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This report details two cases of right upper-lobe lung cancer, of patients aged 62 and 56 years, requiring complex bronchoplasty and thoracoscopic surgeries. In both cases, owing to intraoperative complications, extended thoracotomies were performed to gain access to the right main pulmonary artery. The postoperative courses were uneventful, implying that this approach was safe. Uncomplicated postoperative recoveries underscore the need for adaptable surgical techniques, especially when traditional positioning fails. It emphasizes extending thoracotomy incisions for safer hilar structure access, offering insights for handling similar complex surgeries where standard methods falter.
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Background: In the quantitative assessment of pulmonary blood flow, two different processing algorithms [cross-correlation calculation processing (CCC-pro) and reference frame subtraction processing (RFS-pro)] within dynamic imaging systems have been reported to exhibit high correlations with conventional measurement methods. However, reports still need to evaluate these two processing algorithms regarding the different aspects of pulmonary blood flow. This study aimed to analyze the differences in pulmonary circulation. Methods: We conducted a cross-sectional study to evaluate patients with lung cancer who underwent radical surgery, simultaneous dynamic chest radiography (DCR), and pulmonary perfusion scintigraphy (PPS). We assessed the correlation between PPS and two algorithms (CCC-pro and RFS-pro) regarding calculated blood flow ratio (BFR) using Pearson's correlation and linear regression analysis. Additionally, we evaluated consistency using the Bland-Altman analysis. We compared the pulmonary blood flow distributions across six-division lung fields and evaluated each method's blood flow images and histograms of pixel values. Results: From May 2018 to December 2020, we consecutively enrolled 46 patients with lung cancer who met the inclusion criteria (40 male patients, with a mean age of 72.91 years). In these patients, CCC-pro and RFS-pro were correlated (R=0.718, P<0.01); however, CCC-pro was more strongly correlated with PPS than RFS-pro (R=0.859, P<0.01 vs. R=0.549, P<0.01). The Bland-Altman analysis showed high agreement, although systematic errors were observed in relationships other than RFS-pro to PPS. CCC-pro and RFS-pro showed similar blood flow distributions in the upper and lower lung fields, with RFS-pro being dominant in the middle. RFS-pro showed higher pixel values in the hilar region and a histogram shape similar to PPS; however, posture affected the right upper lung field gradient. RFS-pro showed no difference in the BFR when the pulmonary artery region was symmetric; however, potential inaccuracies existed when it overlapped with the cardiovascular shadow. Conclusions: The CCC-pro algorithm was useful for quantifying BFRs, whereas the RFS-pro algorithm accurately evaluated blood flow distribution in lung fields. Further algorithm development is required to enable versatile pulmonary blood flow analysis.
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Introduction Postoperative bile leakage (POBL) has emerged as a complication following hepatectomy. POBL is associated with an elevated risk of liver failure and surgical death. This study aimed to examine risk factors for POBL in primary hepatocellular carcinoma (HCC) patients. Methods A total of 296 patients who had surgical resection for a preoperative diagnosis of primary HCC from January 2013 to December 2022 at Ehime Prefectural Central Hospital were included in this study. The patients were categorized into two groups based on the presence of POBL. The preoperative, operative, and histopathological findings were analyzed between the two groups. Risk factors were determined using multivariable analysis. Results Regarding preoperative findings, statistically significant differences were observed in white blood cell count, platelet count, C-reactive protein (CRP) level, and CRP-to-Albumin ratio (CAR) between the two groups (p = 0.023, p = 0.025, p = 0.011, and p = 0.012, respectively). As for intraoperative variables, only operation time (p = 0.017) was statistically correlated with the risk of POBL. Regarding pathological variables, there were no statistically significant differences between the two groups. The optimal cut-off value of CAR, as determined by ROC curve analysis, was 0.053. This value had a sensitivity of 80.0% and a specificity of 72.8%. Multivariate logistic regression analysis indicated that CAR ≥ 0.053 (p = 0.030) and operation time ≥ 308 min (p = 0.023) were independent potential markers for POBL after hepatectomy. Conclusion A high CAR level can be an effective predictor for POBL following hepatectomy.
