Plasma-based lipidomics reveals potential diagnostic biomarkers for esophageal squamous cell carcinoma: a retrospective study.

Background: Esophageal squamous cell carcinoma (ESCC) is highly prevalent and has a high mortality rate. Traditional diagnostic methods, such as imaging examinations and blood tumor marker tests, are not effective in accurately diagnosing ESCC due to their low sensitivity and specificity. Esophageal endoscopic biopsy, which is considered as the gold standard, is not suitable for screening due to its invasiveness and high cost. Therefore, this study aimed to develop a convenient and low-cost diagnostic method for ESCC using plasma-based lipidomics analysis combined with machine learning (ML) algorithms. Methods: Plasma samples from a total of 40 ESCC patients and 31 healthy controls were used for lipidomics study. Untargeted lipidomics analysis was conducted through liquid chromatography-mass spectrometry (LC-MS) analysis. Differentially expressed lipid features were filtered based on multivariate and univariate analysis, and lipid annotation was performed using MS-DIAL software. Results: A total of 99 differential lipids were identified, with 15 up-regulated lipids and 84 down-regulated lipids, suggesting their potential as diagnostic targets for ESCC. In the single-lipid plasma-based diagnostic model, nine specific lipids (FA 15:4, FA 27:1, FA 28:7, FA 28:0, FA 36:0, FA 39:0, FA 42:0, FA 44:0, and DG 37:7) exhibited excellent diagnostic performance, with an area under the curve (AUC) exceeding 0.99. Furthermore, multiple lipid-based ML models also demonstrated comparable diagnostic ability for ESCC. These findings indicate plasma lipids as a promising diagnostic approach for ESCC.

Early postoperative systemic inflammatory response as predictor of anastomotic leakage after esophagectomy: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Postesophagectomy anastomotic leakage occurs in up to 16% of patients and is the main cause of morbidity and mortality. The leak severity is determined by the extent of contamination and the degree of sepsis, both of which are related to the time from onset to treatment. Early prediction based on inflammatory biomarkers such as C-reactive protein (CRP) levels, white blood cell counts, albumin levels, and combined Noble-Underwood (NUn) scores can guide early management. This review aimed to determine the diagnostic accuracy of these biomarkers. METHODS: This study was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the PROSPERO (International Prospective Register of Systematic Reviews) database. Two reviewers independently conducted searches across PubMed, MEDLINE, Web of Science, and Embase. Sources of bias were assessed, and a meta-analysis was performed. RESULTS: Data from 5348 patients were analyzed, and 13% experienced leakage. The diagnostic accuracy of the serum biomarkers was analyzed, and pooled cutoff values were identified. CRP levels were found to have good diagnostic accuracy on days 2 to 5. The best discrimination was identified on day 2 for a cutoff value < 222 mg/L (area under the curve = 0.824, sensitivity = 81%, specificity = 88%, positive predictive value = 38.6%, and negative predictive value = 98%). A NUn score of >10 on day 4 correlated with poor diagnostic accuracy. CONCLUSION: The NUn score failed to achieve adequate accuracy. CRP seems to be the only valuable biomarker and is a negative predictor of postesophagectomy leakage. Patients with a CRP concentration of <222 mg/L on day 2 are unlikely to develop a leak, and patients can safely proceed through their enhanced recovery after surgery protocol. Patients with a CRP concentration of <127 mg/L on day 5 can be safely discharged when clinically possible.

The Prognostic Immune and Nutritional Indices Are Independent Prognostic Factors for Esophageal Cancer Patients Who Receive Curative Treatment.

