis for investigating prognostic power for esophageal squamous cell cancer patients undergoing concurrent chemoradiotherapy

PurposeTo investigate the prognostic power of cone-beam computed-tomography (CBCT)-based delta-radiomics in esophageal squamous cell cancer (ESCC) patients treated with concurrent chemoradiotherapy (CCRT). MethodsWe collected data from 26 ESCC patients treated with CCRT. CBCT images acquired at five time points (1st–5th week) per patient during CCRT were used in this study. Radiomic features were extracted from the five CBCT images on the gross tumor volumes. Then, 17 delta-radiomic feature sets derived from five types of calculations were obtained for all the cases. Leave-one-out cross-validation was applied to investigate the prognostic power of CBCT-based delta-radiomic features. Feature selection and construction of a prediction model using Coxnet were performed using training samples. Then, the test sample was classified into high or low risk in each cross-validation fold. Survival analysis for the two groups were performed to evaluate the prognostic power of the extracted CBCT-based delta-radiomic features. ResultsFour delta-radiomic feature sets indicated significant differences between the high- and low-risk groups (p < 0.05). The highest C-index in the 17 delta-radiomic feature sets was 0.821 (95 % confidence interval, 0.735–0.907). That feature set had p-value of the log-rank test and hazard ratio of 0.003 and 4.940 (95 % confidence interval, 1.391–17.544), respectively. ConclusionsWe investigated the potential of using CBCT-based delta-radiomics for prognosis of ESCC patients treated with CCRT. It was demonstrated that delta-radiomic feature sets based on the absolute value of relative difference obtained from the early to the middle treatment stages have high prognostic power for ESCC.

Do higher radiation doses improve survival for cervical esophageal squamous cell cancer patients treated with definitive chemoradiotherapy using intensity-modulated radiotherapy? A propensity-score matched analysis.

This study was conducted to determine whether higher doses of intensity-modulated radiotherapy (IMRT) could improve the survival rate in patients of cervical esophageal squamous cell carcinoma (CESCC), and lead to more severe treatment-related toxicity. The clinical records of stage I-IVA CESCC patients treated with definitive chemoradiotherapy (CRT) using IMRT between January 2013 and June 2018 were retrospectively analyzed. The patients in the high-dose (HD) group received ≥60 Gy and those in the standard-dose group received <60 Gy. A propensity score matching (PSM) was applied to balance the confounding factors between both groups. The primary endpoint was over-survival (OS). progression-free survival (PFS), loco-regional control (LRC), and treatment-related toxicity were also evaluated. A total of 136 patients with CESCC were included. Patients with N1-3 nodal and stages III-IVA of the disease (P < 0.05) were included in the HD group. The differences in the OS, PFS, and LRC between the two groups were not statistically significant (P = 0.350, 0.063, and 0.099, respectively). After PSM, significantly longer PFS and LRC were observed in the HD group. The difference in OS between the two groups was not statistically significant. There was no significant difference in the incidence of treatment-related toxicity between the two groups. The results of this PSM analysis suggested that higher doses may improve PFS and LRC for CESCC patients receiving CRT using OMRT, but do not demonstrate any statistically significant advantage in improving OS.

PCR243 Psychometric Validation of QlQ-OES18 in 2L Esophageal Squamous Cell Cancer (ESCC) Patients Treated with Tislelizumab Versus Chemotherapy

PCR243 Psychometric Validation of QlQ-OES18 in 2L Esophageal Squamous Cell Cancer (ESCC) Patients Treated with Tislelizumab Versus Chemotherapy

Risk of second cancer in esophageal squamous cell carcinoma and adenocarcinoma survivors: a population-based analysis in SEER dataset.

