1.Aprospective study of detection and clinical significance of bone marrow tumor cells in small cell lung cancer
Ying WANG ; Baohua LU ; Yuan GAO ; Yanxia LIU ; Mingming HU ; Nanying CHE ; Haifeng LIN ; Hongxia LI ; Hongmei ZHANG ; Tongmei ZHANG
Chinese Journal of Oncology 2024;46(5):419-427
Objective:To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis.Methods:A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis.Results:The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P<0.001; 77.78% vs 16.84% for bone metastasis, P<0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs<111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant ( P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups ( P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs<111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage ( HR=2.806, 95% CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH ( HR=1.841, 95% CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS ( HR=2.538, 95% CI:1.169-5.512, P=0.019). Conclusions:Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.
2.Aprospective study of detection and clinical significance of bone marrow tumor cells in small cell lung cancer
Ying WANG ; Baohua LU ; Yuan GAO ; Yanxia LIU ; Mingming HU ; Nanying CHE ; Haifeng LIN ; Hongxia LI ; Hongmei ZHANG ; Tongmei ZHANG
Chinese Journal of Oncology 2024;46(5):419-427
Objective:To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis.Methods:A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis.Results:The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P<0.001; 77.78% vs 16.84% for bone metastasis, P<0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs<111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant ( P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups ( P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs<111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage ( HR=2.806, 95% CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH ( HR=1.841, 95% CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS ( HR=2.538, 95% CI:1.169-5.512, P=0.019). Conclusions:Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.
3.Clinicopathological Characteristics and Prognosis Analysis of 39 Patients with Pulmonary Sarcomatoid Carcinoma
CHEN CEN ; REN ZHANLIANG ; DONG YUJIE ; WANG YING ; GAO YUAN ; LI HONGXIA ; ZHANG TONGMEI
Chinese Journal of Lung Cancer 2024;27(7):514-522
Background and objective Pulmonary sarcomatoid carcinoma(PSC)is a rare subtype of non-small cell lung cancer(NSCLC),which is featured by low incidence,high malignancy rate,robust aggressive behavior and inferior prognosis.To date,there is no standardized treatment.The aim of this study is to better understand and accumulate more clini-cal experience of the disease by summarizing the clinicopathological features,diagnosis methods,therapeutic regimen and prognostic factors of PSC.Methods A total of 39 patients with PSC who diagnosed and received treatment in Beijing Chest Hospital from December 2013 to December 2023 were retrospectively recruited,and information including demographic char-acteristics,clinicopathological features,tumor-node-metastasis(TNM)stage,diagnosis method and therapeutic regimen were carefully collected.Meanwhile,follow-up was conducted.Kaplan-Meier method was used to analyze the prognostic factors of the disease.Results The PSC patients in this study ranged in age from 45 to 76 years old,including 35 males and 4 females.There were no specific clinical manifestations of PSC at initial diagnosis.Among the 39 patients,20 underwent surgical resec-tion and 19 received palliative chemoradiation or symptomatic supportive treatment.The 1-year and 5-year survival rates were 61.90%and 35.20%respectively.Univariate analysis indicated that family history of carcinoma,primary tumor site,TNM stage,lymph node metastasis,distant metastasis,whether or not received surgical resection,surgical method,treatment regimens,tumor tissue programmed cell death ligand 1(PD-L1)expression>1%and mesenchymal-epithelial transition factor(MET)pathway abnormalities were correlated with the overall survival(OS)of patients(P<0.05).In the subsequent multivariate analysis,lymph node metastasis emerged as the only independent prognosticator in predicting inferior OS(P=0.037).Conclu-sion PSC is rarely seen in clinical practice and commonly occurs in elder men with smoking history.Tumor tissue PD-L1 ex-pression>1%and MET abnormalities may predict inferior prognosis of PSC and lymph node metastasis was determined as the independent prognosticator of PSC.Surgical resection along with adjuvant medical treatment is the cornerstone for early and locally advanced patients,and the clinical utility of molecular targeting therapy and immunotherapy in PSC needs to be further investigated.