BACKGROUND/AIM: Recently, the prognostic immune and nutritional index (PINI) was developed and reported to be a promising nutritional and inflammatory prognostic marker. The aim of the present study was to clarify the clinical impact of the PINI for esophageal cancer patients who received curative treatment. PATIENTS AND METHODS: We conducted a retrospective review of medical records and collected data on consecutive esophageal cancer patients who underwent curative resection at Yokohama City University between 2005 and 2020. The PINI was calculated by dividing the serum ALB concentration (g/dl) by the serum monocyte concentration, both of which were measured before surgery. RESULTS: A total of 180 patients were included in this study. The cutoff value of the PINI was 3.0 in the present study. The 3- and 5-year overall survival rates were 45.2% and 33.5%, respectively, in the PINI-low subgroup, and 69.1% and 61.8%, respectively, in the PINI-high subgroup. A multivariate analysis demonstrated that the PINI was an independent prognostic factor for overall survival (hazard ratio=2.091, 95% confidence interval=1.287-3.399, p=0.003). Similar results were observed for recurrence-free survival. When comparing the sites of recurrence between the two groups, the incidence of hematological recurrence was significantly greater in the PINI-low subgroup compared to the PINI-high subgroup (46.8% vs. 21.1%, p<0.001). CONCLUSION: The PINI is a promising nutritional and inflammatory marker for esophageal cancer patients. The PINI might be a useful marker for the treatment and management of esophageal cancer patients.

The Clinical Impact of the Pretreatment Albumin to Fibrinogen Ratio in Esophageal Cancer Patients Who Receive Curative Treatment.

BACKGROUND/AIM: The albumin to fibrinogen ratio (AFR) has been identified as a promising prognostic marker for some malignancies. The aim of the present study was to evaluate the clinical impact of AFR in esophageal cancer patients who received curative resection. PATIENTS AND METHODS: The present study included 123 patients who underwent curative treatment for esophageal cancer between 2005 and 2020. The prognosis and clinicopathological parameters were compared between patients with high and low AFRs. RESULTS: The overall survival (OS) stratified by each clinical factor was compared using the log-rank test, and a significant difference was observed when using a pretreatment AFR of 1.23. When comparing the patient backgrounds between the high-AFR (AFR ≥12.3) and low-AFR (AFR<12.3) groups, significant differences were noted in the pathological T status. The high-AFR group had significantly higher OS rates at 3 years (70.8%) and 5 years (59.3%) after surgery in comparison to the low-AFR group (46.6% and 37.4%, respectively). Univariate and multivariate analyses for OS showed that the AFR was a significant prognostic factor. In addition, when comparing the site of first recurrence, a marginally significant difference was noted in hematological recurrence. CONCLUSION: The AFR is a significant risk factor in patients with esophageal cancer, holding promise as a valuable prognostic factor.

Role of IL4 and GMCSF in Predicting Survival in Esophageal Cancer.

BACKGROUND: Esophageal cancer (EC) originates in the setting of chronic inflammation. Although previous studies have sought to understand the role of inflammatory signaling in EC, the effect of these immunologic changes on patient outcomes remains understudied. This study's objective was to identify relationships between cytokine levels and prognosis in a mixed cohort of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) patients. STUDY DESIGN: A total of 37 serum cytokines were profiled at the time of resection using multiplex ELISA in 47 patients (42 esophageal adenocarcinoma, 5 esophageal squamous cell carcinoma). Cytokine levels were median-binarized and assessed using Cox regression models. Findings were validated at the RNA level using The Cancer Genome Atlas EC cohort (81 esophageal adenocarcinoma, 81 esophageal squamous cell carcinoma). RESULTS: Univariable analysis revealed high serum interleukin 4 (IL4) and granulocyte-macrophage colony-stimulating factor (GMCSF) were negatively associated with overall survival (p = 0.046, p = 0.040). Multivariable analysis determined both high serum IL4 or high serum GMCSF were negatively associated with survival independent of important clinical factors (hazard ratio [HR] 7.55, p < 0.001; HR 5.24, p = 0.001). These findings were validated at the RNA level in The Cancer Genome Atlas EC cohort, where multivariable analysis identified high IL4 expression, high CSF2 expression (encodes GMCSF), and advanced pathologic stage as independent negative predictors of survival when controlled for clinical factors (HR 2.35, p = 0.012; HR 1.97, p = 0.040). CONCLUSIONS: These results show that high IL4/GMCSF levels are negatively associated with survival in EC. These relationships are independent of pathologic stage and are identified across modalities, histologic subtypes, and the presence/absence of neoadjuvant therapy.

