Pararespiratory and paradigestive lymph node metastases in esophageal squamous cell carcinoma: predicting survival and refining the N staging system.

BACKGROUND: The site of lymph node metastasis (LNM) may affect the prognosis of patients with esophageal squamous cell carcinoma (ESCC). To investigate the prognoses of pararespiratory and paradigestive LNM and to propose a novel N (nN) staging system that integrates both the LNM site and count. METHODS: This study was a multicenter, large-sample, retrospective cohort study that included ESCC patients with LNM between January 2014 and December 2019 from three Chinese institutes. Patients were set into training (two institutes) and external validation (one institute) cohorts. The primary outcomes were survival differences in LNM site and the development of novel nodal staging system. The overall survival (OS) of patients with pararespiratory LNM only (Group A), paradigestive LNM only (Group B), and both sites (Group C) was evaluated by Kaplan-Meier. Cox proportional hazards models were used to identify the independent prognostic factors. An nN staging system considering both the LNM site and count was developed and evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: In total, 1313 patients were included and split into training (n = 1033) and external validation (n = 280) cohorts. There were 342 (26.0%), 568 (43.3%) and 403 (30.7%) patients in groups A, B and C, respectively. The OS of patients with pararespiratory and patients with paradigestive LNM presented significant differences in the training and validation cohorts (P < 0.050). In the training cohort, LNM site was an independent prognostic factor (hazard ratio: 1.58, 95% confidence intervals: 1.41-1.77, P < 0.001). The nN staging definition: nN1 (1-2 positive pararespiratory/paradigestive LNs), nN2 (3-6 pararespiratory LNs or 1 pararespiratory with 1paradigestive LN), nN3 (3-6 LNs with ≥ 1 paradigestive LN), nN4 (≥ 7 LNs). Subsets of patients with different nN stages showed significant differences in OS (P < 0.050). The prognostic model of the nN staging system presented higher performance in the training and validation cohorts at 3-year OS (AUC, 0.725 and 0.751, respectively) and 5-year OS (AUC, 0.740 and 0.793, respectively) than the current N staging systems. CONCLUSIONS: Compared to pararespiratory LNM, the presence of paradigestive LNM is associated with worse OS. The nN staging system revealed superior prognostic ability than current N staging systems.

Discovery and anticancer evaluation of a formononetin derivative against gastric cancer SGC7901 cells.

Background Gastric cancer (GC) is the second most common cause of cancer-related death worldwide. Novel anticancer drugs against gastric cancer are urgently needed. Methods Compound 10 was designed and synthesized via a molecular hybridization strategy based on the natural product formononetin. It was evaluated for their antiproliferative activity against three gastric cancer cell lines (SGC7901, MKN45 and MGC803). Results Derivative 10 displayed potently antiproliferative activity with an IC50 value of 1.07 µM against SGC7901 cells. Derivative 10 could inhibit the growth and migration against gastric cancer SGC7901 cells through the Wnt/ß-Catenin and AKT/mTOR pathways. From the in vivo expremints, it could effectively inhibited SGC7901 xenograft tumor growth in vivo without significant loss of the body weight. Conclusion Derivative 10 is an novel antitumor agent with potential for further clinical applications to treat gastric cancer. Graphical abstract.

Endoscopic resection of extra-luminal gastric gastrointestinal stromal tumors using a snare assisted external traction technique (with video).

OBJECTIVE: The primary purpose of the study was to explore the clinical efficacy of the novel snare assisted endoscopic resection of extraluminal growing gastric gastrointestinal stromal tumors (gastric GISTs) using external traction, and the secondary purpose was to compare the novel snare assisted endoscopic resection of extraluminal GISTs with the standard laparoscopic procedure. METHODS: We retrospectively analyzed the patients who underwent novel external traction assisted endoscopic resection or laparoscopic resection for their extraluminal gastric GIST ≤5 cm in diameter. RESULTS: A total of 111 patients (27 in the endoscopic group and 84 in the laparoscopic group) were included in this study. There was no significant difference in tumor diameter and complication rate between the two groups. The overall procedure time was slightly higher in the endoscopic group compared to the laparoscopic group (P = 0.034). However, postoperative hospitalization time (P < 0.001) and postoperative fasting time (P = 0.005) were shorter in the endoscopic group compared to the laparoscopic group. CONCLUSION: Snare external traction-assisted endoscopic resection of extraluminal growing gastric GISTs is safe and effective, and it provides a new adjunctive method for endoscopic resection of GIST.

