Technical feasibility and oncological outcomes of robotic esophagectomy compared with conventional thoracoscopic esophagectomy for clinical T3 or T4 locally advanced esophageal cancer: a propensity-matched analysis.

BACKGROUND: Minimally invasive esophagectomy is the first-line approach for esophageal cancer; however, there has recently been a paradigm shift toward robotic esophagectomy (RE). We investigated the clinical outcomes of patients who underwent RE compared with those of patients who underwent conventional minimally invasive thoracoscopic esophagectomy (TE) for locally advanced cT3 or cT4 esophageal cancer using a propensity-matched analysis. METHODS: Overall, 342 patients with locally advanced cT3 or cT4 esophageal cancer underwent transthoracic esophagectomy with total mediastinal lymph node dissection between 2018 and 2022. The propensity-matched analysis was performed to assign the patients to either RE or TE by covariates of histological type, tumor location, and clinical N factor. RESULTS: Overall, 87 patients were recruited in each of the RE and TE groups according to the propensity-matched analysis. The total complication rate and the rates of the three major complications (recurrent laryngeal nerve paralysis, anastomotic leakage, and pneumonia) were not significantly different between the RE and TE groups. However, the peak C-reactive protein concentration on postoperative day 3, rate of surgical site infection, and intensive care unit length of stay after surgery were significantly shorter in the RE group than in the TE group. No significant differences were observed in the harvested total and mediastinal lymph nodes. The total operation time was significantly longer in the RE group, while the thoracic operation time was shorter in the RE group than in the TE group. There was no significant difference between the two groups in the recurrence rate of oncological outcomes after surgery. CONCLUSION: RE may facilitate early recovery after esophagectomy with total mediastinal lymph node dissection and has the same technical feasibility and oncological outcomes as TE.

Surgical vs nonsurgical treatment for esophageal squamous cell carcinoma in patients older than 70 years: a propensity score matching analysis.

PURPOSE: With the rising life expectancy and an aging population, it has become increasingly important to investigate treatments suitable for older adult patients with esophageal cancer. This study investigated whether older adult patients who underwent esophagectomy had better clinical outcomes than those who were nonsurgically treated. METHODS: We retrospectively analyzed patients with esophageal squamous cell carcinoma (ESCC) who were 70 years or older and underwent esophagectomy, radiotherapy (RT), and/or chemoradiotherapy (CRT) between January 2018 and December 2019. Patients were divided into 2 groups: the surgery group (S group) and the nonsurgery group (NS group). We then compared the clinical outcomes of the 2 groups. RESULTS: After a median follow-up duration of 36.6 months, the S group showed better overall survival (OS). The 3-year OS was 59% in the S group and 27% in the NS group (hazard ratio [HR], 0.397; 95% CI, 0.278-0.549; P < .0001). In the S group, the median progression-free survival was 38.3 months (95% CI, 30.6-46.1) compared with 12.3 months in the NS group (HR, 0.511; 95% CI, 0.376-0.695; P < .0001). In addition, the number of adverse events in the NS group was higher than that in the S group (P < .001). CONCLUSION: Overall, patients with ESCC at the age of ≥70 years who underwent esophagectomy had significantly better clinical outcomes than those who underwent nonsurgical treatment with RT and/or CRT.

Effect of cervical paraesophageal lymph node metastasis versus supraclavicular lymph node metastasis on the overall survival of patients with thoracic esophageal squamous cell carcinoma: an observational study.