4. Mechanism of grape seed proanthocyanidin oligomers inhibiting polarization of type Al astrocytes
Qing WANG ; Zhi-Chao YANG ; Yi-Wei DONG ; Shu-Wen YUAN ; Yan-Qing LI ; Li-Juan SONG ; Cun-Gen MA ; Jian-Jun HUANG ; Cun-Gen MA
Chinese Pharmacological Bulletin 2023;39(1):77-83
Aim To explore the mechanism of grape seed proanthocyanidins (GSPs) targeting astrocytes (AS), so as to regulate the phenotype and function of AS and maximize their neuroprotective effect. Methods The effects of GSPs on the phenotype, secretion of pro-inflammatory factors and neurotrophic factors of Al AS induced by TNF-α, IL-1α and Clq were investigated by RT-PCR, Elisa and Western blot in vitro. And JNK phosphorylation was determined using Western blot. Results GSPs significantly reduced the expression of C3d and Clq of Al AS markers and inhibited the phosphorylation of JNK. Moreover, compared with the model group, GSPs could significantly inhibit the release of pro-inflammatory cytokines IL-6, IL-1 α, IL-17 and H
5.Downward referral willingness of rehabilitation patients in an urban medical group and its influencing factors
Jingyu LI ; Yun LÜ ; Yu XIN ; Shuo LI ; Sijing PENG ; Zhongxiang MI
Chinese Journal of Rehabilitation Theory and Practice 2023;29(12):1481-1488
ObjectiveTo investigate the willingness of rehabilitation patients within an urban medical group to accept downward referrals and analyze the influencing factors. MethodsFrom June to October, 2023, a survey was conducted using a simple random sampling method among neurological and orthopedic rehabilitation patients in hospitals within a specific urban medical group. The 2013 version of the Andersen Model was employed to construct a theoretical framework for the willingness of rehabilitation patients to accept downward referrals and influencing factors. Within this framework, a questionnaire was designed using a 5-point Likert scale, comprising three sections including personal characteristics, environmental features and healthcare service utilization choices, totaling 23 questions. A preliminary survey was conducted, and the questionnaire had underwent reliability and validity testing. ResultsA total of 350 questionnaires were collected, with 314 valid questionnaires. The willingness of rehabilitation patients to accept downward referrals was found to be associated with age, rehabilitation specialties, rehabilitation phases, previous experiences with downward referrals, awareness of and perceptions regarding bidirectional referral policies, and understanding and opinions about the urban medical group (χ2 > 7.755, P < 0.05). The primary influencing factors were rehabilitation specialties, rehabilitation phases, previous experiences with downward referrals and perceptions of the necessity of bidirectional referral policies (P < 0.05). ConclusionRehabilitation specialties, rehabilitation phases, previous experiences with downward referrals and perceptions of the necessity of bidirectional referral policies are the primary factors that influenced the willingness of rehabilitation patients to accept downward referrals. We should formulate targeted and focused improvement measures based on the specific circumstances and key influencing factors of rehabilitation patients within the urban medical group regarding their willingness to accept downward referrals. Continuously enhancing the proportion of patients willingness to accept downward referrals is essential for the effective implementation of bidirectional referral for rehabilitation patients.
6.EGFR Mutation Status and PD-L1 Expression in Patients ≤40 Years Old with NSCLC
Mingming HU ; Zichen LIU ; Hongmei ZHANG ; Baohua LU ; Jie LI ; Qunhui WANG ; Fanbin HU ; Haifeng LIN ; Baolan LI ; Tongmei ZHANG
Cancer Research on Prevention and Treatment 2022;49(7):687-691
Objective To retrospectively analyze the clinical data of 47 young NSCLC patients mutation style of EGFR and PD-L1 expression in tumor cells, to understand their clinicopathological and molecular characteristics. Methods We enrolled 47 young (≤40 years old) patients confirmed as NSCLC who underwent surgical resection, and 94 old patients (≥60 years old) were matched as 1:2 by R language. EGFR mutation status was detected by ARMS-PCR, and the expression of PD-L1 was detected by immunohistochemistry. Results The median age of 47 young patients with NSCLC was 37 years old. The disease was more common in women and the majority type was adenocarcinoma. In youth group, the 19del and 20ins were more frequent, but the exon 21 L858R point mutation proportion was higher in elder group. The expression of PD-L1 was significantly increased in the solid predominant histological subtype. The PD-L1 expression in 19del patients was higher than that in the patients with L858R mutation in youth group. Conclusion The majority of young NSCLC patients are female, nonsmokers and suffered from adenocarcinoma cancer. The proportion of EGFR alteration in 19del and 20ins in youth group is higher than that in elder group. The positive rate of PD-L1 expression in solid predominant histological subtype is higher than that with other subtypes. The expression of PD-L1 in young patients with EGFR 19del is higher than that with L858R.
7.Application Progress of Immune Checkpoint Inhibitors in Oncogene-driven Advanced Non-small Cell Lung Cancer.
Chinese Journal of Lung Cancer 2021;24(3):188-195
With the development of precise medicine, targeted therapy has greatly improved the survival and prognosis of patients in advanced non-small cell lung cancer (NSCLC) with oncogenic drivers. However, no matter which kinds of targeted therapy are inevitable to develop therapeutic resistance, treatment options upon exhaustion of targeted therapies are limited. Immune checkpoint inhibitors (ICIs) can bring long-term survival to some patients with advanced NSCLC because of its unique long tailing effect. More and more studies have shown that ICIs can also benefit NSCLC patients with oncogenic drivers. However, the timing of ICIs intervention, the therapeutic regimen and the predictive biomarkers are actually debated, underscoring the need to explore the potential interest of ICIs in these populations.
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8.Expression of CD44 in Tumor Tissue and Serum of Small Cell Lung Cancer and Its Clinical Prognostic Significance.