Prognostic prediction model for patients with pathological T1N0 stage esophageal squamous cell carcinoma undergone esophagectomy.

Background: There is a shortage of reliable predictive models to provide valuable prognostic information for early esophageal squamous cell carcinoma (ESCC) without lymph node metastasis (LNM). We aimed to develop and validate a nomogram using the prognostic factors in T1N0 ESCC patients. Methods: Patients with pathological T1N0 ESCC who underwent esophagectomy between 2014 and 2021 at three institutes were reviewed. The prognostic factors were evaluated by Cox proportional hazards model and a nomogram was developed. Patients were divided into high- and low-risk groups based on cut-off value of total points in the nomogram. Overall survival (OS) was estimated by the Kaplan-Meier method and compared using the log-rank test. Results: A total of 275 patients were included and split into training (n=180) and external validation (n=95) cohorts. In the training cohort, multivariable analysis showed that the surgical approach, T1 substage, and carcinoembryonic antigen (CEA) level were independent prognostic factors. The developed nomogram had relatively high performance, with the area under the receiver operating characteristic (ROC) curve (AUC) of 0.783, 0.711 and 0.612 for 1-, 3-, and 5-year OS, respectively. The calibration curves showed that the predicted probability was in good agreement with the actual probability. Forty-seven was determined as cut-off value of total points. High-risk group (n=148) showed a significant poor OS than low-risk group (n=127) (P<0.001). Conclusions: Left surgical approach, stage T1b, and higher CEA were associated with poorer prognosis in T1N0 ESCC patients. The nomogram demonstrated a good performance to predict the individual survival.

Prognostic factors for patients with pathologic T1-T2N+ esophageal squamous cell carcinoma: A retrospective study with external validation.

BACKGROUND: Lymph node metastasis is significantly associated with a worse prognosis in patients with localized early-stage esophageal squamous cell carcinoma. This study aimed to explore the prognostic factors and develop a nomogram for predicting survival in patients with pathologic T1-2N+ esophageal squamous cell carcinoma. METHODS: Between 2014 and 2022, patients with pT1-2N+ esophageal squamous cell carcinoma who underwent esophagectomy with lymphadenectomy at 2 institutes were reviewed and assigned to training and external validation cohorts. Independent prognostic factors were identified via univariate and multivariate Cox regression analyses. The nomogram model was developed and evaluated by the area under the receiver operating characteristic curve and calibration curve. RESULTS: In total, 268 patients with a median age of 65 years (range, 40-82) were included and assigned to training (n = 190) and external validation (n = 78) cohorts. The Cox proportional hazards model demonstrated that body mass index (P = .031), surgical approach (P < .001), T stage (P = .015), and Clavien-Dindo classification (P < .001) were independent prognostic factors in the training cohort. The nomogram showed good discrimination, with an area under the receiver operating characteristic curve for 1-year, 3-year, and 5-year of 0.810, 0.789, and 0.809 in the training cohort and 0.782, 0.679, and 0.698 in the validation cohort. The calibration curve showed that the predicted survival probability was in good agreement with the actual survival probability. CONCLUSION: Lower body mass index, left surgical approach, T2 stage, and Clavien-Dindo classification grade III to V were related to worse prognosis in patients with pT1-T2N+ esophageal squamous cell carcinoma. The developed nomogram may predict individual survival accurately.

The application of radiomics in esophageal cancer: Predicting the response after neoadjuvant therapy.

Esophageal cancer (EC) is one of the fatal malignant neoplasms worldwide. Neoadjuvant therapy (NAT) combined with surgery has become the standard treatment for locally advanced EC. However, the treatment efficacy for patients with EC who received NAT varies from patient to patient. Currently, the evaluation of efficacy after NAT for EC lacks accurate and uniform criteria. Radiomics is a multi-parameter quantitative approach for developing medical imaging in the era of precision medicine and has provided a novel view of medical images. As a non-invasive image analysis method, radiomics is an inevitable trend in NAT efficacy prediction and prognosis classification of EC by analyzing the high-throughput imaging features of lesions extracted from medical images. In this literature review, we discuss the definition and workflow of radiomics, the advances in efficacy prediction after NAT, and the current application of radiomics for predicting efficacy after NAT.

Machine learning models predict lymph node metastasis in patients with stage T1-T2 esophageal squamous cell carcinoma.