Comprehensive RNA dataset of tissue and plasma from patients with esophageal cancer or precursor lesions.

In the past decades, the incidence of esophageal adenocarcinoma has increased dramatically in Western populations. Better understanding of disease etiology along with the identification of novel prognostic and predictive biomarkers are urgently needed to improve the dismal survival probabilities. Here, we performed comprehensive RNA (coding and non-coding) profiling in various samples from 17 patients diagnosed with esophageal adenocarcinoma, high-grade dysplastic or non-dysplastic Barrett's esophagus. Per patient, a blood plasma sample, and a healthy and disease esophageal tissue sample were included. In total, this comprehensive dataset consists of 102 sequenced libraries from 51 samples. Based on this data, 119 expression profiles are available for three biotypes, including miRNA (51), mRNA (51) and circRNA (17). This unique resource allows for discovery of novel biomarkers and disease mechanisms, comparison of tissue and liquid biopsy profiles, integration of coding and non-coding RNA patterns, and can serve as a validation dataset in other RNA landscaping studies. Moreover, structural RNA differences can be identified in this dataset, including protein coding mutations, fusion genes, and circular RNAs.

A Review of Circulating Tumor DNA in the Diagnosis and Monitoring of Esophageal Cancer.

Circulating tumor DNA (ctDNA) is a type of cell-free DNA released by tumor cells after necrosis and apoptosis, and it can be actively secreted by tumor cells. Since ctDNA is derived from various tumor sites, it can provide far more comprehensive genomic and epigenomic information than a single-site biopsy. Therefore, ctDNA can overcome tumor heterogeneity, which is the major limitation of a traditional tissue biopsy approach. Noninvasive ctDNA assays allow continuous real-time monitoring of the molecular status of cancers. Recently, ctDNA assays have been widely used in clinical practice, including cancer diagnosis, evaluation of therapeutic efficacy and prognosis, and monitoring of relapse and metastasis. Although ctDNA shows a high diagnostic performance in advanced esophageal cancer, it is far from satisfactory for early diagnosis of esophageal cancer. Monitoring the dynamic changes of ctDNA is beneficial for the evaluation of therapeutic efficacy and prediction of early recurrence in esophageal cancer. It is necessary to establish standards for individualized ctDNA detection in the evaluation of treatment response and surveillance of esophageal cancer and to develop clinical practice guideline for the systemic treatment of patients with "ctDNA recurrence." This review aims to provide an update on the role of ctDNA in the diagnosis and monitoring of esophageal cancer.

Prognostic value of hemoglobin combined with Geriatric Nutritional Risk Index scores in patients undergoing postoperative radiotherapy for esophageal squamous cell carcinoma.

Aims: To investigate the prognostic value of hemoglobin combined with geriatric nutritional risk index (GNRI) scores in patients undergoing postoperative radiotherapy for esophageal squamous cell carcinoma (ESCC). Patients & methods: Patients who underwent esophagectomy and postoperative radiotherapy were included in this retrospective study. Their preoperative hemoglobin and GNRI were collected to establish hemoglobin-GNRI (H-GNRI) scores, and their association with OS was evaluated. Results: Patients with high H-GNRI scores had better prognosis than those with low scores (p < 0.001). Differentiation (p = 0.001), T classification (p = 0.010), N classification (p = 0.001) and H-GNRI score (p = 0.018) were independent prognostic factors for all patients. Conclusion: H-GNRI score is an independent prognostic factor for the survival of patients with ESCC managed by surgery and postoperative radiotherapy.

The value of complete blood count for the prognosis analysis of preoperative esophageal squamous cell carcinoma.

