Kongjia Luo

Background: Radical resection is the gold standard for high-risk pulmonary nodules; however, many patients are not candidates for surgery or who decline surgery. Electromagnetic navigation bronchoscopy-guided three-dimensional conformal microwave ablation (ENB-DCMA) is a promising minimally invasive option. This study aimed to assess the mid-term safety and efficacy of a novel ENB-DCMA strategy which employs three-dimensional conformal planning to offset respiratory-induced lesion displacement. Methods: In this single-center retrospective study, we enrolled consecutive patients with peripheral high-risk pulmonary nodules who received ENB-DCMA owing to unsuitability for or refusal to surgery and radiotherapy between March 2021 and August 2023. The three-dimensional conformal strategy enlarged the ablative margin to compensate for respiratory-induced target motion exploratively, in the absence of real-time intraoperative computed tomography/cone-beam computed tomography (CT/CBCT) guidance. The primary efficacy endpoint was local progression-free survival (LPFS) post-ablation. Safety was evaluated according to the incidence of adverse events. Results: In total, 50 patients with 62 eligible pulmonary nodules were included, with 65 ablation procedures performed in total, including repeated ablation for three lesions. The technical success rate of this procedure was 95.2%. No procedure-related mortality was observed. The median follow-up was 37.1 (range, 14.7–59.9) months. The overall 3-year LPFS rate was 82.3%, and this rate reached 95.8% among patients with sub-solid nodules. The overall incidence of adverse events was 18.0% (9/50), including 12.0% (6/50) pneumothorax, 2.0% (1/50) postoperative fever, and 4.0% (2/50) self-limiting pulmonary hemorrhage; the rate of events requiring intervention was 4.0% (2/50). Conclusions: ENB-DCMA serves as a safe and feasible minimally invasive therapeutic option for patients with high-risk pulmonary nodules. Further multicenter prospective trials are required to verify its long-term outcomes and broader clinical popularization value.

Esophageal squamous cell carcinoma (ESCC) remains a major contributor to cancer-related mortality, with molecular residual disease (MRD) detection posing a significant challenge in post-surgical management. This study aimed to evaluate the effectiveness of circulating tumor DNA (ctDNA) in detecting MRD in patients with resectable ESCC undergoing radical surgery. A total of 62 primary tumor tissues, 108 preoperative, and 125 postoperative plasma samples were collected from 125 such ESCC patients who underwent radical surgery, and subjected to sequencing. Next-Generation Sequencing and ultra-high sensitivity Automated Triple Groom Sequencing panels were used to sequence genomic DNA from tumor tissues and ctDNA from plasma, respectively. ctDNA positive mutations included tumor-informed mutations and tumor-naïve mutations. Key findings revealed a high concordance rate of mutation detection between primary tumor tissue and preoperative plasma samples (91.11%, p = 0.62). Critically, the recurrence rate was higher in postoperative ctDNA-positive ESCCs than that in negative ones (66.67% (40/60) vs. 21.54% (14/65), p < 0.001). And postoperative ctDNA-positivity was associated with poorer disease-free survival (DFS) (hazard ratio (HR): 4.58, 95% CI: 2.65–7.92, p < 0.001) and overall survival (OS) (HR: 5.39, 95% CI: 2.96–9.80, p < 0.001). Similar prognostic patterns were observed in patients with preoperative ctDNA-positivity (p = 0.014; p = 0.016; p = 0.071) and ctDNA-nonclearance (p < 0.001; p < 0.001; p < 0.001). Furthermore, in combination with postoperative ctDNA status, the Tumor-Node-Metastasis-Blood (TNMB) staging system was able to better distinguish patients with different prognoses compared with traditional TNM (p < 0.001). In conclusion, postoperative ctDNA-positivity emerges as a promising biomarker for detecting MRD in ESCC patients following surgical resection.

Neoadjuvant chemoradiotherapy (NCRT) followed by surgery is a standard treatment for locally advanced esophageal squamous cell carcinomas (ESCCs). However, the evolution of genome and immunogenome in ESCCs driven by NCRT remains incompletely elucidated. We performed whole‐exome sequencing of 51 ESCC tumors collected before and after NCRT, 36 of which were subjected to transcriptome sequencing. Clonal analysis identified clonal extinction in 13 ESCC patients wherein all pre‐NCRT clones disappeared after NCRT, and clonal persistence in 9 patients wherein clones endured following NCRT. The clone‐persistent patients showed higher pre‐NCRT genomic intratumoral heterogeneity and worse prognosis than the clone‐extinct ones. In contrast to the clone‐extinct patients, the clone‐persistent patients demonstrated a high proportion of subclonal neoantigens within pre‐treatment specimens. Transcriptome analysis revealed increased immune infiltrations and up‐regulated immune‐related pathways after NCRT, especially in the clone‐extinct patients. The number of T cell receptor–neoantigen interactions was higher in the clone‐extinct patients than in the clone‐persistent ones. The decrease in T cell repertoire evenness positively correlated to the decreased number of clonal neoantigens after NCRT, especially in the clone‐extinct patients. In conclusion, we identified two prognosis‐related clonal dynamic modes driven by NCRT in ESCCs. This study extended our knowledge of the ESCC genome and immunogenome evolutions driven by NCRT.