Previous studies have reported increased risk of second cancer in both esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC) survivors. This study aimed to examine the risk and influential factors of second cancer in ESCC and EAC patients. This population-based cohort study included 7,297 ESCC patients and 11,812 EAC patients who were in 1992-2019 from the Surveillance, Epidemiology, and End Results (SEER) program in the United States. These patients were followed up until diagnosis of second cancer, death, or end of the study (December 31, 2019). We calculated standard incidence ratio (SIR) and 95% confidence interval (CI) of second cancer and performed competing-risk regression to estimate the subdistribution hazard ratios (sHR) comparing categories of patients' characteristics. After a total of 49,509.38 person-years of follow-up, 431 (5.9%) ESCC patients and 636 (5.9%) EAC patients developed a second cancer. An overall increased risk of second cancer was observed in both ESCC patients (SIR: 1.66, 95% CI: 1.51-1.83) and EAC patients (SIR: 1.11, 95% CI: 1.02-1.20). ESCC patients were at increased risk of second malignancy in oral cavity and pharynx (SIR: 12.57, 95% CI: 9.87-15.79), stomach (SIR: 3.03, 95% CI: 1.77-4.85), nose and larynx (SIR: 4.79, 95% CI: 2.47-8.37), and lung and bronchus (SIR: 2.44, 95% CI: 1.96-2.99), but decreased risk of prostate cancer (SIR: 0.73, 95% CI: 0.52-0.99). EAC patients had increased risk of second malignancies in stomach (SIR: 4.41, 95% CI: 3.23-5.89), lung and bronchus (SIR: 1.26, 95% CI: 1.02-1.54), and kidney (SIR: 1.57, 95% CI: 1.05-2.25). The risk of second cancer was higher in female ESCC patients than in males (sHR: 1.34, 95% CI: 1.11-1.63) and decreased with more advanced tumor stage in both ESCC patients (sHR: 0.62, 95% CI: 0.50-0.76 for regional stage; sHR: 0.27, 95% CI: 0.20-0.36 for distant stage) and EAC patients (sHR: 0.47, 95% CI: 0.40-0.56 for regional stage; sHR: 0.10, 95% CI: 0.07-0.13 for distant stage). Both ESCC and EAC patients are at considerable risk of certain types of second cancer.

Sarcopenia as a Predictor of Neoadjuvant Therapy-Related Toxicity in Esophageal Squamous Cell Carcinoma Patients

Sarcopenia, characterized by loss of muscle mass, plays a critical role in patients with esophageal squamous cell cancer (ESCC). Preoperative chemoradiotherapy and immunotherapy in ESCC patients has been reported to improve survival. Therefore, we sought to evaluate the predictive value of preoperative sarcopenia for toxicity and pathological tumor response to neoadjuvant therapy (NAT) in ESCC patients. A retrospective analysis was performed using a prospectively collected patient cohort of an academic cancer center diagnosed with cT2-4N0-3M0 ESCC between 2019-2022 and treated with neoadjuvant chemoradiotherapy ± pembrolizumab. Sarcopenia was assessed by skeletal muscle index at the third lumbar vertebra in computed tomography scans before NAT (men: 43cm²/m² for body mass index (BMI) < 25kg/m², 53cm²/m² for BMI≥25 kg/m²; women: 41cm²/m²). Logistic regression was performed to assess the association between sarcopenia and preoperative therapy-related toxicity and tumor response. The study included 59 locally advanced ESCC patients (53 male and 6 female), 48 (81.4%) in the non-sarcopenia group, and 11 (18.6%) in the sarcopenia group. Mean age at diagnosis was 62±8 years. Mean BMI at diagnosis was 22.13±2.85 kg/m². 19 patients (32.2%) were stage ⅢA, 25 patients (42.4%) were ⅢB, 15 patients (25.4%) were ⅣA. No significant differences were found between both groups regarding sex, age, BMI, and clinical stage. Acute grade ≥3 toxicity occurred significantly more frequently in the sarcopenia group (54.5% vs. 22.9%, p = 0.045), which mainly included leukopenia, neutropenia, anemia and thrombocytopenia. The discontinuation of NAT owing to toxicity occurred in 8 patients (13.5%), which was significantly associated with sarcopenia (p = 0.003). All patients proceeded to surgery and 33 patients (55.9%) had a pathological complete response (pCR). Univariate analysis revealed no significant association between sarcopenia and pCR (p = 0.071). Among patients with locally advanced EC, sarcopenia is not a predictor of poor NAT response, but it is strongly associated with discontinuation of NAT due to toxicity.

