Identification and verification of clinically actionable molecular variations to refine currently adopted risk-stratified treatment strategy for esophageal squamous cell carcinoma (ESCC) is urgently needed. Here, we evaluated FGFR3 amplification status by fluorescence in situ hybridization (FISH) performed on tissue microarrays and its prognostic value in 526 ESCC patients. FGFR3 amplification was found in 3.0% (16/526) of ESCC patients enrolled in this study cohort. Intratumor heterogeneity and metastatic heterogeneity of FGFR3 amplification were found in 10% (2/20) and 40% (2/5) FGFR3 amplified ESCC cases, respectively. No statistically significant associations were found between FGFR3 amplification status and common clinicopathological features. Survival analyses demonstrated that FGFR3 amplification was associated with a worse disease-free survival (DFS) and overall survival (OS) (DFS, P = 0.008; OS, P = 0.027). Univariate and multivariate analyses revealed that invasive depth was significantly associated with DFS (P = 0.001, HR: 1.498, 95% CI: 1.172-1.914) and OS (P = 0.002, HR: 1.482, 95% CI: 1.159-1.894), and FGFR3 amplification was significantly associated with DFS (P = 0.020, HR: 2.065, 95% CI: 1.120-3.808) and tend to associate with OS (P = 0.070, HR: 1.756, 95% CI: 0.954-3.233). Furthermore, when patients were stratified into stage I-II group and stage III-IV group, the adverse effect of FGFR3 amplification on prognosis was presented in stage III-IV patients (DFS, P = 0.0047; OS, P = 0.029) rather than stage I-II patients (DFS, P = 0.46; OS, P = 0.53), indicating that the prognostic value of FGFR3 amplification may relying on clinical stage. Our findings might provide a better understanding of the FGFR3 amplification status in ESCC patients and add further insights into its potential prognostic value.

Menopause has far-reaching effects on human physiology, including the gastrointestinal tract, and can negatively influence the quality of life of women who are affected. Menopause can have multiple effects on gastrointestinal function, including altering gut motility and changing the composition of the gut microbiota. As a result, some gastrointestinal and hepatic conditions are more common among individuals in peri- and postmenopause, and people with these conditions before menopause might also experience greater symptom severity and worse health-related quality of life during this time. The use of hormone replacement therapy to treat menopausal symptoms might also affect gastrointestinal health and well-being. Individuals in postmenopause are at risk for bone remodelling and osteoporosis due to ageing and loss of sex hormones. However, secondary osteoporosis can also occur due to medications used to treat gastrointestinal conditions (for example, glucocorticoids and other immunosuppressive medications) and the conditions themselves (for example, autoimmune disease or coeliac disease). Although all people who menstruate will eventually transition to menopause, there are relatively few studies evaluating the effect of menopause on gastrointestinal symptoms and quality of life. This Review aims to summarize available evidence and highlight areas where research is needed.

Radiotherapy plays a critical role in treating esophageal cancer, but individual responses vary significantly, impacting patient outcomes. This study integrates machine learning-driven multimodal radiomics and transcriptomics to develop predictive models for radiotherapy sensitivity and prognosis in esophageal cancer. We applied the SEResNet101 deep learning model to imaging and transcriptomic data from the UCSC Xena and TCGA databases, identifying prognosis-associated genes such as STUB1, PEX12, and HEXIM2. Using Lasso regression and Cox analysis, we constructed a prognostic risk model that accurately stratifies patients based on survival probability. Notably, STUB1, an E3 ubiquitin ligase, enhances radiotherapy sensitivity by promoting the ubiquitination and degradation of SRC, a key oncogenic protein. In vitro and in vivo experiments confirmed that STUB1 overexpression or SRC silencing significantly improves radiotherapy response in esophageal cancer models. These findings highlight the predictive power of multimodal data integration for individualized radiotherapy planning and underscore STUB1 as a promising therapeutic target for enhancing radiotherapy efficacy in esophageal cancer.

Anastomotic leak (AL) is a serious complication following esophagectomy and is often linked to poor perfusion of the gastric conduit (GC) and esophageal stump (EC). The aim of this study is to compare the efficacy of intraoperative Indocyanine green fluorescence angiography (ICG-FA) versus visual assessment VA) to assess perfusion status and its impact on the rate of AL.

Fifty-eight esophageal or gastroesophageal junction carcinoma patients were randomized to ICG-FA (28) and VA (30) groups. Perfusion status was assessed with VA alone in the VA group and with VA followed by ICG-FA in the ICG-FA group.

The ICG-FA group had a lower leak rate of 4% when compared to 27% in the VA group (p = 0.03). ICG-FA identified nine cases where VA misjudged the GC tip vascularity, thereby avoiding unnecessary resections. ICG-FA necessitated revision of the GC tip in one case missed by VA and also identified poor perfusion of ES tip in three cases mandating revision which were deemed well-perfused by VA.

ICG-FA demonstrated superiority over VA in assessing perfusion adequacy of the GC and ES, which resulted in a statistically significant decrease in the rate of anastomotic leaks.

In 2021, the FDA approved the combination of pembrolizumab with platinum and fluoropyrimidine-based chemotherapy for advanced esophageal and gastroesophageal junction (GEJ) cancers, regardless of the PD-L1 score. Pembrolizumab alone may benefit MSI-H gastroesophageal adenocarcinomas, but most patients with pMMR/MSS types require it in combination with standard chemotherapy. The NCCN recognizes the predictive value of PD-L1 CPS and recommends pembrolizumab plus chemotherapy for PD-L1 CPS ≥10. Undifferentiated carcinoma of the esophagus, a rare esophageal cancer subtype with a poor prognosis, still lacks a well-defined optimal treatment. We report a case of an 87-year-old female with advanced, pMMR/MSS, HER2-negative, ARID1A-mutant, undifferentiated carcinoma of the esophagus with a PD-L1 CPS of 20, who has shown a durable ongoing response to pembrolizumab monotherapy for 2 years now. The case highlights a favorable response, possibly attributed to the high CPS score combined with the ARID1A mutation, as recent research suggests that ARID1A mutations may increase immunotherapy susceptibility.

Esophageal squamous cell carcinomas (ESCC) are often accompanied by head and neck squamous cell carcinoma (HNSCC) and vice versa. Our study aimed to describe the prevalence of HNSCC in patients with ESCC, the chronology of appearance and the impact on survival.

A retrospective review was carried out through a computerized database of patients diagnosed with ESCC at Hospital Clinic of Barcelona between January 1999 and June 2019. Demographic data, date of ESCC diagnosis, survival time, primary tumor location, diagnosis of HNSCC and chronological relationship were recorded.