Background: Although electromagnetic navigation bronchoscopy (ENB) is highly sensitive in the diagnosis of peripheral pulmonary nodules (PPNs), its diagnostic yield for subgroups of smaller PPNs is under evaluation. Objectives: Diagnostic yield evaluation of biopsy using ENB for PPNs <2 cm. Design: The diagnostic yield, sensitivity, specificity, positive predictive value, and negative predictive value of the ENB-mediated biopsy for PPNs were evaluated. Methods: Patients who had PPNs with diameters <2 cm and underwent ENB-mediated biopsy between May 2015 and February 2020 were consecutively enrolled. The final diagnosis was made via pathological examination after surgery. Results: A total of 82 lesions from 65 patients were analyzed. The median tumor size was 11 mm. All lesions were subjected to ENB-mediated biopsy, of which 29 and 53 were classified as malignant and benign, respectively. Subsequent segmentectomy, lobectomy, or wedge resection, following pathological examinations were performed on 64 nodules from 57 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value for nodules <2 cm were 53.3%, 91.7%, 92.3%, and 51.2%, respectively. The receiver operating curve showed an area under the curve of 0.721 ( p < 0.001). Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value were 62.5%, 100%, 100%, and 42.9%, respectively, for nodules with diameters equal to or larger than 1 cm; and 30.8%, 86.7%, 66.7%, and 59.1%, respectively, for nodules less than 1 cm. In the subgroup analysis, neither the lobar location nor the distance of the PPNs to the pleura affected the accuracy of the ENB diagnosis. However, the spiculated sign had a negative impact on the accuracy of the ENB biopsy ( p = 0.010). Conclusion: ENB has good specificity and positive predictive value for diagnosing PPNs <2 cm; however, the spiculated sign may negatively affect ENB diagnostic accuracy. In addition, the diagnostic reliability may only be limited to PPNs equal to or larger than 1 cm.

Background and Objectives Advanced esophageal squamous cell carcinoma (ESCC) is a prevalent and highly malignant tumor with a poor prognosis. Recently, the RATIONALE-306 trial demonstrated that tislelizumab combined with chemotherapy provided overall survival benefits for these patients. This study aimed to assess the cost-effectiveness of this treatment approach in Chinese patients with advanced ESCC from the perspective of healthcare system. Methods A Markov model was constructed to assess the economic and health benefits associated with tislelizumab plus chemotherapy over a 10-year lifetime horizon, utilizing data from the RATIONALE-306 trial. The analysis encompassed the calculation of several key parameters, including the incremental cost-effectiveness ratio (ICER), total cost, incremental cost, total effectiveness, and incremental effectiveness. Tislelizumab was considered cost-effective if the ICER obtained was below the willingness-to-pay (WTP) threshold of US$38,223 per quality-adjusted life-year (QALY); otherwise, it would be deemed not cost-effective. To ensure the robustness of the findings, the results were subjected to one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). Results In the base-case analysis, the incremental effectiveness and cost associated with tislelizumab plus chemotherapy, compared to chemotherapy alone, were determined to be 0.40 QALY and US$7604, respectively. This resulted in an ICER of US$18,846 per QALY, which is below the WTP threshold of US$38,223 per QALY. Furthermore, the results from the one-way sensitivity analysis and PSA indicated robustness of the findings. Conclusion Our lifetime simulation study demonstrated that, in the case of advanced ESCC, the combination of tislelizumab and chemotherapy offers increased effectiveness compared to chemotherapy alone, albeit at a higher cost. Moreover, considering the current WTP threshold in China, the addition of tislelizumab to chemotherapy is considered a cost-effective approach.

Objective: To explore the comprehensive role of systemic endoscopic intervention in healing esophageal anastomotic leak. Methods: In total, 3919 consecutive patients with esophageal cancer who underwent esophagectomy and immediate esophageal reconstruction were screened. In total, 203 patients (5.10%) diagnosed with anastomotic leakage were included. The participants were divided into three groups according to differences in diagnosis and treatment procedures. Ninety-four patients received conventional management, 87 patients received endoscopic diagnosis only, and the remaining 22 patients received systematic endoscopic intervention. The primary endpoint was overall healing of the leak after oncologic esophageal surgery. The secondary endpoints were the time from surgery to recovery and the occurrence of adverse events. Results: 173 (85.2%; 95% CI, 80.3-90.1%) of the 203 patients were successfully healed, with a mean healing time of 66.04 ± 3.59 days (median: 51 days; range: 13-368 days), and the overall healing rates differed significantly among the three groups according to the stratified log-rank test (PConclusion: Tailored endoscopic treatment for postoperative esophageal anastomotic leakage based on endoscopic diagnosis is feasible and effective. Systematic endoscopic intervention shortened the treatment period and reduced mortality and should therefore be considered in the management of this disease.

