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Lung cancer is a leading cause of cancer deaths and imposes an enormous economic burden on patients. It is important to develop an accurate risk assessment model to determine the appropriate treatment for patients after an initial lung cancer diagnosis. The Cox proportional hazards model is mainly employed in survival analysis. However, real-world medical data are usually incomplete, posing a great challenge to the application of this model. Commonly used imputation methods cannot achieve sufficient accuracy when data are missing, so we investigated novel methods for the development of clinical prediction models. In this article, we present a novel model for survival prediction in missing scenarios. We collected data from 5,240 patients diagnosed with lung cancer at the Weihai Municipal Hospital, China. Then, we applied a joint model that combined a BN and a Cox model to predict mortality risk in individual patients with lung cancer. The established prognostic model achieved good predictive performance in discrimination and calibration. We showed that combining the BN with the Cox proportional hazards model is highly beneficial and provides a more efficient tool for risk prediction.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Teorema de Bayes , Pronóstico , Calibración , China/epidemiologíaRESUMEN
BACKGROUND: This study was designed to investigate the clinical application, efficacy, and safety of immune checkpoint inhibitors (ICIs) in the treatment of lung cancer in the real world. METHODS: A retrospective, observational analysis was conducted on patients treated with ICIs in four tertiary hospitals in the region from January 2015 to March 2021, to evaluate the clinical efficacy of ICIs single-agent or combined chemotherapy and anti-vascular drugs in the first-line or second-line treatment of patients with lung cancer. RESULTS: Three hundred and fifteen patients were enrolled in this study. In patients with stage III-IV adenocarcinoma and Squamous cell carcinoma, the objective response rate (ORR) and disease control rate (DCR) were 35.5% (87/245) and 93.5% (229/245), respectively, the median progression-free survival (PFS) was 10.8 months, and the median overall survival (OS) was not reached. A total of 132 patients received ICIs as the first-line treatment, the median treatment cycle was 8 cycles (2-20 cycles), the short-term efficacy ORR was 38.6%, DCR was 93.9%, and the median PFS was 11.4 months. One hundred thirteen patients received ICIs treatment as second-line treatment, the median treatment cycle was five cycles (2-10 cycles), the short-term efficacy ORR was 31.9%, DCR was 92.9%, and the median PFS was 10.0 months. There were no statistically significant differences in ORR, DCR, or median PFS with ICIs as the first-line treatment compared with the second-line treatment(P > 0.05). The results of subgroup analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), epidermal growth factor receptor (EGFR) mutation status, pathological type and number of treatment lines were not correlated with median PFS(P > 0.05). However, there were statistically significant differences in programmed death-ligand 1(PD-L1) expression, corticosteroid interference, and antibiotic (Abx) treatment among all groups (P < 0.05). In terms of safety, the overall incidence of adverse reactions in 315 patients was 62.5%, and the incidence of immune-related adverse events (irAEs) was 13.7%. Grade 1-2 and 3-4 incidence of adverse events were 34.9 and 27.65%, respectively. There were four patients who experienced fatal irAEs, two cases were liver damage leading to liver failure, one case was immune related pneumonia, and one case was immune related myocarditis. CONCLUSION: In the real world, ICIs has a good effect on patients with lung cancer and significantly improves ORR and PFS.
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Adenocarcinoma , Antineoplásicos Inmunológicos , Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Adenocarcinoma/tratamiento farmacológico , Antineoplásicos Inmunológicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/complicaciones , Análisis de Datos , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Estudios RetrospectivosRESUMEN
Importance: Despite the recommendations of lung cancer screening guidelines and the evidence supporting the effectiveness of population-based lung screening, a common barrier to effective lung cancer screening is that the participation rates of low-dose computed tomography (LDCT) screening among individuals with the highest risk are not large. There are limited data from clinical practice regarding whether opportunistic LDCT screening is associated with reduced lung-cancer mortality. Objective: To evaluate whether opportunistic LDCT screening is associated with improved prognosis among adults with lung cancer in mainland China. Design, Setting, and Participants: This cohort study included patients diagnosed with lung cancer at Weihai Municipal Hospital Healthcare Group, Weihai City, China, from 2016 to 2021. Data were analyzed from January 2022 to February 2023. Exposures: Data collected included demographic indicators, tumor characteristics, comorbidities, blood indexes, and treatment information. Patients were classified into screened and nonscreened groups on the basis of whether or not their lung cancer diagnosis occurred through opportunistic screening. Main Outcomes and Measures: Follow-up outcome indicators included lung cancer-specific mortality and all-cause mortality. Propensity score matching (PSM) was adopted to account for potential imbalanced factors between groups. The associations between LDCT screening and outcomes were analyzed using Cox regression models based on the matched data. Propensity score regression adjustment and inverse probability treatment weighting were used for sensitivity analysis. Results: A total of 5234 patients (mean [SD] baseline age, 61.8 [9.8] years; 2518 [48.1%] female) with complete opportunistic screening information were included in the analytical sample, with 2251 patients (42.91%) receiving their lung cancer diagnosis through opportunistic screening. After 1:1 PSM, 2788 patients (1394 in each group) were finally included. The baseline characteristics of the matched patients were balanced between groups. Opportunistic screening with LDCT was associated with a 49% lower risk of lung cancer death (HR, 0.51; 95% CI, 0.42-0.62) and 46% lower risk of all-cause death (HR, 0.54; 95% CI, 0.45-0.64). Conclusions and Relevance: In this cohort study of patients with lung cancer, opportunistic lung cancer screening with LDCT was associated with lower lung cancer mortality and all-cause mortality. These findings suggest that opportunistic screening is an important supplement to population screening to improve prognosis of adults with lung cancer.
