Esophageal cancer (EC) is one of the most common causes of cancer-related mortality due in part to challenges in early diagnosis. Biomarker identification is crucial for improved early screening and treatment strategies for patients. Firstly, we employed serum proteomics techniques to screen for potential biomarkers in 15 early-stage EC patients and 5 healthy individuals. Among the differentially expressed proteins, FGL1 emerged as a promising candidate (AUC = 0.974) for early detection of EC. Subsequently, we developed NanoBiT-conjugated dual nanobodies (NBNB) sensors for robust and quantitative signal detection in fetal bovine serum (FBS) in 30 min or less, with a limit of detection (LoD) of 11.38 pM. In a case-control study recruiting 96 EC patients and 99 control samples, testing serum samples with the developed NBNB sensors revealed significantly elevated serum level of FGL1 in all-stage EC patients (AUC = 0.7880) and early-stage EC patients (AUC = 0.8286). Additionally, the combined diagnostic performance of FGL1 and CEA in EC samples is notably enhanced (AUC = 0.8847). These findings propose FGL1 as a novel and promising target for the early-stage EC diagnosis and treatment selection. Furthermore, we applied the assay to patients across six types of cancer, suggesting FGL1 as a potential pan-cancer marker. This study introduces a rapid, easy-to-use, cost-effective, reliable, universal, and high-throughput alternative to meet the growing demand for cancer biomarker testing in both academic and clinical settings.

Advanced esophageal squamous cell carcinoma (ESCC) patients had poor prognosis and few effective drugs based on the randomized controlled trials (RCTs). In such a circumstance, recent RCTs have shown the clinical efficacy of immune checkpoint inhibitors (ICIs) as first- or second-line treatment for advanced ESCC patients. Tislelizumab is one of the anti-Programmed-Death-1 (PD-1) antibodies; at first, tislelizumab monotherapy showed clinical efficacy as a second-line treatment for advanced ESCC patients based on the results of the RATIONALE-302 trial. Since then, tislelizumab plus doublet chemotherapy has shown superiority in overall survival compared to doublet chemotherapy for untreated advanced ESCC patients in the RATIONALE-306 trial. In this review, we share the overview of the development of tislelizumab and discuss the future perspectives on ICIs for advanced ESCC patients. In our opinion, tislelizumab plus doublet chemotherapy is one of the first-line standard treatments for advanced ESCC patients regardless of Programmed cell Death ligand 1 expression. Some other ICI-containing treatments showed clinical efficacy for untreated ESCC patients; we need further investigation to select these treatments appropriately.

Systemic treatment failure and an insufficient treatment response to neoadjuvant treatment underscore the urgency for better tumor-directed treatment for patients with resectable gastric cancer. The angiogenic pathway has repeatedly shown predictive and prognostic value in this cancer subtype; however, the relevance of placental growth factor (PlGF) is unclear. Therefore, we aimed to assess PlGF as a prognostic and predictive biomarker.

This translational study was performed in 2 phases. First, adenogastric (AGS) and Mie-Kinen-45 (MKN-45) gastric cancer cell lines were treated with recombinant angiogenic growth factors and chemotherapeutic agents. Cell count analyses and quantitative polymerase chain reaction were performed to assess proliferative and cytotoxic effects. Second, prospectively collected blood samples of patients undergoing surgical treatment for gastric cancer were assessed by enzyme-linked immunosorbent assay and correlated to clinicopathologic outcomes.

In MKN-45 cells, treatment with PlGF led to increased cell numbers after 72 h (P <.01), whereas proliferative effects of PlGF were less pronounced in the AGS cell line. Addition of PlGF lowered the cytotoxic effect of standard chemotherapeutic agents as evidenced by significant differences in cell growth at low concentrations of cisplatin (5 µM cisplatin vs 5 µM cisplatin plus PlGF) and high concentrations of paclitaxel (25 µM paclitaxel vs 25 µM paclitaxel plus PlGF) in both AGS and MKN-45 cell cultures after 72 h (all comparisons P <.05). In patients with gastric cancer (n = 68), high PlGF concentrations were significantly associated with more recurrences (estimated 5-year-recurrence rate, 34% [high PlGF] vs 6% [low PlGF]; log-rank P =.009) but no association was found with pathologic treatment response, tumor size, nodal stage, or tumor grade.

The association of elevated PlGF expression with disease-specific survival despite no correlation with other tumor-specific prognostic factors may indicate that PlGF could be used as an independent prognostic biomarker in gastric cancer. The ability to predict resistance to neoadjuvant treatment, as demonstrated in cell experiments, requires further investigation in a clinical setting.

to analyze the most robust research and recommendations that have informed the potential superiority of treatments with anticancer drugs over any type of supportive care for advanced esophageal cancer (EC).

We conducted a critical historical review. First, we identified randomized clinical trials (RCTs) from a previous scoping review conducted by our research group, ASTAC, updating the search strategy. Second, we searched for the most important and recognized international clinical practice guidelines (CPGs) in advanced EC. Finally, we performed a systematic document analysis to compare whether the recommendations proposed in the CPGs were supported by the previously identified relevant evidence.

We identified and assessed 15 RCTs and 11 CPGs from ESMO (eight), ASCO (two), and NICE (one) published over the last 40 years. There is a clear mismatch between these guidelines' recommendations and the available RCTs regarding the efficacy of anticancer drugs compared to best supportive care (BSC).

There is a lack of consistent evidence to support the treatment of advanced EC patients with anticancer drugs, and a notable mismatch exists between the available evidence and the recommendations made by relevant CPGs. As a result, these guidelines may be biased in favoring the use of anticancer drugs over supportive care and in consequence it is advisable to be very prudent when proposing systemic treatments to patients with advanced EC. Further rigorous and independent research is needed to better evaluate the true benefits of anticancer treatments in advanced EC and to update the CPGs accordingly.

