The prognostic analysis of different metastatic patterns in extensive-stage small-cell lung cancer patients: a large population-based study.

AIM: To analyze the metastasis patterns and prognosis differences for extensive-stage small-cell lung cancer patients. METHODS: Log-rank tests were used to calculate and compare survival estimates. Cox regression analyses were used to evaluate the prognosis factors. RESULTS: The liver was the most common metastatic site, and lung was the least common. In two metastatic sites, liver and bone metastases were the most common combination of sites. An isolated liver metastasis had the worst overall survival (OS) and cancer-specific survival (CSS) among metastatic sites (both p < 0.001). Liver and lung metastases were associated with worse CSS (p < 0.039) and OS (p < 0.015). However, for patients with three metastatic sites showed no statistical differences in their CSS and OS (all, p > 0.05). CONCLUSION: Extensive-stage small-cell lung cancer patients with metastasis to the liver alone or in combination with other organs appear to have worse outcomes.

The safety and feasibility of three-dimensional visualization planning system for CT-guided microwave ablation of stage I NSCLC (diameter ≤2.5 cm): A pilot study.

Background: Microwave ablation (MWA) of lung tumors is a technique that is dependent on the ablationist's level of expertise. The selection of the optimum puncture path and determination of appropriate ablative parameters is the key to the success and safe of the procedure. The objective of this study was to describe the clinical use of a novel three-dimensional visualization ablation planning system (3D-VAPS) for aided MWA of stage I non-small cell lung cancer (NSCLC). Methods: This was a single-arm, single-center, retrospective study. From May 2020 to July 2022, 113 consented patients with stage I NSCLC received MWA treatment in 120 MWA sessions. The 3D-VAPS was used to determine that: (1) the overlap between the gross tumor region and simulated ablation; (2) the proper posture and appropriate puncture site on the surface of the body; (3) the puncture path; and (4) presetting preliminarily ablative parameters. Patients were monitored with contrast-enhanced CT scans at 1, 3, and 6 months, as well as every 6 months following that. The primary endpoints were technical success and a complete ablation rate. Local progression-free survival (LPFS), overall survival (OS), and comorbidities were secondary study objectives. Results: The mean diameter of tumors was 1.9 ± 0.4 cm (range 0.9-2.5 cm). The mean duration was 5.34 ± 1.28 min (range 3.0-10.0 min). The mean power output was 42.58 ± 4.23 (range 30.0-50.0W). The median follow-up time was 19.0 months (6.0-26.0 months). The technical success rate was 100%. Three-month after the procedure, the complete ablation rate was 97.35%. 6, 9, 12, and 24 months LPFS rates were 100%, 98.23%, 98.23%, and 96.46%, respectively. One-year and 2-year OS rates were 100% and 100%. There were no patients who died both during the procedure and after the MWA of 30 days. The complications after MWA included pneumothorax (38.33%), pleural effusion (26.67%), intrapulmonary hemorrhage (31.67%), and pulmonary infection (2.50%). Conclusions: This research describes and confirms that 3D-VAPS is a feasibility and safe method for MWA of stage I NSCLC treatment. 3D-VAPS may be helpful to optimize the puncture path, assess reasonable ablative parameters, and minimize complications.

Microwave ablation of the lung: Comparison of 19G with 14G and 16G microwave antennas in ex vivo porcine lung.

Background: Percutaneous image-guided thermal ablation has an increasing role in the treatment of primary and metastatic lung tumors. Although microwave ablation (MWA) has emerged advantageous as a new ablation technology, more research is needed to improve it. This study aims to investigate the ablation zone of three microwave antennas in ex vivo porcine lung. Materials and Methods: In the ex vivo standard model and porcine lung model, MWA was performed in three power output settings (50 W, 60 W, and 70 W) for 3, 6, 9, and 12 min using three microwave antennas, with outer diameter of 1.03 mm (19G), 1.6 mm (16G), and 2.0 mm (14G). A total of 108 and 216 sessions were performed (3 or 6 sessions per time setting with the 14G, 16G, and 19G microwave antennas). After the MWA was complete, we evaluated the shape and extent of the coagulation zone and measured the maximum long-axis (along the needle axis; length [L]) and maximum short-axis (perpendicular to the needle; diameter [D]) of the ablation zones using a ruler; subsequently, the sphericity index (L/D) was calculated. The sphericity index can be simplified as long-axis/short-axis. Results: In the ex vivo standard model study, the long- and short-axis diameters and sphericity indices were not statistically different between the 14G, 16G, and 19G groups. In the ex vivo porcine lung study, the long- and short-axis diameters did not differ statistically between the 14G, 16G, and 19G groups (P < 0.05 each). The sphericity index for the 19G microwave antenna was higher than the sphericity indices for the 14G and 16G microwave antennas (P < 0.05); however, the index for the 14G microwave antenna was not statistically different than that for the 16G microwave antenna (P > 0.05). Conclusions: The ablation zone of the 19G antenna was the same as those of the 14G and 16G antennas in vitro. Thus, the 19G antenna may reduce the incidence of complications in lung tumor ablation.