OBJECTIVE: To investigate the predictive value of preoperative complete blood count for the survival of patients with esophageal squamous cell carcinoma. METHODS: A total of 1587 patients with pathologically confirmed esophageal squamous cell carcinoma who underwent esophagectomy in the Cancer Hospital Affiliated to Xinjiang Medical University from January 2010 to December 2019 were collected by retrospective study. A total of 359 patients were as the validation cohort from January 2015 to December 2016, and the remaining 1228 patients were as the training cohort. The relevant clinical data were collected by the medical record system, and the patients were followed up by the hospital medical record follow-up system. The follow-up outcome was patient death. The survival time of all patients was obtained. The Cox proportional hazards regression model and nomogram were established to predict the survival prognosis of esophageal squamous cell carcinoma by the index, their cut-off values obtained the training cohort by the ROC curve. The Kaplan-Meier survival curve was established to express the overall survival rate. The 3-year and 5-year calibration curves and C-index were used to determine the accuracy and discrimination of the prognostic model. The decision curve analysis was used to predict the potential of clinical application. Finally, the validation cohort was used to verify the results of the training cohort. RESULTS: The cut-off values of NLR, NMR, LMR, RDW and PDW in complete blood count of the training cohort were 3.29, 12.77, 2.95, 15.05 and 13.65%, respectively. All indicators were divided into high and low groups according to cut-off values. Univariate Cox regression analysis model showed that age (≥ 60), NLR (≥3.29), LMR (< 2.95), RDW (≥15.05%) and PDW (≥13.65%) were risk factors for the prognosis of esophageal squamous cell carcinoma; multivariate Cox regression analysis model showed that age (≥ 60), NLR (≥3.29) and LMR (< 2.95) were independent risk factors for esophageal squamous cell carcinoma. Kaplan-Meier curve indicated that age <  60, NLR < 3.52 and LMR ≥ 2.95 groups had higher overall survival (p <  0.05). The 3-year calibration curve indicated that its predictive probability overestimate the actual probability. 5-year calibration curve indicated that its predictive probability was consistent with the actual probability. 5 c-index was 0.730 and 0.737, respectively, indicating that the prognostic model had high accuracy and discrimination. The decision curve analysis indicated good potential for clinical application. The validation cohort also proved the validity of the prognostic model. CONCLUSION: NLR and LMR results in complete blood count results can be used to predict the survival prognosis of patients with preoperative esophageal squamous cell carcinoma.

Diagnostic value of serum tumor-associated autoantibodies in esophageal cancer.

Aim: To explore the application value of serum autoantibodies in the early diagnosis of esophageal cancer. Materials & methods: A total of 130 patients with esophageal cancer and 110 controls were included and tested by ELISA. Results: According to the receiver operating characteristic curve, total sensitivity is 83.08%, total specificity is 72.73%. A nomogram was established based on the positive judgment standard, the area under the receiver operating characteristic curve was calculated to be 0.880 after verification with the calibration curve. A 2-week follow-up analysis found compared with the preoperative control, the postoperative model integral value will significantly decrease. Conclusion: The combination of serum autoantibody groups has certain clinical application value in the early diagnosis of esophageal cancer and can be used as an auxiliary index for early diagnosis.

Early dynamics of circulating tumor DNA predict chemotherapy responses for patients with esophageal cancer.

We investigated whether early circulating tumor DNA (ctDNA) changes, measured using digital PCR (dPCR), can predict later chemotherapy responses in esophageal squamous cell cancer (ESCC). We compared the dynamics of ctDNA and tumor volumes during chemotherapy in 42 ESCC. The accuracy of predictions of later chemotherapy responses was evaluated by the ratio of the variant allele frequency of ctDNA (post-/pre-ctDNA) and the total tumor volume (post-/pre-volume) before and after an initial chemotherapy cycle using a receiver-operating characteristic curve analysis. Total positive and negative objective responses (ORs) were defined as either >50 or ≤50% reductions, respectively, in the total tumor volume at the end of first-line chemotherapy. Mutation screening of 43 tumors from 42 patients revealed 96 mutations. The pretreatment dPCR-ctDNA data were informative in 38 patients, using 70 selected mutations (1-3 per patient). The areas under the curve (AUCs) for the post-/pre-volume and post-/pre-ctDNA levels used in predicting the total OR were 0.85 and 0.88, respectively. The optimal cutoff value of post-/pre-ctDNA was 0.13. In 20 patients with post-/pre-volume ≥50%, the total OR could be predicted by the post-/pre-ctDNA with high accuracy; the AUC by post-/pre-ctDNA was higher than that by post-/pre-volume (0.85 versus 0.76, respectively). Patients with low post-/pre-ctDNA (n = 18) had a significantly better overall survival rate than those with high post-/pre-ctDNA (n = 20; P = 0.03). Early ctDNA changes after an initial cycle of chemotherapy predict later responses to treatment with high accuracy in ESCC patients.