Purpose: To investigate the impact of paratracheal lymphadenectomy on survival in patients undergoing an esophagectomy for cancer. The secondary objective was to assess the effect on short-term outcomes. Methods: Between 2011-2017, patients with an esophageal or gastroesophageal junction carcinoma treated with elective transthoracic esophagectomy with two-field lymphadenectomy were included from the Dutch Upper Gastro-intestinal Cancer Audit registry. After 1:1 propensity score matching of patients with and without paratracheal lymphadenectomy within histologic subgroups, short-term outcomes and overall survival were compared between the two groups. Results: A total of 1154 patients with adenocarcinoma and 294 patients with squamous cell carcinoma were matched. Lymph node yield was significantly higher (22 versus 19 nodes, p < 0.001) in patients with paratracheal lymphadenectomy for both tumor types. Paratracheal lymphadenectomy was associated with more recurrent laryngeal nerve injury (10% versus 5%, p = 0.002) and chylothorax in patients with adenocarcinoma (10% versus 5%, p = 0.010) and with more anastomotic leakage in patients with squamous cell carcinoma (42% versus 27%, p = 0.014). The 3- and 5-year survival in patients with and without a paratracheal lymphadenectomy were for adenocarcinoma, respectively, 58% versus 56% and 48% in both groups (log rank: p = 0.578) and for patients with a squamous cell carcinoma, 62% in both groups and 57% versus 54% (log rank: p = 0.668). Conclusions: The addition of paratracheal lymphadenectomy significantly increases lymph node yield in transthoracic esophagectomy but did not result in improved survival for esophageal cancer patients in the current dataset. However, there was an increase in postoperative morbidity in patients who underwent a paratracheal lymphadenectomy.

Half of the patients with esophageal cancer, cancer of the gastro-esophageal junction and gastric cancer present metastasis at the time of diagnosis. In addition, even patients originally thought to be free of metastasis will present metachronous metastasis in the course of the disease. These patients are considered incurable and current standard of care for metastatic esophageal, gastro-esophageal junction and gastric cancers is a systemic therapy without curative intention. However, patients presenting only a low metastatic load are now defined as oligometastatic disease and should benefit from an aggressive, multimodal therapy. We present here a review of recent publications investigating multimodal therapies for oligometastatic disease and showing that a systemic therapy combined with a resection of the primary tumor together with metastasis is associated with a better prognosis than a systemic therapy alone. We also give a precise focus on esophageal squamous cell carcinomas and adenocarcinomas of the gastro-esophageal junction and of the stomach. Interestingly, patients with oligometastatic cancer of the esophago-gastric junction can even be treated in curative intention with such a multimodal therapy as we present here in a short case report. In conclusion, new therapeutic strategies including multimodal approaches for oligometastatic disease have shown promising results in the last years and ongoing randomized prospective trials will provide us the evidence to include them in future European guidelines.

CD8+ T lymphocytes greatly affect the efficacy of immunotherapy, displaying promising potential in various tumors. Here, we aimed to identify immune subtypes associated with CD8+ T cell-related genes to predict the efficacy of treatment in esophageal cancer (ESCA).

We obtained 13 immune cell-related datasets from the Gene Expression Omnibus (GEO) database and removed batch effects. Weighted correlation network analysis (WGCNA) and co-expression analysis were performed to identify highly correlated CD8+ T cell genes. Cox analysis was used to process ESCA clinical information, and the immune clusters (ICs) were constructed through consensus cluster analysis. Furthermore, we constructed an immune risk score model to predict the prognosis of ESCA based on these CD8+ T cell genes. This model was verified using the IMvigor210 dataset, and we functionally validated the immune risk score model in vitro.

The results revealed significant correlations between CD8+ T cell-related genes and immune-related pathways. Three ICs were identified in ESCA, with IC3 demonstrating the most favorable prognosis. The final 6-gene prognostic risk model exhibited stable predictive performance in datasets across different platforms. Compared with that in normal esophageal epithelial (HEEC cells), CHMP7 in the 6-gene prognostic risk model was upregulated in KYSE150 and TE-1 cells. Si-CHMP7 transfection led to a decrease in tumor cell migration, invasion, and proliferation, accompanied by an accelerated apoptotic process.

Collectively, we identified the immune subtypes of CD8+ T cell-related genes with different prognostic significance. We designated CHMP7 in the 6-gene prognostic risk model as a potential target to improve tumor cell prognosis. These insights provide a strong basis for improving prognosis and facilitating more personalized and accurate treatment decisions for the immunotherapy of ESCA.

Human endogenous retroviruses (HERVs) are emerging as critical elements in host genomic regulation. Aberrant HERV transcription has been implicated in developmental and tissue-specific aging and pathological processes. In this study, we presented a comprehensive locus-specific characterization of the HERV expression landscape in esophageal squamous cell carcinoma (ESCC). We demonstrated the transcriptional diversity among patients and identified 12 clinically relevant HERVs in the SCH cohort, which were experimentally validated by Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) in the CAMS cohort. ESCC patients were stratified into three HERV-based subtypes (HERVhigh, HERVmedian and HERVlow) with distinct clinical and biological characteristics. The HERVhigh subtype was associated with worse survival, increased CD4+ T cells infiltration and decreased metabolic activity, whereas the HERVlow subtype was characterized by abundant CD8+ T cells, increased metabolic activity, and better survival. The HERV-based tumor subtyping was further robustly validated by RNA sequencing and RT-qPCR in two additional external cohorts. Our findings demonstrate the clinical significance of HERVs for tumor subtyping and prognosis, provide insights into the functional role of HERVs and a valuable resource for developing novel biomarkers and therapeutic targets in ESCC.

The ORIENT-15 double-blind randomized controlled trial demonstrated that the addition of sintilimab to chemotherapy for locally advanced or metastatic oesophageal squamous cell carcinoma (OSCC) resulted in better clinical outcomes. In this analysis, we sought to evaluate the cost-effectiveness of sintilimab as a first-line treatment for locally advanced or metastatic OSCC from a healthcare system perspective in China.

A partitioned survival model was constructed to perform a cost-effectiveness analysis comparing chemotherapy alone with sintilimab for locally advanced or metastatic OSCC patients. Clinical data were obtained from the ORIENT-15 trial and extrapolated to 10 years. Health state utilities and costs were sourced from the literature and from public healthcare institutions. The primary outcomes included the incremental cost-effectiveness ratio (ICER) and quality-adjusted life-years (QALYs). Two different sensitivity analyses, one-way and probabilistic, were performed to assess model uncertainty.

Sintilimab-based chemotherapy was more costly ($31699.21 vs. $20687.42) and more effective (0.74 vs. 0.53) than placebo-based chemotherapy, resulting in an ICER of $51908.19 /QALY, which is greater than the willingness-to-pay (WTP) threshold of China ($38223/QALY). Sensitivity analysis demonstrated that the PFS and cost of sintilimab were the major influencing factors affecting the results.