A total of 231 patients with ESCC confirmed histologically were included in the study with a median age of 64 years (IQR, 56.0-72.0), and 178 (77%) were male. The majority of the patients had a history of smoking and alcohol consumption (69.7% and 60.6%, respectively). The predominant location of ESCC was the middle esophagus (n=124, 53.7%). Forty-one patients (17.7%) had HNSCC: 21 (51.2%) were previous, 14 (34.1%) synchronous and 6 (14.6%) metachronous. All the patients were followed and 196 (84.8%) died with a median survival time of 19 months (IQR, 7-66). There were not statistically significant differences among the living patients and the deceased.

In our setting, a 17.7% of patients with ESCC have an associated HNSCC with no significant differences in survival between patients with both ESCC and HNSCC compared to those with only ESCC. However, the implementation of a screening program could allow the detection of a second primary tumor at early stages.

PurposeThis study aimed to investigate the risks of esophageal cancer (EC), protective behaviors, and risk awareness among Turkish adults aged 50 years and older, as well as their relationships with sociodemographic characteristics.DesignCross-sectional. Recruitment took place between February-April 2022, via online google forms and WhatsApp.SettingParticipants completed the survey online throught WhatsApp.SampleAnalyses included 214 participants (≥50 years from three provinces of Turkey); 73.8% female (n:158), 62.6% between 50-60 years (n:134 ), 55.6% had a university education (n:47).MeasuresStudy-specific survey items included questions about demographics, risky conditions and diseases, preventive health behaviors and Esophageal Cancer Knowledge Test (ECRKT).AnalysesFrequency or Mean, Percentage, Independent Samples t-Test, one-way analysis of variance (ANOVA), post hoc analysis (Tukey, LSD), and Cohen's effect size and linear regression analysis.ResultsThe participants had low ECRKT scores (x:13.50 ± 9.33, Min:0, Max:31) and reported the most consumed hot beverages (36.9%) among negative EC preventive behaviors. Male gender, not working, not having previously received training on EC, low education and income status cause low knowledge and awareness about EC (P < 0.05). Most of the participants had oral herpes (54.7%), vitamin deficiency (49.1%), and obesity (47.2%) in the past or now. Regarding the participants' EC risk knowledge and, female gender, being between 50-60 years old, and being employed had a weak effect (η2<0.01), while having previous EC training had a moderate effect (η2 = 0.006), and having university or higher education had a large positive effect (η2 = 0.14) (P < 0.05). Participants' level of education and previous educational experiences contribute significantly to esophageal cancer risk knowledge (P < 0.01).ConclusionThese findings highlight adults aged ≥50 years are exposed to significant EC risks, and have poor knowledge of EC risks. These results highlight the urgent need for educational campaigns to improve EC awareness.

Metabolic syndrome (MetS) plays a key role in the progression of esophageal cancer (EC), yet few studies have comprehensively explored research trends on this topic. To fill this gap, this study analyzes global research developments, hotspots, and collaborations related to MetS and EC.

A total of 1008 publications from 1995 to 2024 were analyzed using bibliometric tools like VOSviewer, CiteSpace, and the R package 'bibliometrix', drawing from the Web of Science Core Collection.

The analysis includes contributions from 5,183 researchers at 1500 institutions across 85 countries, with publications appearing in 411 journals. The United States, China, and the United Kingdom are leading in both publication volume and research impact. Karolinska Institutet emerged as a prominent contributor to this body of work. Key journals include the Diseases of the Esophagus and Gastroenterology. Main areas cover metabolic factors, metabolic surgery, adipokines, lifestyle risk factors, cirrhosis & portal hypertension. Emerging trends focus on "metabolic syndrome and EC risk", "inflammation and adipokines", "bariatric surgery and EC prevention", "post-surgical outcomes", "early detection strategies".

As the first comprehensive bibliometric study on MetS and EC, this research highlights metabolism-related factors driving EC progression. Future research should focus on clarifying MetS-EC mechanisms and developing prevention and treatment strategies.

Neoadjuvant chemoradiotherapy followed by surgery is the standard care for locally advanced esophageal adenocarcinoma. However, reliable postoperative prognostic biomarkers are still needed to stratify patients with different clinical outcomes. This study aimed to investigate postneoadjuvant expression changes of CDX2 and its association with histopathological features, biomarkers for targeted therapy, distant metastasis, and survival status. A total of 62 esophagogastrectomy specimens from one institution were evaluated. A tissue microarray was constructed, and IHC staining was performed. CDX2 expression was found in 27 (43.5%) cases with well-to-poor differentiation. Compared with preoperative biopsies, 68.8% of cases demonstrated induced or enhanced CDX2 expression. There were no significant differences in age, tumor location, histologic grade, lymph node metastasis, tumor stage, and treatment response between CDX2-positive and CDX2-negative groups. Neuroendocrine and Paneth cell differentiation induced by neoadjuvant therapy were more commonly seen in CDX2-positive cases. CDX2 expression was associated with higher multidrug resistance-1 and HER-2 expression. Patients with CDX2-positive diseases showed a higher risk of distant metastasis and a worse prognosis than those with CDX2-negative diseases.

Esophageal cancer is the seventh most diagnosed neoplasm, with a higher prevalence in men. Tobacco and alcohol consumption, gastroesophageal reflux disease, and Barrett's esophagus are associated with the development of adenocarcinoma and squamous cell carcinoma.

To identify the clinical profile in patients with esophageal cancer at a tertiary care center.

A cross-sectional, observational study. Patients with esophageal cancer were evaluated between January 2014 and July 2019. The study variables included sex, age, histological type, postoperative complications, mortality, and survival.

A total of 34 patients were evaluated, with a mean age of 61.8 ± 8.9 years. 88.2% were men. Tumor location was as follows: lower third (76.5%), middle third (17.6%), and upper third (5.9%). The most common histological types were adenocarcinoma (67.6%) and squamous cell carcinoma (32.4%). Symptoms included: dysphagia in 34 (100%) and epigastric pain in 20 (58.8%). The types of surgeries performed were: transhiatal in 15 (44.1%), palliative in 15 (44.1%), Ivor Lewis in 1 (2.9%), and McKeown in 1 (2.9%). Postoperative complications included: respiratory (29.4%), anastomotic leak (20.6%), sepsis (11.8%), and fistula (2.9%). Mortality was 13 (38.2%) patients, and survival at 22 months was 22%.

Our study showed a higher prevalence of esophageal cancer in men over 60 years old with adenocarcinoma localized in the lower third of the esophagus. Despite chemotherapy treatment, patient survival remains poor due to late diagnosis in advanced stages of the disease, which limits tumor resectability and operability, leading to increased mortality.