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Neoplasias Pulmonares , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/epidemiología , Estudios de Cohortes , Detección Precoz del Cáncer/métodos , Tomografía Computarizada por Rayos X/métodos , PulmónRESUMEN
Coking coal was extracted with tetrahydrofuran solvent using ultrasonic and microwave-assisted method at 50°C and atmospheric pressure. Wettability of raw coal and its residue (residual coal) was tested with capillary penetration method. The raw and residual coals were studied by Fourier transform infrared spectroscopy (FTIR) with curve-fitting analysis. The variation of main surface functional groups of coking coal before and after extraction and its effect on wettability were analyzed. The results were obtained as the following: after extraction with tetrahydrofuran, hydroxyl, ether oxygen, and carbonyl in the coal structure were dissolved, the content of hydrophilic functional groups reduced, and then the hydrophobicity of coal enhanced. At the same time, part of aliphatic hydrocarbon dissolved, the length of aliphatic chains (I 2) decreased from 3.961 of raw coal to 3.636 of residual coal, the length of aliphatic chains became shorter, aliphatic CH2 side-chains decreased and aliphatic CH3 side-chains increased, and hydrophobic functional groups content increased. In the aromatic structure, four hydrogens per ring increased and two, three, and five hydrogens per ring decreased. Reduction of substitution functional groups and aliphatic hydrocarbon decreased with the side-chains breakage produce more active sites, which increases the degree of condensation of the aromatic ring (I 3). The combined action of the decrease of the hydrophilic functional groups and the increase of the hydrophobic functional groups made the wettability of the coking coal become weak.
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Esophageal squamous cell carcinoma (ESCC) accounts for almost 90% of esophageal cancer cases and is the sixth most common cause of cancer-associated mortality worldwide. Cisplatin is the standard therapeutic reagent for ESCC; however, chemoresistance frequently occurs after a few weeks, which leads to ESCC recurrence. Aberrant expression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1) has been reported to activate multiple growth-regulatory pathways, induce antiapoptotic abilities in numerous types of cancer cells and promote chemoresistance. However, to the best of our knowledge, the role of BMI1 in cisplatin-resistant ESCC, and the interaction between BMI1 and its homologue melanoma nuclear protein 18 (Mel18) remain unknown. The present study identified that knockdown of BMI1 promoted cytotoxic effects of cisplatin, and co-inhibition of Mel18 and BMI1 enhanced cisplatin-induced apoptosis and cytotoxicity. Inhibition of BMI1 and Mel18 also suppressed the expression of c-Myc. Furthermore, this combined inhibition sensitized esophageal xenograft tumors to cisplatin to a greater extent compared with BMI1 inhibition alone. In summary, the current study demonstrated that inhibition of BMI1 and Mel18 could increase the sensitivity of esophageal cancer cells to cisplatin via inhibition of c-Myc. Therefore, combined targeting of BMI1 and Mel18 may serve as a promising therapeutic strategy for sensitizing ESCC to chemotherapy.
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BACKGROUND: Leukemoid reaction (LR) is defined as a reactive leucocytosis with WBC counts exceeding 50,000/mm3, and a significant increase in early neutrophil precursors. LR may be a paraneoplastic manifestation of various malignant tumors. Tumor-related LR is a kind of neoplastic syndrome, unrelated to an infection or other diseases. CASE PRESENTATION: A 74-year-old male visited a local doctor with a 20-day history of progressive dysphagia. The complete blood count revealed leucocytosis. Bone marrow aspirates and a biopsy confirmed LR and excluded chronic myelogenous leukemia. Following radical esophagectomy for an adenocarcinoma the WBC counts successively decreased to 10,450/mm3 and 8670/mm3 within 1 week and 1 month, respectively. CONCLUSION: We report a rare case of esophageal adenocarcinoma complicated with excessive leucocytosis caused by paraneoplastic LR; we also present a review of literature and an investigation of the clinical features. To our knowledge, this is the first report of LR associated with esophageal adenocarcinoma.
