Early-stage Esophageal Cancer Research Articles

1413P Multi-modal deep-learning model for real-time prediction of recurrence in early-stage esophageal cancer: A multi-modal approach

1413P Multi-modal deep-learning model for real-time prediction of recurrence in early-stage esophageal cancer: A multi-modal approach

Exosomes in esophageal cancer: Promising nanocarriers in cancer progression, diagnosis, prognosis, and therapy.

Esophageal cancer (EC) is one of the most fatal cancers all over the world. Sensitive detection modalities for early-stage EC and efficient treatment methods are urgently needed for the improvement of the prognosis of EC. Exosomes are small vesicles for intercellular communication, mediating many biological responses including cancer progression, which are not only promising biomarkers for diagnosis and prognosis but also therapeutic tools for EC. This review provides an overview of the relationships between exosomes and EC progression, as well as the application of exosomes in the diagnosis, prognosis, and treatment of EC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Importance of early detection of esophageal cancer before the tumor progresses too much for effective treatment

This editorial comments on an article by Qu et al published in the World Journal of Gastrointestinal Oncology . It focuses on the importance of early detection of esophageal cancer, including recurrence or secondary malignancy after chemoradiotherapy (CRT). Endoscopic resection is the first choice for treatment for esophageal cancer remaining within the mucous membrane, while surgery or radical CRT are treatment options for advanced stages depending on the patient’s general condition and desire. Although these treatments are potentially curative, they are more invasive than endoscopic resection. Early-stage esophageal cancer is often asymptomatic and difficult to detect. Uniform periodic endoscopy is unrealistic. Although less burdensome tests exist, including liquid biopsy and urinary biomarkers, these have not yet been widely used in clinical practice. Early detection is important after radical CRT because the local recurrence rate is higher than that after surgery. However, endoscopic resection or photodynamic therapy is indicated if detected in the early stages, and positive results have been reported. Early detection of esophageal cancer is crucial. Endoscopy is the main diagnostic method; however, new and less burdensome methods should be established to ensure early treatment for patients with esophageal cancer.

Efficacy and prognostic analysis of carbon nanotracers combined with the da Vinci robot in the treatment of esophageal cancer.

Traditional methods cannot clearly visualize esophageal cancer (EC) tumor contours and metastases, which limits the clinical application of da Vinci robot-assisted surgery. To investigate the efficacy of the da Vinci robot in combination with nanocarbon lymph node tracers in radical surgery of EC. In total, 104 patients with early-stage EC who were admitted to Liuzhou worker's Hospital from January 2020 to June 2023 were enrolled. The patients were assigned to an observation group (n = 52), which underwent da Vinci robot-assisted minimally invasive esophagectomy (RAMIE) with the intraoperative use of nanocarbon tracers, and a control group (n = 52), which underwent traditional surgery treatment. The operation time, intraoperative blood loss, postoperative drainage tube indwelling time, hospital stay, number of lymph nodes dissected, incidence of complications, and long-term curative effects were comparatively analyzed. The postoperative stress response C-reactive protein (CRP), cortisol, epinephrine (E) and inflammatory response interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) were evaluated. Compared with the control group, the observation group had significantly lower postoperative CRP, cortisol, and E levels (P < 0.05) with a milder inflammatory response, as indicated by lower IL-6, IL-10, and TNF-α levels (P < 0.05). Patients who underwent RAMIE had less intraoperative blood loss and shorter operation times and hospital stays than those who underwent traditional surgery. The average number of dissected lymph nodes, time of lymph node dissection, and mean smallest lymph node diameter were all significantly lower in the observation group (P < 0.05). The rate of postoperative complications was 5.77% in the observation group, significantly lower than the 15.38% observed in the control group. Furthermore, the lymphatic metastasis rate, reoperation rate, and 12- and 24-month cumulative mortality in the observation group were 1.92%, 0%, 0%, and 0%, respectively, all of which were significantly lower than those in the control group (P < 0.05). The treatment of EC using the da Vinci robot combined with nanocarbon lymph node tracers can achieve good surgical outcomes and demonstrates promising clinical applications.