Esophageal cancer (EC) is more prevalent in Malawi as compared to other African countries. Environmental and socioeconomic factors may play a role in the increased incidence of EC in eastern Africa. However, the risk factors are not well defined.

We sought to determine the characteristics of patients diagnosed with EC in our rural community.

We conducted a retrospective chart review of patients diagnosed with EC. Age, gender, presence of gastroesophageal reflux disease (GERD), HIV status, and tumor histology type were recorded.

Our study demonstrated that the majority of patients did not use alcohol or tobacco (n = 106 (69.28%) and n = 107 (70.39%), respectively). There was an almost equal distribution of males and females, and the major histologic cell type was squamous cell carcinoma (SCC). There were 149 (82.63%) patients with a history of GERD, and 103 (63.98%) patients had a positive history of HIV.

 SCC was the most common histological subtype in our study. Our study demonstrated that alcohol and tobacco use did not impact the type of tissue histology in EC, and the majority of patients had a history of GERD. Further research is needed to further delineate the characteristics of EC in Malawi to determine areas of focus in prevention and treatment.

Esophageal squamous cell carcinoma (ESCC) is a predominant and highly lethal form of esophageal cancer, with a five-year survival rate below 20%. Despite advancements, most patients are diagnosed at advanced stages, limiting effective treatment options. Multi-omics integration, encompassing somatic genomic alterations, inherited genetic mutations, transcriptomics, proteomics, metabolomics, and single-cell sequencing, has enabled the identification of distinct molecular subtypes of ESCC.

This article systematically reviewed the current status of molecular subtyping of ESCC based on big data, summarized unique subtypes with differing treatment responses and prognostic outcomes.

Key findings included subtype-specific genetic mutations, signaling pathway alterations, and metabolomic profiles, which offer novel biomarkers and therapeutic targets. Furthermore, this review discusses the link between molecular subtypes and immunotherapy efficacy, chemotherapy response, and drug development.

These insights highlight the potential of omics-based molecular typing to transform ESCC management and facilitate personalized treatment strategies.

Esophageal cancer is one of the most common malignant tumors of the digestive tract, and miR-224 can promote the hypoxia tolerance of esophageal cancer cells. The expression of miR-224 and HIF-1α in esophageal cancer cells under hypoxic induction and their relationship with ROS was studied using RT-qPCR and Western Blot assays; cell viability and apoptosis under hypoxia, as well as the effects of miR-224 on cell proliferation and drug resistance, were investigated using CCK8, Annexin V-FITC/PI, H2DCFDA staining and Western Blot assays. Under hypoxic induction, miR-224 and HIF-1α expressions were upregulated, with the upregulation of miR-224 being related to ROS accumulation, while HIF-1α upregulation was not affected by ROS. Furthermore, the upregulation of miR-224 facilitated the survival of esophageal cancer cells under hypoxic conditions and reduced their chemosensitivity to CDDP. This effect was also validated in vitro, as miR-224 overexpression promoted the malignant behaviors in ESCC cells. Under hypoxic induction, ROS accumulation can lead to the upregulation of miR-224. MiR-224 facilitates the survival of esophageal cancer cells under hypoxic conditions and induces chemotherapeutic drug resistance.

Understanding of the factors influencing oesophageal cancer trends is crucial. Therefore, this cross-sectional cohort study sought to disentangle the age, period and cohort effects on the trends of oesophageal cancer in Kuwait.

The data on incident oesophageal carcinoma cases diagnosed between January 1, 1980, through December 31, 2019, and reference population were obtained. Age-period-cohort (APC) analysis was conducted using a loglinear Poisson regression model.

A total of 496 oesophageal carcinoma cases in 12.8 million person-years (i.e. squamous-cell carcinoma, 269, 54.23%), adenocarcinoma,147, 29.64% and unspecified cases, 80,16.13%) were diagnosed. The overall age-standardized incidence rate (per 105 person-years) of oesophageal carcinoma during the study period was 10.51 (95% CI: 6.62-14.41). The APC analysis results showed that the age and birth cohort effects were the significant determinants of declining, and subsequently steadying the oesophageal carcinoma incidence rates.

A substantial decline in oesophageal carcinoma incidence rates was recorded, which significantly varied in all three temporal dimensions. The observed birth cohort patterns suggest changing lifestyle and dietary patterns seem to be responsible for decreasing oesophageal carcinoma risk in Kuwait. Future studies may look for the component causes maintaining the endemicity of oesophageal carcinoma risk in this and similar countries in the region.

Esophageal cancer (EC) is a leading cause of cancer-related mortality worldwide. Methyltransferase-like 3 (METTL3), a key enzyme involved in m6A methylation, has been implicated in the development and progression of various cancers, including EC. However, its potential mechanism of action in EC progression remains unclear. METTL3 expression was found to be upregulated in EC tissues and cells. Knockdown of METTL3 suppressed EC cell proliferation, invasion, migration, and angiogenesis, while promoting apoptosis. Mechanistically, METTL3 maintained PIK3CA mRNA expression and stability in an m6A-dependent and IGF2BP2-dependent manner, respectively. METTL3 silencing inactivated the AKT pathway by regulating PIK3CA expression. Furthermore, overexpression of PIK3CA mitigated the effects of METTL3 silencing on the malignant growth of KYSE180 and TE1 cells in vivo and in vitro. METTL3/IGF2BP2 promoted the malignant progression of EC by activating the PIK3CA/AKT pathway. Targeting the METTL3-PIK3CA axis may offer a novel therapeutic approach for EC treatment.

Prevalence of gastroduodenal endoscopic and histological lesions may modify over time due to different factors. We assessed both macroscopic and histological lesions currently detected at upper endoscopy performed in routine practice.

Clinical, endoscopic, and histological data of consecutive adult patients referred for upper endoscopy in the 28 participating centres were analysed. Only patients who underwent the first endoscopic examination were considered. Prevalence of erosive/ulcerative lesions, cancers and extensive precancerous lesions in the stomach, and Helicobacter pylori infection was computed.

A total of 1,431 patients underwent endoscopy for gastro-oesophageal reflux symptoms (31.5%), dyspepsia (29.4%), or alarm symptoms (18.5%). Erosive oesophagitis or Barrett's oesophagus was detected in 210 (14.7%) cases, peptic ulcer in 49 (3.4%), and a neoplastic lesion in 17 (1.2%). H. pylori was present in 201 (22.6%) cases, and extensive precancerous lesions on gastric mucosa in 46 (5.6%) patients. Gastric lesions were more prevalent in patients aged ≥50 years (26% vs. 18%; p = 0.001), and peptic ulcers were more frequently detected in patients with H. pylori (9.4% vs. 2.3%; p = 0.001) and in males (5.8% vs. 1.6%; p = 0.001), while neoplastic lesions in patients with alarm symptoms (3.8% vs. 0.6%; p = 0.001).

