Asia expert consensus on segmentectomy in non-small cell lung cancer: A modified Delphi study.

Objective: Segmentectomy as a parenchymal-sparing surgical approach has been recommended over lobectomy in select patients with early-stage non-small cell lung cancer. This study aimed to address 3 aspects of segmentectomy ("patient indication"; "segmentectomy approaches"; "lymph node assessment") where there is limited clinical guidance. Methods: A modified Delphi approach comprising 3 anonymous surveys and 2 expert discussions was used to establish consensus on the aforementioned topics among 15 thoracic surgeons (2 Steering Committee; 2 Task Force; 11 Voting Experts) from Asia who have extensive segmentectomy experience. Statements were developed by the Steering Committee and Task Force based on their clinical experience, published literature (rounds 1-3), and comments received from Voting Experts through surveys (rounds 2-3). Voting Experts indicated their agreement with each statement on a 5-point Likert scale. Consensus was defined as ≥70% of Voting Experts selecting either "Agree"/"Strongly Agree" or "Disagree"/"Strongly Disagree." Results: Consensus from the 11 Voting Experts was reached on 36 statements (11 "patient indication" statements; 19 "segmentation approaches" statements; 6 "lymph node assessment" statements). In rounds 1, 2, and 3, consensus was reached on 48%, 81%, and 100% of drafted statements, respectively. Conclusions: A recent phase 3 trial reported significantly improved 5-year overall survival rates for segmentectomy compared with lobectomy, proposing thoracic surgeons to consider segmentectomy as a surgical option in suitable patients. This consensus serves as a guidance to thoracic surgeons considering segmentectomy in patients with early non-small cell lung cancer, outlining key principles that surgeons should consider in surgical decision-making.

Quantum criticality enabled by intertwined degrees of freedom.

Strange metals appear in a wide range of correlated materials. Electronic localization-delocalization and the expected loss of quasiparticles characterize beyond-Landau metallic quantum critical points and the associated strange metals. Typical settings involve local spins. Systems that contain entwined degrees of freedom offer new platforms to realize unusual forms of quantum criticality. Here, we study the fate of an SU(4) spin-orbital Kondo state in a multipolar Bose-Fermi Kondo model, which provides an effective description of a multipolar Kondo lattice, using a renormalization-group method. We show that at zero temperature, a generic trajectory in the model's parameter space contains two quantum critical points, which are associated with the destruction of Kondo entanglement in the orbital and spin channels, respectively. Our asymptotically exact results reveal an overall phase diagram, provide the theoretical basis to understand puzzling recent experiments of a multipolar heavy fermion metal, and point to a means of designing different forms of quantum criticality and strange metallicity in a variety of strongly correlated systems.

Automatic detection and vascular territory classification of hyperacute staged ischemic stroke on diffusion weighted image using convolutional neural networks.

Automated ischemic stroke detection and classification according to its vascular territory is an essential step in stroke image evaluation, especially at hyperacute stage where mechanical thrombectomy may improve patients' outcome. This study aimed to evaluate the performance of various convolutional neural network (CNN) models on hyperacute staged diffusion-weighted images (DWI) for detection of ischemic stroke and classification into anterior circulation infarct (ACI), posterior circulation infarct (PCI) and normal image slices. In this retrospective study, 253 cases of hyperacute staged DWI were identified, downloaded and reviewed. After exclusion, DWI from 127 cases were used and we created a dataset containing total of 2119 image slices, and separates it into three groups, namely ACI (618 slices), PCI (149 slices) and normal (1352 slices). Two transfer learning based CNN models, namely Inception-v3, EfficientNet-b0 and one self-derived modified LeNet model were used. The performance of the models was evaluated and activation maps using gradient-weighted class activation mapping (Grad-Cam) technique were made. Inception-v3 had the best overall accuracy (86.3%), weighted F1 score (86.2%) and kappa score (0.715), followed by the modified LeNet (85.2% accuracy, 84.7% weighted F1 score and 0.693 kappa score). The EfficientNet-b0 had the poorest performance of 83.6% accuracy, 83% weighted F1 score and 0.662 kappa score. The activation map showed that one possible explanation for misclassification is due to susceptibility artifact. A sufficiently high performance can be achieved by using CNN model to detect ischemic stroke on hyperacute staged DWI and classify it according to vascular territory.

