Enhancement of Pulmonary Function and Reduction of Complications Through EIT-Guided Yoga Breathing Exercise After Esophagectomy.

BACKGROUND This study aimed to investigate the impact of EIT-guided yoga breathing training on postoperative pulmonary complications (PPCs) for esophageal cancer patients. MATERIAL AND METHODS Total of 62 patients underwent radical resections of esophageal cancer. Esophageal cancer patients were randomized to the standard care group, or the intervention group receiving an additional complete breathing exercise under the guidance of EIT in AICU. Following extubation after the esophagectomy, pulmonary functions were evaluated by EIT with center of ventilation (CoV), dependent silent spaces (DSS), and non-dependent silent spaces (NSS). RESULTS Sixty-one older esophageal cancer patients (31 in the Control group and 30 in the EIT group) were included in the final analysis. Forty-four patients experienced pulmonary complications after esophagectomy, 27 (87.1%) in the Control group and 17 (36.7%) in the EIT group (RR, 0.42 (95% CI: 0.26, 0.69). The most common pulmonary complication was pleural effusion, with an incidence of 30% in the EIT group and 74.2% in the Control group, with RR of 0.40 (95% CI: 0.23, 0.73). Time for the first pulmonary complication was significantly longer in the EIT group than in the Control group (hazard ratio, HR, 0.43; 95% CI 0.21 to 0.87; P=0.019). Patients in the EIT group had significantly higher scores in CoV, DSS, and NSS than in the Control group. CONCLUSIONS Guided by EIT, the addition of the postoperative breathing exercise to the standardized care during AICU could further improve pulmonary function, and reduce postoperative pulmonary complications after esophagectomy.

A machine learning radiomics based on enhanced computed tomography to predict neoadjuvant immunotherapy for resectable esophageal squamous cell carcinoma.

Background: Patients with resectable esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy (NIT) display variable treatment responses. The purpose of this study is to establish and validate a radiomics based on enhanced computed tomography (CT) and combined with clinical data to predict the major pathological response to NIT in ESCC patients. Methods: This retrospective study included 82 ESCC patients who were randomly divided into the training group (n = 57) and the validation group (n = 25). Radiomic features were derived from the tumor region in enhanced CT images obtained before treatment. After feature reduction and screening, radiomics was established. Logistic regression analysis was conducted to select clinical variables. The predictive model integrating radiomics and clinical data was constructed and presented as a nomogram. Area under curve (AUC) was applied to evaluate the predictive ability of the models, and decision curve analysis (DCA) and calibration curves were performed to test the application of the models. Results: One clinical data (radiotherapy) and 10 radiomic features were identified and applied for the predictive model. The radiomics integrated with clinical data could achieve excellent predictive performance, with AUC values of 0.93 (95% CI 0.87-0.99) and 0.85 (95% CI 0.69-1.00) in the training group and the validation group, respectively. DCA and calibration curves demonstrated a good clinical feasibility and utility of this model. Conclusion: Enhanced CT image-based radiomics could predict the response of ESCC patients to NIT with high accuracy and robustness. The developed predictive model offers a valuable tool for assessing treatment efficacy prior to initiating therapy, thus providing individualized treatment regimens for patients.

The predictors of lymphopenia and its effects on survival in locally advanced esophageal squamous cell carcinoma.

To investigate the impact of the effective radiation dose to immune cells (EDIC) and gross tumor volume (GTV) on lymphopenia and survival in patients with locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2013 and December 2020, 272 LAESCC patients were treated with definitive radiotherapy in two institutions. Based on radiation doses to the lungs, heart, and body region scanned, EDIC was calculated as an equal uniform dose to the total blood considering blood flow and fraction effect. The radiotherapy plan was used to calculate the GTVs. Lymphopenia was graded based on the lowest lymphocyte count during RT. The overall survival (OS), progress-free survival (PFS), and local recurrence-free survival (LRFS) were analyzed statistically. The lowest lymphocyte count was significantly correlated with EDIC (r= -0.389, p < .001) and GTV (r= -0.211, p < .001). Lymphopenia, EDIC, and GTV are risk factors for patients with ESCC. In a Kaplan-Meier analysis with EDIC and GTV as stratification factors, lymphopenia was not associated with OS in the EDIC>12.9 Gy group (p = .294)and EDIC ≤ 12.9 Gy group, and it was also not associated with OS in GTV>68.8 cm3 group (p = .242) and GTV ≤ 68.8 cm3 group(p = .165). GTV and EDIC had an impact on the relationship between lymphopenia and OS in patients with LAESCC undergoing definitive RT. Poorer OS, PFS, and LRFS are correlated with lymphopenia, higher EDIC, and larger GTV.

Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. BACKGROUND: Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. METHODS: Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. RESULTS: A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. CONCLUSION: Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.

Genomic characteristics and evolution of Multicentric Esophageal and gastric Cardiac Cancer.

BACKGROUND: Esophageal carcinoma (EC) and gastric cardiac adenocarcinoma (GCA) have high incidence rates in the Chaoshan region of South China. Multifocal esophageal and cardiac cancer (MECC) is commonly observed in this region in clinical practice. However, the genomic characteristics of MECC remains unclear. MATERIALS AND METHODS: In this study, a total of 2123 clinical samples of EC and GCA were analyzed to determine the frequency of multifocal tumors, as well as their occurrence sites and pathological types. Cox proportional hazards regression was used to model the relationship between age, sex, and tumor state concerning survival in our analysis of the cohort of 541 patients with available follow-up data. We performed whole-genome sequencing on 20 tumor foci and 10 normal samples from 10 MECC patients to infer clonal structure on 6 MECC patients to explore genome characteristics. RESULT: The MECC rate of EC and GCA was 5.65% (121 of 2123). Age and sex were potential factors that may influence the risk of MECC (p < 0.001). Furthermore, MECC patients showed worse survival compared with single tumor patients. We found that 12 foci from 6 patients were multicentric origin model (MC), which exhibited significant heterogeneity of variations in paired foci and had an increased number of germline mutations in immune genes compared to metastatic model. In MC cases, different lesions in the same patient were driven by distinct mutation and copy number variation (CNV) events. Although TP53 and other driver mutation genes have a high frequency in the samples, their mutation sites show significant heterogeneity in paired tumor specimens. On the other hand, CNV genes exhibited higher concordance in paired samples, especially in the amplification of oncogenes and the deletion of tumor suppressor genes. CONCLUSIONS: The extent of inter-tumor heterogeneity suggests both monoclonal and polyclonal origins of MECC, which could provide insight into the genome diversity of MECC and guide clinical implementation.

Identification of intracellular bacteria from multiple single-cell RNA-seq platforms using CSI-Microbes.

The study of the tumor microbiome has been garnering increased attention. We developed a computational pipeline (CSI-Microbes) for identifying microbial reads from single-cell RNA sequencing (scRNA-seq) data and for analyzing differential abundance of taxa. Using a series of controlled experiments and analyses, we performed the first systematic evaluation of the efficacy of recovering microbial unique molecular identifiers by multiple scRNA-seq technologies, which identified the newer 10x chemistries (3' v3 and 5') as the best suited approach. We analyzed patient esophageal and colorectal carcinomas and found that reads from distinct genera tend to co-occur in the same host cells, testifying to possible intracellular polymicrobial interactions. Microbial reads are disproportionately abundant within myeloid cells that up-regulate proinflammatory cytokines like IL1Β and CXCL8, while infected tumor cells up-regulate antigen processing and presentation pathways. These results show that myeloid cells with bacteria engulfed are a major source of bacterial RNA within the tumor microenvironment (TME) and may inflame the TME and influence immunotherapy response.

The distribution of esophageal cancer patients enrolled in care at the Uganda Cancer Institute by sub-regions, districts and ethnicity.