Safety and efficacy of microwave ablation for lung cancer adjacent to the interlobar fissure.

BACKGROUND: This retrospective study aimed to assess the safety and efficacy of microwave ablation for lung tumors adjacent to the interlobar fissures. METHODS: From May 2020 to April 2021, 59 patients with 66 lung tumors (mean diameter, 16.9 ± 7.7 mm; range, 6-30 mm) adjacent to the interlobar fissures who underwent microwave ablation at our institution were identified and included in this study. Based on the relationship between the tumor and the interlobar fissure, tumors can be categorized into close to the fissure, causing the fissure, and involving the fissure. The complete ablation rate, local progression-free survival, complications, and associated factors were analyzed. RESULTS: All 66 histologically proven tumors were treated using computed tomography-guided microwave ablation. The complete ablation rate was 95.5%. Local progression-free survival at 3, 6, 9, and 12 months were 89.4%, 83.3%, 74.2%, and 63.6%, respectively. The complications included pneumothorax (34.8%), pleural effusion (24.2%), cavity (18.2%), and pulmonary infection (7.6%). There were statistical differences in the incidence of pneumothorax, cavity, and delayed complications between the groups with and without antenna punctures through the fissure. CONCLUSIONS: Microwave ablation is a safe and effective treatment for lung tumor adjacent to the interlobar fissure. Antenna puncturing though the interlobar fissure may be a potential risk factor for pneumothorax, cavity, and delayed complications.

Microwave ablation plus camrelizumab monotherapy or combination therapy in non-small cell lung cancer.

Purpose: Immunotherapy has become widely applied in non-small cell lung cancer (NSCLC) patients. However, the relatively low response rate of immunotherapy monotherapy restricts its application. Combination therapy improves the response rate and prolongs patient survival; however, adverse events (AEs) associated with immunotherapies increase with combination therapy. Therefore, exploring combination regimens with equal efficacy and fewer AEs is urgently required. The aim of this study was to evaluate the efficacy and safety of microwave ablation (MWA) plus camrelizumab monotherapy or combination therapy in NSCLC. Materials and methods: Patients with pathologically confirmed, epidermal growth factor receptor/anaplastic lymphoma kinase-wild-type NSCLC were retrospectively enrolled in this study. Patients underwent MWA to the pulmonary lesions first, followed by camrelizumab monotherapy or combination therapy 5-7 days later. Camrelizumab was administered with the dose of 200 mg every 2 to 3 weeks. Treatment was continued until disease progression or intolerable toxicities. The technical success and technique efficacy of ablation, objective response rate (ORR), progression-free survival (PFS), overall survival (OS), complications of ablation, and AEs were recorded. Results: From January 1, 2019 to December 31, 2021, a total of 77 patients underwent MWA and camrelizumab monotherapy or combination therapy. Technical success was achieved in all patients (100%), and the technique efficacy was 97.4%. The ORR was 29.9%. The PFS and OS were 11.8 months (95% confidence interval, 9.5-14.1) and not reached, respectively. Smoking history and response to camrelizumab were correlated with PFS, and response to camrelizumab was correlated with OS in both the univariate and multivariate analyses. No periprocedural deaths due to ablation were observed. Complications were observed in 33 patients (42.9%). Major complications included pneumothorax (18.2%), pleural effusion (11.7%), pneumonia (5.2%), bronchopleural fistula (2.6%), and hemoptysis (1.3%). Grade 3 or higher AEs of camrelizumab, including reactive capillary endothelial proliferation, fatigue, pneumonia, edema, and fever, were observed in 10.4%, 6.5%, 5.2%, 2.6%, and 2.6% of patients, respectively. Conclusion: MWA combined with camrelizumab monotherapy or combination therapy is effective and safe for the treatment of NSCLC.