Biological correlates before esophageal cancer screening and after diagnosis.

Almost 50% of the world's esophageal cancer (EC) cases occur in China, and the impact of cancer screening has long been a controversial topic. The study was designed to evaluate the biological correlates of EC screening and subsequent diagnosis in China. Based on the national cohort of esophageal cancer program, a prospective multicenter study in high-risk regions was conducted from 2017 to 2019. 61 participants received twice esophageal endoscopy screening and pathological biopsy successively (with a mean follow-up of 14.03 months). Box-Cox-power transformation and two-way repeated measures ANOVA were used to evaluate hormone cortisol and immunoglobulin (IgA, IgG, IgM) levels in plasma, reflecting their stress, immune function, and biological correlates before screening and after knowing the diagnosis. The median of cortisol, IgA, IgG, and IgM in pre-screening was 15.46 ug/dL, 1.86 g/L, 12.14 g/L, and 0.91 g/L, corresponding value at post-diagnosis was 15.30 ug/dL, 2.00 g/L, 12.79 g/L, and 0.94 g/L, respectively. No significant differences in biological indicators were found between normal and esophagitis and low-grade intraepithelial neoplasia before screening and after diagnosis. After normality transformation, cortisol, IgA, IgG and IgM levels were (0.25 ± 0.04) U/mL, (0.72 ± 0.13) (g/L), (2.44 ± 0.22) (g/L) and (0.98 ± 0.25) (g/L) before screening, (0.25 ± 0.05) U/mL, (0.70 ± 0.13) (g/L), (2.48 ± 0.21) (g/L) and (1.00 ± 0.25) (g/L) after diagnosis, respectively. Repeated Measures ANOVA showed that the main effects were significant on IgA levels between pre-screening and post-diagnosis (P = 0.019). No interaction effects on biological levels between pre-post screening and esophageal pathology, anxiety states (all P > 0.05). Little biological correlates were found both before screening and after diagnosis. Cortisol and IgA dropped less significantly, while IgM and IgA were increased slightly after diagnosis. Further multi-round longitudinal studies are needed to validate these results.

ctDNA analysis in the personalized clinical management of gastroesophageal adenocarcinoma: turning hope into reality.

Gastroesophageal adenocarcinoma (GEA) is a global health issue with a high fatality-to-case ratio and a 5-year overall survival that has only slightly improved. High-throughput molecular profiling has uncovered a profound complexity and heterogeneity in GEA biology, which limits considerably the treatment advances. Liquid biopsy with circulating tumor (ct)DNA analysis could elucidate GEA molecular heterogeneity and provide diagnostic, prognostic and predictive information to guide clinical decision-making. However, only a handful of studies have shown positive results for the application of ctDNA analysis in GEA clinical management. As a result, no comprehensive information is available to date on this continuously evolving topic. Here, we discuss the current state of knowledge, along with promises and challenges related to ctDNA analysis in GEA.

Perioperative change in neutrophil count predicts worse survival in esophageal squamous cell carcinoma.

Aims: This study aimed to investigate the relationship between perioperative change in neutrophil count and survival of patients with esophageal squamous cell carcinoma. Method: Neutrophil change (Nc) (where Nc = post-surgery neutrophil count - pre-surgery neutrophil count) was counted according to data within 1 week before surgery and 2 weeks after surgery. Patients were divided into two groups, Nc ≥2.60 and Nc <2.60, according to the median of Nc. Results: Multivariate analysis revealed that Nc ≥2.60 was an independent prognostic marker for overall survival. Subgroup analysis suggested that the overall survival of male patients, patients aged ≤60 years, patients without vessel invasion and patients without nerve infiltration was dramatically worse for those with Nc <2.60. Conclusion: Perioperative change in neutrophil count predicts worse survival in esophageal squamous cell carcinoma after surgery.