Background: Esophageal cancer (EC) is a major global health burden, with a particularly high incidence in East Asia. The authors aimed to investigate the effect of metastasis in cervical paraesophageal lymph nodes (station 101) and supraclavicular lymph nodes (station 104) on the survival of patients who underwent esophagectomy for esophageal squamous cell carcinoma (ESCC). Materials and Methods: Data were obtained from the database of the authors' hospital. The authors retrospectively analyzed the patients with EC who underwent esophagectomy from January 2010 to December 2017. These patients were allocated into two groups based on the presence of lymph node metastasis (LNM) in the cervical paraesophageal or supraclavicular regions. Clinical outcomes and survival data were compared using the TNM staging system of the 8th edition of the American Joint Committee on Cancer (AJCC). Results: After a median follow-up of 62.1 months, 122 patients with LNM in the supraclavicular region were included in the study. Among these patients, 53 showed cervical paraesophageal LNM and an overall survival (OS) of 19.9 months [95% confidence interval (CI): 16.3-23.5]. In contrast, 69 patients showed supraclavicular LNM with an OS of 34.9 months (95% CI 25.7-44.1). The OS rates at 1, 3, and 5 years were 77%, 29%, and 21%, respectively, for patients with cervical paraesophageal LNM. Moreover, patients with supraclavicular LNM demonstrated OS rates of 88%, 48%, and 34%, respectively [Hazard ratio (HR): 0.634, 95% CI: 0.402-1.000, P=0.042]. Conclusions: Patients with ESCC with cervical paraesophageal LNM had significantly worse OS than those with supraclavicular LNM. This study underscores the importance of accurately identifying and managing ESCC with cervical paraesophageal LNM, as it may require more tailored and aggressive treatment strategies to prolong patient survival.

Spatiotemporal distribution of mediastinal neoplasms: A comprehensive multi-center study.

OBJECTIVES: Mediastinal neoplasms are typical but uncommon thoracic diseases with increasing incidence and unfavorable prognoses. A comprehensive understanding of their spatiotemporal distribution is essential for accurate diagnosis and timely treatment. However, previous studies are limited in scale and data coverage. Therefore, this study aims to elucidate the distribution of mediastinal lesions, offering valuable insights into this disease. MATERIALS AND METHODS: This multi-center, hospital-based observational study included 20 nationwide institutions. A retrospective search of electronic medical records from January 1st, 2009, to December 31st, 2020, was conducted, collecting sociodemographic data, computed tomography images, and pathologic diagnoses. Analysis focused on age, sex, time, location, and geographical region. Comparative assessments were made with global data from a multi-center database. RESULTS: Among 7,765 cases, thymomas (30.7%), benign mediastinal cysts (23.4%), and neurogenic tumors (10.0%) were predominant. Distribution varied across mediastinal compartments, with thymomas (39.6%), benign cysts (28.1%), and neurogenic tumors (51.9%) most prevalent in the prevascular, visceral, and paravertebral mediastinum, respectively. Age-specific variations were notable, with germ cell tumors prominent in patients under 18 and aged 18-29, while thymomas were more common in patients over 30. The composition of mediastinal lesions across different regions of China remained relatively consistent, but it differs from that of the global population. CONCLUSION: This study revealed significant heterogeneity in the spatiotemporal distribution of mediastinal neoplasms. These findings provide useful demographic data when considering the differential diagnosis of mediastinal lesions, and would be beneficial for tailoring disease prevention and control strategies.

Longitudinal patient-reported outcomes after minimally invasive McKeown esophagectomy for patients with esophageal squamous cell carcinoma.

PURPOSE: Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. METHODS: We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. RESULTS: A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). CONCLUSION: Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable.

Impact of Metastatic Lymph Nodes on Survival of Patients with pN1-Category Esophageal Squamous Cell Carcinoma: A Long-Term Survival Analysis.