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There have rarely been reports on the neoplastic transformation in other organs during immunotherapy for lung cancer. We report the case of a 71-year-old man who was diagnosed with advanced pulmonary adenocarcinoma and a thyroid tumor. The patient responded to chemoradiotherapy but developed a recurrence of pulmonary metastasis. Therefore, nivolumab was started, and a complete response for pulmonary metastasis was achieved. After 32 nivolumab cycles, he experienced neck pain, and the thyroid tumor grew rapidly. Histological examination revealed anaplastic thyroid carcinoma. Although rare, immunotherapy for lung cancer has the potential to induce neoplastic transformation in other organs.
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BACKGROUND AND AIM: Rapidly aging societies have become a major issue worldwide including Japan. This study aimed to elucidate relative changes in the characteristics of inpatients in Japan related to this issue. METHODS: A total of 23 835 Japanese inpatients treated from 2010 to 2021 were enrolled (2010-2013, period I; 2014-2017, period II; 2018-2021, period III). Changes in clinical features were retrospectively analyzed based on ICD-10 diagnosis data. RESULTS: The percentage of patients aged over 75 years increased over time (period I, 38.0%; II, 39.5%, III, 41.4%). Emergency admissions comprised 27.5% of all in period I, which increased to 43.2% in period II and again to 44.5% in period III (P < 0.001). In period I, gastrointestinal disease, liver disease, pancreatic-biliary disease, and other disease types were noted in 47.4%, 29.5%, 19.2%, and 3.9%, respectively, while those values were 44.0%, 18.0%, 33.9%, and 4.1%, respectively, in period III (P < 0.001). The frequency of liver disease decreased by approximately 0.6-fold from periods I to III, while that of biliary-pancreatic disease increased by approximately 1.8-fold during that time. Both percentage and actual numbers of patients with biliary-pancreatic disease increased during the examined periods. Analysis of changes in the proportion of organs affected by malignancy during periods I, II, and III showed a marked increase in cases of biliary-pancreatic malignancy (11.6%, 19.5%, 26.6%, respectively) (P < 0.001). CONCLUSION: In association with the rapidly aging Japanese society, there has been an increasing frequency of biliary-pancreatic disease cases requiring hospitalization for treatment in the west Japan region of Shikoku.
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Gastroenterologia , Pacientes Internados , Humanos , Japão/epidemiologia , Idoso , Estudos Retrospectivos , Masculino , Pacientes Internados/estatística & dados numéricos , Feminino , Gastroenterologia/estatística & dados numéricos , Gastroenterologia/tendências , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Envelhecimento , Hepatopatias/epidemiologia , Hepatopatias/terapia , Hepatopatias/diagnóstico , Doenças Biliares/epidemiologia , Doenças Biliares/terapia , Gastroenteropatias/epidemiologia , Gastroenteropatias/terapia , Gastroenteropatias/diagnóstico , Hospitalização/estatística & dados numéricos , Fatores de Tempo , Fatores Etários , Adulto , Pancreatopatias/epidemiologia , Pancreatopatias/terapiaRESUMO
BACKGROUND: Heartbeat-based cross-sectional area (CSA) changes in the right main pulmonary artery (MPA), which reflects its distensibility associated with pulmonary hypertension, can be measured using dynamic ventilation computed tomography (DVCT) in patients with and without chronic obstructive pulmonary disease (COPD) during respiratory dynamics. We investigated the relationship between MPA distensibility (MPAD) and respiratory function and how heartbeat-based CSA is related to spirometry, mean lung density (MLD), and patient characteristics. METHODS: We retrospectively analyzed DVCT performed preoperatively in 37 patients (20 female and 17 males) with lung cancer aged 70.6 ± 7.9 years (mean ± standard deviation), 18 with COPD and 19 without. MPA-CSA was separated into respiratory and heartbeat waves by discrete Fourier transformation. For the cardiac pulse-derived waves, CSA change (CSAC) and CSA change ratio (CSACR) were calculated separately during inhalation and exhalation. Spearman rank correlation was computed. RESULT: In the group without COPD as well as all cases, CSACR exhalation was inversely correlated with percent residual lung volume (%RV) and RV/total lung capacity (r = -0.68, p = 0.003 and r = -0.58, p = 0.014). In contrast, in the group with COPD, CSAC inhalation was correlated with MLDmax and MLD change rate (MLDmax/MLDmin) (r = 0.54, p = 0.020 and r = 0.64, p = 0.004) as well as CSAC exhalation and CSACR exhalation. CONCLUSION: In patients with insufficient exhalation, right MPAD during exhalation was decreased. Also, in COPD patients with insufficient exhalation, right MPAD was reduced during inhalation as well as exhalation, which implied that exhalation impairment is a contributing factor to pulmonary hypertension complicated with COPD. RELEVANCE STATEMENT: Assessment of MPAD in different respiratory phases on DVCT has the potential to be utilized as a non-invasive assessment for pulmonary hypertension due to lung disease and/or hypoxia and elucidation of its pathogenesis. KEY POINTS: ⢠There are no previous studies analyzing all respiratory phases of right main pulmonary artery distensibility (MPAD). ⢠Patients with exhalation impairment decreased their right MPAD. ⢠Analysis of MPAD on dynamic ventilation computed tomography contributes to understanding the pathogenesis of pulmonary hypertension due to lung disease and/or hypoxia in patients with expiratory impairment.