Ying WANG ; Yi GUO ; Haifeng LIN ; Lina ZHANG ; Hongmei ZHANG ; Qunhui WANG ; Fanbin HU ; Jie LI ; Baolan LI ; Tongmei ZHANG
Chinese Journal of Lung Cancer 2021;24(8):583-590
BACKGROUND:
Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid growth, early metastasis and acquired therapeutic resistance, and the prognosis is extremely poor. Studies have proved that the stem cell marker CD44 is correlated with tumor recurrence and treatment resistance, however, there are limited reports yet concerning on the CD44 expression and its clinical prognostic significance in SCLC patients. The purpose of this study is to investigate the expression of CD44 in tumor tissues as well as serum of SCLC patients and explore its correlation with the clinical characteristics, therapeutic effect and prognosis.
METHODS:
The tumor tissues and serum samples of 47 newly diagnosed SCLC patients were collected. Immunohistochemistry and enzyme-linked immunosorbent assay were applied to detect CD44. The relationship between CD44 level and the clinical characteristics as well as prognosis of the patients was analyzed.
RESULTS:
The stem cell marker CD44 was detectable both in serum sample and tumor tissue of SCLC patients. The positive rate of CD44 in tumor tissue was significantly higher in patients with performance status (PS) 2 than that of patients with PS 0-1 (85.71% vs 30%, P=0.017). Patients were divided in to different groups according to the treatment efficacy. The CD44 immunohistochemical score and serum level in the disease progression group were significantly higher than those in the disease control group, and the differences were statistically significant (P=0.006, P=0.034), Univariate analysis depicted that the progression-free survival (PFS) of CD44 positive patients was significantly shorter than that of CD44 negative patients (5.23 mon vs 9.03 mon, P=0.036).
CONCLUSIONS
The positive expression of CD44 in tumor tissues of pre-treatment SCLC patients is correlated with poor PFS. The clinical significance of CD44 is worthy to be further studied.
9.A Single Center Analysis of Advanced Non-small Cell Lung Cancer Patients Treated with Immunotherapy in Real-world Practice.
Yanxia LIU ; Tongmei ZHANG ; Yuan GAO ; Yang QU ; Baohua LU ; Hongmei ZHANG ; Qunhui WANG ; Jie LI ; Fanbin HU ; Baolan LI
Chinese Journal of Lung Cancer 2019;22(11):687-695
BACKGROUND:
In recent years, a number of clinical trials have shown that immunocheckpoint inhibitors (ICI) have brought survival benefits to patients with advanced non-small cell lung cancer (NSCLC), however, such clinical trials comprise cohorts selected based on strict and complex entry and exclusion criteria, and the results cannot fully reflect the real world situation. The purpose of this study was to investigate the clinical efficacy and safety of immunotherapy in the real world, as well as possible prognostic factors.
METHODS:
Patients with advanced NSCLC receiving immunotherapy in Beijing Chest Hospital from January 2017 to July 2019 were retrospectively collected, and the following information were collected: curative effect, progression-free surival (PFS) and adverse reactions. The occurrence of adverse reactions and clinical curative effect and prognosis factors that may be relevant were explored.
RESULTS:
34 patients were enrolled in this study, median PFS was 5.66 months (95%CI: 4.48-6.84), grade 1-2 and 3-4 incidence of adverse events was 61.71% (22/34) and 14.71% (5/34), there were 3 patients (8.82%) experienced fatal immune related adverse events (irAE), 2 cases were immune associated pneumonia, 1 case was immune related myocarditis. Univariate analysis showed that tumor-node-metastasis (TNM) stage and metastatic site were correlated with median PFS (P<0.05), and multivariate analysis showed that patients with extrapulmonary metastasis (OR=6.42, P=0.029) and pleural metastasis (OR=14.14, P=0.006) had shorter median PFS.
CONCLUSIONS
In the real world, immunotherapy has good efficacy in patients with advanced NSCLC, but the incidence of severe irAE is also higher. Distant metastasis and pleural metastasis are poor prognostic factors for advanced NSCLC patients receiving immunotherapy.
10.Diagnostic value of MSCT postprocessing techniques in the diagnosis of spontaneous isolated dissection of superior mesenteric artery
Tongmei JIN ; Yangjuan GAO ; Lianliang ZHANG ; Dapeng LI ; Shanshan LU
Journal of Practical Radiology 2017;33(12):1840-1843
Objective To evaluate the diagnostic value of MSCT angiography and postprocessing techniques in the diagnosis of spontaneous isolated dissection of superior mesenteric artery(SIDSMA).Methods Twenty patients with SIDSMA performed with MSCT angiography were analyzed retrospectively.The volume data were transferred to the workstation for image postprocessing and performed with various postprocessing techniques such as multi-planar reconstruction(MPR),curved planar reconstruction(CPR), volume rendering(VR)and maximum intensity projection(MIP).Results The dissection length of SIDSMA was positively correlated with visual analogue scale(VAS).MPR,CPR and VR clearly showed the intimal flap,true and false lumen.MPR and CPR displayed more entries of dissection than VR.VR demonstrated the extension of the involved aorta and its branches,but cannot satisfactorily demonstrate the entry of SIDSMA.Conclusion MSCT angiography is of positive applicable value to the diagnosis of SIDSMA.MPR, CPR and VR may be optimal choice as post processing techniques for diagnosis of SIDSMA.

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