Effect of MTA3 Inhibition of Glutamine Synthetase-Mediated Glutaminolysis on Radiosensitivity of Patients with Esophageal Cancer

Metastasis-associated protein 3 (MTA3) can serve as a tumor suppressor in many cancer types. However, the role of MTA3 in radiosensitivity of patients with esophageal squamous cell cancer (ESCC) remains unclear. We thus investigated the function of MTA3 in radiosensitivity for ESCC, one of the most common digestive cancers. The colony formation assay and nude mice xenograft tumor assay were performed to investigate the effect of MTA3 on radiosensitivity in ESCC. Glutamine consumption assay kit and glutamate production assay kit were used to assess the glutaminolysis. Glutaminase (GLS) Activity Assay Kit and Glutamine Synthetase (GS) Activity Assay Kit were used to analyze the activity of specific metabolic enzymes dominate glutaminolysis. The regulatory mechanism of glutaminolysis by MTA3 was confirmed using Chromatin immunoprecipitation assay and Gaussia luciferase assay. The expression levels of MTA3 and GS in ESCC primary tissues were evaluated using immunohistochemistry. Survival curves were plotted with the Kaplan-Meier method and compared by log-rank test. The colony formation assay showed that MTA3 depletion and overexpression caused significantly higher and lower clonogenic survival after different doses of irradiation (IR), respectively. When these cells were subcutaneously injected into nude mice, the tumors derived from the cells with MTA3 overexpression and MTA3 knockdown were significantly smaller and bigger after IR, respectively. These findings suggest that MTA3 can enhance radiosensitivity in vitro and in vivo. Meanwhile, overexpressed and knockdown MTA3 can repress and expedite glutamine consumption and glutamate production uniformly, respectively. To determine how MTA3 acts on glutaminolysis, the activity of two specific metabolic enzymes dominate this metabolism, GS and GLS, were evaluated. It found that overexpressed and knockdown MTA3 can restrain and enhance the activity of GS, respectively, but have less effect on GLS. Moreover, the decreased radiosensitivity mediated by MTA3 knockdown is significantly increased when treated with GS inhibitor, suggesting that GS plays a crucial role in MTA3-mediated radiosensitivity enhancement. Mechanistically, Chromatin immunoprecipitation assay and Gaussia luciferase assay showed that MTA3 was recruited to the promoter of GS and suppressed GS transcription. However, knockdown of GATA3 abolished MTA3's repressive effect on GS and inhibited the MTA3's occupation on the promoter region of GS. These results collectively demonstrated that, in ESCC cells, MTA3 is recruited by GATA3 to inhibit GS expression, then ultimately represses glutaminolysis and enhances radiosensitivity. Finally, we showed that the ESCC patients in the MTA3low/GShigh group is significantly associated with shorter overall survival. MTA3 is capable of enhancing radiosensitivity through downregulating GS and MTA3low/GShigh might be a potential prognostic factor for ESCC patients.

Using Liquid Biopsy to Predict Relapse After Radiotherapy in Squamous Cell Head-Neck and Esophageal Cancer.

Circulating cell-free DNA (cfDNA) in the blood of cancer patients contains tumor-specific mutated genes and viral genome that can be identified and quantified as 'tumor-specific cfDNA' (circulating tumor DNA, ctDNA). Various technologies are available that offer reliable detection of ctDNA at a low concentration. Quantitative and qualitative analysis of ctDNA may be of prognostic and predictive value in oncology. Here, we present concisely the experience on the assessment of ctDNA levels and kinetics during therapy in the outcome of radiotherapy (RT) and chemo-radiotherapy (CRT) in squamous cell head-neck cancer and esophageal squamous cell cancer patients. The levels of circulating viral (human papilloma virus or Epstein-Barr) ctDNA, and levels of total, mutated or methylated ctDNA at diagnosis are linked with tumor burden and clinical aggressiveness, and may be of prognostic or even predictive value of RT/CRT efficacy. Persistent ctDNA levels after therapy seem to predict high rates of tumor relapse several months before radiological documentation. This can prove of value for the identification of subgroups of patients who could benefit from RT dose-escalation or consolidation chemotherapy and immunotherapy, a hypothesis that should be tested in clinical trials.