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Hipertensão Pulmonar , Pneumopatias , Doença Pulmonar Obstrutiva Crônica , Masculino , Humanos , Feminino , Artéria Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/complicações , Estudos Retrospectivos , Pulmão/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/complicações , Tomografia Computadorizada por Raios X/métodos , Hipóxia/complicaçõesRESUMO
BACKGROUND/AIM: Unresectable recurrence after curative treatments for hepatocellular carcinoma (HCC) is a life-limited event. Although the IMbrave050 trial (IM050) showed a favorable reduction in recurrence with adjuvant immune-combination chemotherapy, inclusion criteria of the radiofrequency ablation (RFA) group were lower risk than that of the resection group. This study aimed to elucidate the clinical features of patients treated with RFA, which really need adjuvant-chemotherapy. METHODS: From 2000 to 2022, 528 patients with Child-Pugh A and HCC within the Milan criteria (MC), who met the IM050 criteria for RFA and undergone resection or RFA, were enrolled (71 years, HCV:HBV:HBV/HCV:alcohol:others = 337:44:5:53:89, multi-tumor = 138, RFA:resection = 309:219). Unresectable recurrence was defined as beyond the MC. Risk factors for recurrence beyond the MC were retrospectively evaluated. RESULTS: Multivariate Cox-hazard analysis showed HCV-positive (HR 1.49), AFP-L3 > 10% (HR 1.75), and DCP > 100 mAU/mL (HR1.80) as significant prognostic factors for recurrence beyond the MC (each P < 0.05). Summing of positive factors (1 point for each) was used for scoring (AD-ON score), which showed increased positive rates for micro-hepatic vein invasion (score 0:1:2:3 = 0%:1.1%:6.6%:15.8%), micro-portal vein invasion (0:1:2:3 = 2.0%:12.1%:14.1%:31.6%), and poor differentiation (0:1:2:3 = 6.0%:6.7%:15.3%:15.8%) in the resection group associated with a greater score (each P < 0.01). In patients treated with RFA, those with greater AD-ON scores showed shorter time to recurrence beyond the MC, recurrence-free time, and overall survival (score 0:1:2:3 = no-estimation:97:66:23 months, 35:27:20:12 months, and 91:82:67:52 months, respectively, each P < 0.05). CONCLUSION: HCC patients treated by RFA and with a high AD-ON score (â§2) should be considered for aggressive adjuvant-chemotherapy to prolong the period of recurrence beyond the MC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Recidiva Local de Neoplasia , Ablação por Radiofrequência , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Quimioterapia Adjuvante , Fatores de Risco , Idoso de 80 Anos ou maisRESUMO
OBJECTIVES: Many studies have demonstrated that sarcopenia among lung cancer predicts poor prognosis due to cancer progression. However, the cytokines that link sarcopenia and lung cancer progression remain unidentified. This study aimed to investigate whether lung cancer producing myostatin, which induces skeletal muscle atrophy, leads to sarcopenia and promotes cancer progression in patients with resected lung cancer. METHODS: Tumor tissues were obtained from 148 patients who underwent curative resection for lung cancer. Tumor cells were stained with myostatin and tumor-associated macrophages (TAM) in the tumor microenvironment were stained with CD68. We assessed the association between myostatin expression and the clinicopathological features. RESULTS: High myostatin expression in lung cancer was significantly associated with low skeletal muscle mass. The 5-year overall survival and relapse-free survival were significantly worse among patients with high myostatin expression than those with low expression. A multivariate analysis showed that TAM count was positively correlated with high myostatin expression. CONCLUSION: Sarcopenia may be induced by myostatin secreted by lung cancer cells. Moreover, myostatin may promote TAM migration into the tumor microenvironment, leading to advance lung cancer. As a result, patients with high myostatin expression had poor prognosis.