Background: For patients with stage T1-T2 esophageal squamous cell carcinoma (ESCC), accurately predicting lymph node metastasis (LNM) remains challenging. We aimed to investigate the performance of machine learning (ML) models for predicting LNM in patients with stage T1-T2 ESCC. Methods: Patients with T1-T2 ESCC at three centers between January 2014 and December 2019 were included in this retrospective study and divided into training and external test sets. All patients underwent esophagectomy and were pathologically examined to determine the LNM status. Thirty-six ML models were developed using six modeling algorithms and six feature selection techniques. The optimal model was determined by the bootstrap method. An external test set was used to further assess the model's generalizability and effectiveness. To evaluate prediction performance, the area under the receiver operating characteristic curve (AUC) was applied. Results: Of the 1097 included patients, 294 (26.8%) had LNM. The ML models based on clinical features showed good predictive performance for LNM status, with a median bootstrapped AUC of 0.659 (range: 0.592, 0.715). The optimal model using the naive Bayes algorithm with feature selection by determination coefficient had the highest AUC of 0.715 (95% CI: 0.671, 0.763). In the external test set, the optimal ML model achieved an AUC of 0.752 (95% CI: 0.674, 0.829), which was superior to that of T stage (0.624, 95% CI: 0.547, 0.701). Conclusions: ML models provide good LNM prediction value for stage T1-T2 ESCC patients, and the naive Bayes algorithm with feature selection by determination coefficient performed best.

Gustave Roussy Immune Score based on a three-category risk assessment scale serves as a novel and effective prognostic indicator for surgically resectable early-stage non-small-cell lung cancer: A propensity score matching retrospective cohort study.

BACKGROUNDS: The Gustave Roussy Immune score (GRIm-Score) emerges as a novel prognostic scoring system for patient selection in phase I trials testing targeted immunotherapy for advanced-stage cancer. We tried to assess potential prognostic roles of preoperative GRIm-Score in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for stage I-II non-small-cell lung cancer (NSCLC) by propensity score-matching (PSM) analysis. METHODS: This PSM-based analysis was performed on our single-center prospectively-maintained database between January 2014 and October 2015. A Kaplan-Meier survival analysis using the log-rank test was used to distinguish differences in both overall survival (OS) and disease-free survival (DFS) between the patients stratified by preoperative GRIm-Score. Multivariable Cox-proportional hazards regression analysis and PSM analysis were both carried out to determine the final independent prognostic parameters. RESULTS: There were 405 patients with surgically resectable stage I-II NSCLC included. Both OS and DFS were significantly shortened along with each number increase in the GRIm-Score group, showing a step-wise fashion. Such strong correlations between preoperative GRIm-Score estimated by a modified 3-category risk scale and survival outcomes still remained validated after PSM analysis. In addition, this GRIm-Score held the superior discriminatory power for predicting both OS and DFS to the other peripheral blood biomarkers. Multivariable analyses on the entire cohort and the PSM cohort demonstrated that GRIm-Score based on a 3-category risk assessment scale could be independently predictive of both OS and DFS. CONCLUSIONS: The GRIm-Score tool can also serve as an effective and noninvasive marker to optimize prognostic prediction for surgically resectable stage I-II NSCLC.

Rabies Outbreaks and Vaccination in Domestic Camels and Cattle in Northwest China.

In contrast to many countries where rabies has been well controlled in humans and livestock, even in wildlife, rabies is still endemic in almost regions of China. In Northwest China, rabies transmitted by stray dogs and wild foxes has caused heavy economic losses to local herdsmen, as well as causing numbers of human cases. In this study, as part of an investigation of ways to prevent rabies epidemics in livestock, we report an analysis of domestic cattle and camel rabies cases in Ningxia Hui (NHAR) and Inner Mongolia Autonomous Region (IMAR) and the immune efficacy of canine inactivated rabies vaccines in these animals. We found that rabies viruses from these animals are closely related to dog-hosted China I and fox-associated China III lineages, respectively, indicating that the infections originated from two different sources (dogs and wild foxes). As well as the previously reported Arctic and Arctic-related China IV lineage in IMAR, at least three separate phylogenetic groups of rabies virus consistently exist and spread throughout Northwest China. Since there is no licensed oral vaccine for wild foxes and no inactivated vaccine for large livestock, local canine inactivated vaccine products were used for emergency immunization of beef and milk cattle and bactrian (two-humped) camels in local farms. Compared with a single injection with one (low-efficacy) or three doses (high-cost), a single injection of a double dose of canine vaccine provided low-price and convenience for local veterinarians while inducing levels of virus neutralizing antibodies indicative of protection against rabies for at least 1 year in the cattle and camels. However, licensed vaccines for wildlife and large domestic animals are still needed in China.