BACKGROUND: The morbidity and mortality rates of esophageal squamous cell carcinoma (ESCC) are high in China. The overall survival (OS) of patients with ESCC is related to lymph node (LN) metastasis (LNM). This study aimed to discuss the impact of metastasis in LN stations on the OS of patients with pathologic N1 (pN1) ESCC. METHODS: Data were obtained from the Esophageal Cancer Case Management database of Sichuan Cancer Hospital and Institute (SCCH-ECCM). Additionally, data of patients with pN1-category ESCC collected between January 2010 and December 2017 were retrospectively analyzed. RESULTS: Data from 807 patients were analyzed. The median OS of the patients with one metastatic LN (group 1) was 49.8 months (95 % confidence interval [CI], 30.8-68.9 months), whereas the OS of those with two metastatic LNs (group 2) was only 33.3 months (P = 0.0001). Moreover, group 1 did not show a significantly longer OS than group 2.1 (patients with 2 metastatic LNs in 1 LNM station; P = 0.5736), but did show a significantly longer OS than group 2.2 (patients with 2 metastatic LNs in 2 LNM stations; P < 0.0001). After propensity score-matching, the 5-year survival rate for group 1 was 28 %, whereas that for group 2 was 14 % (P = 0.0027). CONCLUSIONS: The OS for the patients with one metastatic LN in one LNM was not significantly longer than for the patients with two metastatic LNs in one LNM station. Patients with one LNM station had a significantly longer OS than those with two LNM stations. Thus, the number of LNM stations is a significant determinant of OS in pN1 ESCC.

Optimal Time-to-Surgery Recommendations Based on Primary Tumor Volume Regression for Patients with Resectable Esophageal Cancer after Neoadjuvant Chemoradiotherapy: A Retrospective Study.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) has shown promise in improving the prognosis of individuals with locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, the factors influencing tumor response and long-term survival in these patients remain unknown. The optimal timing for surgery after the completion of radiotherapy in LA-ESCC remains controversial. Therefore, this study was designed to identify biomarkers and to determine the optimal post-NCRT time-to-surgery (TTS) for patients with LA-ESCC. METHODS: This retrospective study included patients with resectable LA-ESCC who underwent NCRT between May 2017 and June 2021. The tumor shrinkage rate was calculated as the difference between the pre- and post-primary gross tumor volume (GTVp) divided by the pre-GTVp. Univariate and multivariate Cox regression analyses and Kaplan-Meier curves were used to calculate overall survival (OS) and progression-free survival (PFS). RESULTS: We collected data from 248 patients with resectable LA-ESCC who underwent computed tomography (CT) scans before the initiation of treatment. The median follow-up time was 37.7 months. The optimal cutoff of tumor shrinkage was 45%. In the univariate and multivariate analyses, we found a significant association between the tumor shrinkage rate and PFS (p = 0.001). Among the subgroup of patients who responded to treatment, extending the TTS was associated with improved OS (p = 0.037) and PFS (p = 0.028). CONCLUSIONS: For patients with resectable LA-ESCC, the tumor shrinkage rate is an independent prognostic factor for PFS. Thus, for responders, prolonging TTS is recommended to obtain a better OS.

Development and Validation of a Recurrence-Free Survival Prediction Model for Locally Advanced Esophageal Squamous Cell Carcinoma with Neoadjuvant Chemoradiotherapy.

BACKGROUND: A recurrence-free survival (RFS) prediction model was developed and validated for patients with locally advanced esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy (NCRT) in combination with surgery. PATIENTS AND METHODS: We included 282 patients with esophageal squamous cell carcinoma who received neoadjuvant chemoradiotherapy (NCRT) combined with surgery, constructed three models incorporating pathological factors, investigated the discrimination and calibration of each model, and compared the clinical utility of each model using the net reclassification index (NRI) and the integrated discrimination index (IDI). RESULTS: Multivariable analysis showed that pathologic complete response (pCR) and lymph node tumor regression grading (LN-TRG) (p < 0.05) were independent prognostic factors for RFS. LASSO regression screened six correlates of LN-TRG, vascular invasion, nerve invasion, degree of differentiation, platelet grade, and a total diameter of residual cancer in lymph nodes to build model three, which was consistent in terms of efficacy in the training set and validation set. Kaplan-Meier (K-M) curves showed that all three models were able to distinguish well between high- and low-risk groups (p < 0.01). The NRI and IDI showed that the clinical utility of model 2 was slightly better than that of model 1 (p > 0.05), and model 3 was significantly better than that of model 2 (p < 0.05). CONCLUSIONS: Clinical prediction models incorporating LN-TRG factors have high predictive efficacy, can help identify patients at high risk of recurrence after neoadjuvant therapy, and can be used as a supplement to the  AJCC/TNM staging system while offering a scientific rationale for early postoperative intervention.