In patients with locally advanced or metastatic OSCC, sintilimab chemotherapy could improve survival time and health benefits compared with traditional chemotherapy, but the present analysis suggests that sintilimab is not a cost-effective treatment option in China.

The development of cancer has been a multistep process involving mutation, proliferation, survival, invasion, and metastasis. Of all the characteristics of cancer, metastasis is believed to be the hallmark as it is responsible for the highest number of cancer-related deaths. In connection with this, Matrix metalloproteinases (MMPs), that has a role in metastasis, are one of the novel therapeutic targets. MMPs belong to the family of zinc-dependent endopeptidases and are capable of degrading the components of the extracellular matrix (ECM). The role of MMPs in ECM remodeling includes tissue morphogenesis, uterine cycling, growth, tissue repair, and angiogenesis. During pathological conditions, MMPs play a critical role in the excessive degradation of ECM which includes arthritis, tumour invasion, tumour metastasis, and several other autoimmune disorders. Moreover, they are believed to be involved in many physiological aspects of the cell, such as proliferation, migration, differentiation, angiogenesis, and apoptosis. It is reported that dysregulation of MMP in a variety of cancer subtypes have a dual role in tumour growth and metastasis processes. Further, multiple studies suggest the therapeutic potential of targeting MMP in invading cancer. The expression of MMP-2 correlates with the clinical characteristics of cancer patients, and its expression profile is a new diagnostic and prognostic biomarker for a variety of human diseases. Hence, manipulating the expression or function of MMP-2 may be a potential treatment strategy for different diseases, including cancers. Hence, the present review discusses the therapeutic potential of targeting MMP in various types of cancers and their recent patents.

Advances in treatment strategies for gastric and esophageal cancer have led to improved long-term outcomes, however the local and systemic effects of the primary tumor, neoadjuvant therapies and surgery, result in specific nutritional challenges. Comprehensive nutritional evaluation and support represents a core component of multidisciplinary holistic care for this patient population.

We provide a detailed overview of nutritional challenges in gastric and esophageal cancer, with a focus on malignant obstruction, preoperative optimization and survivorship. We discuss current management strategies and evidence base, and describe future therapeutic targets.

Data to support the optimal management of malignant dysphagia and obstruction, particularly regarding patient reported outcomes, is currently lacking. The advantages of nutritional optimization in the pre- and immediate postoperative phase are well described, but further research is needed to inform optimal personalised strategies. Emerging data regarding the physiologic regulation of appetite and body weight have provided key insights and informed the development of novel therapeutic targets to improve nutritional status among patients undergoing treatment for oesophageal and gastric cancer.

This review synthesised the evidence for the effect of prehabilitation interventions on biopsychosocial and service outcomes.

A systematic review was conducted. 10 databases were searched to December 2023. Prospective experimental studies exploring prehabilitation interventions in adults undergoing upper gastrointestinal surgery were included. Prehabilitation was any preoperative intervention to improve physical or psychological outcomes. Included studies required a comparator group or alternative preoperative intervention as well as baseline, presurgical and postoperative assessment points. Study quality was assessed using the Cochrane risk of bias tool (v.2). Data synthesis was narrative (SWiM guidance).

6028 studies were screened, with 25 studies included. Prehabilitation interventions were: inspiratory muscle training (five studies n = 450); exercise (nine studies n = 683); psychological (one study n = 400); and nutritional (ten studies n = 487). High quality studies showed preoperative improvements in impairments directly targeted by the interventions. Generally, these did not translate into functional or postoperative improvements, but multimodal interventions were more promising.

Current evidence supports prehabilitation as safe to preserve or improve preoperative function. Heterogeneity in outcomes and variable study quality means definitive conclusions regarding interventions are not yet possible, limiting implementation. Agreement of clinical outcomes and cost effectiveness evaluation is required.

This study aims to evaluate the prognostic implications of pretreatment [18F]FDG-PET metrics in esophageal cancer patients through a meta-analysis of the existing literature.

We carefully searched electronic databases, including PubMed and Embase, from inception to April 1, 2024, to identify studies describing the prognostic value of pretreatment PET metrics for advanced esophageal cancer. Clinical endpoints examined were overall survival (OS), recurrence-free survival (RFS)/disease-free survival (DFS), and progression-free survival (PFS). Hazard ratios (HRs) for PFS and OS were taken directly from the original reports.

Forty-seven publications, including 5504 patients, were included in our analysis. OS and PFS were analyzed in 31 and nine studies, respectively, and DFS/RFS was analyzed in 16 studies. The comprehensive pooled analysis revealed significant associations between metabolic parameters derived from positron emission tomography (PET) imaging and clinical outcomes. Expressly, the pooled HR indicated that patients with higher SUVmax were significantly associated with poor PFS (HR: 1.06; 95% CI: 1.01-1.12, p = 0.011) and poor RFS/DFS (HR: 1.09; 95% CI: 1.02-1.18, p = 0.019). Patients with higher SUVmean were significantly associated with poorer OS (HR: 1.07; 95% CI: 1.01-1.14, p = 0.025). High MTV was significantly associated with inferior OS (HR: 1.02; 95% CI: 1.00-1.05, p = 0.049). High TLG was significantly associated with poorer RFS/DFS (HR: 2.02; 95% CI: 1.11-3.68, p = 0.022).

This study unveiled pretreatment FDG-derived parameters as valuable prognostic indicators in assessing esophageal cancer outcomes. Specifically, SUVmax is associated with PFS and RFS/DFS. SUVmean and MTV were correlated with OS, and TLG was only associated with RFS/DFS.

Question Inconsistent findings on the prognostic value of pretreatment [18F]FDG PET parameters in esophageal cancer require comprehensive analysis to clarify their role in outcome prediction. Findings Higher pretreatment [18F]FDG-PET metrics (SUVmax, SUVmean, MTV, TLG) are associated with poor survival outcomes, emphasizing their potential value in enhancing prognostic assessments for esophageal cancer. Clinical relevance This study highlights the prognostic significance of pretreatment [18F]FDG-PET metrics in esophageal cancer, providing valuable insights for patient outcome prediction and potentially guiding personalized treatment strategies.