Background: There is limited published data regarding the distribution of esophageal cancer patients by sub-regions, districts and ethnicity in Uganda. Objectives: To study the distribution by sub-regions, districts, ethnicity and sub-regions post-care outcomes of esophageal cancer patients in care over ten years at the Uganda Cancer Institute. Methods: Patients' charts with confirmed diagnoses of esophageal cancer for 2009-2019 were identified. Case information, which included demographics, clinical presentation, distribution by sub-regions, districts, ethnicity and sub-regions post-care outcomes, were retrospectively abstracted. Results: Central 671(34.15%), Southwestern 308(15.67%), Elgon 176(8.95%) and East central 163(8.29%) sub-regions had most patients. Mostly from administrative districts of Wakiso 167(8.50%), Mbarara 51(2.59%), Tororo 53(2.70%), Busia 33(1.68). Baganda, Banyakole, Bagisu and Basoga ethnic groups predominate. Patients from neighbouring countries were mainly from Rwanda 56(2.85%), South Sudan 24(1.22%), then Kenya 21(1.07%), and Rwandese, Dinka and Luo by ethnicity, respectively. Central and Southwestern sub-regions had the most post-care outcomes of the patients regarding living, death, and loss to follow-up. Conclusion: Patients are commonly from the administrative districts of Central, Southwestern, Elgon and East Central sub-regions and neighbouring countries of Rwanda, South Sudan and Kenya. Baganda, Banyakole, Bagisu and Basoga are the main ethnic groups. Central and Southwestern sub-regions are with most post-care outcomes.

Disease-specific health-related quality of life trajectories up to 15 years after curative treatment for esophageal cancer-a prospective cohort study.

BACKGROUND: The presence of distinct long-term disease-specific HRQL trajectories after curative treatment for esophageal cancer and factors associated with such trajectories are unclear. MATERIALS AND METHODS: This population-based and longitudinal cohort study included 425 esophageal cancer patients who underwent curative treatment, including esophagectomy, in Sweden in 2001-2005 and were followed up until 2020, that is, 15-year follow-up. The outcomes were 10 disease-specific HRQL symptoms, measured by the well-validated EORTC QLQ-OES18 questionnaire at 6 months (n = 402 patients), and 3 (n = 178), 5 (n = 141), 10 (n = 92), and 15 years (n = 52) after treatment. HRQL symptoms were examined for distinct trajectories by growth mixture models. Weighted logistic regression models provided odds ratios (OR) with 95% confidence intervals (95% CI) for nine factors in relation to HRQL trajectories: age, sex, education, proxy baseline HRQL, comorbidity, tumor histology, chemo(radio)therapy, pathological tumor stage, and postoperative complications. RESULTS: Distinct HRQL trajectories were identified for each of the 10 disease-specific symptoms. HRQL trajectories with more symptoms tended to persist or alleviate over time, while trajectories with fewer symptoms were more stable. Eating difficulty had three trajectories: persistently less, persistently moderate, and persistently more symptoms. The OR of having a persistently more eating difficulty trajectory was decreased for adenocarcinoma histology (OR = 0.44, 95% CI 0.21-0.95), and increased for pathological tumor stage III-IV (OR = 2.19, 95% CI 0.99-4.82) and 30-day postoperative complications (OR = 2.54, 95% CI 1.26-5.12). CONCLUSION: Distinct trajectories with long-term persistent or deteriorating disease-specific HRQL symptoms were identified after esophageal cancer treatment. Tumor histology, tumor stage, and postoperative complications may facilitate detection of high-risk patients for unwanted trajectories.

A comparative assessment of ACS NSQIP-predicted and actual surgical risk outcomes of robotic transhiatal esophagectomy for esophageal adenocarcinoma resection at a high volume institution.

Esophageal adenocarcinoma incidence is increasing in Western nations. There has been a shift toward minimally invasive approaches for transhiatal esophagectomy (THE). This study compares the outcomes of robotic THE for esophageal adenocarcinoma resection at our institution with the predicted metrics from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). With Institutional Review Board (IRB) approval, we prospectively followed 83 patients who underwent robotic THE from 2012 to 2023. Predicted outcomes were determined using the ACS NSQIP Surgical Risk Calculator. Our outcomes were compared with these predicted outcomes and with general outcomes for transhiatal esophagectomy reported in ACS NSQIP, which includes a mix of surgical approaches. The median age of patients was 70 years, with a body mass index (BMI) of 26.4 kg/m2 and a male prevalence of 82%. The median length of stay was 7 days. The rates of any complications and in-hospital mortality were 16% and 5%, respectively. Seven patients (8%) were readmitted within a 30-day postoperative window. The median survival is anticipated to surpass 95 months. Our outcomes were generally aligned with or surpassed the predicted ACS NSQIP metrics. The extended median survival of over 95 months highlights the potential effectiveness of robotic THE in the resection of esophageal adenocarcinoma. Further exploration into its long-term survival benefits and outcomes is warranted, along with studies that provide a more direct comparison between robotic and other surgical approaches.