Is there a role for lung surgery in initially unresectable non-small cell lung cancer after tyrosine kinase inhibitor treatment?

BACKGROUND: The role of lung surgery in initially unresectable non-small cell lung cancer (NSCLC) after tyrosine kinase inhibitor (TKI) treatment remains unclear. We aimed to assess the survival benefits of patients who underwent surgery for regressed or regrown tumors after receiving TKI treatment. METHODS: The details of patients diagnosed with unresectable NSCLC treated with TKI followed by lung resection from 2010 to 2020 were retrieved from our database. The primary endpoint was 3-year overall survival (OS), whereas the secondary endpoints were a 2-year progression-free survival (PFS), feasibility, and the safety of pulmonary resection. The statistical tests used were Fisher's exact test, Kruskal Wallis test, Kaplan-Meier method, Cox proportional hazards model, and Firth correction. RESULTS: Nineteen out of thirty-two patients were selected for the study. The patients underwent lung surgery after confirmed tumor regression (17 [89.5%]) and regrowth (two [10.5%]). All surgeries were performed via video-assisted thoracoscopic surgery: 14 (73.7%) lobectomies and five (26.3%) sublobar resections after a median duration of 5 months of TKI. Two (10.5%) postoperative complications and no 30-day postoperative mortality were observed. The median postoperative follow-up was 22 months. The 2-year PFS and 3-year OS rates were 43.9% and 61.5%, respectively. Patients who underwent surgery for regressed disease showed a significantly better OS than for regrowth disease (HR=0.086, 95% CI 0.008-0.957, p=0.046). TKI-adjuvant demonstrated a better PFS than non-TKI adjuvant (HR=0.146, 95% CI 0.027-0.782, p=0.025). CONCLUSION: Lung surgery after TKI treatment is feasible and safe and prolongs survival via local control and directed consequential therapy. Lung surgery should be adopted in multimodality therapy for initially unresectable NSCLC.

Peri-treatment adverse events of primary mediastinal non-seminomatous germ cell tumors.

Primary mediastinal non-seminomatous germ cell tumors (PMNSGCT) are rare but life-threatening thoracic cancers. We report our experience from eight patients with peri-treatment adverse events. By analyzing changes in tumor extent, serum tumor markers, and pathologies between diagnosis and transfer, those events could be attributed to postbiopsy respiratory insufficiency, growing teratoma syndrome, secondary histiocytic malignancy, and PMNSGCT progression. Subjecting patients to respiratory therapy, conventional or high-dose chemotherapy, and surgery controlled the disease, with five of the eight patients surviving disease free. These outcomes indicate that integrated appropriate and timely approaches are important in tackling peri-treatment adverse events.

Non-destructive acoustic screening of pineapple ripeness by unsupervised machine learning and Wavelet Kernel methods.

In a pineapple exporting factory, manual lines are usually built to screen fruits of non-ripen hitting sounds from millions of undecided fruits for long-haul transportation. However, human workers cannot concentratedly listen and make consistent judgments over long hours. Pineapple screening becomes arbitrary after approximately an hour. We developed a non-destructive screening device aside from the conveyor sorter to classify pineapples automatically. The device makes intelligent judgments by tapping a sound source to the skin of pineapples and analyzing the penetrated sounds by wavelet kernel decomposition and unsupervised machine learning (ML). The sound tapping relies on the well-touch of the skin. We also design several acoustic couplers to adapt the vibrator to the skin and pick high-quality penetrated sounds. A Taguchi experiment design was used to determine the most suitable coupler. We found that our unsupervised ML method achieves 98.56% accuracy and 0.93 F1-score by using a specially designed thorn-board for assisting tapping sound to fruit skin.

Ten-Year Trends of Clinicopathologic Features and Surgical Treatment of Lung Cancer in China.