Oesophageal cancer is the seventh leading cause of cancer mortality worldwide. Two major pathological subtypes exist: oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. Epidemiological studies in the last decade have shown a gradual increase in the incidence of oesophageal adenocarcinoma worldwide. The prognosis of oesophageal cancer has greatly improved due to breakthroughs in screening, surgical procedures, and novel treatment modalities. The success achieved with combined modality therapies, including surgery, chemotherapy, and radiotherapy, to treat locally advanced oesophageal cancer is particularly notable. Immunotherapy has become a crucial treatment for oesophageal cancer, with immune checkpoint inhibitor-based therapies now established as the standard of care in adjuvant and metastatic first-line settings. This Seminar provides an overview of advances in the screening, diagnosis, and treatment of oesophageal squamous cell carcinoma and oesophageal adenocarcinoma, with a particular focus on neoadjuvant therapies for locally advanced oesophageal cancer and immune checkpoint inhibitor-based therapies.

Programmed cell death ligand-1 (PD-L1) is an ideal checkpoint for immunohistochemical detection. The method of obtaining PD-L1 expression through biopsy can impact the accurate assessment of PD-L1 expression due to the spatial and temporal heterogeneity of tumors. Because of the limited sample size, biopsies often give only a localized picture of the tumor. In this retrospective study, a total of 2,386 metabolic tumor volume (MTV) features were extracted from 18F-FDG PET-CT images. A radiomics model was developed to holistically and non-invasively assess PD-L1 expression in patients with esophageal squamous cell carcinoma by identifying seven independent factors through feature screening. The radiomics model shows effective discrimination, with an area under the receiver operating characteristic curve of 0.888 [95% confidence interval (CI): 0.831-0.945] and 0.889 (95% CI: 0.706-1.000) for the training and validation cohorts, respectively. The results of the decision curve analysis demonstrated that utilizing the radiation model to forecast PD-L1 expression levels yielded more net benefits at threshold probabilities below 0.669. The clinical impact curves demonstrate that when the threshold probability is less than 0.501, the loss-to-benefit ratio is less than one in all cases.

Minimally invasive surgery is becoming the method of choice for the resection of esophageal cancer worldwide.

Retrospective analysis of prospectively collected clinical data in a tertiary care center with a detailed description of the course of the program.

A total of 136 transthoracic esophageal resections were performed between 2010 and 2023. The study group included 116 operations, 69 of which were fully minimally invasive and 47 hybrid. 80.0% of the study group underwent surgery using a multimodality approach. The median operation time was 431 min (± 103). The R0 resection rate was 100%. Forty-two patients (36.2%) had no postoperative complications. The postoperative Clavien-Dindo > IIIb morbidity was 27%. The postoperative 90-d mortality rate was 1.7%. The average number of lymph nodes removed in the last quarter of cancer patients was 31. The anastomotic insufficiency rate for reoperation was 4% (Ivor-Lewis 4.2%, McKeown 5%).

With extensive expertise in high-end minimally invasive abdominal and thoracic surgery, implementation of a minimally invasive esophageal resection program with a clinical and oncologic outcome within generally accepted limits is feasible.

FGF8, ALK, and EML4 have been identified as promising biomarkers in a number of malignancies. The aim of this study was to examine the prognostic role of FGF8, ALK, and EML4 in esophageal squamous cell carcinoma (ESCC). Methods: Consecutive patients with ESCC who underwent upfront resection were included in this study. ALK and EML4 gene status was evaluated by fluorescence in situ hybridization (FISH) using a triple-color break-apart single-fusion probe and a probe against 2p11. FGF8, ALK, and EML4 protein expression was determined by immunohistochemistry. Results: A total of 122 patients were included in this study. Multivariate analysis revealed that FGF8 overexpression is an independent negative prognostic factor for patients' overall survival (OS) (p = 0.04). Furthermore, a significant correlation between the expression of FGF8, and ALK (p = 0.04) and EML4 (p = 0.01) alteration was found. Conclusions: FGF8 overexpression is an adverse independent prognostic factor in patients with upfront resected ESCC. Furthermore, FGF8 expression significantly correlates with ALK and EML4 amplification and may therefore qualify as a future therapeutic target.

Multimodal therapy regimens became the standard of care for patients with esophageal cancer, whereas surgical resection remains at the center of curative treatment modalities. Current guidelines provide no recommendations on the extent of the oral resection margin, especially in the era of neoadjuvant therapy. Therefore, this study aimed to evaluate the relationship between the oral tumor-free resection margin and overall survival.

Retrospective study with 382 1:1 propensity-matched patients out of 660 patients, operated between 2013 and 2019, with an Ivor-Lewis-esophagectomy for adenocarcinoma and squamous cell carcinoma of the esophagus or esophagogastric junction after neoadjuvant therapy. Independent pathologists measured the oral resection margin after formalin fixation.

The mean oral tumor-free resection margin was 37.2 ± 0.6 mm. The ideal cut-off for survival differences was determined for 33 mm. Patients with an oral resection margin of more than 33 mm had a better median overall survival (≤33 mm: 45.0 months, 95% confidence interval: 22.4-67.6 months, >33 mm: not reached, P = .005). An oral resection margin of more than 33 mm proved to be an independent favorable prognostic factor for patients' overall survival in multivariate Cox regression analyses (P = .049).

This study analyzed a patient cohort retrospectively after curative intended Ivor-Lewis-esophagectomy after neoadjuvant therapy. An oral resection margin of more than 33 mm is a factor for improved overall survival. Therefore, a minimum resection margin of 34 mm after fixation could be suggested.

NRG/RTOG 0436 evaluated cetuximab added to chemoradiation (CRT) for non-operative esophageal cancer management. PRO objectives assessed improvement in the FACT-Esophageal cancer subscale (ECS), version 4, with cetuximab, and if improved ECS correlated with clinical complete response (cCR).

Patients were randomized to cisplatin/paclitaxel/radiation ± cetuximab. Overall survival (OS) was the primary endpoint, with a 420 patient target, which also provided 82% power to detect ≥ 15 increase in the proportion of cetuximab patients with ECS improvement from baseline to 6-8 weeks post-CRT; α = 0.05, using a χ2 test. Improvement in ECS and its Swallowing and Eating Indices (SI, EI) was defined as 5, 4 and 2 point increases, respectively, from baseline to 6-8 weeks post-CRT. Univariate logistic regression assessed if cCR was associated with improved ECS.