Co-occurrence of mutations and related signal pathway analysis of CCND1 amplification in esophageal squamous cell cancer.

e16044 Background: Profiling molecular subtypes was usually necessary for cancer patients to facilitate better treatment strategy. Esophageal squamous cell cancer (ESCC) has four subtypes including cell cycle pathway activation (CCA), NRF2 oncogenic activation (NRFA), immune suppression (IS), and immune modulation (IM). CCND1 amplification is one of the important molecular biomarkers for CCA subtype. Previous research showed that CCND1 amplification was associated with immune resistance in ESCC. The co-occurred mutations and related signaling pathways are of great interest to study molecular mechanism in ESCC. Methods: This study enrolled 50 ESCC patient samples comprising 19 whole exome sequencing (WES) samples, 18 whole genome sequencing (WGS) samples and 13 NGS panel (667 genes) samples. To use all the samples, the minimal set of 667 genes was analyzed in detail for gene amplifications and mutations. Kaplan-Meier (KM) survival analysis was applied to study the prognosis associations with the frequently occurred amplifications including CCND1, FGF3, FGF4 and FGF19, etc. Gene expression profiles were then investigated by RNA-Seq sequencing on ESCC cell lines with CCND1 (K30-N) and without CCND1 gene (K30-S, knocked out). PCA analysis was applied to explore the differences between K30-S and K30-N, and KEGG and GO enrichment analysis were performed on the differential expressed genes (DEGs). All analyses were carried out through R4.1.0. Results: The mutational profiles showed that TP53, CCND1, FGF4, FGF19, FGF3, and CDKN2A/B were the most frequently mutated genes in ESCC patients, with the mutation frequencies of 62%, 58%, 56%, 50%, 48% and 40%, respectively. Among those genes, CCND1 and FGF3/4/19 co-occurred amplifications presented in almost all the samples and no other co-existent gene amplifications were identified. The CCND1 and FGF3/4/19 amplification patients were associated with worse prognosis. A total of 1494 differential expressed genes were identified between K30-N and K30-S cell lines, including 998 up-regulated genes and 496 down-regulated gene in K30-S cell line. KEGG enrichment analysis showed that these DEGs were mainly enriched in MAPK signaling pathway, p53 signaling pathway, mTOR signaling pathway and etc. GO enrichment analysis revealed that these differential genes are mainly enriched in cell growth, developmental cell growth, Ras protein signal transmission. Those results were consistent with CCA molecular subtype and highlighted the important role of CCND1 in ESCC subtype classification. Conclusions: This study demonstrated that CCND1 and FGF3/4/19 amplifications frequently co-occurred in ESCC and they were associated with worse prognosis. Signal pathway analysis showed CCND1 play important roles in subtype classification of ESCC.

Combination of neutrophil-to-lymphocyte ratio and albumin concentration to predict the prognosis of esophageal squamous cell cancer patients undergoing esophagectomy.

Esophageal squamous cell cancer (ESCC) is an aggressive cancer with high incidence and mortality. It is crucial to predict prognosis of these patients individually. Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic indicator in several tumors, including esophageal cancer. Besides inflammatory factors, nutritional status can impact survival of cancer patients. Albumin (Alb) concentration is an easily obtained indicator to reflect nutritional status. In this study, we retrospectively collected the data of patients with ESCC and used univariate and multivariate analysis to investigate the relationship between combination of NLR and Alb (NLR-Alb) and survival. Meanwhile, we compared clinical features among NLR-Alb cohorts. Univariate analysis showed that age (P=0.013), gender (P=0.021), surgical type (P=0.031), preoperative therapy (P=0.007), NLR-Alb (P=0.001), and tumor-node-metastasis (TNM) status (P<0.001) were associated with 5-year overall survival (OS). In multivariate analysis, NLR-Alb [hazard ratio (HR) =2.53, 95% confidence interval (95% CI): 1.38-4.63, P=0.003] and TNM status (HR =4.76, 95% CI: 3.09-7.33, P<0.001) were independent predictive factors for 5-year OS. The 5-year OS rates were 83%, 62%, and 55% for NLR-Alb 1, NLR-Alb 2, and NLR-Alb 3, respectively (P=0.001). In summary, pre-operative NLR-Alb is a favorable and cost-effective index to predict prognosis of patients with ESCC individually.

Randomized controlled trial of intravenous sedation vs general anesthesia for esophageal dilation with percutaneous endoscopic gastrostomy in esophageal cancer patients.