Background: The prognostic value of ABO blood types is not well clarified for esophageal carcinoma (EC). This study attempted to elucidate the associations between different ABO blood types and disease-free survival (DFS) and overall survival (OS) of EC.Methods: This study was a retrospective review of the records of 2179 patients with EC who received surgery from December 2000 to December 2008. The prognostic impact of ABO blood group on DFS and OS were estimated using the Kaplan-Meier method and cox proportional hazard models.Results: Univariate analyses found significant differences in DFS and OS among the four blood types. Multivariate analyses showed ABO blood type independently predicted DFS (P=0.001) and OS (P=0.002). Furthermore, patients with non-B blood types had a significantly shorter DFS (HR=1.22, 95%CI:1.07–1.38, P=0.002) and OS (HR=1.22, 95%CI:1.07–1.38, P=0.003) than patients with blood type B, and patients with non-O blood types had a significantly better DFS (HR=0.86, 95%CI:0.77–0.96, P=0.006) and OS (HR=0.86, 95%CI:0.77–0.96, P=0.007) than patients with blood type O. Subgroup analyses found that blood type B had a better DFS and OS than non-B in patients who were male, younger, early pathological stages and had squamous-cell carcinomas (ESCC). Blood type O had a worse DFS and OS than non-O in patients who were male, younger, and had ESCC (P<0.05).Conclusions: The results demonstrate that ABO blood group is an independent prognostic factor of survival, and that type B predicts a favorable prognosis, whereas type O predicts an unfavorable prognosis for survival in patients with EC, especially those with ESCC.

TRPV6 is over-expressed and promotes the proliferation and invasion in many cancers. The association between the expression of TRPV6 and clinical outcome in esophageal squamous cell carcinoma (ESCC) has not been studied yet. We aim to elucidate the role of TRPV6 in predicting prognosis of patients with ESCC. In the retrospective study, mRNA level of TRPV6 was examined in patients (N = 174) from Sun Yat-sen University Cancer Center (mRNA cohort) and protein level of TRPV6 was examined in patients (N = 218) from Linzhou Cancer Hospital (protein cohort). Statistical analysis was performed to test the clinical and prognostic significance of TRPV6. TRPV6 was down-regulated in ESCC tissues and cell lines. Patients with downregulation of TRPV6 trended to have a higher rate of advanced pT stage in both mRNA cohort (P = 0.089) and protein cohort (P = 0.073), though not statistically significant. No significant association was observed between TRPV6 expression and disease-specific survival (DSS) in both two cohorts. However, stratified survival analysis based on the gender showed that in mRNA cohort, downregulation of TRPV6 was associated with an unfavorable 3-year DSS in patients with male (47.3 % vs 63.6 %, P = 0.027) and with favorable 3-year DSS in patients with female (66.7 % vs 43.0 %, P = 0.031). The result was confirmed in protein cohort. Male patients with downregulation of TRPV6 had a poor 3-year DSS (20.0 % vs 57.1 %,P < 0.001) while female counterparts showed an enhanced 3-year DSS (56.1 % vs 28.6 %, P = 0.005). TRPV6 is down-regulated in ESCC. As a predictive biomarker, TRPV6 plays a Janus-like role in predicting survival of male and female ESCC patients.

Despite numerous previous studies, the consideration of tumor location as a prognostic factor in resectable non–small cell lung cancer (NSCLC) remains controversial. The present study analyzed the association between tumor location and clinical outcome in patients with resectable NSCLC who had undergone lobectomy with systematic lymphadenectomy and who had presented with varying nodal statuses. The data from a cohort of 627 eligible patients treated in Sun Yat-sen University Cancer Center between January 2000 and December 2008 were retrospectively collected, and the nodal statuses of patients with different tumor locations were compared. Cox proportional hazards regression model was used to determine the independent factors related to cancer-specific survival (CSS). Multivariate analysis demonstrated that left lower lobe (LLL) tumors [hazard ratio (HR): 1.465, 95% confidence interval (CI) 1.090–1.969, P = 0.011], lymph node metastasis (HR: 2.742, 95% CI 2.145–3.507, P < 0.001), and a tumor size of >4 cm (HR: 1.474, 95% CI 1.151–1.888, P = 0.002) were three independent prognosticators in patients with resectable NSCLC. However, LLL tumors were associated only with CSS in node-positive patients (HR: 1.528, 95% CI 1.015–2.301, P = 0.042), and a tumor size of >4 cm was the only independent risk predictor in the node-negative subgroup (HR: 1.889, 95% CI 1.324–2.696, P < 0.001). Tumor location is related to the long-term CSS of NSCLC patients with lymph node metastasis. LLL tumors may be upstaged in node-positive patients to facilitate an optimal treatment strategy.