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Quantitative Imaging in Medicine and... May 2024The parietal pleural adhesion/invasion of lung cancer can contribute substantially to poor prognosis and difficulty in surgery. The value of ultrasound in evaluating the...
BACKGROUND
The parietal pleural adhesion/invasion of lung cancer can contribute substantially to poor prognosis and difficulty in surgery. The value of ultrasound in evaluating the parietal pleural adhesion or invasion (pleural adhesion/invasion) of lung cancer remains uncertain. This study investigated the value of B-mode ultrasound and contrast-enhanced ultrasound (CEUS) in diagnosing parietal pleural adhesion/invasion of subpleural lung cancer.
METHODS
The study animals included 40 male New Zealand white rabbits. A rabbit subpleural lung cancer model was constructed by injecting VX2 tumor tissue under ultrasound guidance. In the 1-3 weeks after subpleural lesion formation, parietal pleural adhesion/invasion of the largest subpleural lesion was evaluated with B-mode ultrasound and CEUS by two sonographers. The parietal pleural adhesion/invasion was also determined using the gold standard method of findings from anatomical and pathological examination.
RESULTS
Ultimately, 34 rabbits were subjected to complete ultrasonic evaluation. There were 20 and 14 cases with and without parietal pleural adhesion/invasion, respectively, as confirmed by anatomical and pathological evaluations. The diagnostic sensitivity, specificity, and accuracy of sonographer 1 using B-mode ultrasound were 50.0% [95% confidence interval (CI): 26.0-74.0%], 100%, and 70.6% (95% CI: 54.5-86.7%), respectively; for CEUS, they were 90.0% (95% CI: 75.6-100.0%), 100.0%, and 94.1% (95% CI: 85.8-100.0%), respectively. The diagnostic sensitivity, specificity, and accuracy of sonographer 2 using B-mode ultrasound were 45.0% (95% CI: 21.1-68.9%), 92.9% (95% CI: 77.5-100.0%), and 64.7% (95% CI: 47.8-81.6%), respectively; for CEUS, they were 85.0% (95% CI: 67.9-100.0%), 100.0%, and 91.2% (95% CI: 81.1-100.0%), respectively. The diagnostic accuracy of sonographer 1 was higher with CEUS than with B-mode ultrasound, but not significantly so (94.1% 70.6%; P=0.08). The diagnostic accuracy of sonographer 2 was significantly higher with CEUS than with B-mode ultrasound (91.2% 64.7%; P=0.03). The interrater reliability was higher for CEUS than for B-mode ultrasound (κ=0.941 κ =0.717).
CONCLUSIONS
Based on an animal model, B-mode ultrasound and CEUS both exhibited good diagnostic efficacy and interrater reliability in evaluating parietal pleural adhesion/invasion of subpleural lung cancer although CEUS outperformed B-mode ultrasound for both measures.
PubMed: 38720836
DOI: 10.21037/qims-23-1542 -
Respiratory Research May 2024The association between tuberculous fibrosis and lung cancer development has been reported by some epidemiological and experimental studies; however, its underlying...
BACKGROUND
The association between tuberculous fibrosis and lung cancer development has been reported by some epidemiological and experimental studies; however, its underlying mechanisms remain unclear, and the role of macrophage (MФ) polarization in cancer progression is unknown. The aim of the present study was to investigate the role of M2 Arg-1 MФ in tuberculous pleurisy-assisted tumorigenicity in vitro and in vivo.
METHODS
The interactions between tuberculous pleural effusion (TPE)-induced M2 Arg-1 MФ and A549 lung cancer cells were evaluated. A murine model injected with cancer cells 2 weeks after Mycobacterium bovis bacillus Calmette-Guérin pleural infection was used to validate the involvement of tuberculous fibrosis to tumor invasion.
RESULTS
Increased CXCL9 and CXCL10 levels of TPE induced M2 Arg-1 MФ polarization of murine bone marrow-derived MФ. TPE-induced M2 Arg-1 MФ polarization facilitated lung cancer proliferation via autophagy signaling and E-cadherin signaling in vitro. An inhibitor of arginase-1 targeting M2 Arg-1 MФ both in vitro and in vivo significantly reduced tuberculous fibrosis-induced metastatic potential of lung cancer and decreased autophagy signaling and E-cadherin expression.
CONCLUSION
Tuberculous pleural fibrosis induces M2 Arg-1 polarization, and M2 Arg-1 MФ contribute to lung cancer metastasis via autophagy and E-cadherin signaling. Therefore, M2 Arg-1 tumor associated MФ may be a novel therapeutic target for tuberculous fibrosis-induced lung cancer progression.