Supersulfide metabolome of exhaled breath condensate for diagnostic biomarkers of esophageal cancer.

e15027 Background: The early estimate and detection of esophageal cancer (EC) is essentially required for continuous esophagogastroduodenoscopy and histopathological diagnosis. However, endoscopic examination is sometimes invasive, which may cause somehow limited clinical application and compliance. Also, the traditional blood tumor marker is unsuitable for a cancer screening. In recent years, the energy production by sulfur respiration in hypoxic environments in cancer tissues is getting spotlighted in tumor biology. The current study is aimed to evaluate usefulness of sulfur containing compounds as new biomarkers for EC by using blood samples and exhaled breath condensate (EBC) that can be readily obtained in a non-invasive fashion. Methods: Fifty EC patients were included in the study between June 2021 and September 2021. EBC and plasma samples were collected before starting any medicinal remedy including medication, chemotherapy, radiation, surgery, and endoscopic and dentistry maneuvers. Thirty healthy controls were recruited if they did not have any cancer history, surgery and aged over 50s preferred age for esophageal cancer. All samples were stored at -80℃ immediately after appropriate preparation until the following inspection. Then, sulfur metabolome analysis using LC-MS/MS was performed to see the difference of metabolic profile between the two groups. We used Student t tests for comparing two groups, and one -way ANOVA test for more than two groups, with significance set at P&lt;0.05. To evaluate the diagnostic value of some metabolites, ROC curves and the AUC were calculated. Results: The supersulfide metabolic profiles were remarkably different between EC patients and controls. Especially, cysteine persulfide (CysSSH) was significantly increased in both EBC and plasma of the EC patients. The sensitivity and specificity of CysSSH in EBC were 60% and 96%, respectively, with an AUC of 0.71. The sensitivity and specificity of CysSSH in plasma were 49% and 96%, respectively, with an AUC of 0.73. In addition, homocysteine persulfide (HomoCysSSH) in plasma showed more significant difference than CysSSH and was able to distinguish EC patients from healthy subjects with AUC of 0.93 (sensitivity, 89%; specificity, 96%). The level of HomoCysSSH was correlated with that of CysSSH in EBC. The subgroup analysis for histological subtypes and tumor progression showed that both two metabolites were increased in EC patients regardless of histological type and disease’ progression. In particular, the amount of homoCysSSH in plasma was statistically higher in early-stage EC than that of controls (p&lt;0.0001). Conclusions: Supersulfides like CysSSH and HomoCysSSH could be potential biomarkers for detecting EC. Cysteine persulfide from EBC may serve as a valuable non-invasive biomarker with similar detectable ability compared with several biomarkers of blood samples that are currently reported.

Injury to the Muscle Layer and Risk of Non-cardiac Chest Pain after Endoscopic Submucosal Dissection for Esophageal Cancer.

Non-cardiac chest pain (NCCP) is a frequent complication of endoscopic submucosal dissection (ESD) for early-stage esophageal cancer. However, little is known about relationships between ESD findings and NCCP. This study aims to evaluate the risk factors for NCCP, including ESD findings related to injury to the muscle layer. We enrolled a total of 296 lesions from 270 patients with esophageal squamous cell carcinoma (ESCC), who underwent ESD in our center. The grade of injury to the muscle layer caused by ESD was categorized as follows: grade 0: no exposure of muscularis propria; grade 1: muscularis propria exposure and/or whitish color change by the electrocoagulation; grade 2: torn muscularis propria with whitish color change by the electrocoagulation; and grade 3, esophageal perforation. The risk factors for NCCP, including ESD findings, were analyzed by univariate and multivariate analyses. NCCP occurred in 89 patients (33.0%) after esophageal ESD. Multivariate analysis demonstrated that younger age [odds ratio (OR) 0.95, 95% confidence interval (95%CI) 0.92-0.98, p=0.003), postoperative fever (>= 38°C) (OR=25.9, 95%CI: 2.89-232.10, p=0.004), ESD findings (grade 1: OR=3.99, 95%CI: 1.63-9.75, p=0.003 and grade 2: OR=3.18, 95%CI: 1.54-6.57, p=0.002) were independently associated with the incidence of post ESD NCCP. ESD findings relate to slight Injury to the muscle layer, such as muscularis propria exposure and whitish color change by the electrocoagulation were identified as risk factor for post ESD NCCP. We should therefore perform esophageal ESD carefully to avoid injuring the muscle layers.

Similar survival after endoscopic submucosal dissection and esophagectomy in early esophageal cancer and synchronous or metachronous head and neck cancer.