Multicentre randomized clinical trial on robot-assisted versus video-assisted thoracoscopic oesophagectomy (REVATE trial).

BACKGROUND: Surgery for oesophageal squamous cell carcinoma involves dissecting lymph nodes along the recurrent laryngeal nerve. This is technically challenging and injury to the recurrent laryngeal nerve may lead to vocal cord palsy, which increases the risk of pulmonary complications. The aim of this study was to compare the efficacy and safety of robot-assisted oesophagectomy (RAO) versus video-assisted thoracoscopic oesophagectomy (VAO) for dissection of lymph nodes along the left RLN. METHODS: Patients with oesophageal squamous cell carcinoma who were scheduled for minimally invasive McKeown oesophagectomy were allocated randomly to RAO or VAO, stratified by centre. The primary endpoint was the success rate of left recurrent laryngeal nerve lymph node dissection. Success was defined as the removal of at least one lymph node without causing nerve damage lasting longer than 6 months. Secondary endpoints were perioperative and oncological outcomes. RESULTS: From June 2018 to March 2022, 212 patients from 3 centres in Asia were randomized, and 203 were included in the analysis (RAO group 103; VAO group 100). Successful left recurrent laryngeal nerve lymph node dissection was achieved in 88.3% of the RAO group and 69% of the VAO group (P < 0.001). The rate of removal of at least one lymph node according to pathology was 94.2% for the RAO and 86% for the VAO group (P = 0.051). At 1 week after surgery, the RAO group had a lower incidence of left recurrent laryngeal nerve palsy than the VAO group (20.4 versus 34%; P = 0.029); permanent recurrent laryngeal nerve palsy rates at 6 months were 5.8 and 20% respectively (P = 0.003). More mediastinal lymph nodes were dissected in the RAO group (median 16 (i.q.r. 12-22) versus 14 (10-20); P = 0.035). Postoperative complication rates were comparable between the two groups and there were no in-hospital deaths. CONCLUSION: In patients with oesophageal squamous cell carcinoma, RAO leads to more successful left recurrent laryngeal nerve lymph node dissection than VAO, including a lower rate of short- and long-term recurrent laryngeal nerve injury. Registration number: NCT03713749 (http://www.clinicaltrials.gov).

Oesophageal cancer often requires complex surgery. Recently, minimally invasive techniques like robot- and video-assisted surgery have emerged to improve outcomes. This study compared robot- and video-assisted surgery for oesophageal cancer, focusing on removing lymph nodes near a critical nerve. Patients with a specific oesophageal cancer type were assigned randomly to robot- or video-assisted surgery at three Asian hospitals. Robot-assisted surgery had a higher success rate in removing lymph nodes near the important nerve without permanent damage. It also had shorter operating times, more lymph nodes removed, and faster drain removal after surgery. In summary, for oesophageal cancer surgery, the robotic approach may provide better lymph node removal and less nerve injury than video-assisted techniques.

Neoadjuvant chemoimmunotherapy for small cell carcinoma of the esophagus: Clinical efficacy and biomarker exploration.

Small cell carcinoma of the esophagus (SCCE) is a rare and highly malignant type of esophageal cancer with no standard treatment, facing challenges of resistance to conventional therapies. This study presents the cases of one extensive-stage and two limited-stage SCCE patients treated with chemoimmunotherapy. The two limited-stage patients underwent surgery post-treatment and experienced notable and enduring positive responses. This represents the first documented application of neoadjuvant chemoimmunotherapy in limited-stage SCCE patients. Additionally, comprehensive immunohistochemical analysis and whole exome sequencing were performed on the case patients. The findings revealed that infiltration of CD8+ T cells and PD-L1 expression in the SCCE tumor were key factors for favorable responses in SCCE patients receiving chemoimmunotherapy.