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Neoplasias Pulmonares , Sarcopenia , Humanos , Neoplasias Pulmonares/patologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Miostatina/metabolismo , Recidiva Local de Neoplasia/patologia , Sarcopenia/complicações , Microambiente TumoralRESUMO
Background: Surgical intervention for lung resection can cause ventilation-perfusion mismatches and affect gas exchange; however, minimally invasive assessment of blood flow is difficult. This study aimed to evaluate changes in pulmonary blood flow after radical lung cancer surgery using a minimally invasive dynamic digital chest radiography system. Methods: We evaluated 64 patients who underwent radical lobectomies. Postoperative changes in pulmonary blood flow, assessed using dynamic chest radiography-based blood flow ratios (BFRs), were compared with the temporal evolution of both functional lung volumes (FLVs) and estimated lung weight (ELW) derived from computed tomography (CT) volumetry. Results: FLVs on the affected side gradually recovered over time from the lowest value observed 3 months after surgery in all procedures. BFRs on the affected side also showed a gradual recovery from the lowest value 1 month after surgery, except for left upper lobectomies (LULs). In LULs, FLVs and ELWs increased proportionally up to 3 months after surgery, with lung volumes continuing to increase thereafter. The recovery of BFRs differed depending on the resected lobe. Conclusions: A relationship between pulmonary blood flow and FLV was observed in the postoperative period. Despite varying compensatory responses depending on the surgical procedure, FLV recovery coincided with increased pulmonary blood flow.
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p16 has been used as a surrogate marker for human papillomavirus (HPV)-related tumours. However, it remains unclear whether p16 is also a potential marker for pulmonary tumours. Herein, we report the case of an 80-year-old woman with a history of papillary squamous cell carcinoma of the uterine cervix, presenting with a left pulmonary tumour. A bronchoscopic biopsy revealed squamous cell carcinoma with a papillary pattern, which did not rule out pulmonary metastasis from the cervix. Immunohistochemical staining revealed that the cervical tumour was positive for p16, whereas the pulmonary tumour was negative and was effectively diagnosed as primary pulmonary carcinoma.
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Programmed cell death-ligand 1 (PD-L1) on tumor cells can be degraded to soluble form (sPD-L1) and enter circulation, however, the clinical significances of sPD-L1 in peripheral blood remains to be elucidated in non-small-cell lung cancer (NSCLC). We monitored plasma sPD-L1 levels during perioperative periods and evaluated PD-L1-positive cells in tumor tissues in patients with operable NSCLC. Then the correlation between preoperative plasma sPD-L1 levels and relapse-free survival (RFS) was analyzed retrospectively. In patients who underwent radical surgery (n = 61), plasma sPD-L1 levels (median; 63.5 pg/mL) significantly increased 1 month after surgery (72.2 pg/mL, P < 0.001). The combined score of PD-L1-positive cells including tumor cells and tumor-associated macrophages (TAMs) was significantly associated with preoperative plasma sPD-L1 levels. In