Esophageal squamous cell cancer (ESCC) is mostly diagnosed in its later stages, when patients present with dysphagia and weight loss. Esophageal dilation with percutaneous endoscopic gastrostomy (PEG) is a common surgical procedure in patients with locally advanced ESCC because of tumor obstruction and enteral nutrition support during neoadjuvant or definitive concurrent chemoradiotherapy (CCRT). Esophageal dilation with PEG is widely performed under general anesthesia (GA) with endotracheal intubation. To determine the overall success rate of completing this procedure using intravenous (IV) sedation with dexmedetomidine (DEX) relative to GA and to compare its perioperative conditions, including procedure times, pain scores (visual analog scale), adverse events, and costs. SongklanagarindHospital, Faculty of Medicine, Prince of Songkla University, Thailand. Prospective randomized controlled trial (RCT) of locally advanced ESCC patients who had dysphagia and needed esophageal dilation with PEG between January 2020 and December 2021. Esophageal dilation (using a Savary-Gilliard dilator) and PEG were performed using the pull technique. Seventy patients were randomly assigned to either the DEX group (n = 34) or the GA group (n = 36). All patients in both groups underwent successful surgery. The DEX group had a significantly shorter procedure time, lower procedure cost, and lower total hospital cost than the GA group. However, there were no significant between-group differences in pain scores or length of hospital stay. There were no serious adverse events in either group; however, the GA group had some incidences of sore throat, transient hoarseness, and atelectasis. This study found that IV sedation with DEX during esophageal dilation with PEG was as effective and safe as using GA.

1H NMR-based metabolomics of paired tissue, serum and urine samples reveals an optimized panel of biofluids metabolic biomarkers for esophageal cancer.

The goal of this study was to establish an optimized metabolic panel by combining serum and urine biomarkers that could reflect the malignancy of cancer tissues to improve the non-invasive diagnosis of esophageal squamous cell cancer (ESCC). Urine and serum specimens representing the healthy and ESCC individuals, together with the paralleled ESCC cancer tissues and corresponding distant non-cancerous tissues were investigated in this study using the high-resolution 600 MHz 1H-NMR technique. We identified distinct 1H NMR-based serum and urine metabolic signatures respectively, which were linked to the metabolic profiles of esophageal-cancerous tissues. Creatine and glycine in both serum and urine were selected as the optimal biofluids biomarker panel for ESCC detection, as they were the overlapping discriminative metabolites across serum, urine and cancer tissues in ESCC patients. Also, the were the major metabolites involved in the perturbation of "glycine, serine, and threonine metabolism", the significant pathway alteration associated with ESCC progression. Then a visual predictive nomogram was constructed by combining creatine and glycine in both serum and urine, which exhibited superior diagnostic efficiency (with an AUC of 0.930) than any diagnostic model constructed by a single urine or serum metabolic biomarkers. Overall, this study highlighted that NMR-based biofluids metabolomics fingerprinting, as a non-invasive predictor, has the potential utility for ESCC detection. Further studies based on a lager number size and in combination with other omics or molecular biological approaches are needed to validate the metabolic pathway disturbances in ESCC patients.

Impact of Relative Dose Intensity of Docetaxel, Cisplatin, and 5-Fluorouracil Neoadjuvant Chemotherapy on Survival of Esophageal Squamous Cell Cancer Patients

Introduction: This study aimed to clarify the impact of the average relative dose intensity (RDI) of neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-NAC) for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Materials and Methods: To identify the optimal RDI, recurrence-free survival (RFS) and cumulative incidence function (CIF) for recurrence were calculated in low and high RDI groups with any cut-off points. The optimal RDI was defined as the highest RDI administered with a significant increase in either RFS or CIF. The clinicopathological characteristics of the two groups divided by optimal RDI were investigated. The preoperative prognostic factors associated with RFS were confirmed by multivariable Cox proportional hazards model. Results: Among the 150 eligible patients treated with DCF-NAC from 2010 to 2020, 3-year RFS and CIF were 56.3% and 37.8% in 90 patients in the less than 80% RDI group (<80% RDI) and 73.3% and 26.7% in 60 patients in the more than or equal to 80% RDI group (≥80% RDI), respectively. The optimal cut-off RDI was identified as 80%. The <80% RDI group included older individuals, a lower value of creatinine clearance, a higher Charlson Comorbidity Index, reduced RDI at first course, and grade 1–0 in the histopathological tumor response than the ≥80% RDI group. R0 resection and postoperative complication rates were equal in both groups. Cox proportional hazards model identified the response rate and RDI as predictors of RFS. Conclusion: An average RDI of more than or equal to 80% improved prognosis in patients receiving DCF-NAC for ESCC.