Refining postoperative monitoring of recurrent laryngeal nerve injury in esophagectomy patients through transcutaneous laryngeal ultrasonography.

BACKGROUND: Recurrent laryngeal nerve injury (RLNI) leading to vocal cord paralysis (VCP) is a significant complication following minimally invasive esophagectomy (MIE) with upper mediastinal lymphadenectomy. Transcutaneous laryngeal ultrasonography (TLUSG) has emerged as a non-invasive alternative to endoscopic examination for evaluating vocal cord function. Our study aimed to assess the diagnostic value of TLUSG in detecting RLNI by evaluating vocal cord movement after MIE. METHODS: This retrospective study examined 96 patients with esophageal cancer who underwent MIE between January 2021 and December 2022, using both TLUSG and endoscopy. RESULTS: VCP was observed in 36 out of 96 patients (37.5%). The incidence of RLNI was significantly higher on the left side than the right (29.2% vs. 5.2%, P < 0.001). Postoperative TLUSG showed a sensitivity and specificity of 88.5% (31/35) and 86.5% (45/52), respectively, with an AUC of 0.869 (P < 0.001, 95% CI 0.787-0.952). The percentage agreement between TLUSG and endoscopy in assessing VCP was 87.4% (κ = 0.743). CONCLUSIONS: TLUSG is a highly effective screening tool for VCP, given its high sensitivity and specificity. This can potentially eliminate the need for unnecessary endoscopies in about 80% of patients who have undergone MIE.

Collaborative multidisciplinary management and expertise of cT2-3 locally advanced operable esophageal squamous cell carcinoma: a report of two cases.

Background: The accurate clinical staging of esophageal squamous cell carcinoma (ESCC) is pivotal for guiding treatment strategies. However, the current precision in staging for clinical T (cT)2 and cT3 stages remains unsatisfactory. This article discusses the role of multidisciplinary teams (MDTs) in the clinical staging and formulation of neoadjuvant treatment strategies for locally advanced operable ESCC. These challenges underscore the importance of precise staging in the decision-making process for appropriate therapeutic interventions. Case Description: Through the lens of two patient case studies with locally advanced resectable ESCC, the article showcases the intricate process of treatment planning undertaken by MDTs. It captures a range of expert perspectives from Japan, China, Hong Kong (China), Korea, the USA, and Europe, focusing on the challenges of differentiating between cT2 and cT3 stages of the disease, which is a critical determinant in the management and therapeutic approach for patients. Conclusions: The article concludes that the accurate staging of ESCC is a cornerstone in determining the most suitable treatment strategies. It underscores the vital role that MDTs play in both clinical staging and the decision-making process for treatment. Highlighting the limitations in current diagnostic methods, the article emphasizes the urgent need for advanced research and the refinement of diagnostic tools to improve the precision of staging, particularly between the cT2 and cT3 stages. It suggests that future research should consider whether a reclassification of these stages could be warranted to enhance treatment planning and outcomes for patients with ESCC.

Clinical value of folate receptor-positive circulating tumor cells in patients with esophageal squamous cell carcinomas: a retrospective study.