BACKGROUND: Lung cancer has changed significantly during the past 2 decades in its epidemiology and treatment. This retrospective analysis used data from 7 major areas of China over 10 years to evaluate clinicopathologic and surgical treatment trends of lung cancer in China during the past decade. METHODS: Data from 7184 patients with primary lung cancer who were treated between 2005 and 2014 in 8 provinces of China were retrospectively collected. Their clinicopathologic features and surgical treatment information were recorded. Simple linear regression models and the Cochrane-Armitage trend test were used to assess temporal trends. RESULTS: The proportion of female patients (from 57.4% to 59.6%; P < .001) and nonsmoking patients (from 37.1% to 48.9%; P < .001) and of patients with a family history of malignant tumors (from 7.0% to 11.5%; P < .001) increased significantly. The percentage of adenocarcinomas increased significantly (from 36.4% to 53.5%; P < .001), with a decrease in squamous cell carcinomas (from 45.4% to 34.4%; P < .001). After 2008, the application of minimally invasive surgery significantly increased in China (from 2.4% in 2008 to 34.4% in 2014; P < .001), with a decline in the rate of conversion to open operation (from 14.3% in 2008 to 4.8% in 2014; P = .146) and an increase in the proportion of systematic mediastinal lymph node dissection (from 50.0% in 2008 to 84.1% in 2014; P = .001). CONCLUSIONS: This study investigated recent 10-year trends in the clinicopathologic features and surgical treatment of lung cancer in China and found significant important changes. These findings provide valuable information and evidence for the future control of the disease in China.

Sequential localization of a complex electron fluid.

Complex and correlated quantum systems with promise for new functionality often involve entwined electronic degrees of freedom. In such materials, highly unusual properties emerge and could be the result of electron localization. Here, a cubic heavy fermion metal governed by spins and orbitals is chosen as a model system for this physics. Its properties are found to originate from surprisingly simple low-energy behavior, with 2 distinct localization transitions driven by a single degree of freedom at a time. This result is unexpected, but we are able to understand it by advancing the notion of sequential destruction of an SU(4) spin-orbital-coupled Kondo entanglement. Our results implicate electron localization as a unified framework for strongly correlated materials and suggest ways to exploit multiple degrees of freedom for quantum engineering.

Involvement of increased p53 expression in the decrease of mitochondrial DNA copy number and increase of SUVmax of FDG-PET scan in esophageal squamous cell carcinoma.

We appraised Warburg effect through analysis of mitochondrial DNA (mtDNA) copy number and maximum standard uptake value (SUVmax) of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan and their alterations in esophageal squamous cell carcinoma (ESCC). Later T-status and longer longitudinal tumor length were associated with lower mtDNAESCC copy number (p < .05) but higher SUVmax-ESCC (p < .05), respectively. Lower mtDNAESCC copy number correlated with higher SUVmax-ESCC, reciprocally (p < .05). ESCCs expressing mutant p53 protein had lower mtDNAESCC copy number (p = .056) but higher SUVmax-ESCC (p = .046). We conclude that mutant p53 protein may be involved in the Warburg effect of ESCC.

A Nomogram for Predicting Cancer-Specific Survival of TNM 8th Edition Stage I Non-small-cell Lung Cancer.

BACKGROUND: Models for predicting the survival outcomes of stage I non-small-cell lung cancer (NSCLC) defined by the newly released 8th edition TNM staging system are scarce. This study aimed to develop a nomogram for predicting the cancer-specific survival (CSS) of these patients and identifying individuals with a higher risk for CSS. METHODS: A total of 30,475 NSCLC cases were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified and integrated the risk factors to build a nomogram. The model was subjected to bootstrap internal validation with the SEER database, and external validation with a multicenter cohort of 1133 patients from China. The difference in the impact of adjuvant chemotherapy on model-defined high- and low-risk patients was examined using the National Cancer Database (NCDB). RESULTS: Eight independent prognostic factors were identified and integrated into the model. The calibration curves showed good agreement. The concordance index (C-index) of the nomogram was higher than that of the staging system (IA1, IA2, IA3, and IB) (internal validation set 0.63 vs. 0.56; external validation set 0.66 vs. 0.55; both p < 0.01). Specifically, 21.7% of stage IB patients (7.5% of all stage I) were categorized into the high-risk group (score > 30). There was a significant interaction effect between the adjuvant chemotherapy and risk groups in the NCDB cohort (p = 0.003). CONCLUSIONS: We established a practical nomogram to predict CSS for 8th edition stage I NSCLC. A prospective study is warranted to determine its role in identifying adjuvant chemotherapy candidates.

Conventional transbronchial needle aspiration is promising for identifying EGFR mutations in lung adenocarcinoma.