Early-stage esophageal cancer is treated using endoscopic submucosal dissection and esophagectomy. Field cancerization in patients with early-stage esophageal cancer affects treatment outcomes and causes synchronous or metachronous head and neck cancers. We hypothesized that esophagectomy could provide better overall and relapse-free survivals in patients with esophageal cancer and synchronous or metachronous head and neck cancer. We retrospectively identified patients with early esophageal squamous cell carcinoma and synchronous or metachronous head and neck cancers. We separated the patients into endoscopic submucosal dissection and esophagectomy groups to compare overall and relapse-free survivals. The study included 106 patients, 25 of whom underwent endoscopic submucosal dissection and 81 underwent esophagectomy. Overall and relapse-free survivals did not show significant differences between the two groups for both synchronous and metachronous head and neck cancers. Endoscopic submucosal dissection could provide similar overall and relapse-free survivals in patients with esophageal cancer and synchronous or metachronous head and neck cancer.

Recent breakthroughs in graphene quantum dot-enhanced sonodynamic and photodynamic therapy.

Water-soluble graphene quantum dots (GQDs) have recently exhibited considerable potential for diverse biomedical applications owing to their exceptional optical and chemical properties. However, the pronounced heterogeneity in the composition, size, and morphology of GQDs poses challenges for a comprehensive understanding of the intricate correlation between their structural attributes and functional properties. This variability also introduces complexities in scaling the production processes and addressing safety considerations. Light and sound have firmly established their role in clinical applications as pivotal energy sources for minimally invasive therapeutic interventions. Given the limited penetration depth of light, photodynamic therapy (PDT) predominantly targets superficial conditions such as dermatological disorders, head and neck malignancies, ocular ailments, and early-stage esophageal cancer. Conversely, ultrasound-based sonodynamic therapy (SDT) capitalizes on its superior ability to propagate and focus ultrasound within biological tissues, enabling a diverse range of therapeutic applications, including the management of gliomas, breast cancer, hematological tumors, and modulation of the blood-brain barrier (BBB). Considering the advancements in theranostic and precision therapies, reevaluating these conventional energy sources and their associated sensitizers is imperative. This review introduces three prevalent treatment modalities that harness light and sound stimuli: PDT, SDT, and a synergistic approach that integrates PDT and SDT. This study delineated the therapeutic dynamics and contemporary designs of sensitizers tailored to these modalities. By exploring the historical context of the field and elucidating the latest design strategies, this review underscores the pivotal role of GQDs in propelling the evolution of PDT and SDT. This aspires to stimulate researchers to develop "multimodal" therapies integrating both light and sound stimuli.

Esophageal cancer: Does inaccuracy in clinical staging affect our ability to reach optimal outcomes?

BackgroundPretreatment clinical staging is used to decide the course of treatment in early-stage esophageal cancer. Few studies assess the effect of inaccurate clinical staging on oncologic outcomes. MethodsWe queried the National Cancer Database to identify patients undergoing esophagectomy for clinical stage cT1bN0 esophageal carcinoma between 2010 and 2019. Patients were categorized as being upstaged if, on final pathology, they had histopathologic disease that would have warranted treatment with neoadjuvant therapy. The textbook oncologic outcome was defined as margin-negative resection, 15 lymph nodes examined, a hospital stay of <21 days, no unplanned 30-day readmission or mortality, and stage-appropriate use of neoadjuvant therapy. ResultsIn total, 916 patients met inclusion criteria; 378 (41.2%) had a pathologic stage that differed from their pretreatment clinical stage. By multivariable regression, factors associated upstaging included: presentation between 2015 and 2019 (odds ratio 1.92 95% confidence interval [1.19, 3.13]), delay to esophagectomy of >30 days (odds ratio 2.38 95% confidence interval [1.13, 5.57]), larger tumor size (>2 cm relative to <2 cm, odds ratio 2.73 95% confidence interval [1.72, 4.39]), and poorly differentiated histology (odds ratio 2.79 95% confidence interval [1.75, 4.49]). The rate of textbook oncologic outcome assuming reliable clinical staging was 43.8%; accounting for upstaging, the rate of textbook oncologic outcome was 22.5% (P < .001). ConclusionIn patients with cT1bN0 esophageal cancer, tumor size and histology are associated with the risk of inaccurate pretreatment clinical staging. Inaccuracies in clinical staging impact the rate at which providers achieve optimal oncologic outcomes.