Identification of serum prognostic marker miRNAs and construction of microRNA-mRNA networks of esophageal cancer.

Esophageal cancer is a common tumor of the digestive system with poor prognosis. This study was to gain a better understanding of the mechanisms involved in esophageal cancer and to identify new prognostic markers. We downloaded the esophageal cancer miRNA expression profile microarray data (GSE113740, GSE112264, GSE122497, GSE113486, and GSE106817) from the GEO database, extracted the esophageal cancer miRNA sequencing data from The Cancer Genome Atlas (TCGA) database, and then used a bioinformatics approach to select common differentially expressed miRNAs (DEMs). Differentially expressed genes (DEGs) were selected by predicting DEM target genes using the miRWalk database and intersecting with differential genes obtained from TCGA database for esophageal cancer. The STRING database was used to obtain protein-protein interaction (PPI) relationships to construct the DEM-DEG network. Furthermore, we selected core genes and core miRNAs associated with esophageal cancer prognosis by performing survival and univariate/multivariate COX analysis on DEMs and DEGs in the network and performed GSEA analysis on core genes alone, and finally the expression of the markers was verified by qPCR in esophageal cancer cell lines Eca109, SKGT-4 and normal esophageal epithelial cells HEEC. Nine DEMs were obtained, of which three were upregulated and six were downregulated, and 326 DEGs were obtained, of which 105 were upregulated and 221 were downregulated. Survival univariate/multivariate COX analysis revealed that five genes, ZBTB16, AQP4, ADCYAP1R1, PDGFD, and VIPR2, and two microRNAs, miR-99a-5p, and miR-508-5p, were related to esophageal cancer prognosis. GSEA analysis showed that the following genes may be involved in esophageal cancer prognosis: ZBTB16 may through the MTOR signaling pathway, AQP4 through the GNRH signaling pathway, ADCYAP1R1 through the PPAR signaling pathway, VIPR2 through the P53 signaling pathway and PDGFD through the PENTOSE-PHOSPHATE signaling pathway.

Elevated serum eotaxin and IP-10 levels as potential biomarkers for the detection of esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Esophageal squamous cell cancer (ESCC) is one of the leading malignant cancers with a high incidence and mortality. Exploring novel serum biomarkers will help improve the management and monitoring of ESCC. METHODS: In the present study, we first used a ProcartaPlex Array to screen for serum proteins that were increased in 40 ESCC patients compared with matched normal controls; we found that eight proteins (IL-2, IL-5, IP-10, IL-8, eotaxin, TNF-α, HGF, and MIP-1b) had higher serum levels in ESCC patients than in normal controls. We further verified the clinical relevance of the candidate biomarkers with a larger sample of sera. RESULTS: In the 174 tested ESCC patients and 189 normal controls, the serum levels of eotaxin and IP-10 were significantly higher in patients than in normal controls (p = 0.0038, 0.0031). In particular, these two proteins were also elevated in the sera of patients with early-stage (0-IIA) ESCC (p = 0.0041, 0.0412). When combining CEA and CYFRA21-1 (in use clinically) with eotaxin or IP-10, the effectiveness of detecting ESCC was superior to that of CEA and/or CYFRA21-1 alone. Moreover, the serum level of eotaxin dropped significantly after surgical resection of primary tumors compared with that in preoperative ESCC samples (p < 0.001). CONCLUSIONS: The data suggest that serum eotaxin and IP-10 might be potential biomarkers for the detection of ESCC.

OSK-0028 in Patients With Esophageal Cancer Undergoing Esophagectomy: A Double-blind, Randomised Controlled Trial.