BACKGROUND: Conventional transbronchial needle aspiration (TBNA) is advantageous for the one-step diagnosis and staging of lung adenocarcinoma under topical anesthesia and conscious sedation. We examined its efficacy for identifying EGFR mutations. METHODS: Forty-seven patients with proven or suspected lung adenocarcinoma indicated for hilar-mediastinal lymph node (LN) staging between June 2011 and December 2017 were enrolled. The cellblock was prepared using the plasma-thrombin method. TaqMan PCR was used to detect mutations. Considering cost effectiveness, only the sample with the highest tumor cell fraction in the same patient was chosen for analysis. RESULTS: TBNA provided positive results of malignancy in 27 patients. Seventeen patients (63.0%) had cellblocks eligible for mutation testing. Bronchial biopsy (n = 6), neck LN fine needle aspiration (n = 1), and brushing (n = 1), provided higher tumor cell fractions for analysis in eight patients. TBNA was the exclusive method used in nine patients (19.1%). For patients with an inadequate TBNA cellblock, bronchial biopsy (n = 5), neck LN fine needle aspiration (n = 3), computed tomography-guided transthoracic needle biopsy (n = 1), and brushing (n = 1) were used for analysis. Modification to specimen processing to prevent exhaustion by cytology after June 2016 improved the adequacy of cellblock samples (9/10, 90% vs. 8/17, 47.1%; P = 0.042). CONCLUSIONS: These findings suggest the promising role of conventional TBNA and highlight the challenges of doing more with less in an era of precision medicine.

Neoadjuvant Chemoradiation Versus Upfront Esophagectomy in Clinical Stage II and III Esophageal Squamous Cell Carcinoma.

BACKGROUND: The benefits of neoadjuvant chemoradiation (NCRT) compared to upfront esophagectomy (UE) in esophageal squamous cell carcinoma (ESCC) is controversial. Our purpose was to determine whether clinical stages based on the 8th edition American Joint Committee on Cancer Tumor-Node-Metastasis staging system could guide treatment decision. METHODS: Data from 2503 patients with clinical stages II and III ESCC diagnosed between 2008 and 2014 were obtained from a nationwide database. Propensity score matching was used to identify well-balanced pairs of patients. Cox proportional hazards regression and log-rank test were used in the survival analysis. The outcomes of patients receiving "NCRT followed by surgery" or "UE" strategies were compared. RESULTS: The treatment modality (UE or NCRT) was not a prognostic factor in clinical stage II ESCC (HR: 0.97; p = 0.778). In contrast, the UE group demonstrated a significantly worse outcome compared with the NCRT group in clinical stage III ESCC (HR: 1.39; p < 0.001). After matching, patients who underwent UE for clinical stage II ESCC had median survival/3-year overall survival (OS) rates of 27.8 months/39.2% compared with 32.7 months/49.8% in the NCRT group (p = 0.508). The patients who underwent UE for clinical stage III ESCC had median survival/3-year OS rates of 17.9 months/28.2% in the UE group compared with 24.0 months/41.8% in the NCRT group (p < 0.001). CONCLUSIONS: Our data suggest that NCRT strategy improved survival compared with UE in clinical stage III ESCC but not in clinical stage II tumors.

Accuracy of a 3-Dimensionally Printed Navigational Template for Localizing Small Pulmonary Nodules: A Noninferiority Randomized Clinical Trial.

Importance: Localization of small lung nodules are challenging because of the difficulty of nodule recognition during video-assisted thoracoscopic surgery. Using 3-dimensional (3-D) printing technology, a navigational template was recently created to assist percutaneous lung nodule localization; however, the efficacy and safety of this template have not yet been evaluated. Objective: To assess the noninferiority of the efficacy and safety of a 3-D-printed navigational template guide for localizing small peripheral lung nodules. Design, Setting, and Participants: This noninferiority randomized clinical trial conducted between October 2016 and October 2017 at Shanghai Pulmonary Hospital, Shanghai, China, compared the safety and precision of lung nodule localization using a template-guided approach vs the conventional computed tomography (CT)-guided approach. In total, 213 surgical candidates with small peripheral lung nodules (<2 cm) were recruited to undergo either CT- or template-guided lung nodule localization. An intention-to-treat analysis was conducted. Interventions: Percutaneous lung nodule localization. Main Outcomes and Measures: The primary outcome was the accuracy of lung nodule localization (localizer deviation), and secondary outcomes were procedural duration, radiation dosage, and complication rate. Results: Of the 200 patients randomized at a ratio of 1:1 to the template- and CT-guided groups, most were women (147 vs 53), body mass index ranged from 15.4 to 37.3, the mean (SD) nodule size was 9.7 (2.9) mm, and the mean distance between the outer edge of target nodule and the pleura was 7.8 (range, 0.0-43.9) mm. In total, 190 patients underwent either CT- or template-guided lung nodule localization and subsequent surgery. Among these patients, localizer deviation did not significantly differ between the template- and CT-guided groups (mean [SD], 8.7 [6.9] vs 9.6 [5.8] mm; P = .36). The mean (SD) procedural durations were 7.4 (3.2) minutes for the template-guided group and 9.5 (3.6) minutes for the CT-guided group (P < .001). The mean (SD) radiation dose was 229 (65) mGy × cm in the template-guided group and 313 (84) mGy × cm in CT-guided group (P < .001). Conclusions and Relevance: The use of the 3-D-printed navigational template for localization of small peripheral lung nodules showed efficacy and safety that were not substantially worse than those for the CT-guided approach while significantly simplifying the localization procedure and decreasing patient radiation exposure. Trial Registration: ClinicalTrials.gov identifier: NCT02952261.