patients with high levels of preoperative plasma sPD-L1, the probability of 5-year RFS was significantly poor for patients with low PD-L1 expression intensity of tumor cells (tcPD-L1) compared with those with high tcPD-L1 (33.3% vs. 87.5%, respectively, P = 0.016; 95% CI, 0.013-0.964). In former group, PD-L1-positive TAMs were markedly infiltrating compared with those from latter group (246.4 vs. 76.6 counts/mm2, respectively, P = 0.003). In NSCLC, plasma sPD-L1 can reflect the accumulation of PD-L1-posotive TAMs, not just PD-L1-positive tumor cells. In patients with high levels of preoperative plasma sPD-L1, the prognoses after surgery depends on which PD-L1-positive cells, tumor cells or TAMs, are the primary source of the sPD-L1. Thus, measuring both plasma sPD-L1 levels and PD-L1 expression status of tumor cells and TAMs is of benefit for assessment of postoperative prognosis in operable NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1 , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Macrófagos Associados a Tumor/patologiaRESUMO
Purpose: To correlate the ratio of the non-dependent to dependent aspects of the maximal pleural movement vector (MPMVND/D) and gravity-oriented collapse ratio (GCRND/D), and the mean lung field density (MLD) obtained using four-dimensional (4D) dynamic-ventilation computed tomography (DVCT) with airflow limitation parameters and the Brinkman index. Materials and Methods: Forty-seven patients, including 22 patients with COPD, 13 non-COPD smokers, and 12 non-smokers, with no/slight pleural adhesion confirmed using a thoracoscope, underwent 4D-DVCT with 16 cm coverage. Coordinates for the lung field center, as well as ventral and dorsal pleural points, set on the central trans-axial levels in the median and para-median sagittal planes at end-inspiration, were automatically measured (13-17 frame images, 0.35 seconds/frame). MPMVND/D and GCRND/D were calculated based on MPMV and GCR values for all the included points and the lung field center. MLD was automatically measured in each of the time frames, and the maximal change ratio of MLD (MLDCR) was calculated. These measured values were compared among COPD patients, non-COPD smokers, and non-smokers, and were correlated with the Brinkman index, FEV1/FVC, FEV1 predicted, RV/TLC, and FEF25-75% using Spearman's rank coefficients. Results: MPMVND/D was highest in non-smokers (0.819±0.464), followed by non-COPD smokers (0.405±0.131) and patients with COPD (-0.219±0.900). GCRND/D in non-smokers (1.003±1.384) was higher than that in patients with COPD (-0.164±1.199). MLDCR in non-COPD smokers (0.105±0.028) was higher than that in patients with COPD (0.078±0.027). MPMVND/D showed positive correlations with FEV1 predicted (r=0.397, p=0.006), FEV1/FVC (r=0.501, p<0.001), and FEF25-75% (r=0.368, p=0.012). GCRND/D also demonstrated positive correlations with FEV1 (r=0.397, p=0.006), FEV1/FVC (r=0.445, p=0.002), and FEF25-75% (r=0.371, p=0.011). MPMVND/D showed a negative correlation with the Brinkman index (r=-0.398, p=0.006). Conclusion: We demonstrated that reduced MPMVND/D and GCRND/D were associated with respiratory functional indices, in addition to a negative association of MPMVND/D with the Brinkman index, which should be recognized when assessing local pleural adhesion on DVCT, especially for ventral pleural aspects.