The overall endoscopic lesions were more prevalent in patients aged ≥50 years, peptic ulcer and erosions were more frequent in H. pylori-infected patients, and extensive gastric precancerous lesions were present in less than 6% of cases.

Recent studies in patients with resectable adenocarcinoma of the esophagus or gastroesophageal junction (GEJ)-Neo-AEGIS and ESOPEC-have explored the comparison of neoadjuvant chemoradiotherapy (nCRT) with chemotherapy, with conflicting results. To contextualize the findings from these studies using nCRT as a comparator, we aimed to investigate contemporary real-world outcomes of nCRT in patients with adenocarcinoma of the esophagus or GEJ.

From the Netherlands Cancer Registry, patients were selected who were diagnosed between 1 January 2015 and 31 December 2022 with a resectable (cT1N+M0 or cT2-4aNanyM0) esophageal, GEJ or gastric cardia adenocarcinoma and started treatment with nCRT according to the CROSS regimen, that is 5 weekly cycles of carboplatin (AUC 2 mg/mL per minute) and paclitaxel (50 mg/m2) combined with concurrent radiotherapy (41.4 Gy in 23 fractions of 1.8 Gy). Pathologic complete response (pCR) according to Mandard was the primary outcome of this study and defined as complete tumor regression of the primary tumor (Mandard grade I) irrespective of residual nodal involvement.

Of the 4765 included patients, 4170 (87.5%) completed the full CROSS regimen of radiotherapy and chemotherapy. A pCR was observed in 704 (20.5%) of 3439 patients who underwent surgical resection within 16 weeks after completing the CROSS regimen. In the complete study population, the median overall survival (OS) was 33.7 months (95% CI 32.0-35.6), with a 3-year OS rate of 48.1%.

Although survival rates in real-world settings are often lower compared to clinical trials, in our real-world cohort the 3-year OS was only 2.6% lower compared to that reported for the group that underwent nCRT in ESOPEC. These real-world results underscore the potential of the CROSS regimen in daily clinical practice.

None.

Esophageal cancer (EC) is a major global health issue characterized by high morbidity and mortality rates, with a notably low five-year survival rate. Comprehensive analyses of the global burden of EC remain limited and outdated, despite its global significance. This study aimed to systematically assess the global burden and trends of esophageal cancer across diverse populations.

Data on the burden of EC were collected from the Global Burden of Disease (GBD) 2021 study, including estimates of incidence, mortality, and disability-adjusted life years (DALYs), as well as risk factors, spanning 204 countries and territories. Age-standardized rates (ASRs) were calculated to allow comparisons across populations. The study further explored the relationship between EC burden and socioeconomic development by utilizing the Socio-demographic Index (SDI), aggregating data by regions. The Bayesian age-period-cohort model was applied to project future trends until 2050.

In 2021, there were 576,529 new esophageal cancer cases, with an age-standardized incidence rate (ASIR) of 6.65 per 100,000, reflecting a 24.87% decrease since 1990. The global number of deaths reached 538,602, with an age-standardized death rate (ASDR) of 6.25 per 100,000, representing a 30.67% decline. DALYs totaled 12,999,264, corresponding to an estimated annual percentage change (EAPC) of a 1.73% decrease in the age-standardized DALYs rate. East Asia accounted for nearly two-thirds of global EC cases and deaths, while Central Sub-Saharan Africa recorded the highest ASIR and ASDR. Central Asia experienced the largest reductions, whereas Western Sub-Saharan Africa showed increasing trends. Middle-SDI countries, such as Malawi and Lesotho, had disproportionately high burdens, while high-SDI countries, including Tunisia and Kuwait, had lower burdens. Males had higher incidence and mortality rates across all age groups. By 2050, the ASIR is projected to decrease to 6.17 per 100,000, and the ASDR to 5.23 per 100,000, though the absolute number of cases and deaths is expected to rise.

The global burden of EC remains significant, with ongoing challenges in regions such as Africa and East Asia. These findings highlight the need for sustained and targeted prevention efforts, particularly in high-risk populations, to address the increasing absolute number of cases and deaths.

Altered glucose metabolism is a critical characteristic from the beginning stage of esophageal squamous cell carcinoma (ESCC), and the phenomenon is presented as a pink-color sign under endoscopy after iodine staining. Therefore, calculating the metabolic score based on the glucose metabolic gene sets may bring some novel insights, enabling the prediction of prognosis and the identification of treatment choices for ESCC.

A total of 8, 99, and 140 individuals from The Gene Expression Omnibus database, The Cancer Genome Atlas database, and the Memorial Sloan Kettering Cancer Center, respectively, were encompassed in the investigation. Patients diagnosed with ESCC after surgery were enrolled for further validation.

A total of 13 kinds of cell clusters were screened, and the squamous epithelium was identified with the highest score. And 558 differential genes were selected from the single-cell RNA sequencing (scRNA-seq) dataset. Four glucose metabolism-related genes, namely, SERP1, CTSC, RAP2B, and SSR4, were identified as hub genes to develop a risk prognostic model. The model was validated in another external cohort. According to the risk score (RS) determined by the model, the patients were categorized into low- and high-risk groups (LRG and HRG). Compared with LRG, HRG indicated poor survival and decreased drug sensitivity. Additionally, the immune microenvironment and pathway enrichment were different between the two groups. Immunohistochemical staining revealed that hub genes were expressed differently in ESCC tissues, high- and low-grade intraepithelial neoplasia, and adjacent normal tissues.

Four hub genes (SERP1, CTSC, RAP2B, and SSR4) screened based on glucose metabolism developed a predictive model in ESCC patients. The RS was established as an independent risk factor for predicting prognosis. These findings may enhance understanding of ESCC's molecular profile and serve as a new prognostic tool for better patient stratification and treatment planning in clinical practice.

Leptomeningeal carcinomatosis (LC) is an uncommon but severe complication of advanced esophageal adenocarcinoma. Typically diagnosed through MRI and cerebrospinal fluid analysis, LC carries a poor prognosis despite aggressive management.

A 64-year-old male with a history of coronary artery disease, diabetes, and other comorbidities presented with progressive dysphagia. Diagnostic imaging and biopsy confirmed esophageal adenocarcinoma with local invasion and distant metastases, including mediastinal lymphadenopathy. Despite treatment with chemotherapy, radiation, and surgical interventions such as jejunostomy tube placement, the patient developed neurological symptoms suggestive of LC. MRI confirmed leptomeningeal involvement, and cerebrospinal fluid analysis revealed malignant cells.

