Thoracic Cancer最新文献

Objectives: This study aimed to analyze the role of circSEC24A in non-small cell lung cancer (NSCLC) and its underlying mechanism.

Methods: RNA levels of circSEC24A, microRNA-1253 (miR-1253), and KLF transcription factor 8 (KLF8) were detected by quantitative real-time polymerase chain reaction. Protein expression was analyzed by western blot or immunohistochemistry assay. Cell proliferation and apoptosis were investigated by colony formation assay, 5-ethynyl-2'-deoxyuridine assay, and flow cytometry analysis. Glycolysis was evaluated by commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to identify the associations among circSEC24A, miR-1253, and KLF8. Xenograft mouse model assay was used to evaluate the effect of circSEC24A on tumor tumorigenesis.

Results: CircSEC24A and KLF8 were upregulated, while miR-1253 was downregulated in NSCLC. CircSEC24A knockdown inhibited proliferation and glycolysis but induced the apoptosis of NSCLC cells. CircSEC24A acted as a miR-1253 sponge and regulated NSCLC cell malignancy by targeting miR-1253. KLF8 was identified as a target of miR-1253, and its overexpression attenuated miR-1253-induced effects in NSCLC cells. Besides, circSEC24A upregulated KLF8 by sponging miR-1253. Further, circSEC24A knockdown suppressed NSCLC cell tumorigenesis in vivo.

Conclusions: CircSEC24A silencing inhibited NSCLC cell malignancy through the miR-1253/KLF8 pathway, providing a potential therapeutic target for NSCLC.

Hemolytic anemia is a rare and unique complication of alectinib, not observed with other anaplastic lymphoma kinase (ALK) inhibitors. Here, we present a case of an ALK fusion-positive non-small-cell lung cancer (NSCLC) patient who developed liver failure due to diffuse liver metastasis at initial diagnosis. Treatment was initiated with low-dose alectinib, but the patient developed severe hemolytic anemia. Switching to lorlatinib allowed for the continuation of ALK inhibitor therapy and successful tumor reduction. ALK inhibitors are crucial for ALK fusion-positive NSCLC patients. Managing severe side effects by switching medications is essential to maintain effective therapy. In this case, lorlatinib effectively controlled the tumor and improved the patient's liver function and performance status. This case highlights the importance of adapting treatment strategies to manage adverse effects while ensuring the continued use of ALK inhibitors for optimal patient outcomes.

Objective: To analyze the pattern of lymph node metastasis in esophageal cancer based on the theory of membrane anatomy.

Methods: A retrospective analysis was conducted on 143 patients who underwent esophageal surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences from March 2021 to March 2022. Lymph node metastasis was observed and categorized according to postoperative T staging. The characteristics and patterns of lymph node metastasis in different regions were observed, and the lymph node metastasis patterns in patients with clinical T3 esophageal cancer were analyzed using membrane anatomy theory.

Results: Among the 143 patients with esophageal squamous cell carcinoma, 21 were treated with surgery alone, while the rest received preoperative adjuvant therapy. A total of 5456 lymph nodes were cleared from the 143 patients, with 204 positive lymph nodes, resulting in a positive rate of 3.74%. In the thoracic lymph node dissection, the metastatic rates exceeded 5% for the following regions: 106recR (17.36%), 106recL (12.5%), 107 (10.42%), and 108 (5.56%) station. When analyzing the abdominal lymph node metastasis, the metastatic rates exceeded 5% for regions 7 (13.19%), 3a (7.64%), 2 (6.94%), and 1 (6.25%) station. Group analysis of patients with esophageal squamous cell carcinoma before postoperative pathological T3 stage revealed an increasing trend in tumor lymph node metastasis rate with later T staging. Lymph node metastasis in region 106recR can occur early, with a metastasis rate of 18.37% in T1 tumors. Analysis of lymph node metastasis characteristics in 103 patients clinically staged as T3 showed that 3966 lymph nodes were cleared, with 186 positive nodes, resulting in a positive rate of 4.69%. Lymph node metastasis rates were higher in regions 106recL, 106recR, 107, 108, 110, 1, 2, 3a, and 7, all exceeding 5%.

Conclusion: The theory of membrane anatomy can effectively explain the pattern of lymph node metastasis in esophageal cancer.

This study aimed to conduct a systematic review and meta-analysis comparing video-assisted thoracoscopic surgery (VATS) and open thoracotomy (OT) in the context of pulmonary metastasectomy. Three databases were assessed. The primary outcome was overall survival. The secondary outcomes were recurrence-free survival, ipsilateral recurrence, and hospital length of stay (LOS). Hazard ratios (HRs), odds ratios (ORs), and mean difference (MD) with 95% confidence intervals (CIs) were calculated. Reconstruction of time-to-event data and sensitivity analyses were performed for the primary endpoint. After screening, 11 studies were included encompassing 2159 patients undergoing lung metastasectomy (VATS: 827; OT: 1332). Compared to OT, patients who underwent VATS had higher overall survival rates (HR 0.75; 95% CI 0.67-0.85; p < 0.01), no significant difference in recurrence-free survival (HR 1.07; 95% CI 0.88-1.29; p = 0.48), shorter hospital LOS (MD -1.99 days; 95% CI -2.59 to -1.39; p < 0.01), and no significant difference in ipsilateral recurrence rates (OR 0.86; 95% CI 0.52-1.42; p = 0.56). For patients undergoing pulmonary metastasectomy, VATS strategy is associated with higher survival rates and reduced hospital LOS when compared with OT. Moreover, metastasis recurrence does not seem to be associated with long-term mortality in this population.