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Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Fumar/efeitos adversos , Fumantes , Tomografia Computadorizada QuadridimensionalRESUMO
Epidermal growth factor receptor (EGFR)-mutated (mt) lung adenocarcinoma (LA) is refractory to immune checkpoint inhibitors (ICIs). However, the mechanisms have not been fully elucidated. CD8+ T cell infiltration was significantly lower in EGFR-mt than in EGFR-wild-type LA, which was associated with suppression of chemokine expression. Since this T cell-deserted tumor microenvironment may lead to the refractoriness of ICIs against EGFR-mt LA, we investigated the mechanism by focusing on the regulation of chemokine expression. The expression of C-X-C motif ligand (CXCL) 9, 10 and 11, which constitute a gene cluster on chromosome 4, was suppressed under EGFR signaling. The assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) revealed open chromatin peaks near this gene cluster following EGFR-tyrosine kinase inhibitor (TKI) treatment. The histone deacetylase (HDAC) inhibitor recovered the expression of CXCL9, 10 and 11 in EGFR-mt LA. Nuclear HDAC activity, as well as histone H3 deacetylation, were dependent on oncogenic EGFR signaling. Furthermore, the Cleavage Under Targets and Tagmentation (CUT & Tag) assay revealed a histone H3K27 acetylation peak at 15 kb upstream of CXCL11 after treatment with EGFR-TKI, which corresponded to one of the open chromatin peaks detected by ATAC-seq. The data suggest that EGFR-HDAC axis mediates silencing of the chemokine gene cluster through chromatin conformational change, which might be relevant to the ICI resistance by creating T cell-deserted tumor microenvironment. Targeting this axis may develop a new therapeutic strategy to overcome the ICI resistance of EGFR-mt LA.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Histonas/metabolismo , Receptores ErbB/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Cromatina/genética , Neoplasias Pulmonares/metabolismo , Expressão Gênica , Inibidores de Proteínas Quinases/farmacologia , Linhagem Celular Tumoral , Mutação , Resistencia a Medicamentos Antineoplásicos , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Several studies of early-stage non-small cell lung cancer (NSCLC) have reported a notable therapeutic effect of segmentectomy. However, the secondary benefits of lung volume preservation remain unclear. This study aimed to investigate the potential benefits of segmentectomy, in terms of its impact on postoperative bronchial change. METHODS: Patients who underwent left-sided upper lobectomy and upper division segmentectomy for pStage 0-IA2 NSCLC, were retrospectively analyzed. Degree of the left main bronchial deviation was measured by the curvature index (CI), determined using computed tomography. Variables, including CI value and postoperative rate of change in CI were compared for postoperative cough management the lobectomy and segmentectomy groups. RESULTS: Sixty-seven patients were reviewed. Thirty-seven and 30 patients underwent lobectomy and segmentectomy, respectively, without any significant differences in baseline and surgical variables. The 5-year overall survival rates in the lobectomy and segmentectomy groups were 86.7 and 95.2%, respectively (p = 0.437). While there was no significant difference in postoperative complications, the rate of change in CI was significantly higher in the lobectomy group than in the segmentectomy group (113 vs. 106%, p = 0.005). In addition, the analysis based on postoperative cough reveals the rate of change in CI to be significantly higher in patients requiring medical treatment (p = 0.005). Conclusions Left upper division segmentectomy provides satisfactory treatment and relief of postoperative bronchial tortuosity. Our study suggests that there is a possibility the mitigation of environmental changes in the thoracic cavity may reduce symptoms, thus contributing to an improved quality of life.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Pneumonectomia/métodos , Estudos Retrospectivos , Tosse , Qualidade de Vida , Estadiamento de NeoplasiasRESUMO
In lung cancer, tumor-associated macrophages (TAMs), especially M2-like TAMs, represent the main tumor progression components in the tumor microenvironment (TME). Therefore, M2-like TAMs may serve as a therapeutic target. The purpose of this study was to investigate the effect of M2-like TAM depletion in the TME on tumor growth and chemotherapy response in lung cancer. The levels of secreted monocyte chemoattractant protein (MCP-1) and prostaglandin E2 (PGE2) in the supernatants of lung cancer cell lines A549 and LLC were evaluated via ELISA. Cell migration assays were performed to assess the recruitment ability of macrophage cell lines THP-1 and J774-1 cells. Differentiation of macrophages was assessed via flow cytometry. Immunohistochemical staining was performed to visualize M2-like TAMs in transplanted lung cancer in mouse. We used the COX-2 inhibitor nimesulide to inhibit the secretion of MCP-1 and PGE2, which promotes macrophage migration and M2-like differentiation. Nimesulide treatment decreased the secretion of MCP-1 and PGE2 from lung cancer cells. Nimesulide treatment suppressed the migration of macrophages by blocking MCP-1. Lung cancer supernatant induced the differentiation of macrophages toward the M2-like phenotype, and nimesulide treatment inhibited M2-like differentiation by blocking MCP-1 and PGE2. In the lung cancer mouse model, treatment with nimesulide depleted M2-like TAMs in the TME and enhanced the tumor inhibitory effect of cisplatin. Our results indicated that blocking the secretion of MCP-1 and PGE2 from tumor cells depleted M2-like TAMs in the TME and the combination therapy with cisplatin considerably suppressed tumor growth in the LLC mouse model.