Screening for Esophageal Squamous Cell Carcinoma: A Review

Esophageal cancer is amongst the most common types of cancer in Asia. It is a deadly disease where incidence almost parallels mortality. It is of 2 major subtypes, adenocarcinoma being more common in the global north and squamous cell carcinoma being more common in the global south. China, Japan, India, Iran, and other Asian countries contribute to roughly 80% of the global disease burden. Fortunately, esophageal squamous cell cancers (ESCC) are also amenable for screening. Natural history studies have shown that severe dysplasia carries the highest risk of progression to ESCC. Early detection has shown to be extremely beneficial, with cure rates above 90% for precursor lesions and early-stage esophageal cancer. There are various modalities available for screening—Chinese balloon cytology is a low cost technique that can be applied for mass screening but has only moderate sensitivity (39%-62%). Recent studies have demonstrated that using methylated DNA markers and applying artificial intelligence technology can significantly improve the yield of cytology. Lugol’s chromo-endoscopy has been demonstrated to have good sensitivity and specificity (&gt;85%), but is an invasive technique and requires operator expertise. Other image enhancing techniques such as narrow-band imaging, autofluorescence, endocytoscopy and micro-endoscopy are promising, but currently not cost effective for mass screening. There are 3 large randomized trials underway in China, initial published results have demonstrated a detection rate between 0.7% to 1.2% for ESCC and 4% to 6% for pre cursor lesions. These trials, with some of them involving &gt;100 000 patients have demonstrated the feasibility of endoscopic screening, but long term results are awaited.

Application of polyglycolic acid sheets and basic fibroblast growth factor to prevent esophageal stricture after endoscopic submucosal dissection in pigs.

Endoscopic submucosal dissection (ESD) has been the first-line treatment for early-stage esophageal cancer. However, it often causes postoperative stricture in cases requiring wide dissection. Basic fibroblast growth factor (bFGF) reportedly has anti-scarring effects during cutaneous wound healing. We hypothesized that suppressing myofibroblast activation will prevent stricture after esophageal ESD. We resected a complete porcine esophagus circumference section by ESD. To investigate the preventive effect of bFGF on esophageal stricture formation after ESD, we endoscopically applied bFGF-soaked poly-glycolic acid (PGA) sheets onto the wound bed after ESD and fixed them by spraying fibrin glue (PGA + bFGF group), PGA sheets alone onto the wound bed and fixed them by spraying fibrin glue (PGA group), or nothing (control group). After removing the esophagus on day 22, we evaluated the mucosal constriction rate. Compared with those in the control group, esophageal stricture was significantly reduced in the PGA + bFGF group, and the areas stained with α-SMA and calponin-1 antibodies were significantly inhibited in the PGA + bFGF and PGA groups. The thickness of the fibrous layer in the PGA + bFGF group was uniform compared to that of the other groups. Thus, PGA + bFGF inhibited the development of unregulated fibroblasts in the acute phase, leading to uniform wound healing. Stenosis after esophageal ESD is related to fibrosis in the acute phase. Administration of PGA and bFGF suppresses myofibroblast activation in the acute phase, thereby preventing esophageal constriction in pigs.

Neoadjuvant and adjuvant therapy in esophageal cancer.

Esophageal cancer is an aggressive malignancy that carries a high mortality rate. The treatment of locally advanced resectable esophageal cancer requires a multimodal approach involving chemotherapy, radiation therapy, and surgical resection. Optimal treatment combinations and sequences for squamous cell carcinoma (SCC) versus adenocarcinoma (AC) histological subtypes are still being determined. For very early stage esophageal cancers, endoscopic therapies or surgical resection without chemotherapy and radiation are preferred. Neoadjuvant chemoradiation followed by surgical resection has been the standard in locally advanced resectable esophageal cancer based on the landmark CROSS trial. Definitive chemoradiation is recommended for patients who are not surgical candidates or decline surgery. Perioperative chemotherapy without radiation can be considered for lower esophageal AC and gastroesophageal (GE)-junction AC based on landmark MAGIC and FLOT4 trials. Additional trials are underway to compare preoperative chemoradiation to perioperative chemotherapy in esophageal and GE-junction ACs. Thus far, targeted therapies against vascular endothelial growth factor (VEGF) and human epidermal growth factor receptor 2 (HER2) have not been successful in the neoadjuvant/adjuvant setting. The roll of immunotherapy in perioperative/adjuvant setting is promising. Based on the CheckMate 577 trial, adjuvant nivolumab should be considered for all patients following neoadjuvant chemoradiation and R0 resection with residual pathologic disease. Additional trials involving various immunotherapy agents are underway.