This study was stopped early for not meeting a pre-specified OS endpoint and did not show survival benefit. Of 420 planned patients, 344 enrolled and 281 consented to PROs. ECS was completed by 261 (93%) at baseline, 173 (66%) 6-8 weeks post-CRT, and 117 (64%) at 1 year. At 6-8 weeks, patients receiving CRT + Cetuximab didn't have improved ECS; they experienced a lower proportion of improvement compared to standard CRT (37% vs. 53%; P = 0.04). The proportion of CRT patients with improvement in SI was 9% higher than with cetuximab, but not statistically significant (39% vs. 30%, P = 0.22). There was no association between treatment and EI. When examining ECS scores at 1 year by cCR vs. residual disease, a higher proportion of cCR patients improved, but not statistically significant (48% vs. 45%, P = 0.74).

The addition of cetuximab to CRT for the nonoperative management of esophageal cancer did not improve PROs.

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.

Gastric cancer has a high prevalence in Asia and may only be diagnosed in advanced stages. Therefore, patients with gastric cancer may experience fatal symptoms, such as bleeding or stenosis at the time of consultation. In this review, we aimed to describe the effectiveness and toxicity of hemostatic radiotherapy (RT).

A total of 17 retrospective and 3 prospective studies were analyzed. The prescription dose, biologically effective dose, equivalent dose in 2 Gy fractions, response rate, survival prognosis, and toxicities were also reported.

Using 20 studies, the following observations were made the hemostatic effect was ∼ 80 %, the mean survival time after irradiation was about 3 months, and prescribed doses of 30 Gy/10 fractions and 20 Gy/5 fractions were considered suitable.

In this review, studies on hemostatic irradiation have been summarized, and the most optimal treatment method has been proposed. 30 Gy/10 fractions and 20 Gy/5 fractions were ideal. However, because palliative RT is preferably completed within a short period of time, a randomized trial is needed to determine whether the 8 Gy/single fraction treatment is equivalent to fractionated RT. Therefore, more prospective studies are warranted to establish a standard of care for palliative RT in gastric cancer.

Esophageal and gastroesophageal junction cancer (EC/GEJC) is a poor prognosis disease with a high risk of recurrence even in patients curatively resected. Adjuvant nivolumab is currently used for patients with completely resected (R0) EC/GEJC who have residual pathologic disease following prior neoadjuvant chemoradiotherapy. This study aimed to determine the cost effectiveness of nivolumab in this indication in France according to the collective perspective excluding indirect costs.

A simplified four-health-state semi-Markov model was developed to model EC/GEJC patients who have residual disease after neoadjuvant chemoradiotherapy followed by R0 over a 15-year time horizon, comparing adjuvant nivolumab versus surveillance, which was the recommended French clinical practice before immunotherapy arrival. Time-to-recurrence (TTR) from CheckMate 577 was used to inform transition from disease-free to post-recurrence health state; patients who recurred were split according to the distribution of type of recurrence observed during the trial. Post-recurrence survival (PRS) according to the type of recurrence was derived from a real-world registry.

Adjuvant treatment with nivolumab led to an incremental survival gain of 1.19 years (+ 34%), mostly in the disease-free state, an incremental cost of €48,634 and QALY of 0.98 resulting in an incremental cost-utility ratio (ICUR) of €49,572/QALY with limited uncertainty. 'Cure assumption' at 5 years had an important impact on the results (€41,115/QALY; - 17%), as that tends to increase life-years and QALYs while costs remain the same. Probabilistic sensitivity analyses confirmed reference ICUR (€52,542/QALY) with 80% probability of nivolumab being cost effective at a willingness-to-pay threshold of €75,000/QALY.

Our analysis suggests that adjuvant nivolumab is cost effective in the treatment of EC/GEJC patients who have residual disease after neoadjuvant CRT followed by R0 resection. Compared with previously evaluated cost-effectiveness analyses for other immune-checkpoint inhibitors indicated in metastatic settings, ICUR appears particularly low in this early setting thanks to the important impact on health outcomes and capped treatment duration.

The optimal management of patients with locally advanced esophageal adenocarcinoma is unclear. Neoadjuvant chemoradiotherapy followed by esophagectomy (trimodality therapy) is supported as a standard of care, but definitive chemoradiotherapy is frequently given in practice to patients who may have been surgical candidates. This multi-institutional retrospective cohort study compared the outcomes of consecutive patients diagnosed with stage II to IVA esophageal adenocarcinoma between 2004 and 2018 who planned to undergo trimodality therapy or definitive chemoradiotherapy. A total of 493 patients were included, of whom 435 intended to undergo trimodality therapy and 56 intended to undergo definitive chemoradiotherapy. After a median follow-up of 7.3 years, trimodality therapy was associated with a lower risk of locoregional failure (5-year risk, 30.5% vs. 61.3%; HR, 0.39; 95% CI, 0.24-0.62; p<0.001) but not distant metastases (5-year risk, 58.2% vs. 53.9%; HR, 1.21; 95% CI, 0.77-1.91; p=0.40). There were no differences in overall survival (HR, 0.78; 95% CI, 0.56-1.09; p=0.14) or cancer-specific survival (HR, 0.83; 95% CI, 0.57-1.21; p=0.33). Findings were consistent on propensity score-matched sensitivity analyses. In conclusion, trimodality therapy was associated with a lower risk of locoregional failure, but this did not translate into a significantly lower risk of distant failure or improved survival. Further studies are required to accurately estimate the trade-offs between the two treatment strategies.

Many patients undergo dose reduction or early termination of chemotherapy to reduce chemoradiotherapy-related toxicity, which may increase their risk of survival. However, this strategy may result in underdosing patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). This study aimed to analyze the relationship between the relative dose intensity (RDI) and survival outcomes in patients with LA-ESCC.

This retrospective study assessed patients with LA-ESCC (cT2N + M0, cT3-4NanyM0) receiving neoadjuvant chemoradiotherapy (NCRT) with curative-intent esophagectomy. The patients received 2 courses of paclitaxel plus carboplatin (TC) combination radiotherapy prior to undergoing surgery. During NCRT, RDI was computed, defined as the received dose as a percentage of the standard dose, and the incidence of dose delays was estimated (≥ 7 days in any course cycle). The best RDI cutoff value (0.7) was obtained using ROC curve. The Kaplan-Meier survival curves were compared using the log-rank test, the treatment effect was measured using hazard ratios (HR) and 95% confidence intervals (CI).

We included 132 patients in this study, divided into RDI < 0.7 and RDI ≥ 0.7 groups using cut-off value of 0.7. RDI grade was an independent prognostic factor for OS. Baseline demographic and clinical characteristics were well balanced between the groups. There was no evidence that patients with RDI < 0.7 experienced less toxicity or those with RDI ≥ 0.7 resulted in more toxicity. However, patients with RDI < 0.7 who were given reduced doses had a worse overall survival [HR 0.49, 95% CI 0.27-0.88, P = 0.015]. The risk of a lower RDI increased with a longer dose delay time (P < 0.001).