Prognostic value of proliferation markers Ki-67 and PCNA in esophageal squamous cell carcinoma.

Ki-67 and proliferating cell nuclear antigen (PCNA) are markers of proliferation used to assess the growth fraction of the cell population. The present study aimed to explore the prognostic value of these proliferative markers in patients with resected esophageal squamous cell cancer (ESCC) in a large cohort. A total of 807 patients with ESCC who underwent radical resection were retrospectively reviewed. Ki-67 and PCNA index were examined as the percentage of positively nuclear-stained cells among total number of cancer cells in three high-power fields by a pathologist who was blinded to the patients' history and outcome. Overall survival (OS) and disease-free survival (DFS) were estimated. The Cox regression model was used to evaluate the independent factor. The cut-off value as 60 and 80% for Ki-67 and PCNA were verified, respectively. Higher Ki-67 expression was associated with low differentiation and more lymph node metastasis. Higher PCNA expression was associated with elevated T stage. However, either expression of Ki-67 or PCNA was not correlated with OS and DFS. While in combination of Ki-67 and PCNA analysis, higher expression of these two proliferative markers predicted worse prognosis (median OS, 47 months versus 54 months, P = 0.04). Whatever the combined proliferative marker, differentiation, lymph node metastasis stage and vascular invasion act as factors in univariate survival analysis, but combined Ki-67 and PCNA is not an independent prognostic variable in multivariate analysis (P = 0.10). Our results suggest that proliferative markers of Ki-67 and PCNA may correlate with tumor stage but cannot act as independent predictor of prognosis in ESCC patients.

Combination of neutrophil-to-lymphocyte ratio and albumin concentration to predict the prognosis of esophageal squamous cell cancer patients undergoing esophagectomy

Combination of neutrophil-to-lymphocyte ratio and albumin concentration to predict the prognosis of esophageal squamous cell cancer patients undergoing esophagectomy

Post-treatment serum triglyceride: An effective biomarker for body fat mass and overall survival in esophageal squamous cell cancer patients treated with chemoradiotherapy.

Although lipids have been assessed for their possible roles in cancer survival prediction, studies on the association between serum triglyceride (TG) levels and the prognosis of esophageal squamous cell carcinoma (ESCC) patients are limited. This study aimed to evaluate whether serum TG is associated with outcomes in patients with ESCC and investigate any interaction between serum TG and clinical parameters, especially body fat mass. We conducted a prospective case study on patients diagnosed with ESCC between March 2012 and November 2018. We measured patients' serum TG levels before and after treatment. The association between serum TG and overall survival (OS) was evaluated using hazard ratios. We sought to determine a threshold point using optimal stratification. Survival analysis was performed using Kaplan-Meier curves and a Cox proportional hazards model. Of the 257 participants diagnosed with ESCC, 200 (77.8%) were men. Median follow-up time was 22.4 months (range 3.3-92.4 months). Using univariate Cox proportional hazard analysis and subsequent multivariate analysis, post-TG levels, Karnofsky performance scores, T stages, and chemotherapy cycles were shown to be independent prognostic factors for OS (p < 0.05). The post-TG cut-off point to best classify patients with respect to time to mortality was 1.47 mmol/L. A post-TG level of ≥ 1.47 mmol/L could independently predict a better OS (hazard ratio: 0.55, 95% confidence interval: 0.37-0.79). The associations were consistent across the subtypes of clinical parameters. Furthermore, the post-body mass index, post-subcutaneous adipose tissue area, post-visceral adipose tissue area, post-total adiposity tissue area, and post-total adipose density exhibited a strong positive association with post-TG levels. Post-TG levels were found to be a significant positive prognostic biomarker for body fat mass and OS in ESCC patients.