The Optimal Treatment for Stage IIIA-N2 Non-Small Cell Lung Cancer: A Network Meta-Analysis.

BACKGROUND: The optimal treatment for stage IIIA-N2 non-small cell lung cancer (NSCLC) is controversial. We aimed to address this important issue through a Bayesian network meta-analysis. METHODS: We performed a search of electronic databases for randomized controlled trials comparing the following treatments: surgery, radiotherapy, chemotherapy, and their multiple combinations before March 25, 2018. Pooled data on overall survival and treatment-related deaths were analyzed within the Bayesian framework. RESULTS: Eighteen eligible trials reporting 13 treatments were included. In terms of overall survival, neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy, which tended to be consistent (hazard ratio [HR] 1.14, 95% credible interval [CrI] 0.21 to 5.93), ranked superior to other treatments. Notably, neoadjuvant chemotherapy followed by surgery and adjuvant radiotherapy was significantly more effective in prolonging survival than surgery alone (HR 0.38, 95% CrI 0.18 to 0.81), surgery plus adjuvant radiotherapy (HR 0.51, 95% CrI 0.29 to 0.92) and potentially surgery plus adjuvant chemotherapy (HR 0.49, 95% CrI 0.23 to 1.05). Overall, with 29% as the highest possibility of causing the fewest treatment-related deaths, neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy was the safest treatment option. CONCLUSIONS: Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy has the greatest possibility to be the optimal treatment with the best overall survival and fewest treatment-related deaths for stage IIIA-N2 NSCLC.

Comparison of survival between lung cancer patients receiving single or multiple-incision thoracoscopic surgery.

BACKGROUND: The effect of single-incision thoracoscopic surgery for lung cancer on long-term survival is unknown and no studies have investigated whether there are differences in survival between single and multiple incision approaches. We aimed to compare long-term overall survival and disease-free survival of patients who underwent single-incision thoracoscopic surgery with those who received multiple-incision thoracoscopic surgery for lung cancer. METHODS: We retrospectively analyzed 532 patients with lung cancer who underwent either single-incision (n=150) or multiple-incision thoracoscopic resection (n=382) during the period January 2000 to December 2014. Patients were matched on propensity score at a 1:2 ratio to estimate the effect of treatment on long-term and disease-free survival. Overall survival and disease-free survival were assessed using the Kaplan-Meier method, the log-rank test and Cox proportional-hazards regression. RESULTS: Propensity matching resulted in 138 patients in the single-incision group and 276 patients in the multiple-incision group. The matched patients in the single-incision group had a significantly better 5-year overall survival than those in the multiple-incision group (P=0.027). Disease-free survival was similar between the two groups before and after matching. The number of chest wall incisions did not influence overall survival or disease-free survival. CONCLUSIONS: The long-term outcomes of single-incision thoracoscopic surgery are comparable to those of multiple-incision thoracoscopic surgery for lung cancer.

Esophageal cancer in elderly patients: a population-based study.