Background: With the rising incidence of pulmonary nodules (PNs), lung adenocarcinoma in situ (AIS) is a critical early stage of lung cancer, necessitating accurate diagnosis for early intervention. This study applies artificial intelligence (AI) for quantitative imaging analysis to differentiate AIS from atypical adenomatous hyperplasia (AAH) and minimally invasive adenocarcinoma (MIA), aiming to enhance clinical diagnosis and prevent misdiagnosis.

Methods: The study analyzed 1215 PNs with confirmed AAH, AIS, and MIA from six centers using the Shukun AI diagnostic module. Parameters evaluated included demographic data and various CT imaging metrics to identify indicators for clinical application, focusing on the mean CT value's predictive value.

Results: Significant differences were found in several parameters between AAH and AIS, with nodule mass showing the highest predictive value. When comparing AIS to MIA, total nodule volume was the best predictor, followed by the maximum CT value.

Conclusion: The mean CT value has limited discriminative power for AIS diagnosis. Instead, the maximum CT value and maximum 3D diameter are recommended for clinical differentiation. Nodule mass and volume of solid components are strong indicators for differentiating AIS from AAH and MIA, respectively.

Arising from the urachal epithelial lining, the urachal carcinoma is a rare tumor, which accounts for 0.35%-0.7% of all bladder cancers. Urachal carcinoma has a higher predilection in men with median age around 50-60 years old. The most common clinical symptom is intermittent painless gross hematuria, and less-reported presentations include suprapubic mass, dysuria, lower abdominal pain, and frequent urination. The pathological study reveals that most cases (90%) are categorized as an intestinal adenocarcinoma subtype, while other morphological variants, including mucinous, enteric, signet ring cell subtype, not otherwise specified (NOS), squamous cell carcinoma, urothelial carcinoma, sarcoma, small cell carcinoma, and undifferentiated carcinoma, totally account for about 10%. The urachal carcinoma occurs mostly in the lower segment of urachal tube and bladder dome or anterior wall. However, due to the classically silent nature of the early lesions and high malignancy, urachal carcinoma patients are commonly diagnosed in advanced stage. Treatment modalities for local recurrence or metastatic urachal cancer include surgery and chemotherapy (cisplatin and 5-FU based-chemotherapy). Meanwhile, the EGFR-, PD-L1-, and MEK-targeted therapies in the metastatic urachal carcinoma cases showed satisfactory response. We presented a rare case of Sheldon stage IVB urachal adenocarcinoma with pulmonary metastasis, and the patient had no progression of disease 6 months following surgical treament without chemoradiotherapy.

Background: Patients with non-small-cell lung cancer (NSCLC) receiving immunotherapy face a potential risk of developing checkpoint inhibitor-related pneumonitis (CIP). However, there is no clear understanding of the specific link between interstitial lung abnormality (ILA) and CIP in patients with small-cell lung cancer (SCLC). In addition, the prognosis of SCLC patients with ILA who receive chemoimmunotherapy is uncertain. Our study aimed to investigate the effect of ILA on the occurrence of CIP in SCLC patients receiving first-line chemoimmunotherapy and to assess its relationship with prognosis.

Methods: We conducted a retrospective analysis of SCLC patients who received chemoimmunotherapy as a first-line treatment between January 2018 and April 2024. The diagnosis of ILA was assessed by two experienced pulmonologists based on pretreatment chest computed tomography images. We investigated independent risk factors for CIP using logistic regression analysis and factors affecting PFS and OS using Cox regression analysis.

Results: A total of 128 patients with SCLC were included in the study. ILA was present in 41 patients (32.03%), and CIP occurred in 16 patients (12.50%). In multivariate logistic regression analysis, previous ILA (OR, 5.419; 95% CI, 1.574-18.652; p = 0.007) and thoracic radiation therapy (TRT) (OR, 5.259; 95% CI, 1.506-18.365; p = 0.009) were independent risk factors for CIP. ILA (HR, 2.083; 95% CI, 1.179-3.681; p = 0.012) and LDH (HR, 1.002; 95% CI, 1.001-1.002; p < 0.001) were statistically significant for increased mortality risk in multivariate Cox regression analysis.

Conclusions: In SCLC patients receiving first-line chemoimmunotherapy, baseline ILA is a risk factor for CIP and is associated with poorer prognosis.