HPV16 E6-specific T cell response and HLA-A alleles are related to the prognosis of patients with cervical cancer.

BACKGROUND: T cell epitopes are polypeptide fragments presented to T cell receptors by MHC molecules encoded by human leukocyte antigen (HLA) genes after antigen-presenting cell processing, which is the basis for the study of antigen immune mechanism and multi-epitope vaccine. This study investigated T cell response to HPV16 E6 and E7 in patients with cervical squamous cell carcinoma (CSCC). Also, the HLA-A allele distribution was compared among patients and evaluated as a factor to predict prognosis in these patients. MATERIALS AND METHODS: This study recruited a total of 76 patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IIB-IIIB CSCC. Mononuclear cells were isolated from the peripheral blood before any treatment and then enzyme-linked immunosorbent spot (ELISpot) assay was employed to measure the E6 and E7-specific T cell response. HLA-A alleles were typed using Sanger sequencing-based typing techniques with DNA extracted from the peripheral blood. The correlation between the T cell responses, HLA-A allele distribution and patient prognosis were analysed using the Kaplan-Meier method, univariate and multivariate Cox proportional hazard models. RESULTS: The frequency of HPV E6-specific T cell responses in patients with pelvic lymph node metastasis was lower than that in patients without metastasis (P = 0.022). The 5-year overall survival (OS) rates of patients were 87.5% for those responding to multiple overlapping peptides, 72.7% for those responding to 1-2 overlapping peptides and 47.7% for non-responders (P = 0.032). Cox regression analysis indicated that the presence of HLA*A02:07 was independently associated with worse OS (hazard ratio [HR] 3.042; 95% confidence interval [CI] 1.348-6.862; P = 0.007), while concurrent chemoradiation therapy (CCRT) was independently associated with better OS (HR 0.475; 95% CI 0.232-0.975; P = 0.042). CONCLUSION: The results of our study demonstrated that the level of HPV16 E6-specific T cell response and HLA*A02:07 were correlated with prognosis in patients with advanced CSCC.

PD-1 Expression Status on CD8+ Tumour Infiltrating Lymphocytes Associates With Survival in Cervical Cancer.

Despite the expansion of PD-1 checkpoint blockade to multiple types of cancer, whether the programmed cell death 1 (PD-1) expression status on CD8+ tumour infiltrating lymphocytes (TILs) could be a prognostic factor in cervical cancer is still unclear. In this study, we performed ex vivo phenotypic analysis of PD-1 expression on CD8+ TILs by flow cytometry from 47 treatment-naïve cervical cancer patients. With a median follow-up of 26.1 months (95% confidence interval [CI], 24-28.2 months), we then linked the quantitative cellular expression results to progression-free survival and overall survival. Based on the intensity of PD-1 expression, we further categorised the cervical cancer patients into PD-1high expressers (29.8%, 14/47) and PD-1low expressers (70.2%, 33/47). Multivariate analysis revealed that PD-1high expressers are correlated with early recurrence (HR, 5.91; 95% CI, 1.03-33.82; P= 0.046). Univariate analysis also demonstrated that PD-1high expressers are associated with poor overall survival in cervical cancer (HR, 5.365; 95% CI, 1.55-18.6; P=0.008). Moreover, our study also demonstrated that CD8+/CD4+ TIL ratio and HPV infection status are risk factors for early relapse and mortality in cervical cancer patients. In conclusion, this study confirms that PD-1 expression status is an independent prognostic factor for progression free survival in cervical cancer. These findings could be important in predicting the relapse of cervical cancer as a cellular diagnosis method and could be important knowledge for the selection of prospective PD-1 blockade candidates.

Maternal hypoxia increases hippocampal cell susceptibility to ischemia after middle cerebral artery occlusion in rat offspring.