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Adenocarcinoma/sangre , Neoplasias Esofágicas/sangre , Reacción Leucemoide/etiología , Adenocarcinoma/complicaciones , Adenocarcinoma/terapia , Anciano , Médula Ósea/patología , Quimioterapia Adyuvante/métodos , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/terapia , Esofagectomía/métodos , Humanos , Reacción Leucemoide/diagnóstico , Recuento de Leucocitos , Masculino , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Organizing pneumonia (OP) is a rare disease that is often easily misdiagnosed as a malignancy. The diagnosis of OP can prove quite challenging. Patients typically receive treatment with high-dose corticosteroids. Relapse is common if corticosteroid treatment is reduced or stopped. However, given that long-term corticosteroid treatment often results in significant side-effects, the aim of this study was to discuss the diagnosis and surgical treatment of OP. MATERIAL AND METHODS: The medical records of 24 patients with pathologically diagnosed OP between October 2007 and January 2019 were retrospectively reviewed. All patients underwent thoracic computed tomography (CT) and transbronchial biopsy or CT-guided percutaneous needle aspiration. We analysed the clinical manifestations, radiological findings, diagnostic methods, treatment, and follow-up outcomes of all patients. RESULTS: In total, 24 patients with OP were identified. The study included 17 (70.8%) men and 7 (29.2%) women, and the mean age was 61.25 ± 11.33 years (range: 31-82). The most common symptom was cough (n = 16; 66.6%), and the most common radiological finding was consolidation (n = 13; 54.2%) on thoracic CT. The diagnosis of OP was made by transbronchial biopsy in 11 patients (45.8%), and percutaneous needle aspiration biopsy in 13 (54.2%). We performed 11 wedge resections, 9 segmentectomy, and 4 lobectomies. Twenty patients underwent video-assisted thoracoscopic surgery (VATS), and 4 underwent thoracotomy. Complete lesion resection was obtained in all patients, and all patients were discharged from the hospital between 5 and 11 days after surgery. The mean follow-up period was 59.1 ± 34.5 (range: 2-134) months. Residual lesions or local or distant recurrence were not observed. CONCLUSIONS: OP is a rare disease, and the exact aetiology remains unclear. Preoperative diagnosis is difficult to achieve despite the use of transbronchial biopsy or CT-guided percutaneous needle aspiration. Complete surgical resection represents an effective method for the treatment of OP.
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Neumonía en Organización Criptogénica/cirugía , Cirugía Torácica Asistida por Video/métodos , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Neumonía en Organización Criptogénica/diagnóstico , Errores Diagnósticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Raras , Recurrencia , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
Previous studies found that glucocorticoids were closely associated with the oncogenesis and development of numerous types of tumors. The aim of the present study was to investigate the effect of dexamethasone on the growth and angiogenesis of Lewis lung cancer cells in mice who received palliative surgery. Lewis lung carcinoma cells were inoculated subcutaneously into the right axilla of C57BL/6 mice. When tumor diameter reached 0.5 cm, 2 weeks later, palliative surgery was performed, and the mice were randomly divided into 3 groups with 6 animals in each group (control group, cisplatin group and dexamethasone group). From the first postoperative day, all the mice were administered with saline, cisplatin or dexamethasone for 10 days, and changes in xenograft tumor volumes were monitored. Cisplatin and dexamethasone were dissolved in normal saline (0.9%). All mice were sacrificed on postoperative day 11, and the whole body and the local tumors were weighed immediately. The expression levels of hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen and the microvessel density (MVD) in the tumor mass, were measured by immunohistochemistry, western blotting and quantitative polymerase chain reaction. In the present study, tumor growth was inhibited in the cisplatin group and dexamethasone group, and the weights of tumors were significantly decreased in the cisplatin group and dexamethasone group compared with the control group (P<0.001). The expression levels of HIF-1α and VEGF and the MVD were significantly lower in the cisplatin group and dexamethasone group than in the control group (P<0.01). In conclusion, dexamethasone can inhibit the growth and angiogenesis of residual Lewis lung carcinoma subsequent to palliative surgery partially through downregulation of HIF-1α and VEGF signaling pathways.