BACKGROUND: As the aging issue and increased elderly esophageal cancer (EC) patients, we sought to study the clinical characteristics, treatment modality and outcomes of EC patients 70 years or older compared with those younger than 70 years old. METHODS: The national surveillance, epidemiology, and end results (SEER) database for the period from 1973 to 2013 was analyzed. The patient and treatment characteristics were compared between the age groups. Multivariate Cox proportional hazard regression analyses were also performed to identify independent prognostic factors. Propensity-score matching analyses (PSA) regarding survival after different treatments were also performed in locoregional EC. RESULTS: Compared with the younger group, patients 70 years or older were characterized by having a higher proportion of patients with female gender, white race, localized disease, non-adenocarcinoma and without any treatment, as well as inferior overall survival (OS) [hazard ratio (HR), 1.324] and EC-specific survival (HR, 1.270). In addition, older patients shared same independent prognostic factors with younger patients, including age, histology and race. Specifically, compared with those receiving no intensive treatments, surgery alone (HR, 0.342), both surgery and RT (HR, 0.323) and RT only (HR, 0.525) were favorable among elderly patients, as confirmed by both multivariate adjustment and PSA. CONCLUSIONS: Compared to younger EC patients, those 70 years or older showed distinctive clinical characteristics and inferior survival. Despite showing a higher proportion of localized disease, patients 70 years or older were less likely to be subjected to surgery or/and RT. Thus, the role of intensive treatments, which were identified as favorable factors among elderly patients in this study, warrants further investigation.

Upfront surgery and pathological stage-based adjuvant chemoradiation strategy in locally advanced esophageal squamous cell carcinoma.

Adjuvant chemoradiation is reported to have a survival benefit for esophageal squamous cell carcinoma (ESCC). We evaluated the "upfront surgery and pathological stage-based adjuvant chemoradiation" strategy, in which adjuvant therapy is guided by pathological stage, in locally advanced ESCC. Data from 2976 clinical stage II/III ESCC patients, including 1735 in neoadjuvant chemoradiation and 1241 in upfront surgery groups, were obtained from a nationwide database. Patients in the upfront surgery group were further categorized into the "upfront surgery and pathological stage-based adjuvant chemoradiation" and "upfront surgery only" groups. The 3-year overall survival (OS) rates in the "neoadjuvant chemoradiation", "upfront surgery and pathological stage-based adjuvant chemoradiation", and "upfront surgery only" groups were 41.5%, 45.8%, and 28.5%, respectively. In propensity score matched patients, the 3-year OS rate was 41.7% in the neoadjuvant chemoradiation group, compared to 35.6% in the "upfront surgery and pathological stage-based adjuvant chemoradiation" group (p = 0.147), and 20.3% in the "upfront surgery only" group (p < 0.001). No survival difference was observed between the "neoadjuvant chemoradiation followed by surgery" protocol and the "upfront surgery and pathological stage-based adjuvant chemoradiation" strategy.

Application of the Eighth AJCC TNM Staging System in Patients With Esophageal Squamous Cell Carcinoma.

BACKGROUND: The eighth edition of the American Joint Committee on Cancer Tumor-Node-Metastasis staging system separates classifications for the clinical (c), pathologic (p), and postneoadjuvant pathologic (yp) stages. We aimed to evaluate its application in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Patient data were obtained from the Taiwan Cancer Registry database. Patients who underwent esophagectomy for c stage I to III ESCC were included for survival analysis. RESULTS: Data of 3,399, 1,805, and 1,594 patients were included for c, p, and yp staging, respectively. The 3-year overall survival (OS) rates for c stage I, II, and III were 67.4%, 46.7%, and 38.4%, respectively. The 3-year OS rates for p stage I, II, III, and IV were 70.7%, 49.8%, 30.8%, and 10.6%, respectively. The 3-year OS rates for yp stage I, II, III, and IV were 59.4%, 37.8%, 27.6%, and 3.7%, respectively. Survival curve analysis demonstrated a robust discriminatory capability and monotonicity of gradients of the new system. However, yp stage I was observed in a heterogeneous group of patients with substantial survival differences. Meanwhile, patients in the ypT0 N0 stage had a 5-year OS rate of 52.1%, which was equivalent to that of patients with p stage I (54.5%). The 5-year OS rate of patients in the ypTis-2N0 was 39.1%, which was equivalent to that of patients in p stage II (40.1%). CONCLUSIONS: The present study serves as an external validation of the newly released staging system in the prognostication of patients with ESCC and suggests subgrouping of the yp stage I into ypT0 N0 and non-ypT0 N0 in the future.