Management focused on palliative care, including chemotherapy and radiation. The patient's condition deteriorated rapidly, consistent with the poor prognosis associated with LC in esophageal cancer.

This case discusses the importance of early detection and intervention in managing esophageal adenocarcinoma, particularly when neurological symptoms suggest central nervous system involvement. Despite advances in cancer treatment, LC remains a difficult condition to manage, with limited effective therapeutic options.

Esophageal cancer is a major public health issue, yet risk factors for its occurrence are still insufficiently known. This study aimed to estimate the global burden of esophageal cancer and its risk factors.

This ecological study presented the incidence, mortality, and Disability-Adjusted Life Years (DALYs) of esophageal cancer in the world. This study collected the Global Burden of Disease study data from 1990 to 2019. Trends in esophageal cancer burden were assessed using the joinpoint regression analysis and calculating the average annual percent change (AAPC).

Globally, in 2019, in both sexes and all ages, the ASR for the incidence of esophageal cancer was 6.5 per 100,000 and for mortality, 6.1 per 100,000. The global proportion of DALYs for esophageal cancer attributable to selected behavioral, metabolic, and dietary risk factors was similar in males and females: chewing tobacco (3.8% vs. 5.1%), diet low in fruits (10.1% vs. 12.6%), diet low in vegetables (3.3% vs. 4.6%), and high body mass index (18.8% vs. 19.3%). However, the proportion of DALYs for esophageal cancer attributable to smoking and alcohol use was 4-5 times higher in males than in females (50.1% vs. 11.3%, and 29.6% vs. 5.1%, respectively). From 1990 to 2019, a significant decrease in global trends in rates of DALYs for esophageal cancer attributable to smoking (AAPC = -1.6%), chewing tobacco (AAPC = -0.5%), alcohol use (AAPC = -1.0%), a diet low in fruits (AAPC = -3.1%), and a diet low in vegetables (AAPC = -3.6%) was observed, while a significant increase in trends was observed in DALYs rates for esophageal cancer attributable to a high body mass index (AAPC = +0.4%).

More epidemiological research is needed to elucidate the relationship between esophageal cancer and certain risk factors and guide prevention efforts.

Tumor mutation burden (TMB) has been considered a biomarker for utilization of immune checkpoint inhibitors(ICIs), but whole exome sequencing(WES) and cancer gene panel(CGP) based on next generation sequencing for TMB detection are costly. Here, we use transcriptome data of TCGA to construct a model for TMB prediction in gastrointestinal tumors.

Transcriptome data, somatic mutation data and clinical data of four gastrointestinal tumors from TCGA, including esophageal cancer (ESCA), stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ). Using R, we performed visual analysis of somatic mutation data, differentially expressed genes (DEGs) function enrichment analysis, gene set enrichment analysis (GSEA), and estimated TMB value in clinic. Finally, a deep neural network (DNN) model was constructed for TMB prediction.

Visualization of somatic mutation data summarized the classification of mutation, frequency of each mutation type, and top-mutated genes. GSEA showed the enrichment of CD4+/CD8+ T cells in the high TMB group and the activation of tumor suppressing pathways. Single-sample GSEA (ssGSEA) manifested that the high-TMB group had higher level of multiple immune cells infiltration. In addition, distribution of TMB was related to clinical parameters. Like age, M stage, N stage, AJCC stage, and overall survival(OS). After model optimization using genetic algorithm, in the training set, validation set, and testing set, the Pearson relevance coefficient r between predicted values and actual values reaches 0.98, 0.82, and 0.92, respectively; the coefficient of determination R2 is 0.95, 0.82, and 0.7, respectively.

TMB correlates with clinicopathological parameters in gastrointestinal carcinoma, and patients with high TMB have higher levels of immune infiltration. In addition, the DNN model based on 31 genes predicts TMB of gastrointestinal tumors in a high accuracy.

Esophageal squamous cell carcinoma (ESCC) remains a major clinical challenge due to its poor prognosis and the scarcity effective therapeutic targets. Circular RNAs (circRNAs) are crucial in cancer progression. In this study, high-throughput sequencing was employed to profile ESCC tissues, revealing that hsa_circ_0001165 is notably elevated in both ESCC tumor samples and cell lines, with its expression is positively associated with patients' TNM staging. Knockdown of hsa_circ_0001165 resulted in reduced malignant biological behavior of ESCC cells in vitro and also inhibited tumor growth in vivo. Mechanism experimental analysis found that hsa_circ_0001165 expression is positively enhanced by eukaryotic translation initiation factor 4A3 (EIF4A3). Hsa_circ_0001165 acts as a miRNA sponge for miR-381-3p, increasing the expression of tensin-3 (TNS3) through a series of related mechanism assays include dual-luciferase reporter gene, RNA Immunoprecipitation and RNA-pulldown. The downregulation in miR-381-3p expression was observed in ESCC tissues, and the cell proliferation, invasion, and migration of ESCC were suppressed. The upregulated expression of hsa_circ_0001165 modulates the miR-381-3p/TNS3 axis and promotes aggressive phenotypes of ESCC. Hsa_circ_0001165 is regarded as a encouraging biomarker and potential therapeutic target for ESCC, presenting innovative options for both diagnostic and treatment approaches.

Esophageal squamous cell carcinoma (ESCC) is often diagnosed at advanced stages due to the inherent limitations of current screening methodologies. Central to evaluating tumor invasion and prognostic assessment in ESCC is the integrity of the basement membrane (BM). However, current research on the implications of BM-related genes (BMRGs) in diagnosing ESCC remains sparse.

We performed a comprehensive analysis using single-cell RNA-sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, alongside gene expression profiles acquired from GEO and The Cancer Genome Atlas (TCGA) databases. This identified differentially expressed BMRGs in ESCC. Employing LASSO, RF, and SVM-RFE, we selected potential BM biomarkers and crafted a diagnostic nomogram for ESCC, validated by ROC curves and AUC values. We also explored immune infiltration and biological mechanisms through consensus clustering and GSVA, and utilized single cell trajectory analysis and GSCALite to study gene distributions and pathways. In vitro experiments further elucidated the role of these genes in ESCC carcinogenesis.

Here, we discovered that ESCC cell types exhibited markedly elevated BM-related scores. Our analysis pinpointed seven BM genes upregulated and linked to immune infiltration, showcasing unique gene expression profiles and varying immune cell densities across the BM-related subtypes. Furthermore, a robust positive correlation was observed between these genes expression and EMT activity. The knockdown of BGN significantly suppressed cell proliferation, migration, invasion, while also augmenting cell viability following chemotherapy drug treatment.