Introduction: Maternal hypoxia induces an adverse uterine environment and may induce long-term effects in offspring. This study investigated whether maternal hypoxia increases hippocampal cell vulnerability and exacerbates neurological impairments in adult rat offspring following ischemia. Material and methods: Pregnant Sprague-Dawley rats were randomly assigned to no maternal hypoxia or maternal hypoxia treatment groups. Adult male rat offspring were subjected to middle cerebral artery occlusion (MCAO). There were four groups: maternal + sham (MH + Sham), sham (Sham), maternal hypoxia + MCAO (MH + MCAO), and MCAO only (MCAO). Neurological deficits were evaluated. Hippocampal cell damage was observed by hematoxylin and eosin (HE) staining. Cell apoptosis in the hippocampus was detected by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining. Caspase-3, cytochrome c, Bax, and bcl-2 expression in the hippocampus was detected by Western blot. Results: More severe hippocampal cell damage was found in the MH + MCAO group than in the MCAO group. Additionally, neurological deficits, percentage of TUNEL positive cells, and expression of caspase-3, cytochrome c, and Bax in the hippocampus were significantly higher (p < 0.05), whereas bcl-2 expression was significantly lower (p < 0.05) in the MH + MCAO group compared to the MCAO group. Conclusions: These findings suggest that maternal hypoxia may exacerbate hippocampal cell apoptosis in rat offspring after MCAO via alterations in the expression of cytochrome c, caspase-3, Bax, and bcl-2, which ultimately affects ischemic stroke prognosis. To our knowledge, this is the first study demonstrating that maternal hypoxia increases hippocampal cell susceptibility to ischemia in adult rat offspring. .

[The effects of prenatal stress on the astrocytes after cerebral ischemia/reperfusion injury in adult offspring rats].

OBJECTIVE: To investigate the effects of prenatal stress on astrocytes after ischemia/reperfusion of cerebral middle artery in adult offspring rats. METHODS: Pregnant rats were randomly assigned to prenatal stress treatment group, which was exposed to restraint three times daily in the last week of pregnancy, and no prenatal stress treatment group. Adult male offspring rats were subjected to transient focal cerebral ischemia by middle cerebral artery occlusion (MCAO). There were three groups:prenatal stress+sham group, MCAO group and prenatal stress+MCAO group (n=10). After 5 days of reperfusion, the infarct size was evaluated. The morphology of astrocytes, co-local-ization of erythropoietin-producing hepatocellular receptor A4 (EphA4) and glial fibrillary acidic protein (GFAP) were detected by double im-munofluorescent staining. And the protein expressions of EphA4, GFAP and Neurocan in peri-ischemic regions were detected by Western blot. RESULTS: The infarct size and the expression of EphA4, GFAP and Neurocan were significantly increased in prenatal stress+MCAO group compared with MCAO group (all P<0.05). And the morphological changes of GFAP-positive astrocytes and co-localization of EphA4/GFAP were more obvious in prenatal stress+MCAO group compared with MCAO group. CONCLUSIONS: Prenatal stress may upregulate the expression of EphA4 on astrocytes in the offspring rats after cerebral ischemia/reperfusion, which promotes the reactivity of astrocyte and increases the ex-pression of neurocan.

[The effects of prenatal stress on the cell apoptosis after MCAO in adult offspring rats].

OBJECTIVE: To evaluate the effects of prenatal stress on neurological functions after middle cerebral artery occlusion (MCAO) in adult offspring rats. METHODS: Pregnant rats were randomly assigned to prenatal stress treatment, which was exposed to restraint three times daily in the last week of pregnancy, and no prenatal stress treatment. Adult male offspring rats were subjected to transient focal cerebral ischemia by MCAO. They were randomly divided into four groups: sham group, prenatal stress + sham group, MCAO group and prenatal stress + MCAO group (n = 10). After 24 hours of reperfusion, the neurological deficits were evaluated. The infarct size, cell apoptosis and expression of Caspase 3, cleaved Caspase 3 and Bcl-2 were detected. RESULTS: Compared with MCAO group, the neurological deficits, infarct size and apoptotic cells in prenatal stress + MCAO group were increased significantly (all P < 0.05). The expressions of Caspase 3 and cleaved Caspase 3 were much greater in prenatal stress + MCAO group than those of MCAO group, while the expression of Bcl-2 was significantly decreased in prenatal stress + MCAO group compared with MCAO group (all P < 0.05). CONCLUSION: Prenatal stress might exacerbate neuroloeical deficits in the offspring rats after MCAO by increasing cell apoptosis.