BACKGROUND: The aim of the study is to explore the role of preoperative folate receptor-positive circulating tumor cell (FR+CTC) levels in predicting disease-free survival (DFS) and overall survival (OS) in patients with esophageal squamous cell carcinomas (ESCC). METHODS: Three ml blood samples were prospectively drawn from ESCC patients, and ligand-targeted polymerase chain reaction (LT-PCR) was used for the quantification of FR+CTCs. Other serum indicators were measured by traditional methods. Clinicopathological characteristics were obtained from the hospital medical record system, DFS and OS data were obtained by follow-up. The correlation between clinico-pathological characteristics, DFS, and OS and FR+CTCs were analyzed, respectively. Risk factors potentially affecting DFS and OS were explored by Cox regression analysis. RESULTS: there were no significant correlations between FR+CTCs and patient age, sex, albumin, pre-albumin, C-reactive protein (CRP), ferritin and CRP/Albumin ratio, tumor size, grade of differentiation, lymph node metastasis, TNM stage, perineural invasion/vessel invasion (all P > 0.05). Nevertheless, preoperative FR+CTCs were an independent prognostic factor for DFS (HR 2.7; 95% CI 1.31-, P = 0.007) and OS (HR 3.37; 95% CI 1.06-, P = 0.04). DFS was significantly shorter for patients with post-operative FR+CTCs ≥ 17.42 FU/3ml compared with patients < 17.42 FU/3ml (P = 0.0012). For OS, it was shorter for patients with FR+CTCs ≥ 17.42 FU/3ml compared with patients < 17.42 FU/3ml, however, the difference did not reach statistical significance (P = 0.51). CONCLUSIONS: ESCC patients with high FR+CTCs tend to have a worse prognosis. FR+CTCs may monitor the recurrence of cancers in time, accurately assess patient prognosis, and guide clinical decision-making. TRIAL REGISTRATION: The study was approved by the Sichuan Cancer Hospital & Institute Ethics Committee (No. SCCHEC-02-2022-050).

Utility of G protein-coupled oestrogen receptor 1 as a biomarker for pan-cancer diagnosis, prognosis and immune infiltration: a comprehensive bioinformatics analysis.

BACKGROUND: The G protein-coupled oestrogen receptor (GPER) 1 mediates non-genomic oestrogen-related signalling and plays an important role in the regulation of cell growth and programmed cell death through multiple downstream pathways. Despite the increasing interest in the role of GPER1 in cancer development, no pan-cancer analysis has been available for GPER1. METHODS: In this study we performed a comprehensive analysis of the role of GPER1 in pan-cancer via Human Protein Atlas (HPA), The Cancer Genome Atlas (TCGA), University of California, Santa Cruz Xena (UCSC XENA), Genotype-Tissue Expression (GTEx), MethSurv, The University of Alabama at Birmingham CANcer data analysis Portal (UALCAN), cBioPortal, STRING and TISIDB detabases, followed by enrichment analysis using R software. RESULTS: GPER1 was widely expressed in tissues and organs and differed in expression from normal tissue in a variety of cancers. In diagnostic assessment, it's Area Under the Curve (AUC) surpassed 0.9 in nine cancer types. Survival analysis showed that GPER1 was correlated with the prognosis of 11 cancer types. Moreover, GPER1 expression was associated with immune infiltration in multiple cancers. CONCLUSIONS: In summary, GPER1 has good diagnostic or prognostic value across various malignancies. Together with its extensive correlation with immune components, the aforementioned results suggests that GPER1 shows promise in tumour diagnosis and prognosis, providing new ideas for precise and personalised anti-tumour strategies.

EUS-derived maximum tumor thickness and tumor shrinkage rate as independent prognostic factors in locally advanced esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy.

Background and Objectives: EUS-derived maximum tumor thickness (MTT) pre- and post-neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) indicates treatment response. However, the accuracy of predicting long-term survival remains uncertain. This study aimed to investigate the association between EUS-derived MTT pre- and post-NCRT and tumor shrinkage rate as well as long-term survival in patients with LA-ESCC receiving NCRT. Methods: We retrospectively enrolled patients with LA-ESCC who underwent EUS examination from 2017 to 2021. Tumor shrinkage rate was the ratio of the difference between pre- and post-MTT to pre-MTT. The most fitted cutoff values were determined by the receiver operating characteristic curve. Univariate and multivariate Cox regression analyses and Kaplan-Meier curves were used to calculate overall survival (OS) and progression-free survival. Data from another center were also used for external validation testing. Results: Two hundred thirty patients were enrolled. Of the patients, 178 completed the first EUS pre-NCRT and obtained pre-MTT, 200 completed the reexamined EUS post-NCRT and obtained post-MTT, and 148 completed both EUS and achieved tumor shrinkage. For all the patients, the 1- and 3-year OS rates were 93.9% and 67.9%, and progression-free survival rates were 77.7% and 54.1%, respectively. The median follow-up period was 30.6 months. Thinner post-MTT (≤8.8 mm) and EUS responder (tumor shrinkage rate ≥52%) were independently associated with better OS. Conclusions: EUS-derived MTT and tumor shrinkage post-NCRT are independent prognostic factors for long-term survival and may be an alternative method for evaluating tumor response in patients with LA-ESCC after NCRT.