Long-term survival in esophagectomy for early-stage esophageal cancer versus endoscopic resection plus additional chemoradiotherapy: a systematic review and meta-analysis.

Esophagectomy is still advised as an additional treatment for patients with superficial esophageal cancer (EC, T1a-T1b) after endoscopic resection (ER). However, esophagectomy often deteriorates the general condition of EC patients. In recent years, adjuvant chemoradiotherapy (CRT) has been recognized as a reliable, non-surgical treatment that can improve the prognosis. How to combine ER with adjuvant therapy to bring maximal benefits to patients has become a hot clinical research hot topic. However, the current studies have mostly been conducted retrospectively, in single centers, and with small clinical samples; there have been few prospective and large sample size randomized controlled trials (RCTs). The aim of this systematic review and meta-analysis was to compare the outcomes of adjuvant CRT versus esophagectomy in the treatment of early EC, and to provide a reference for clinical research and practice. A comprehensive and extensive literature search was performed via the databases of PubMed, Cochrane Library, Embase, and Web of Science online and all randomized cohort studies and retrospective cohort studies were collected. The quality of research was evaluated according to Cochrane's quality standards, and statistical analysis was conducted with Stata 13.0 and RevMan 5.3 software and followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). A total of 9 cohort studies, including 790 patients, were included for meta-analysis. The long term effects of the esophagectomy group were better than those of the CRT after ER group [odds ratio (OR) =6.08, 95% confidence interval (CI): 1.96 to 18.84, P=0.002] in disease-free survival (DFS) [hazard ratio (HR) =0.24, 95% CI: 0.07 to 0.85, P=0.03] and overall survival (OS) (HR =1.02, 95% CI: 0.57 to 1.82, P=0.94). Other survival indicators showed no significant difference (P>0.05). The 2 groups showed no significant results in OS. Although we found that CRT may be suitable for patients with high-risk of relapse or unable to tolerate surgery, it cannot totally replace surgical treatment; further randomized trials are required to verify this view.

Optimizing management for early-stage esophageal adenocarcinoma: longitudinal results from a multidisciplinary program.

The management of early-stage esophageal cancer is nuanced. A multidisciplinary approach may optimize management through selection of candidates for surgical or endoscopic therapies. The objective of this research was to examine long-term outcomes of patients with early-stage esophageal cancer who undergo treatment with endoscopic resection or surgery. Data on patient demographics, co-morbidities, pathology results, OS and RFS were obtained for both the endoscopic resection group and esophagectomy group. Univariate analysis of OS and RFS were conducted using the Kaplan-Meier method with calculation of the log-rank test. Multivariate cox-proportional hazards models were created for OS and RFS using a hypothesis-driven approach. A multivariate logistic regression model was created to identify predictors of esophagectomy among patients undergoing initial endoscopic resection. A total of 111 patients were included. The median OS for the surgery group was 67.0months compared to 74.0months in the endoscopic resection group (log-rank p = 0.93). The median RFS for the surgery group was 109.4months compared to 63.3months in the endoscopic resection group (log-rank p = 0.0127). On multivariable analysis, patients undergoing endoscopic resection had significantly worse RFS (HR 2.55, 95% CI 1.09-6.00; p = 0.032), but equivalent OS (HR 1.03, 95% CI 0.46-2.32; p = 0.941), compared to patients undergoing esophagectomy. High-grade disease (OR 5.43, 95% CI 1.13-26.10; p = 0.035) and submucosal involvement (OR 7.75, 95% CI 1.90-31.40; p = 0.004) were identified as significant predictors of proceeding to esophagectomy. Through a multidisciplinary approach, patients with early-stage esophageal cancer achieve excellent RFS and OS. Submucosal involvement and high-grade disease place patients at increased risk for local disease recurrence; these patients may undergo endoscopic resection safely if treated with a multidisciplinary approach incorporating endoscopic surveillance and surgical consultation. Further risk-stratification models may enable better patient selection and optimization of long-term outcomes.

Mechanisms of esophageal cancer metastasis and treatment progress.