Topics: Animals; Lung Neoplasms; Humans; Mice; Autophagy; Arginase; Disease Progression; Signal Transduction; Macrophages; Tuberculosis, Pleural; A549 Cells; Mice, Inbred C57BL; Pleural Effusion; Cell Polarity
PubMed: 38720340
DOI: 10.1186/s12931-024-02829-8 -
Journal of Radiation Research May 2024The effectiveness of single-fraction 8-Gy radiotherapy for painful bone metastases has been verified in numerous randomized controlled trials. However, few reports have...
The effectiveness of single-fraction 8-Gy radiotherapy for painful bone metastases has been verified in numerous randomized controlled trials. However, few reports have described the effectiveness of single-fraction 8-Gy radiotherapy in painful tumors other than bone metastases. We conducted a retrospective analysis to evaluate the pain response to single-fraction 8-Gy radiotherapy in painful non-bone-metastasis tumors. We included patients who had received single-fraction 8-Gy radiotherapy for such tumors between January 2017 and December 2022, excluding those with brain metastases, hematological tumors and those who received re-irradiation. Pain response assessment was based on the best responses documented in the medical records and conducted by two radiation oncologists. A total of 36 eligible patients were included in this study. The irradiation sites included primary lesions in eight patients, lymph node metastases in eight, muscle metastases in seven, pleural dissemination in four, skin/subcutaneous metastases in four and other sites in five. Pain response was assessed in 24 patients after radiotherapy. Pain response rate was 88% in evaluable patients; 21 of the 24 patients experienced response. The median assessment date for pain response was 37 days (range: 8-156 days) after radiotherapy. Re-irradiation was performed in four patients (11%). Single-fraction 8-Gy radiotherapy seemed to be a promising treatment option for painful non-bone-metastasis tumors and warrants further investigation.
Topics: Humans; Male; Female; Retrospective Studies; Middle Aged; Aged; Adult; Aged, 80 and over; Pain; Dose Fractionation, Radiation; Treatment Outcome; Cancer Pain; Bone Neoplasms; Neoplasms; Neoplasm Metastasis
PubMed: 38718386
DOI: 10.1093/jrr/rrae025 -
Esophagus : Official Journal of the... Jul 2024Real-world clinical outcomes of and prognostic factors for nivolumab treatment for esophageal squamous-cell carcinoma (ESCC) remain unclear. This study aimed to evaluate...
Efficacy and survival of nivolumab treatment for recurrent/unresectable esophageal squamous-cell carcinoma: real-world clinical data from a large multi-institutional cohort.
BACKGROUND
Real-world clinical outcomes of and prognostic factors for nivolumab treatment for esophageal squamous-cell carcinoma (ESCC) remain unclear. This study aimed to evaluate real-world outcomes of nivolumab monotherapy in association with relevant clinical parameters in recurrent/unresectable advanced ESCC patients.
METHODS
This population-based multicenter cohort study included a total of 282 patients from 15 institutions with recurrent/unresectable advanced ESCC who received nivolumab as a second-line or later therapy between 2014 and 2022. Data, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively collected from these patients.
RESULTS
Objective response and disease control rates were 17.0% and 47.9%, respectively. The clinical response to nivolumab treatment significantly correlated with development of overall immune-related adverse events (P < .0001), including rash (P < .0001), hypothyroidism (P = .03), and interstitial pneumonia (P = .004). Organ-specific best response rates were 20.6% in lymph nodes, 17.4% in lungs, 15.4% in pleural dissemination, and 13.6% in primary lesions. In terms of patient survival, the median OS and PFS was 10.9 and 2.4 months, respectively. Univariate analysis of OS revealed that performance status (PS; P < .0001), number of metastatic organs (P = .019), C-reactive protein-to-albumin ratio (CAR; P < .0001), neutrophil-lymphocyte ratio (P = .001), and PMI (P = .024) were significant. Multivariate analysis further identified CAR [hazard ratio (HR) = 1.61, 95% confidence interval (CI) 1.15-2.25, P = .0053)] in addition to PS (HR = 1.65, 95% CI 1.23-2.22, P = .0008) as independent prognostic parameters.
CONCLUSIONS
CAR and PS before nivolumab treatment are useful in predicting long-term survival in recurrent/unresectable advanced ESCC patients with second-line or later nivolumab treatment.
TRIAL REGISTRATION
UMIN000040462.
Topics: Humans; Nivolumab; Male; Female; Middle Aged; Aged; Retrospective Studies; Esophageal Neoplasms; Neoplasm Recurrence, Local; Esophageal Squamous Cell Carcinoma; Antineoplastic Agents, Immunological; Treatment Outcome; Aged, 80 and over; Adult; Prognosis; Progression-Free Survival
PubMed: 38717686
DOI: 10.1007/s10388-024-01056-w -
Journal of Cardiothoracic Surgery May 2024To evaluate the efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy (IPHC) in treating malignant pleural effusion (MPE). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy (IPHC) in treating malignant pleural effusion (MPE).