The RDI below 0.7 for avoiding chemoradiotherapy toxicity administration led to a reduction in the dose intensity of treatment and decreased overall survival.

Gastroesophageal reflux disease (GERD) remains a significant global health concern, with increasing prevalence and a substantial impact on quality of life. This narrative review explores recent advances in our understanding of GERD pathophysiology, diagnosis, and management. The complex interplay of factors contributing to GERD, including lower esophageal sphincter dysfunction, transient sphincter relaxations, and esophageal motility disorders, is discussed. Emerging diagnostic techniques, such as high-resolution manometry and impedance-pH monitoring, have enhanced our ability to accurately identify and characterize GERD. The review highlights the evolving landscape of GERD treatment, from conventional approaches like lifestyle modifications and proton pump inhibitors to novel strategies including potassium-competitive acid blockers, endoscopic therapies, and minimally invasive surgical techniques. The potential role of the microbiome in GERD pathogenesis and as a therapeutic target is examined. The concept of personalized medicine in GERD management is explored, considering genetic factors, biomarkers, and individual patient profiles. Complications of GERD, including erosive esophagitis, Barrett's esophagus, and esophageal adenocarcinoma, are reviewed, emphasizing the importance of early detection and appropriate management. The economic burden and impact on the quality of due to GERD are also addressed. This comprehensive review underscores the multifaceted nature of GERD and the need for a personalized, multidisciplinary approach to its management. It highlights ongoing research efforts and emerging therapies that promise to improve outcomes for GERD patients, while also identifying areas requiring further investigation to optimize diagnosis and treatment strategies.

Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC.

This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis.

In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC.

An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.

The optimal strategy for cervical advanced esophageal cancer remains controversial in terms of oncologic outcome as well as vocal and swallowing function. Recently, in East Asian countries, neoadjuvant chemotherapy (NAC) has been a standard strategy for advanced esophageal cancer.

This study included 37 patients who underwent NAC, and 33 patients who underwent definitive chemoradiation therapy (dCRT) as larynx-preserving treatment for locally advanced cervical esophageal cancer from 2016 to 2021. This study retrospectively investigated outcomes, with comparison between NAC and dCRT for locally advanced cervical esophageal cancer.

Larynx preservation was successful for all the patients with NAC and dCRT. After NAC, the rate of complete or partial response was 78.4%, and 30 patients underwent larynx-preserving surgery. On the other hand, after dCRT, the complete response rate was 71.9%, and 4 patients underwent larynx-preserving salvage surgery. Overall survival (OS) and progression free survival were similar between the two groups. However, for the patients with resectable cervical esophageal cancer (cT1/2/3), the 2-year OS rate was significantly higher with NAC (79.9%) than with dCRT (56.8%) (P = 0.022), and the multivariate analyses identified only NAC and cN0, one of the two as a significantly independent factor associated with a better OS (NAC: P = 0.041; cN0, 1: P = 0.036).

The study showed that NAC as larynx-preserving surgery for resectable cervical esophageal cancer preserved function and had a better prognosis than dCRT. The authors suggest that NAC may be standard strategy for larynx preservation in patients with resectable cervical esophageal cancer.

To assess adjuvant treatment patterns on survival in patients with pT3N0M0 esophageal cancer who underwent esophagectomy without neoadjuvant chemoradiotherapy. Stage pT3N0M0 esophageal cancer patients were assessed between 2000 and 2020 from the Surveillance, Epidemiology, and End Results databases. Kaplan-Meier analysis was used to compare overall survival (OS) among various treatment patterns. We identified 445 patients: 252 (56.6%) received surgery alone, 85 (19.1%) received surgery+chemoradiotherapy, 80 (18.0%) underwent surgery+chemotherapy, and 28 (6.3%) received surgery+ radiotherapy. For squamous cell carcinoma, surgery+chemoradiotherapy ([hazard ratio] HR = 1.04, 95% confidence interval (CI): 0.65-1.66; P = 0.873), surgery+chemotherapy (HR = 0.72, 95% CI: 0.42-1.22; P = 0.221), and surgery+radiotherapy (HR = 1.33, 95% CI: 0.74-2.39; P = 0.341) had similar OS compared to surgery alone. For adenocarcinoma, surgery+chemoradiotherapy (HR = 0.51, 95% CI: 0.36-0.74; P < 0.001) and surgery+chemotherapy (HR = 0.61, 95% CI: 0.42-0.87; P = 0.006) had better OS compared to surgery alone. However, surgery+radiotherapy had a comparable OS (HR = 0.81, 95% CI: 0.44-1.49; P = 0.495).Adjuvant treatments did not improve survival in stage pT3N0M0 esophageal squamous cell carcinoma patients. In contrast, adjuvant chemoradiotherapy and chemotherapy were recommended for esophageal adenocarcinoma patients.

The prognosis of metastatic esophageal cancer (EC) remains poor with an average life expectancy of around 9-12 months with standard systemic chemotherapy. The concept of oligometastatic disease (OMD) in EC cancer is controversial with no universally accepted definition. From the original cohort of metastatic oesophago-gastric (OG) cancer patients, 4 cases were identified that developed unusually favourable outcome with long-term survival and probable cure. In retrospect, all patients had OMD at presentation with striking similarities in terms of their clinical presentation, staging, treatment response and outcomes. All patients presented with locally advanced EC and 1-2 areas of metastatic disease (bone, lung, non-regional lymph node (LN) involvement). All were treated with combined therapeutic strategy using initial systemic chemotherapy followed by local radiotherapy to primary tumor and adjacent areas of visible/residual metastatic disease (metastasis-directed therapy). All patients experienced long-term survival (range = 7-13 years) with no evidence of recurrence and probable cure. The present case series adds to the growing pool of evidence indicating OM EC cancer represents a distinct and prognostically favorable subgroup.

Sarcopenia has been demonstrated to be adversely correlated with the prognosis of various cancers. Our study aimed to estimate the prognostic value of sarcopenia in conjunction with inflammatory indices [neutrophil-to-lymphocyte ratio (NLR)] for evaluating the prognosis of patients with esophageal squamous cell carcinoma (ESCC) undergoing chemoradiotherapy.