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The Polycomb group genes are a general class of regulators that are responsible for maintaining homeotic gene expression throughout cell division. Polycomb group expression plays an important role in oncogenesis of several types of human cancer. Melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 are key Polycomb group proteins. Studies have shown that melanoma nuclear protein 18 is a potential tumor suppression, and B-cell-specific Moloney leukemia virus insert site 1 is overexpressed in several human malignancies. However, the roles of melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 in esophageal squamous cell carcinoma are still unclear. In this study, we analyzed the expression levels of melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 in 89 esophageal cancer tissues and paired normal mucosal tissues using immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction analyses. We found that the expression of melanoma nuclear protein 18 in the carcinoma tissues was significantly lower than that in the noncancerous mucosal tissues (P < .05), and B-cell-specific Moloney leukemia virus insert site 1 expression in the carcinoma tissues was significantly higher than that in the noncancerous mucosal tissues (P < .05). In addition, the expression of melanoma nuclear protein 18 was correlated with clinical stage, depth of invasion, and lymph node metastasis (P < .05) but was not correlated with gender, age, degree of differentiation, or disease-free survival (P > .05). B-cell-specific Moloney leukemia virus insert site 1 expression was strongly correlated with the degree of differentiation, clinical stage, and lymph node metastasis (P <.05) but was not correlated with the gender, age, depth of invasion or disease-free survival (P > .05). Moreover, there was a negative correlation between melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 expressions in esophageal squamous cell carcinoma (P < .05). Our study suggests that melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 may play a crucial role in esophageal squamous cell carcinoma. Melanoma nuclear protein 18 or B-cell-specific Moloney leukemia virus insert site 1 may be a potential biomarker for diagnosis and prognosis of esophageal squamous cell carcinoma.
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High expression of B-cell specific Moloney leukemia virus insert site 1 (Bmi-1) and peptidyl arginine deiminase IV (PADI4) is associated with esophageal carcinoma. However, few studies have investigated the association between the Bmi-1 and PADI4 genes. The aim of the present study was to evaluate the expression of Bmi-1 and PADI4 and identify the association between the Bmi-1 and PADI4 genes in esophageal squamous cell carcinoma (ESCC) tissues. Bmi-1 and PADI4 gene expression levels were measured using immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction in ESCC tissues from 86 patients who had not received pre-operative chemoradiation. The results revealed that the Bmi-1 and PADI4 genes had increased expression in carcinoma tissues compared with pericarcinous tissue (P<0.05). Bmi-1 gene expression was revealed to be associated with differentiation degree, clinical stage and lymph node metastasis (P<0.05), but had no association with gender, age or depth of invasion (P>0.05). The expression of PADI4 was associated with clinical stage, depth of invasion and lymph node metastasis (P<0.05), but was not associated with gender, age or differentiation degree (P>0.05). In addition, there was a positive association between Bmi-1 and PADI4 gene expression in ESCC (P<0.05). These results indicated that Bmi-1 and PADI4 positively regulate carcinogenesis and progression of ESCC.
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BACKGROUND: Angiolipoma is a rare benign neoplasm composed of mature fatty tissue and multiple small abnormal blood vessels. Infiltrating mediastinal angiolipoma is an extremely rare tumor associated with delayed diagnosis. CASE PRESENTATION: A 42-year-old woman was presented with 3-month history of mild chest tightness. Imaging of the chest showed a large mass with fat densities in the middle superior mediastinum. A presumptive diagnosis was a tumor of liposarcoma. The patient was scheduled for a thoracotomy. After the excision, the symptoms were relieved and histological study revealed that the tumor was an angiolipoma. The patient recovered very well and was discharged 7 days after the surgery. After 7 months of follow-up the patient was clinically well and asymptomatic. CONCLUSIONS: We described a giant infiltrating mediastinal angiolipoma and its removal, and discussed the tumor characteristics and prognosis. Although extremely rare, infiltrating angiolipoma should be considered in the differential diagnosis of mediastinum lesions. The prognosis after surgical management of our patient is favorable.
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Angiolipoma/patología , Angiolipoma/cirugía , Neoplasias del Mediastino/patología , Neoplasias del Mediastino/cirugía , Adulto , Femenino , Humanos , Carga TumoralRESUMEN
Bronchogenic cyst most commonly occurs in the mediastinum, followed by the lung. We admitted a 59-year female patient with bronchogenic cyst being uniquely located on the right chest wall of the parietal pleura. Preoperative CT scan showed a local low-density lesion on the right chest wall. The lesion was removed by the thoracoscopic surgery. During the surgical resection, the lesion was observed to be located on the right chest wall. The lesion was surrounded by adipose tissue and covered with entire parietal pleura, which looks like lipoma. Pathological examination demonstrated that the lesion was bronchogenic cyst. In addition, previously reported cases of bronchogenic cyst were reviewed, and the relevant clinical knowledge was discussed.