Clinical Efficacy of Taxol Plus Platinum (TP) Chemotherapy Combined with Delayed Administration of PD-1 Inhibitors in Patients with Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma: A Retrospective Study.

Purpose: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line standard treatment for locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). The evidence also demonstrates improved synergistic effects of chemotherapy when combined with delayed administration of ICIs. In this study, we conducted a retrospective investigation into the treatment efficacy of taxol plus platinum (TP) chemotherapy combined with delayed administration of PD-1 inhibitors for ESCC patients. Patients and Methods: Clinical data of ESCC patients who received PD-1 inhibitors 3-5 days after TP chemotherapy as first-line treatment was retrospectively reviewed between January 2019 and April 2023. Clinical outcomes and treatment safety were analyzed. The potential roles of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) were investigated. Results: A total of 34 locally advanced, recurrent or metastatic ESCC patients received PD-1 inhibitors 3-5 days following TP chemotherapy were included. The objective response rate (ORR) and disease control rate (DCR) were 85.3% and 97.1% respectively. The median progression-free survival (PFS) and overall survival (OS) were 13.2 and 19.1 month respectively. Seven patients received radical surgery, 1 patient achieved pathologic complete response (pCR) and 3 patients achieved major pathologic response (MPR). Among the 27 patients without surgery, the median PFS and OS were 9.7 and 19.1 month respectively. A more favorable prognosis was correlated with NLR less than 3 at the 3rd and 4th cycle of immunochemotherapy. No significant correlations between other parameters (PLR, MLR and PIV) and prognosis were observed. A total of 22 patients developed grade 3-4 toxicity events. Conclusion: The optimized sequence of PD-1 inhibitors administered 3-5 days after TP chemotherapy as the first-line treatment of ESCC demonstrated favorable treatment efficacy. Pretreatment NLR of less than 3 at the 3rd and 4th cycle of immunochemotherapy is associated with a better prognosis.

Minimally Invasive transCervical oEsophagectomy (MICE) for oesophageal cancer: prospective cohort study (IDEAL stage 2A).

BACKGROUND: Minimally invasive transcervical oesophagectomy is a surgical technique that offers radical oesophagectomy without the need for transthoracic access. The aim of this study was to evaluate the safety and feasibility of the minimally invasive transcervical oesophagectomy procedure and to report the refinement of this technique in a Western cohort. METHODS: A single-centre prospective cohort study was designed as an IDEAL stage 2A study. Patients with oesophageal cancer (cT1b-4a N0-3 M0) who were scheduled for oesophagectomy with curative intent were eligible for inclusion in the study. The main outcome parameter was the postoperative pulmonary complication rate and the secondary outcomes were the anastomotic leakage, recurrent laryngeal nerve palsy, and R0 resection rates, as well as the lymph node yield. RESULTS: In total, 75 patients underwent minimally invasive transcervical oesophagectomy between January 2021 and November 2023. Several modifications to the surgical technique were registered, evaluated, and implemented in the context of IDEAL stage 2A. A total of 12 patients (16%) had postoperative pulmonary complications, including pneumonia (4 patients) and pleural effusion with drainage or aspiration (8 patients). Recurrent laryngeal nerve palsy was observed in 33 of 75 patients (44%), with recovery in 30 of 33 patients (91%). A total of 5 of 75 patients (7%) had anastomotic leakage. The median number of resected lymph nodes was 29 (interquartile range 22-37) and the R0 resection rate was 96% (72 patients). CONCLUSION: Introducing minimally invasive transcervical oesophagectomy for oesophageal cancer in a Dutch institution is associated with a low rate of postoperative pulmonary complications and a high rate of temporary recurrent laryngeal nerve palsy.

Genome-Scale Multimodal Analysis of Cell-Free DNA Whole-Methylome Sequencing for Noninvasive Esophageal Cancer Detection.