METHODS
PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Chinese Science and Technology Journal Full-text Database (VP-CSJFD), and Wanfang database were searched by computer from database establishment to January 17, 2024. Relevant randomized controlled articles with IPHC as the observational group and intrapleural perfusion chemotherapy (IPC) as the control group for MPE were included. Then, the methodological quality of the included articles was evaluated and statistically analyzed using Stata 16.0.
RESULTS
Sixteen trials with 647 patients receiving IPHC and 661 patients receiving IPC were included. The meta-analysis found that MPE patients in the IPHC group had a more significant objective response rate [RR = 1.31, 95%CI (1.23, 1.38), P < 0.05] and life quality improvement rate [RR = 2.88, 95%CI (1.95, 4.24), P < 0.05] than those in the IPC group. IPHC and IPC for MPE patients had similar incidence rates of asthenia, thrombocytopenia, hepatic impairment, and leukopenia.
CONCLUSION
Compared with IPC, IPHC has a higher objective response rate without significantly increasing adverse reactions. Therefore, IPHC is effective and safe. However, this study is limited by the quality of the literature. Therefore, more high-quality, multi-center, large-sample, rigorously designed randomized controlled clinical studies are still needed for verification and evaluation.
Topics: Humans; Pleural Effusion, Malignant; Hyperthermia, Induced; Treatment Outcome; Chemotherapy, Cancer, Regional Perfusion; Antineoplastic Agents
PubMed: 38711077
DOI: 10.1186/s13019-024-02751-6 -
European Journal of Histochemistry : EJH May 2024Pleural mesothelioma is a devastating malignancy primarily associated with asbestos exposure. However, emerging evidence suggests that exposure to fluoro-edenite fibers,...
Pleural mesothelioma is a devastating malignancy primarily associated with asbestos exposure. However, emerging evidence suggests that exposure to fluoro-edenite fibers, a naturally occurring mineral fiber, can also lead to the development of pleural mesothelioma. In this study, based on the hypothesis that pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-preferring receptor (PAC1R) expressions could be dysregulated in pleural mesothelioma samples and that they could potentially act as diagnostic or prognostic biomarkers, we aimed to investigate the immunohistochemical expression of PACAP and PAC1R in pleural biopsies from patients with pleural mesothelioma exposed to fluoro-edenite fibers. A total of 12 patients were included in this study, and their biopsies were processed for immunohistochemical analysis to evaluate the expression of PACAP and its receptor. The study revealed a correlation between the overexpression of PACAP and PAC1R and shorter overall survival in patients with malignant mesothelioma. These findings suggest that PACAP and PAC1R expression levels could serve as potential prognostic biomarkers for malignant mesothelioma. Furthermore, the immunohistochemical analysis of PACAP and PAC1R may provide valuable information for clinicians to guide therapeutic decisions and identify patients with poorer prognosis.
Topics: Humans; Pituitary Adenylate Cyclase-Activating Polypeptide; Male; Mesothelioma; Middle Aged; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; Female; Pleural Neoplasms; Aged; Asbestos, Amphibole; Mesothelioma, Malignant; Lung Neoplasms; Immunohistochemistry; Biomarkers, Tumor
PubMed: 38699968
DOI: 10.4081/ejh.2024.3994 -
Lung Cancer (Amsterdam, Netherlands) Jun 2024The role of cytoreductive surgery for epithelioid pleural mesothelioma within a multimodal treatment approach remains controversial. Carefully selected patients benefit...
BACKGROUND
The role of cytoreductive surgery for epithelioid pleural mesothelioma within a multimodal treatment approach remains controversial. Carefully selected patients benefit from cytoreductive surgery and adjuvant chemotherapy, but there is no established biomarker to predict tumor recurrence or progression during the course of the disease. The aim of this study was to identify potential biomarkers to predict therapeutic response in terms of progression-free survival.
METHODS
Between 03/2014 and 08/2022, preoperative blood samples were collected from 76 patients with epithelioid pleural mesothelioma who underwent cytoreductive surgery as part of a multimodal treatment approach. Identification of potential biomarkers was performed by determination of mesothelin and calretinin, as well as specific long non-coding RNAs and microRNAs. Receiver operating characteristic analysis, Kaplan-Meier survival analysis, and Cox regression were used to assess the association between biomarker concentrations and patient recurrence status and survival.
RESULTS
MALAT1, GAS5, and calretinin showed statistically significant increased biomarker levels in patients with recurrence in contrast to recurrence-free patients after surgical treatment (p < 0.0001, p = 0.0190, and p = 0.0068, respectively). The combination of the three biomarkers resulted in a sensitivity of 68 % and a specificity of 89 %.