Our study identified seven key BMRGs (BGN, LAMB3, SPARC, MMP1, LUM, COL4A1, and NELL2) and established a diagnostic nomogram for ESCC. Of noteworthy significance is the discovery of BGN as a promising drug target, indicating a novel strategy for future clinical combination therapies in ESCC.

The goal of the study was to create a nomogram based on clinical risk factors to forecast the rate of locoregional recurrence-free survival (LRFS) in patients with esophageal squamous cell carcinoma (ESCC) who underwent radiotherapy (RT).

In this study, 574 ESCC patients were selected as participants. Following radiotherapy, subjects were divided into training and validation groups at a 7:3 ratio. The nomogram was established in the training group using Cox regression. Performance validation was conducted in the validation group, assessing predictability through the C-index and AUC curve, calibration via the Hosmer-Lemeshow (H-L) test, and evaluating clinical applicability using decision curve analysis (DCA).

T stage, N stage, gross tumor volume (GTV) dose, location, maximal wall thickness (MWT) after RT, node size (NS) after RT, Δ computer tomography (CT) value, and chemotherapy were found to be independent risk factors that impacted LRFS by multivariate cox analysis, and the findings could be utilized to create a nomogram and forecast LRFS. the area under the receiver operating characteristic (AUC) curve and C-index show that for training and validation groups, the prediction result of LRFS using nomogram was more accurate than that of TNM. The LRFS in both groups was consistent with the nomogram according to the H-L test. The DCA curve demonstrated that the nomogram had a good prediction effect both in the groups for training and validation. The nomogram was used to assign ESCC patients to three risk levels: low, medium, or high. There were substantial variations in LRFS between risk categories in both the training and validation groups (p<0.001, p=0.003).

For ESCC patients who received radiotherapy, the nomogram based on clinical risk factors could reliably predict the LRFS.

Esophageal carcinoma is a growing concern in regions that have a high incidence of human papillomavirus (HPV) infection such as East Africa. HPV, particularly the high-risk genotypes, is increasingly recognized as a risk factor for esophageal carcinoma. We set out to investigate the prevalence and associated factors of high-risk HPV in formalin-fixed paraffin-embedded (FFPE) tissue blocks with esophageal carcinoma at Bugando Medical Center, a tertiary referral hospital in Mwanza, Tanzania, East Africa.

A total of 118 esophageal carcinoma FFPE tissue blocks, collected from January 2021 to December 2022, were analyzed. Genomic DNA was extracted from these tissues, and multiplex polymerase chain reaction (PCR) was performed to detect HPV using degenerate primers for the L1 region and type-specific primers for detecting HPV16, HPV18, and other high-risk HPV genotypes. Data were collected using questionnaires and factors associated with high-risk HPV genotypes were analyzed using STATA version 15 software.

Of the 118 patients' samples investigated, the mean age was 58.3 ± 13.4 years with a range of 29-88 years. The majority of the tissue blocks were from male patients 81/118 (68.7%), and most of them were from patients residing in Mwanza region 44/118 (37.3%). Esophageal Squamous Cell Carcinoma (ESCC) was the predominant histological type 107/118 (91.0%). Almost half of the tissue blocks 63/118 (53.3%) tested positive for high-risk HPV. Among these, HPV genotype 16 (HPV16) was the most common 41/63 (65.1%), followed by HPV genotype 18 (HPV18) 15/63 (23.8%), and the rest were other high-risk HPV genotypes detected by the degenerate primers 7/63 (11.1%). The factors associated with high-risk HPV genotypes were cigarette smoking (p-value < 0.001) and alcohol consumption (p-value < 0.001).

A substantial number of esophageal carcinomas from Bugando Medical Center in Tanzania tested positive for HPV, with HPV genotype 16 being the most prevalent. This study also revealed a significant association between HPV status and cigarette smoking and alcohol consumption. These findings provide important insights into the role of high-risk HPV in esophageal carcinoma in this region.

Oesophageal cancer (OC) is a significant public health issue, despite the decreasing trends in OC mortality rates observed globally in the past decades. The objective of our study is to analyze the pattern of OC mortality in Montenegro between 1990 and 2018 and contribute to the development of a national long-term strategy for the prevention and control of this malignancy.

The data on OC death cases in Montenegro between 1990 and 2018 were collected. The mortality rates were standardized according to the World Standard Population. The Joinpoint, Linear and Poisson regressions were applied to analyze the OC mortality trend.

Joinpoint regression analysis showed an increase in death rates for men and the overall level which were not statistically significant. However, the number of cases increases significantly with an average annual percentage change (AAPC) increase of 2.6% for the overall level [AAPC (95% CI)=2.6 (1.0-4.2); P = 0.002] at the expense of the increase in men, which on average was 2.6% annually [AAPC (95%CI) = 2.6 (1.2-4.1); P = 0.001]. The age groups 55-64 and 65-74 have the highest percentage of deaths cases from OC with 30.6% and 31.4%, respectively.

Montenegro has witnessed a recent increase in the number of deaths from OC, although the mortality rates remain stable. National strategies to further reduce mortality rates for OC are necessary. Individuals aged 55-64 and 65-74 need specific attention during the ongoing monitoring of this cancer.

Lactylation, an emerging post-translational modification, plays a pivotal role in the initiation and progression of digestive system tumors. This study presents a comprehensive review of lactylation in digestive system tumors, underscoring its critical involvement in tumor development and progression. By focusing on metabolic reprogramming, modulation of the tumor microenvironment, and the molecular mechanisms regulating tumor progression, the potential of targeting lactylation as a therapeutic strategy is highlighted. The research reveals that lactylation participates in gene expression regulation and cell signaling by affecting the post-translational states of histones and non-histone proteins, thereby influencing metabolic pathways and immune evasion mechanisms in tumor cells. Furthermore, this study assesses the feasibility of lactylation as a therapeutic target, providing insights for clinical treatment of gastrointestinal cancers. Future research should concentrate on elucidating the mechanisms of lactylation, developing efficient lactylation inhibitors, and validating their therapeutic efficacy in clinical trials, which could transform current cancer treatment and immunotherapy approaches. In summary, this review emphasizes the crucial role of lactylation in tumorigenesis and progression through a detailed analysis of its molecular mechanisms and clinical significance.

Current studies have substantiated the sparing effect of ultra-high dose rate irradiation (FLASH) in various organs including the brain, lungs, and intestines. Whether this sparing effect extends to esophageal tissue remains unexplored. This study aims to compare the different responses of esophageal tissue in histological and protein expression levels following conventional dose rate irradiation (CONV) and FLASH irradiation to ascertain the presence of a sparing effect.