PURPOSE: Simultaneous profiling of cell-free DNA (cfDNA) methylation and fragmentation features to improve the performance of cfDNA-based cancer detection is technically challenging. We developed a method to comprehensively analyze multimodal cfDNA genomic features for more sensitive esophageal squamous cell carcinoma (ESCC) detection. MATERIALS AND METHODS: Enzymatic conversion-mediated whole-methylome sequencing was applied to plasma cfDNA samples extracted from 168 patients with ESCC and 251 noncancer controls. ESCC characteristic cfDNA methylation, fragmentation, and copy number signatures were analyzed both across the genome and at accessible cis-regulatory DNA elements. To distinguish ESCC from noncancer samples, a first-layer classifier was developed for each feature type, the prediction results of which were incorporated to construct the second-layer ensemble model. RESULTS: ESCC plasma genome displayed global hypomethylation, altered fragmentation size, and chromosomal copy number alteration. Methylation and fragmentation changes at cancer tissue-specific accessible cis-regulatory DNA elements were also observed in ESCC plasma. By integrating multimodal genomic features for ESCC detection, the ensemble model showed improved performance over individual modalities. In the training cohort with a specificity of 99.2%, the detection sensitivity was 81.0% for all stages and 70.0% for stage 0-II. Consistent performance was observed in the test cohort with a specificity of 98.4%, an all-stage sensitivity of 79.8%, and a stage 0-II sensitivity of 69.0%. The performance of the classifier was associated with the disease stage, irrespective of clinical covariates. CONCLUSION: This study comprehensively profiles the epigenomic landscape of ESCC plasma and provides a novel noninvasive and sensitive ESCC detection approach with genome-scale multimodal analysis.

Correlation of PD-L1 expression with CD8+ T cells and oxidative stress-related molecules NRF2 and NQO1 in esophageal squamous cell carcinoma.

Oxidative stress and the immune microenvironment both contribute to the pathogenesis of esophageal squamous cell carcinoma (ESCC). However, their interrelationships remain poorly understood. We aimed to examine the status of key molecules involved in oxidative stress and the immune microenvironment, as well as their relationships with each other and with clinicopathological features and prognosis in ESCC. The expression of programmed death-ligand 1 (PD-L1), CD8, nuclear factor erythroid-2 related factor-2 (NRF2), and NAD(P)H quinone oxidoreductase 1 (NQO1) was detected using immunohistochemistry in tissue samples from 176 patients with ESCC. We employed both combined positive score (CPS) and tumor proportion score (TPS) to evaluate PD-L1 expression and found a positive correlation between CPS and TPS. Notably, PD-L1 expression, as assessed by either CPS or TPS, was positively correlated with both NRF2 nuclear score and NQO1 score in stage II-IV ESCC. We also observed a positive correlation between the density of CD8+ T cells and PD-L1 expression. Furthermore, high levels of PD-L1 CPS, but not TPS, were associated with advanced TNM stage and lymph node metastases. Moreover, both PD-L1 CPS and the nuclear expression of NRF2 were found to be predictive of shorter overall survival in stage II-IV ESCC. By using the Mandard-tumor regression grading (TRG) system to evaluate the pathological response of tumors to neoadjuvant chemotherapy (NACT), we found that the TRG-5 group had higher NRF2 nuclear score, PD-L1 CPS, and TPS in pre-NACT biopsy samples compared with the TRG-3 + 4 group. The NQO1 scores of post-NACT surgical specimens were significantly higher in the TRG-5 group than in the TRG 3 + 4 group. In conclusion, the expression of PD-L1 is associated with aberrant NRF2 signaling pathway, advanced TNM stage, lymph node metastases, and unfavorable prognosis. The dysregulation of PD-L1 and aberrant activation of the NRF2 signaling pathway are implicated in resistance to NACT. Our findings shed light on the complex interrelationships between oxidative stress and the immune microenvironment in ESCC, which may have implications for personalized therapies and improved patient outcomes.

Dynamics of Long-Term Quality of Life After Treatment for Esophageal Cancer: A Community-Based Patient Study.