Advantages of Totally Stapled Collard Over Circular Stapled Technique for Cervical Esophagectomy Anastomosis.

BACKGROUND: The quality of life between the totally stapled Collard (TSC) and circular stapled (CS) techniques from the patient's perspective has not been assessed. This longitudinal patient-reported outcome and objective data assessment study aimed to compare the effects of TSC vs CS for cervical anastomosis with minimally invasive esophagectomy (MIE) on the quality of life. METHODS: This single-center, retrospective study included patients with esophageal cancer who underwent MIE and cervical anastomosis between April 2019 and February 2021; of whom, 105 and 216 patients received TSC and CS anastomosis, respectively. The objective metrics were evaluated based on postoperative complications. Patient-reported outcomes instruments using the European Organization for Research and Treatment of Cancer modules were assessed preoperatively. The Quality of Life Questionnaire (QLQ) Core 30 and the QLQ-Oesophagus Module 18 assessed the quality of life. Mixed-effects models examined changes in questionnaire scores. RESULTS: The stenosis rate in the TSC group was significantly lower than that in the CS group. There were no significant differences in other postoperative complications between the groups. In the QLQ Core 30 scale, the TSC group had better emotional function, less fatigue, less appetite loss, and better function than the CS group, with significant differences in different time points between the groups. QLQ-Oesophagus Module 18 revealed that the TSC group had significantly less appetite loss, dysphagia, dry mouth, pain, and obstruction, and better eating and speech than the CS group. CONCLUSIONS: TSC has significant advantages over the CS technique in lowering postoperative symptom burden and improving quality of life for cervical anastomosis on patient-reported outcomes.

Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma.

Neoadjuvant chemoimmunotherapy (NACI) has shown promise in the treatment of resectable esophageal squamous cell carcinoma (ESCC). The microbiomes of patients can impact therapy response, and previous studies have demonstrated that intestinal microbiota influences cancer immunotherapy by activating gut immunity. Here, we investigated the effects of intratumoral microbiota on the response of patients with ESCC to NACI. Intratumoral microbiota signatures of ß-diversity were disparate and predicted the treatment efficiency of NACI. The enrichment of Streptococcus positively correlated with GrzB+ and CD8+ T-cell infiltration in tumor tissues. The abundance of Streptococcus could predict prolonged disease-free survival in ESCC. Single-cell RNA sequencing demonstrated that responders displayed a higher proportion of CD8+ effector memory T cells but a lower proportion of CD4+ regulatory T cells. Mice that underwent fecal microbial transplantation or intestinal colonization with Streptococcus from responders showed enrichment of Streptococcus in tumor tissues, elevated tumor-infiltrating CD8+ T cells, and a favorable response to anti-PD-1 treatment. Collectively, this study suggests that intratumoral Streptococcus signatures could predict NACI response and sheds light on the potential clinical utility of intratumoral microbiota for cancer immunotherapy. SIGNIFICANCE: Analysis of intratumoral microbiota in patients with esophageal cancer identifies a microbiota signature that is associated with chemoimmunotherapy response and reveals that Streptococcus induces a favorable response by stimulating CD8+ T-cell infiltration. See related commentary by Sfanos, p. 2985.