This study retrospectively analyzed 255 patients with ESCC who received chemoradiotherapy from January 2012 to December 2018. Multivariate Cox regression analysis was employed to identify prognostic values of assessed factors following a novel prognostic scoring system (SMI-NLR), covering sarcopenia and NLR during different treatment courses.

Kaplan-Meier analysis revealed significantly greater overall survival (OS) rates in the nonsarcopenia group than in the sarcopenia group (P = 0.011). The low NLR group (< 4.84) demonstrated significantly higher OS rates than the high NLR group (≥ 4.84) (P < 0.001). The SMI-NLR prognostic model was established through multivariate analysis, revealing that Karnofsky performance status [hazard ratio (HR) = 0.285; 95% confidence interval (CI) = 0.117-0.699; P = 0.006], clinical staging (HR = 5.223; 95% CI = 1.879-14.514; P = 0.002), and preSMI-NLR (HR = 0.544; 95% CI = 0.330-0.898; P = 0.017) were independent factors affecting the prognosis of patients with ESCC. Nomograms were constructed based on these data providing more accurate 1-, 3-, and 5-year survival rates for patients with ESCC.

Our study indicates the effectiveness of the combined sarcopenia and NLR prognostic model for the prognostic evaluation of patients with ESCC having undergone chemoradiotherapy.

Oesophageal adenocarcinoma (OAC) is a highly heterogeneous cancer with poor survival. Standard curative treatment is chemotherapy with or without radiotherapy followed by oesophagectomy. Genomic heterogeneity is a feature of OAC and has been linked to treatment resistance.

Whole-genome sequencing data from 59 treatment-naïve and 18 post-treatment samples from 29 OAC patients was analysed. Twenty-seven of these were enrolled in the DOCTOR trial, sponsored by the Australasian Gastro-Intestinal Trials Group. Two biopsies from each treatment-naïve tumour were assessed to define 'shared' (between both samples) and 'private' (present in one sample) mutations.

Mutational signatures SBS2/13 (APOBEC) and SBS3 (BRCA) were almost exclusively detected in private mutation populations of treatment-naïve tumours. Patients presenting these signatures had significantly worse disease specific survival. Furthermore, mutational signatures associated with platinum-based chemotherapy treatment as well as high platinum enrichment scores were only detected in post-treatment samples. Additionally, clones with high putative neoantigen binding scores were detected in some treatment-naïve samples suggesting immunoediting of clones.

This study demonstrates the high intra-tumour heterogeneity in OAC, as well as indicators for treatment-induced changes during tumour evolution. Intra-tumour heterogeneity remains a problem for successful treatment strategies in OAC.

The systematic review and network meta-analysis (NMA) consolidate all relevant randomized controlled trials (RCTs) related to initial immunotherapy treatments for advanced esophageal squamous cell carcinoma (ESCC). Our goal is to thoroughly assess the effectiveness and safety of various immunotherapy methods, focusing on overall survival (OS) and progression-free survival (PFS) among patients with advanced ESCC positive for PD-L1.

We conducted a systematic search of the PubMed, Embase, Cochrane Library, and Web of Science databases, covering all records from their inception until January 22, 2024. The inclusion criteria targeted patients with advanced ESCC undergoing first-line immunotherapy or chemotherapy, limiting the study selection to randomized controlled trials (RCTs) exclusively. The study upholds the values of openness, originality, and dependability, as evidenced by its enrollment in the Prospective Register of Systematic Reviews (CRD42024504992).

Our analysis encompasses 7 RCTs, totaling 4688 patients, and evaluates 8 distinct immunotherapy combinations. In advanced ESCC patients irrespective of PD-L1 expression, both sintilimab-chemotherapy and toripalimab-chemotherapy regimens demonstrated comparable OS benefits (HR=0.92, 95% CI: 0.64-1.33). The most pronounced PFS advantages were seen with sintilimab-chemotherapy and camrelizumab-chemotherapy as compared to standard chemotherapy (HR=0.56, 95% CI: 0.46-0.58). Notably, camrelizumab-chemotherapy (HR=0.83, 95% CI: 0.59-1.16) and nivolumab-ipilimumab (HR=0.84, 95% CI: 0.60-1.17) demonstrated significant safety profiles over chemotherapy alone. Subgroup analysis based on PD-L1 expression revealed nivolumab-chemotherapy to yield the highest OS benefit (HR=0.54, 95% CI: 0.37-0.79) in ESCC patients with PD-L1 expression ≥1%. Furthermore, camrelizumab-chemotherapy (HR=0.51, 95% CI: 0.39-0.67) exhibited superior PFS benefits. Among patients with PD-L1 expression ≥10%, camrelizumab-chemotherapy (HR=0.52, 95% CI: 0.35-0.78) emerged as the most efficacious in improving OS, while serplulimab-chemotherapy (HR=0.48, 95% CI: 0.34-0.68) was associated with the longest PFS benefit.

The integration of immune checkpoint inhibitors (ICIs) with chemotherapy appears to significantly enhance survival outcomes in patients with advanced ESCC compared to chemotherapy alone. Sintilimab-chemotherapy is potentially the optimal regimen for patients without PD-L1 expression. In contrast, nivolumab-chemotherapy and camrelizumab-chemotherapy are likely to offer the best OS and PFS benefits, respectively, in patients with PD-L1 expression ≥1%. Among those with PD-L1 expression ≥10%, camrelizumab-chemotherapy is projected to provide the greatest OS advantage, whereas serplulimab-chemotherapy is anticipated to offer the most prolonged PFS benefit. Since most of the patients in this study originated from Asia, the above findings are more applicable to the Asian population.

https://www.crd.york.ac.uk/prospero/, identifier CRD42024504992.

The current National Comprehensive Cancer Network advises neoadjuvant chemoradiotherapy followed by surgery for locally advanced cases of esophageal cancer. The role of immunotherapy in this context is under heavy investigation.

Patients with esophageal adenocarcinoma were identified in the National Cancer Database (NCDB) from 2004 to 2019. Three groups were generated as follows: (a) no immunotherapy, (b) neoadjuvant immunotherapy, and (c) adjuvant immunotherapy. Overall survival was evaluated using the Kaplan-Meier method and Cox proportional hazard analysis, adjusting for previously described risk factors for mortality.