CONCLUSION
MALAT1, GAS5, and calretinin could be potential biomarkers for the prediction of tumor recurrence, improving the benefit from multimodal treatment including cytoreductive surgery.
Topics: Humans; Male; Female; RNA, Long Noncoding; Biomarkers, Tumor; Aged; Disease Progression; Middle Aged; Prognosis; Calbindin 2; Mesothelioma; Pleural Neoplasms; Neoplasm Recurrence, Local; Cytoreduction Surgical Procedures; Adult; Aged, 80 and over; Lung Neoplasms
PubMed: 38692217
DOI: 10.1016/j.lungcan.2024.107802 -
Biomedicine & Pharmacotherapy =... Jun 202417-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using...
DHEA-S, Androstenedione, 17-β-estradiol signature as novel biomarkers for early prediction of risk of malignant pleural mesothelioma linked to asbestos-exposure: A preliminary investigation.
17-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-β-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-β-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-β-estradiol, DHEA-S, and androstenedione. The results revealed significant differences in 17-β-estradiol levels between mesothelioma patients and both non-asbestos-exposed and asbestos-exposed healthy subjects. No significant variations in serum 17-β-estradiol levels were observed among mesothelioma patients at different stages, suggesting its potential as an early diagnostic marker. 17-β-estradiol levels were similar in mesothelioma patients with environmental and occupational asbestos exposure, while males with occupational asbestos exposure exhibited significantly higher levels of 17-β-estradiol compared to females. Significant reduction in androstenedione and an increase in DHEA-S were observed in asbestos-exposed individuals compared to non-asbestos-exposed individuals. The analysis of DHEA-S-androstenedione-17-β-estradiol signature score showed an increase in asbestos-exposed individuals and mesothelioma patients compared to non-asbestos-exposed individuals, and this score effectively distinguished between the groups. The Cancer Genome Atlas data was utilized to analyze the expression of 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 genes. The findings indicated that mesothelioma patients with elevated gene values for 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 have a worse or better prognosis on overall survival, respectively. In conclusion, this study suggests 17-β-estradiol, DHEA-S, and androstenedione as biomarkers for mesothelioma risk and early diagnosis of mesothelioma in asbestos-exposed individuals, aiding timely intervention and improved care.
Topics: Humans; Estradiol; Male; Biomarkers, Tumor; Androstenedione; Asbestos; Female; Middle Aged; Occupational Exposure; Aged; Mesothelioma, Malignant; Lung Neoplasms; Mesothelioma; Pleural Neoplasms; Dehydroepiandrosterone; Case-Control Studies; Early Detection of Cancer
PubMed: 38692064
DOI: 10.1016/j.biopha.2024.116662 -
Pediatric Rheumatology Online Journal Apr 2024Immune checkpoint inhibitors (ICIs) have expanded the arsenal of cancer therapeutics over the last decade but are associated with a spectrum of immune-related adverse...
BACKGROUND
Immune checkpoint inhibitors (ICIs) have expanded the arsenal of cancer therapeutics over the last decade but are associated with a spectrum of immune-related adverse events (irAEs), including inflammatory arthritis. While these complications are increasingly recognized in the adult population, no cases of inflammatory arthritis irAEs have been reported in the pediatric literature.
CASE PRESENTATION
A 14-year-old female with metastatic epithelioid mesothelioma was referred to the pediatric rheumatology clinic after developing progressive inflammatory joint pain in her bilateral shoulders, hips, and small joints of hands following the second cycle of Nivolumab and Ipilimumab. Initial examinations showed bilateral shoulder joint line tenderness, positive FABERs test bilaterally, tenderness over bilateral greater trochanters, and bilateral second PIP effusions. Her serological profile was notable for positive HLA-B27, positive anti-CCP, negative Rheumatoid Factor, and negative ANA. PET-CT scan performed for disease response following immunotherapy showed symmetric increased metabolic activity primarily involving the supraspinatus, gluteus medius and minimus, and semimembranosus tendon insertions. Her presentation was consistent with a grade 1 irAE that worsened to a grade 2 irAE despite NSAID therapy, prompting a short course of oral prednisolone. She achieved clinical remission of her mesothelioma following six cycles of Nivolumab and Ipilimumab and her inflammatory arthritis was controlled on Celebrex monotherapy.
CONCLUSIONS
To our knowledge, this is the first pediatric case of ICI-induced inflammatory arthritis and enthesitis. This case highlights the importance of increasing awareness of diagnosis and management of irAEs in children.
Topics: Humans; Ipilimumab; Female; Nivolumab; Adolescent; Immune Checkpoint Inhibitors; Arthritis; Mesothelioma, Malignant
PubMed: 38685034
DOI: 10.1186/s12969-024-00983-3