Esophageal cancer is a prevalent tumor of the digestive tract worldwide. The detection rate of early-stage esophageal cancer is very low, and most patients are diagnosed with metastasis. Metastasis of esophageal cancer mainly includes direct diffusion metastasis, hematogenous metastasis, and lymphatic metastasis. This article reviews the metabolic process of esophageal cancer metastasis and the mechanisms by which M2 macrophages, CAF, regulatory T cells, and their released cytokines, including chemokines, interleukins, and growth factors, form an immune barrier to the anti-tumor immune response mediated by CD8+ T cells, impeding their ability to kill tumor cells during tumor immune escape. The effect of Ferroptosis on the metastasis of esophageal cancer is briefly mentioned. Moreover, the paper also summarizes common drugs and research directions in chemotherapy, immunotherapy, and targeted therapy for advanced metastatic esophageal cancer. This review aims to serve as a foundation for further investigations into the mechanism and management of esophageal cancer metastasis.

Evaluation of neoadjuvant immunotherapy and traditional neoadjuvant therapy for resectable esophageal cancer: a systematic review and single-arm and network meta-analysis.

This systematic review and meta-analysis aimed to investigate the role of neoadjuvant immunochemotherapy with or without radiotherapy [NIC(R)T] compared to traditional neoadjuvant therapies, without immunotherapy [NC(R)T]. NCRT followed by surgical resection is recommended for patients with early-stage esophageal cancer. However, it is uncertain whether adding immunotherapy to preoperative neoadjuvant therapy would improve patient outcomes when radical surgery is performed following neoadjuvant therapy. We searched PubMed, Web of Science, Embase, and Cochrane Central databases, as well as international conference abstracts. Outcomes included R0, pathological complete response (pCR), major pathological response (mPR), overall survival (OS) and disease-free survival (DFS) rates. We included data from 5,034 patients from 86 studies published between 2019 and 2022. We found no significant differences between NICRT and NCRT in pCR or mPR rates. Both were better than NICT, with NCT showing the lowest response rate. Neoadjuvant immunotherapy has a significant advantage over traditional neoadjuvant therapy in terms of 1-year OS and DFS, with NICT having better outcomes than any of the other three treatments. There were no significant differences among the four neoadjuvant treatments in terms of R0 rates. Among the four neoadjuvant treatment modalities, NICRT and NCRT had the highest pCR and mPR rates. There were no significant differences in the R0 rates among the four treatments. Adding immunotherapy to neoadjuvant therapy improved 1-year OS and DFS, with NICT having the highest rates compared to the other three modalities. https://inplasy.com/inplasy-2022-12-0060/, identifier INPLASY2022120060.

Influence of adverse effects of neoadjuvant chemoradiotherapy on the prognosis of patients with early-stage esophageal cancer (cT1b-cT2N0M0) based on the SEER database.

To analyze the prognostic impact of neoadjuvant chemoradiotherapy (NCRT) on early-stage (cT1b-cT2N0M0) esophageal cancer (ESCA) and construct a prognostic nomogram for these patients. We extracted the clinical data about patients diagnosed with early-stage esophageal cancer from the 2004-2015 period of the Surveillance, Epidemiology, and End Results (SEER) database. We applied the independent risk factors affecting the prognosis of patients with early-stage esophageal cancer obtained after screening by univariate and multifactorial COX regression analyses to establish the nomogram and performed model calibration using bootstrapping resamples. The optimal cut-off point for continuous variables is determined by applying X-tile software. After balancing the confounding factors by propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) method, Kaplan-Meier(K-M) curve, and log-rank test were applied to evaluate the prognostic impact of NCRT on early-stage ESCA patients. Among patients who met the inclusion criteria, patients in the NCRT plus esophagectomy (ES) group had a poorer prognosis for overall survival (OS) and esophageal cancer-specific survival (ECSS) than patients in the ES alone group (p < 0.05), especially in patients who survived longer than 1 year. After PSM, patients in the NCRT + ES group had poorer ECSS than patients in the ES alone group, especially after 6 months, while OS was not significantly different between the two groups. IPTW analysis showed that, prior to 6 months patients in the NCRT + ES group had a better prognosis than patients in the ES group, regardless of OS or ECSS, whereas after 6 months, patients in the NCRT + ES group had a poorer prognosis. Based on multivariate COX analysis, we established a prognostic nomogram which showed areas under the ROC curve (AUC) for 3-, 5-, and 10-year OS 0.707, 0.712, and 0.706, respectively, with the calibration curves showing that the nomogram was well calibrated. Patients with early-stage ESCA (cT1b-cT2) did not benefit from NCRT, and we established a prognostic nomogram to provide clinical decision aid for the treatment of patients with early-stage ESCA.