C57 female mice were randomly divided into three groups: control, CONV, and FLASH groups. The chest region of the mice in the radiation groups was exposed to a prescribed dose of 20 Gy using a modified electron linear accelerator. The CONV group received an average dose rate of 0.1 Gy/s, while the FLASH group received an average dose rate of 125 Gy/s. On the 10th day after irradiation, the mice were euthanized and their esophagi were collected for histopathological analysis. Subsequently, label-free proteomic quantification analysis was performed on esophageal tissue. The validation process involved analyzing transmission electron microscopy images and utilizing the parallel reaction monitoring method.

Histopathology results indicated a significantly lower extent of esophageal tissue damage in the FLASH group compared to the CONV group (p < 0.05). Label-free quantitative proteomic analysis revealed that the sparing effect observed in the FLASH group may be attributed to a reduction in radiation-induced protein damage associated with mitochondrial functions, including proteins involved in the tricarboxylic acid cycle and oxidative phosphorylation, as well as a decrease in acute inflammatory responses.

Compared with CONV irradiation, a sparing effect on esophageal tissue can be observed after FLASH irradiation. This sparing effect is associated with alleviated mitochondria damage and acute inflammation.

Esophagectomy is an important cornerstone in the management of esophageal cancer. Post-operative feeding options in Ivor-Lewis esophagectomy include nasojejunal tube (NJT), feeding jejunostomy, and direct oral feeding. NJT is traditionally placed endoscopically or under fluoroscopic guidance. In this case report we present an alternate technique for NJT placement. A 55-year-old male presented to our clinic with dysphagia. On esophagogastroduodenoscopy, a gastroesophageal junction (GOJ) tumor was noted. A diagnosis of moderately differentiated adenocarcinoma was made on biopsy. The patient received eight cycles of epirubicin, cisplatin, and capecitabine (ECX), following which an Ivor-Lewis esophagectomy was carried out. This case report highlights the technical aspects and potential pitfalls of placing NJT in patients undergoing Ivor-Lewis esophagectomy without the use of endoscopy or fluoroscopic guidance. Direct oral feeding after Ivor-Lewis esophagectomy may lead to suboptimal caloric provision while feeding jejunostomy is associated with complications such as dermatitis, wound infection, and intestinal obstruction. On the other hand, endoscopic or fluoroscopic insertion of NJT can expose the anastomosis to potentially harmful mechanical forces. NJT can be easily placed using our technique in patients undergoing hybrid Ivor-Lewis esophagectomy. The safety of this technique can be investigated by further studies.

Detecting a group of esophageal cancer (EC) cases in endemic regions is essential in identifying high-risk populations and executing appropriate interventions. The main aim of this study was to determine the epidemiology of EC in Eritrea.

A retrospective (period: 2011 - 2021) study was carried out by abstracting data on EC patients from the logbook kept at the National Health Laboratory (ENHL). Information on socio-demographic, clinical history, and biopsy analysis findings was collected. For the statistical assessment of data, the End Results (SEER) Joinpoint Regression Program (V.4.5.0.1) was used to calculate crude incidence rate (CIR), age-adjusted incidence rate (ASR), and estimated annual percentage change (EAPC) by sex, age, and histotype.

A total of 189 patient's samples (134 (70.9%) females vs. 55 (29.1%) males, ratio 2.43 : 1) were evaluated. Of the 155 patients with EC, 44 (28.4%) and 111 (71.6%) were diagnosed with esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), respectively (AC/ESCC ratio, 0.4). The median age (IQR) of patients with EC was 60 years (46.0 - 70 years) - (males 62 (IQR: 49.0 - 77 years) vs. females 60 (IQR: 46 -67 years), p-value =0.43. Within age bands, the F: M ratios in patients with ESCC were as follows: >20 -29 years =2: 1; 30-39 years =8 : 1; 40 - 49 years =10.5 : 1; 50-59 years =6.67 : 1; 60-69 years =3.25.1; 70-79 years =1.5 : 1 and>80 years =2 : 1. The all-age CIR and ASR for EC were 0.468 per 100 000 and 2.281 per 100 000 persons, respectively. Similarly, the all-age ASR for both males and females was 2.88 per 100 000 and 1.61 per 100 000. Over the study period, the EAPC for all cases was -3.0% (95% CI, -11.3 to 6.1, p-value =0.455).

In large part, EC is a women's disease in Eritrea. The unusually high incidence of ESCC and the high female-to-male ratio point at sex-dependent exposures as a major driver of the EAC epidemic in the country. Therefore, research on the risk factors of EC in Eritrea is urgently needed.

Preoperative chemoradiotherapy is a standard treatment for patients with locally advanced, resectable esophageal cancer. The treatment completion rates impact the survival outcomes (Eyck et al J Clin Oncol 39(18):1995-2004, 2021). Thus, we aimed to estimate the effect of neoadjuvant chemoradiotherapy (NACRT) in terms of treatment completion rates and survival in this subset of patients and bring out the clinical outcomes in that context. This was a retrospective study done at a tertiary cancer center in North-East India. The study period was from 1 January 2018 to 31 December 2021. We included patients diagnosed with locally advanced and resectable esophageal cancer (cT2-3NanyM0) involving the middle and/or lower thoracic esophagus and who were planned for trimodality treatment in the Joint Tumor Board. Out of the 82 patients who were planned for trimodality treatment, all were squamous cell carcinomas. We found that 54.9% of patients completed the entire trimodality treatment. The median age was 56 years (range 34 to 73 years). The male to female ratio was 59:23. Adverse events, of any grade, were seen in 76% of patients who received NACRT. Fatigue (66%) was the most common toxicity. The common hematologic toxicities were neutropenia and anemia (7.3% each). A total of 45 patients (54.9%) were able to complete all the three modalities of treatment. Transthoracic esophagectomy was the preferred approach (84.4%). The site of anastomosis was in the neck of all the patients. Anastomotic leak was seen in 17.7% of patients. Postoperative pulmonary and cardiac complications occurred in 31.1% and 8.9% of patients respectively. The 30-day mortality was 6.7% (three deaths). A pathological complete response was seen in 35.6% among patients who underwent an esophagectomy. R0 resection was achieved in 93.3% of patients. The median overall survival and disease-free survival were 19 months and 17 months respectively. The completion rate of trimodality treatment in the real-world scenario was found to be low in our study, the reasons for which need to be identified and effectively resolved. Oncological outcomes were similar to the published literature.