BACKGROUND/AIM: An excessive postoperative inflammatory response is correlated with the development of pneumonia and an unfavourable prognosis in patients undergoing esophagectomy for esophageal cancer. We assessed the influence of OSK-0028, a synthetic human ghrelin on inflammatory response and energy metabolism, on the postoperative course of patients following radical esophagectomy. PATIENTS AND METHODS: Esophageal cancer patients were randomly assigned to low-dose (LD; 0.25 µg/kg/h) or high-dose (HD; 0.5 µg/kg/h) intravenous OSK-0028 or placebo for 7 days after esophagectomy. The primary endpoint was serum interleukin-6 level on postoperative day (POD) 3. RESULTS: A total of 75 patients were enrolled (23 LD, 26 HD, 26 placebo). The median interleukin-6 levels on POD 3 were 40.95, 35.85, and 64.50 pg/ml in the placebo, LD, and HD groups, respectively, with no significant differences (p=0.78). Postoperative complications did not differ between groups. Bodyweight loss was significantly lower in patients receiving OSK-0028 than in those receiving placebo (-0.17% vs. 1.78%, p=0.043). CONCLUSION: Although OSK-0028 did not attenuate inflammatory response after esophagectomy, it prevented postoperative bodyweight loss.

Combining Preoperative Immunoinflammatory Scores and 18F-Fluorodeoxyglucose Positron-emission Tomography Predicts Beneficiaries of Salvage Esophagectomy.

BACKGROUND: This study evaluated the prognostic value of preoperative immunoinflammatory scores and 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) for patients undergoing salvage esophagectomy to identify suitable candidates for surgery. PATIENTS AND METHODS: Twenty-five patients undergoing salvage esophagectomy were included. The prognostic value of the preoperative C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and maximum standardized FDG uptake value (SUVmax) were investigated. RESULTS: Multivariate analysis demonstrated high CAR to be an independent prognostic factor for overall survival (p=0.013). CAR had no association with clinicopathological variables, whereas the SUVmax was significantly positively associated with tumor aggressiveness. Multivariate analysis using residual tumor and the combination of CAR and SUVmax revealed both residual tumor (p=0.009) and high CAR/high SUVmax (p=0.016) to be independent prognostic factors for overall survival. CONCLUSION: Preoperative evaluation of CAR as an immunoinflammatory indicator and SUVmax as a marker of tumor aggressiveness will be useful to identify suitable candidates for this high-risk surgery.

TP53 Targeted Deep Sequencing of Cell-Free DNA in Esophageal Squamous Cell Carcinoma Using Low-Quality Serum: Concordance with Tumor Mutation.

Circulating cell-free DNA (cfDNA) is emerging as a potential tumor biomarker. CfDNA-based biomarkers may be applicable in tumors without an available non-invasive screening method among at-risk populations. Esophageal squamous cell carcinoma (ESCC) and residents of the Asian cancer belt are examples of those malignancies and populations. Previous epidemiological studies using cfDNA have pointed to the need for high volumes of good quality plasma (i.e., >1 mL plasma with 0 or 1 cycles of freeze-thaw) rather than archival serum, which is often the main available source of cfDNA in retrospective studies. Here, we have investigated the concordance of TP53 mutations in tumor tissue and cfDNA extracted from archival serum left-over from 42 cases and 39 matched controls (age, gender, residence) in a high-risk area of Northern Iran (Golestan). Deep sequencing of TP53 coding regions was complemented with a specialized variant caller (Needlestack). Overall, 23% to 31% of mutations were concordantly detected in tumor and serum cfDNA (based on two false discovery rate thresholds). Concordance was positively correlated with high cfDNA concentration, smoking history (p-value = 0.02) and mutations with a high potential of neoantigen formation (OR; 95%CI = 1.9 (1.11-3.29)), suggesting that tumor DNA release in the bloodstream might reflect the effects of immune and inflammatory context on tumor cell turnover. We identified TP53 mutations in five controls, one of whom was subsequently diagnosed with ESCC. Overall, the results showed that cfDNA mutations can be reliably identified by deep sequencing of archival serum, with a rate of success comparable to plasma. Nonetheless, 70% non-identifiable mutations among cancer patients and 12% mutation detection in controls are the main challenges in applying cfDNA to detect tumor-related variants when blindly targeting whole coding regions of the TP53 gene in ESCC.