Objectives: Podoplanin (PDPN) expression in cancer-associated fibroblasts (CAFs) (CAF-PDPN) is considered a poor prognostic factor in nonsmall cell lung cancer, but little is known about its clinical significance in high-grade neuroendocrine carcinoma of the lung (HGNEC). This study examines the association between CAF-PDPN and stromal programmed death-ligand 1 (PD-L1) expression and the prognostic implications of CAF-PDPN and PD-L1 expression status in surgically resected HGNEC patients.

Methods: Immunohistochemical analyses were performed on 121 resected HGNEC specimens using antibodies against PDPN and PD-L1. Correlations between CAF-PDPN, stromal PD-L1 expression, and clinicopathologic features and their implications for survival were analyzed statistically.

Results: There were substantially more large-cell neuroendocrine carcinomas in the stromal PD-L1-positive group and more vascular invasion in the tumoral PD-L1-positive group. PDPN expression in CAF was moderately correlated with stromal PD-L1 expression (ρ = 0.567, p < 0.001). In a survival analysis combining CAF-PDPN and stromal PD-L1 status, the 5-year RFS rates for Group A: CAF-PDPN (+)/stromal PD-L1 (+), Group B: CAF-PDPN (+)/stromal PD-L1 (-), Group C: CAF-PDPN (-)/stromal PD-L1 (+), and Group D: CAF-PDPN (-)/stromal PD-L1 (-) were 62.0%, 46.8%, 17.5%, and 20.2%, respectively, with corresponding 5-year OS rates of 76.6%, 69.2%, 27.0%, and 25.3%. The log-rank test showed statistically significant differences among the groups in RFS (p < 0.001) and OS (p < 0.001).

Conclusions: There is a correlation between CAF-PDPN and tumoral/stromal PD-L1 expression, and positive status for either CAF-PDPN or stromal PD-L1 expression could be an independent favorable prognostic factor in surgically resected HGNEC patients.

Background: Increasing evidence shows that exosome-mediated delivery of circular RNA (circRNA) is implicated in breast cancer progression. This study aimed to elucidate the role of exosome-transported circ_0001955 in breast cancer.

Methods: The expression of circ_0001955, miR-708-5p, and phosphoglycerate kinase 1 (PGK1) messenger RNA (mRNA) was detected by quantitative real-time polymerase chain reaction (qRT-PCR); the protein levels of PGK1 and hexokinase 2 (HK2) were detected by western blot (WB). 5'-Ethynyl-2'-deoxyuridine (EdU) and colony formation assay were used to determine cell proliferation. Glycolytic metabolism was analyzed by corresponding kits to detect the associated indicators. The role of circ_0001955 in vivo was studied by establishing animal models. The potential binding relationship between miR-708-5p and circ_0001955 or PGK1 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.

Results: Circ_0001955 was highly expressed in breast cancer tissues and cell lines, as well as in exosomes from breast cancer cell lines. The deficiency of circ_0001955 blocked proliferation, decreased the IC50 value of paclitaxel (PTX), and blocked glycolysis in MCF-7 and MDA-MB-231 cells. Circ_0001955 knockdown also inhibited tumor growth in vivo. Circ_0001955 directly combined with miR-708-5p, and the miR-708-5p inhibitor reversed the effects of sh-circ_0001955. PGK1 was a target of miR-708-5p, and circ_0001955 indirectly promoted PGK1 expression by binding to miR-708-5p. PGK1 overexpression abolished the function of miR-708-5p in breast cancer.

Conclusion: Exosomal circ_0001955 excreted from breast cancer cells facilitated proliferation and glycolysis and enhanced the IC50 value of PTX in breast cancer cells by sponging miR-708-5p to upregulate PGK1.

Introduction: Paraneoplastic neurological syndrome (PNS) is associated with small-cell lung cancer (SCLC). However, the frequency and characteristics of PNS and the efficacy of anticancer treatment for these patients have not been investigated in the Japanese/Asian population previously. Therefore, we aimed to better understand PNS by evaluating real-world data from patients with PNS complicated by SCLC.

Methods: Patients diagnosed with Stage II-IV SCLC at a single center between August 2007 and April 2021 were retrospectively analyzed. The primary outcome was the incidence of PNS. The secondary outcomes were the change in performance status (PS) after treatment commencement and outcomes following anticancer treatment, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results: A total of 318 patients were evaluated; PNS was present in 2.8% (n = 9) of the overall population. All patients with PNS exhibited poor Eastern Cooperative Oncology Group PS (≥2); moreover, 78% of patients had a PS score of 3-4. An improvement in PS was observed in 56% (n = 5) of patients. Patients with PNS exhibited treatment efficacies similar to patients without PNS (ORR: 89% vs. 83%, p = 1.0; PFS: 7.6 vs. 5.7 months, p = 0.69; OS: not reached vs. 15.6 months, p = 0.23).

Conclusions: A total of 2.8% of patients had SCLC complicated by PNS, with poor PS observed. However, anticancer therapy led to an improvement in PS and comparable ORR, as well as PFS and OS similar to those observed in patients without PNS. Thus, anticancer therapy should be considered in patients with PNS.