We aimed to determine whether monitoring tumor-derived exosomal microRNAs (miRNAs) could be used to assess radiotherapeutic sensitivity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). RNA sequencing was employed to conduct a comparative analysis of miRNA expression levels during radiotherapy, focusing on identifying miRNAs associated with progression. Electron microscopy confirmed the existence of exosomes, and co-cultivation assays and immunofluorescence validated their capacity to infiltrate macrophages. To determine the mechanism by which exosomal miR-143-3p regulates the interplay between ESCC cells and M2 macrophages, ESCC cell-derived exosomes were co-cultured with macrophages. Serum miR-143-3p and miR-223-3p were elevated during radiotherapy, suggesting resistance to radiation and an unfavorable prognosis for ESCC. Increased levels of both miRNAs independently predicted shorter progression-free survival (p = 0.015). We developed a diagnostic model for ESCC using serum microRNAs, resulting in an area under the curve of 0.751. Radiotherapy enhanced the release of miR-143-3p from ESCC cell-derived exosomes. Immune cell infiltration analysis at the Cancer Genome Atlas (TCGA) database revealed that ESCC cell-derived miR-143-3p triggered M2 macrophage polarization. Mechanistically, miR-143-3p upregulation affected chemokine activity and cytokine signaling pathways. Furthermore, ESCC cell exosomal miR-143-3p could be transferred to macrophages, thereby promoting their polarization. Serum miR-143-3p and miR-223-3p could represent diagnostic and prognostic markers for patients with ESCC undergoing radiotherapy. Unfavorable prognosis could be linked to the increased levels of ESCC cell-derived exosomal miR-143-3p, which might promote tumor progression by interacting with macrophages.

Atrial fibrillation (AF) commonly occurs in approximately 2% of cancer patients, and the incidence of AF among cancer patients is greater than in the general population. This observational study presented the incidence risk of AF among cancer patients, including specific cancer types, using a population database. The Taiwan Cancer Registry was used to identify cancer patients between 2008 and 2017. The diagnosis of AF was based on the International Classification of Diseases codes (ICD-9-CM: 427.31 or ICD-10-CM: I48.0, I48.1, I48.2, and I48.91) in Taiwan national health insurance research datasets. The incidence of developing AF in the cancer population was calculated as the number of new-onset AF cases per person-year of follow-up during the study period. The overall incidence of AF among cancer patients was 50.99 per 100,000 person-years. Patients aged older than 65 years and males had higher AF incidence rates. Lung cancer males and esophageal cancer females showed the highest AF incidence risk (185.02 and 150.30 per 100,000 person-years, respectively). Our findings identified esophageal, lung, and gallbladder cancers as the top three cancers associated with a higher incidence of AF. Careful monitoring and management of patients with these cancers are crucial for early detection and intervention of AF.

Treatment options for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) are improving. Current guidelines recommend first-line pembrolizumab plus chemotherapy for patients with unresectable or metastatic ESCC, which has led to improvements in survival outcomes. Antiangiogenic therapy combined with immune checkpoint inhibitors can act synergistically to convert the immunosuppressive tumor microenvironment to an immune supportive microenvironment, thus enhancing antitumor immune responses. In preclinical models, the antiangiogenic agent lenvatinib combined with an anti-PD-1 agent showed synergistic antitumor activity. We describe the design and rationale for the randomized, open-label, phase III LEAP-014 study of lenvatinib in combination with pembrolizumab plus chemotherapy in patients with advanced or metastatic ESCC. Overall survival and progression-free survival are the dual primary end points.Clinical Trial Registration: NCT04949256 (ClinicalTrials.gov).

To determine the pattern, tumor characteristics of esophageal cancer (EC) and survival of esophageal carcinoma patients presenting to upper GI Unit at Dr. Ruth K.M. Pfau Civil Hospital Karachi.

We conducted a retrospective analysis of histologically confirmed EC patients from 2016 to 2021 at Upper GI Unit - Dr. Ruth K.M. Pfau Civil Hospital, Karachi. Data were collected using a filled Proforma, medical records, pathology reports and surgical notes, and patients or their family members were contacted for informed consent. Statistical analyses were performed using STATA version 16.0. Time to event was measured from the date of diagnosis to the date of the last follow-up or recorded death. Descriptive statistics and survival analyses, including Kaplan-Meier method and log-rank test, were employed. Univariate and multivariate Cox regression analyses were conducted to assess independent predictors of survival.

Total 152 patients with a median age of 45 (range 80-15) years were enrolled in this study. Clinical stages-III, IV-A and IV-B were identified in 35.5% (n = 54), 23.7% (n = 36) and 34.2% (n = 52), respectively. Total of 62% (n=94) had died at median follow up of 9.56 months and three years overall survival rate was 10.0%. Univariate survival analysis revealed that patients with clinical stage-II (p-value 0.002) and patients treated with combined surgery plus chemo-radiotherapy (p-value 0.040) was significantly associated with lower risk of mortality among other stages and treatment modality groups. Conversely, patients having metastasis (p value <0.001) and those with vascular involvement >90 degrees (p value <0.001) showed worse survival outcomes.

Our study reveals a three years survival rate of 10.0%, emphasizing the formidable challenge of advanced-stage malignancies. Clinical stage, vascular involvement, and metastasis emerged as significant predictors of mortality. Moreover, integrating surgery with chemo-radiotherapy significantly improved three years survival (36.8% vs. 14.2%). Despite single-center limitations, our findings provide crucial regional insights into esophageal carcinoma outcomes.

The presence of an immunosuppressive tumour microenvironment in oesophageal adenocarcinoma (OAC) is a major contributor to poor responses. Novel treatment strategies are required to supplement current regimens and improve patient survival. This study examined the immunomodulatory effects that radiation therapy and chemokine receptor antagonism impose on T cell phenotypes in OAC with a primary goal of identifying potential therapeutic targets to combine with radiation to improve anti-tumour responses. Compared with healthy controls, anti-tumour T cell function was impaired in OAC patients, demonstrated by lower IFN-γ production by CD4+ T helper cells and lower CD8+ T cell cytotoxic potential. Such diminished T cell effector functions were enhanced following treatment with clinically relevant doses of irradiation. Interestingly, CCR5+ T cells were significantly more abundant in OAC patient blood compared with healthy controls, and CCR5 surface expression by T cells was further enhanced by clinically relevant doses of irradiation. Moreover, irradiation enhanced T cell migration towards OAC patient-derived tumour-conditioned media (TCM). In vitro treatment with the CCR5 antagonist Maraviroc enhanced IFN-γ production by CD4+ T cells and increased the migration of irradiated CD8+ T cells towards irradiated TCM, suggesting its synergistic therapeutic potential in combination with irradiation. Overall, this study highlights the immunostimulatory properties of radiation in promoting anti-tumour T cell responses in OAC and increasing T cell migration towards chemotactic cues in the tumour. Importantly, the CCR5 antagonist Maraviroc holds promise to be repurposed in combination with radiotherapy to promote anti-tumour T cell responses in OAC.