Of the total 14,244 patients diagnosed with esophageal adenocarcinoma who received neoadjuvant chemoradiation, 14,065 patients did not receive immunotherapy, 110 received neoadjuvant immunotherapy, and 69 received adjuvant immunotherapy. When adjusting for established risk factors, adjuvant immunotherapy was associated with significantly improved survival compared to no immunotherapy and neoadjuvant immunotherapy during a median follow-up period of 35.2 months. No difference was noted among patients who received no immunotherapy vs. neoadjuvant immunotherapy in the same model.

In this retrospective analysis of the NCDB, receiving adjuvant immunotherapy offered a significant survival advantage compared to no immunotherapy and neoadjuvant immunotherapy in the treatment of esophageal adenocarcinoma. The addition of neoadjuvant immunotherapy to patients treated with neoadjuvant chemoradiation did not improve survival in this cohort. Further studies are warranted to investigate the long-term outcomes of immunotherapy in esophageal cancer.

Esophagectomy is associated with significant mortality. A better understanding of the causes leading to death may help to reduce mortality. A root cause analysis of mortality after esophagectomy was performed.

Root cause analysis was retrospectively applied by an independent expert panel of 4 upper gastrointestinal surgeons and 1 anesthesiologist-intensivist to patients included in the French national multicenter prospective cohort FREGAT between August 2014 and September 2019 who underwent an esophagectomy for cancer and died within 90 days of surgery. A cause-and-effect diagram was used to determine the root causes related to death. Death was classified as potentially preventable or non-preventable.

Among the 1,040 patients included in the FREGAT cohort, 70 (6.7%) patients (male: 81%, median age 68 [62-72] years) from 17 centers were included. Death was potentially preventable in 37 patients (53%). Root causes independently associated with preventable death were inappropriate indication (odds ratio 35.16 [2.50-494.39]; P = .008), patient characteristics (odds ratio 5.15 [1.19-22.35]; P = .029), unexpected intraoperative findings (odds ratio 18.99 [1.07-335.55]; P = .045), and delay in diagnosis of a complication (odds ratio 98.10 [6.24-1,541.04]; P = .001). Delay in treatment of a complication was found only in preventable deaths (28 [76%] vs 0; P < .001). National guidelines were less frequently followed (16 [43%] vs 22 [67%]; P = .050) in preventable deaths. The only independent risk factor of preventable death was center volume <26 esophagectomies per year (odds ratio 4.71 [1.55-14.33]; P = .006).

More than one-half of deaths after esophagectomy were potentially preventable. Better patient selection, early diagnosis, and adequate management of complications through centralization could reduce mortality.

Gastro-oEsophageal Cancers (GECs) are severe diseases whose management is rapidly evolving. The European Society of Surgical Oncology (ESSO) is committed to the generation and spread of knowledge, and promotes the multidisciplinary management of cancer patients through its core curriculum. The present work discusses the approach to GECs, including the management of oligometastatic oesophagogastric cancers (OMEC), the diagnosis and management of peritoneal metastases from gastric cancer (GC), the management of Siewert Type II tumors, the importance of mesogastric excision, the role of robotic surgery, textbook outcomes, organ preserving options, the use of molecular markers and immune check-point inhibitors in the management of patients with GECs, as well as the improvement of current clinical practice guidelines for the management of patients with GECs. The aim of the present review is to provide a concise overview of the state-of-the-art on the management of patients with GECs and, at the same time, to share the latest advancements in the field and to foster the debate between surgical oncologists treating GECs worldwide. We are sure that our work will, at the same time, give an update to the advanced surgical oncologists and help the training surgical oncologists to settle down the foundations for their future practice.

The objective of this study was to evaluate the prognostic nutritional index (PNI) as a predictor of short-term postoperative complications in esophageal squamous cell carcinoma patients undergoing neoadjuvant immunochemotherapy.

Clinical data were collected from 77 patients undergoing radical esophageal cancer surgery after neoadjuvant immunochemotherapy at Tongji Hospital from January 2022 to January 2023. The receiver operating characteristic curve (ROC) was utilized to establish the optimal cut-off point for the PNI. Subsequently, patients were stratified into low and high PNI groups according to this cut-off point, and comparisons were made between the two groups in terms of clinical data and postoperative complications.

Out of the 77 patients included in the study, 31 were categorized in the low PNI group and 46 in the high PNI group, with a defined cutoff point of 47.38. Significant statistical variances were noted in the occurrence rates of general complications (P < 0.001), pulmonary infections (P < 0.001), and anastomotic fistula (P = 0.034) between the two groups. The low PNI group displayed elevated rates of these complications in comparison to the high PNI group.

The research findings indicate that preoperative nutritional assessment using the PNI can effectively predict short-term postoperative complications in esophageal squamous cell carcinoma patients who have undergone neoadjuvant therapy. Furthermore, the results suggest that implementing nutritional interventions for patients with moderate-to-severe malnutrition, as indicated by preoperative PNI evaluation, may help reduce the incidence of postoperative complications.

Pulmonary complications (PC) are common after esophagectomy and their impact on long-term survival is not defined yet. The present study aimed to assess the effect of postoperative PCs on long-term survival after esophagectomy for cancer. Systematic review of the literature through February 1, 2023, was performed. The included studies evaluated the effect of PC on long-term survival. Primary outcome was long-term overall survival (OS). Cancer-specific survival (CSS) and disease-free survival (DFS) were secondary outcomes. Restricted mean survival time difference (RMSTD), hazard ratio (HR), and 95% confidence intervals (CI) were used as pooled effect size measures. Eleven studies were included (3423 patients). Overall, 674 (19.7%) patients developed PC. The RMSTD analysis shows that at 60-month follow-up, patients not experiencing PC live an average of 8.5 (95% CI 6.2-10.8; p < 0.001) months longer compared with those with PC. Similarly, patients not experiencing postoperative PC seem to have significantly longer CSS (8 months; 95% CI 3.7-12.3; p < 0.001) and DFS (5.4 months; 95% CI 1.6-9.1; p = 0.005). The time-dependent HRs analysis shows a reduced mortality hazard in patients without PC at 12 (HR 0.6, 95% CI 0.51-0.69), 24 (HR 0.64, 95% CI 0.55-0.73), 36 (HR 0.67, 95% CI 0.55-0.79), and 60 months (HR 0.69, 95% CI 0.51-0.89). This study suggests a moderate clinical impact of PC on long-term OS, CSS, and DFS after esophagectomy. Patients not experiencing PC seem to have a significantly reduced mortality hazard up to 5 years of follow-up.