Fusobacterium nucleatum promotes the early occurrence of esophageal cancer through upregulation of IL-32/PRTN3 expression.

Previous studies have shown that gastrointestinal microbiome is associated with the development of esophageal cancer, but the relationship and molecular mechanism between esophageal microbiota and the early development of esophageal cancer remain unclear. Here, we found that Lactobacillus, Escherichia-Shigella, Rikenellaceae-RC9-gut-group, Morganella, and Fusobacterium were more abundant in early-stage esophageal cancer (EEC) tissues compared with normal esophageal tissues. The abundance of bacteria such as Prevotella, Fusobacterium, Porphyromonas, Actinobacillus, and Neisseria in advanced esophageal cancer (AEC) was higher than that in EEC. Then, we further verified that Fusobacterium nucleatum (Fn) was enriched in EEC tissues and that its abundance increased with the progression of esophageal cancer by FISH and RT-PCR. Next, we demonstrated that Fn promoted the proliferation of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. Finally, we confirmed that Fn promoted ESCC proliferation by upregulating the expression of interleukin (IL)-32/proteinase 3 (PRTN3) and then activating the PI3K/AKT signaling pathway. In conclusion, Fn promoted the early development of ESCC by upregulating the expression of IL-32/PRTN3 and thereby activating the PI3K/AKT signaling pathway. A better understanding of the molecular mechanism of Fn in early esophageal cancer may contribute to the development of early screening markers to diagnose ESCC and provide new targets for treatment.

Frailty Assessed by the Clinical Frailty Scale is Associated with Prognosis After Esophagectomy

The Clinical Frailty Scale (CFS) is a simple and validated tool for assessing frailty, and higher CFS scores are correlated with worse perioperative outcomes after cardiovascular surgery. However, the relationship between the CFS scores and postoperative outcomes after esophagectomy remain unclear. We retrospectively analyzed data from 561 patients with esophageal cancer (EC) who underwent resection from August 2010 to August 2020. We defined a CFS score of ≥4 as indicative of frailty; thus, patients were classified into frail patients (CFS scores of ≥4) and non-frail patients (CFS scores of ≤3). The Kaplan-Meier method was used to describe the overall survival (OS) distributions with the log-rank test. Of the 561 patients, 90 (16%) had frailty and 471 (84%) did not. Frail patients had a significantly older age, lower body mass index, higher American Society of Anesthesiologists physical status classification, and greater cancer progression than non-frail patients. The 5-year survival rate was 68% in non-frail patients and 52% in frail patients. OS was significantly shorter in frail than non-frail patients (p=0.017 by log-rank test). In particular, OS was significantly shorter in frail patients with clinical stage I-II EC (p=0.0024 by log-rank test) but was not correlated with frailty in patients with clinical stage III-IV EC (p=0.87 by log-rank test). Preoperative frailty was associated with shorter OS after resection of EC. The CFS score may be a prognostic biomarker for patients with EC, especially early-stage EC.

Chinese expert consensus on early diagnosis and treatment of esophageal cancer

Although the incidence rate of esophageal cancer in China is on the decline, China is still a high-incidence country of esophageal cancer with great regional variation. In recent years, the five-year survival of esophageal cancer in China has improved significantly. However, due to the absence of typical symptoms in early stage, there still exists a large esophageal cancer diagnostic yield gap between China and developed countries. At present, there are no international guidelines defining the target population for esophageal squamous cell carcinoma (ESCC) screening. Exploring and implementing effective esophageal cancer screening together with early diagnosis and early treatment are the keys to reducing the mortality and improving the survival rate and life quality. Endoscopic therapies, such as endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and radiofrequency ablation (RFA), are used to treat early-stage esophageal cancer. If the tumor invasion is deep or lymph node metastasis is suspected, surgery is needed, meanwhile radiation therapy could also be an optional treatment. Regular follow-up and surveillance are required for any strategy above to deal with relapse and metachronous primary cancers. The Early Diagnosis and Treatment Group of the Chinese Medical Association Oncology Branch has reached an expert consensus on screening and diagnostic protocols for esophageal cancer, on endoscopic and surgical treatment of early esophageal cancer and precancerous lesions, as well as on postoperative monitoring and adjuvant therapy. This consensus follows the evidence-based medicine at both domestic and international levels, combines the current clinical practice and application experience in the treatment of esophageal cancer in China, is based on a multidisciplinary treatment model, and can be used as a reference for clinicians.