PURPOSE: To characterize the pattern of post-treatment quality of life (QoL) for esophageal cancer (EC) survivors and construct models predicting their long-term QoL. METHODS: On the basis of a randomized trial in an EC high-risk region in China, we interviewed 363 EC survivors and 25,245 permanent residents matched with the survivors on age, sex, and township as the baseline. QoL was measured using three-level version of European Quality of Life 5-Dimensions instrument. We constructed piecewise mixed models estimating the QoL of EC survivors that varied by age, sex, patient type, hospital level, and therapy to ascertain QoL determinants. RESULTS: The post-treatment QoL of EC survivors dropped by 15.7% within the first year and recovered by 9.3% between 1 and 9 years compared with the baseline. Therapy was found to be a determinant of QoL, and a series of therapy-specific models were fitted accordingly, which all showed the pattern of decreasing rapidly and recovering gradually. Endoscopic treatment had the least impact on post-treatment QoL (7.5% drop within 5 years) compared with esophagectomy (12.2% drop within 1 year) and chemoradiotherapy (37.8% drop within 2 years). The usual activities dimension showed the greatest impairment among those patients (34.4% drop within 1 year). CONCLUSION: This community-based study described the long-term QoL trajectory for EC survivors after different therapeutic modalities and constructed models to predict therapy-specific QoL at different time points after treatment. It provided new insights into decision making in treatment for EC from the perspective of QoL protection, offering a convenient tool for estimating quality-adjusted life-years.

A Rare Case of Ileocecal Lymph Node Recurrence After Surgery in Siewert's Classification Type I Esophagogastric Junction Adenocarcinoma.

BACKGROUND Although recurrence after surgery for esophagogastric junction (EGJ) adenocarcinoma frequently develops in the mediastinal and para-aortic lymph nodes (LN), distant LN recurrence in the mesocolon is rare. We report a rare case of ileocecal LN metastasis in the ascending mesocolon after radical surgery for an EGJ adenocarcinoma. CASE REPORT We performed subtotal esophagectomy with mediastinal and para-gastric LN dissection in a patient with an advanced EGJ adenocarcinoma. Clinicopathologically, the patient was diagnosed with type I EGJ adenocarcinoma based on Siewert's classification (pathological T3N1M0). One year after surgery, computed tomography showed enlarged lymph nodes around the ileocolic artery, and further examination was performed. Although positron emission tomography-computed tomography showed that the lesion had moderate uptake of fluorodeoxyglucose, we did not find the reason for the enlarged lymph nodes. Finally, laparoscopic ileocecal resection was performed for diagnostic and therapeutic purposes. Clinicopathological tests revealed that the specimen was a moderately differentiated adenocarcinoma, which was strongly suspected to be a metastasis of the EGJ adenocarcinoma. CONCLUSIONS We encountered a rare case of EGJ adenocarcinoma that spread to the ileocecal LN in the ascending mesocolon. To the best of our knowledge, this is the first such report in the literature to date. Laparoscopic ileocecal resection for metastasis to the ascending mesocolon seems reasonable as a local control.

[Clinical significance of combined therapy with immune checkpoint inhibitor in perioperative treatment for locally advanced gastric cancer or adenocarcinoma of gastroesophageal junction].

The clinical application of immune checkpoint inhibitor (ICI) offers novel treatment modality for locally advanced gastric cancer (LAGC) and adenocarcinoma of the gastroesophageal junction (AGEJ), with the crucial benefit of providing higher cure rates. These agents have become part of standard treatments in the perioperative setting for selected cases, such as tumor with MSI-H/dMMR, high expression of CPS (≥5) or EBV (+), MSI-H and MSS/TP53+ according to tumor immunohistochemical, genetic testing or molecular characterization. An in-depth understanding of the immune response mechanisms in "cold" and "hot" tumors enables us to better identify ICI beneficiary and further provide a rationale for converting nonresponsive "cold" tumors into responsive "hot" tumors, subsequently allowing nonresponders to benefit from ICI immunotherapy. Several recent clinical trials clearly demonstrated a synergistic and complementary effect of combining ICI with chemotherapy or chemoradiotherapy, as well as combining ICI with anti-HER2 or anti-VEGF/VEGFR and chemotherapy. Compared with chemotherapy alone, the combination treatment can significantly improve pCR, MRR or ypT0N0, and is expected to improve the prognosis. This article reviews the results of a series of clinical trials in recent years in the field of perioperative application of ICI with other modalities in LAGC/AGEJ, aiming at expanding upon the discussion of current standard neoadjuvant and adjuvant therapies for LAGC/AGEJ and exploring the feasibility of new perioperative combined immunotherapy in the future.