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Cisplatino , Neoplasias Pulmonares , Animais , Camundongos , Cisplatino/uso terapêutico , Macrófagos Associados a Tumor/metabolismo , Dinoprostona/uso terapêutico , Neoplasias Pulmonares/patologia , Microambiente Tumoral/genética , Linhagem Celular TumoralRESUMO
Spontaneous hemothorax is less common. We report the case of an 83-year-old woman with spontaneous hemothorax caused by lung cancer with nontuberculous mycobacteriosis. She presented with chest pain and hemoptysis. Computed tomography revealed a tumor in the right middle lobe with middle syndrome and pleural effusion. Hemothorax was confirmed, and the right middle lobe was resected to control bleeding. The lung tumor invaded the mediastinal tissue, and tumor rupture was observed. Histological examination revealed pulmonary spindle cell carcinoma and epithelioid granulomas with caseous necrosis. Rapid tumor growth and mediastinal invasion could have led to intratumoral hemorrhage and tumor rupture.
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Background: Accurate perioperative risk assessment can enhance the perioperative management of patients undergoing radical surgery for lung cancer. In this study, we compared the accuracy of predicting perioperative complications by lung function values, estimated by blood flow ratios (BFRs), to determine whether dynamic perfusion digital radiography (DPDR) could substitute for pulmonary perfusion scintigraphy (PPS). Methods: Patients scheduled for radical surgery for lung cancer who underwent simultaneous dynamic chest radiography (DCR) and lung perfusion scintigraphy were assessed. We confirmed the agreement between two methods in the assessment of the BFR and its predicted postoperative (ppo) value. Besides, the best spirometry thresholds for the risk of perioperative respiratory or cardiovascular complications were calculated from a receiver operating characteristic (ROC) analysis. The imaging methods were compared for sensitivity and specificity. Results: Among the 44 cases enrolled, DPDR and PPS showed high correlations in BFR (r=0.868, P<0.01) and its postoperative value (r=0.975, P<0.01) and between the predicted and measured spirometry values. In both imaging modalities, the estimated postoperative diffusing capacity test for carbon monoxide (DLco) had the best prediction [area under the curve (AUC) >0.7] for respiratory complications within 1 month (with different cut-offs for same target cases). For predicting, respiratory complications within 1-3 months after surgery, these values were similar between two modalities. Furthermore, the ppoDLco values from both imaging methods were excellent indicators of the induction of postoperative long term oxygen therapy, with the AUC greater than 0.8. Conclusions: This study showed that simple and less invasive DPDR can be a good alternative to PPS for predicting postoperative pulmonary function values and the risk of postoperative respiratory complications. This new imaging modality will offer new insights and possible functional analyses of pulmonary circulation.
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Background: Mediastinal lymph node (LN) dissection during lung resection is essential for accurate staging. Station 4L dissection is anatomically difficult. Therefore, care should be taken to avoid complications. We investigated the importance of mediastinal LN dissection in left upper lobe lung cancer and evaluated intraoperative videos to identify relevant steps during dissection. Methods: We retrospectively reviewed 151 consecutive patients with left upper lobe lung cancer. Finally, 139 patients were enrolled to examine the survival effects of clinical factors of metastatic LN stations. The association between risk factors or surgical procedures and recurrent laryngeal nerve palsy was analyzed. Results: LN dissection of the left upper lobe revealed station 4L LN metastasis in nine patients, three of whom were node-negative on mediastinoscopy. Station 4L LN status was confirmed intraoperatively in 12 of 33 patients. Twenty patients had recurrent laryngeal nerve palsy, four of whom were complicated with aspiration pneumonia. Station 4L LN dissection was an independent risk factor for recurrent laryngeal nerve palsy (P=0.03). The use of an energy device near the recurrent laryngeal nerve was a significant risk factor for recurrent laryngeal nerve palsy. Incidentally, pathological N stage ≥2 was an independent prognostic factor for disease-free survival (DFS) (P=0.005) herein. Conclusions: In patients with left upper lobe lung cancer, pathological N2 disease is an important predictor of recurrence. Therefore, accurate mediastinal LN dissection, including at station 4L, should be performed. We propose to standardize the dissection procedure at each institution to avoid complications, such as recurrent laryngeal nerve palsy.