Michihito Toda

Sarcopenia is a novel poor prognostic factor in male patients with pathological Stage I non-small cell lung cancer

Objectives Sarcopenia is the progressive loss of muscle mass and strength, and has a risk of adverse outcomes such as disability, poor quality of life and death. As prognosis depends not only on disease aggressiveness, but also on a patients physical condition, sarcopenia can predict survival in patients with various cancer types. However, its effects on postoperative prognosis in patients with localized non-small cell lung cancers (NSCLC) have never been reported. Methods We retrospectively investigated 215 male patients with pathological Stage I NSCLC. L3 muscle index is defined as the cross-section area of muscle at the third lumbar vertebra level, normalized for height, and is a clinical measurement of sarcopenia. We then investigated the effect of preoperative sarcopenia on their postoperative prognosis. Results Our 215 subjects included 30 patients with sarcopenia. Sarcopenia was significantly associated with body mass index, nutritional condition, serum CYFRA 21-1 level and pathological stage, but not with preoperative respiratory function or performance status. Frequency of postoperative complications, length of postoperative hospital stay, thoracic drainage period or causes of death were not correlated with the presence of sarcopenia. The sarcopenia group had a significantly shorter median overall survival (32 months) than the no-sarcopenia group. Conclusion Sarcopenia might not affect short-term outcomes in patients with early-stage lung cancer. Sarcopenia was a predictor of poor prognosis in male patients with Stage I NSCLC. As sarcopenic patients with NSCLC patients are at risk for significantly worse outcomes, their treatments require careful planning, even for those with Stage I disease.

Attenuation of Bleomycin-Induced Pulmonary Fibrosis in Rats with S-Allyl Cysteine

Pulmonary fibrosis is a complex disease with high mortality and morbidity. As there are currently no effective treatments, development of new strategies is essential for improving therapeutic outcomes. S-allyl cysteine (SAC) is a constituent of aged garlic extract that has demonstrated efficacy as an antioxidant and anti-inflammatory agent. The current study examines the effects of SAC on pulmonary fibrosis induced by a single intratracheal instillation of bleomycin (2.5 mg/kg). SAC was administered to rats as 0.15% SAC-containing diet from seven days prior to instillation up until the conclusion of the experiment (14 days post-instillation). SAC significantly reduced collagen mRNA expression and protein deposition (33.3 ± 2.7 μg/mg and 28.2 ± 2.1 μg/mg tissue in vehicle- and SAC-treated rats, respectively), and decreased fibrotic area, as assessed histologically. In the rats’ lungs, SAC also attenuated the increased expression of transforming growth factor-β1 (TGF-β1), a central regulator of myofibroblast recruitment, activation, and differentiation. While bleomycin instillation increased the number of myofibroblasts within the lung mesenchymal area, this change was significantly reduced by SAC treatment. SAC may exert efficacy as an anti-fibrotic by attenuating myofibroblast differentiation through TGF-β1-mediated fibroproliferative processes. Thus, our results indicate SAC may be useful for the prevention or treatment of pulmonary fibrosis.

Platelet‐to‐lymphocyte ratio predicts the prognosis of patients with non‐small cell lung cancer treated with surgery and postoperative adjuvant chemotherapy

Markers of preoperative tumor immunity, such as platelet‐to‐lymphocyte ratio (PLR), have been reported to be prognostic factors for patients with various cancers. However, the relationship between PLR and the prognosis of non‐small cell lung cancer (NSCLC) patients treated with surgery and adjuvant chemotherapy as a multidisciplinary treatment is unknown.

Loss of Muscle Mass is a Novel Predictor of Postoperative Early Recurrence in N2-Positive Non-Small-Cell Lung Cancer

Background: We often experienced early recurrence in patients with completely resected N2-positive non-small-cell lung cancer (NSCLC). Loss of muscle mass is a poor prognostic factor in patients with several stages of NSCLC. This study aimed to investigate the relationship between preoperative loss of muscle mass and postoperative early recurrence in patients with N2-positive NSCLC. Methods: We retrospectively analyzed 47 male patients with completely resected pathological N2-positive NSCLC. Early recurrence was defined as that diagnosed within 1 year after the operation. We used the L3 muscle index (cross-sectional area of muscle at the L3 level, normalized for height) as a clinical measurement of loss of muscle mass (cutoff value, 52.4 cm2/m2). Results: In all, 18 patients with early recurrence had significantly poorer outcomes compared with those without (P <0.01). In univariate analysis, loss of muscle mass (P = 0.023), carcinoembryonic antigen (CEA) level >5.0 ng/mL (P = 0.002), and absence of postoperative chemotherapy (P = 0.042) were predictors of postoperative early recurrence. In multivariate analysis, loss of muscle mass (P = 0.004) and CEA level >5.0 ng/mL (P = 0.001) were independent predictors. Conclusions: Loss of muscle mass is an independent predictor of postoperative early recurrence in pathological N2-positive NSCLC patients.

Positive correlation between sarcopenia and elevation of neutrophil/lymphocyte ration in pathological stage IIIA (N2-positive) non-small cell lung cancer patients

ObjectiveSurgical indication in stage IIIA (N2) non-small cell lung cancer is still controversial. Hence, there is a need for the identification of predictors of the postoperative outcome in these patients. Although sarcopenia is expected to be a novel predictor of postoperative outcome in these patients, the underlying clinical features of sarcopenia have not been well investigated. Elevation of neutrophil/lymphocyte ratio indicates cancer-associated inflammation and depression of anticancer immunity. We analyzed the influence of sarcopenia on postoperative prognosis, and investigated the relationship between sarcopenia and neutrophil/lymphocyte ratio in patients with stage IIIA (N2) non-small cell lung cancer.MethodsWe retrospectively investigated 69 patients with stage IIIA (N2) non-small cell lung cancer. We used the L3 muscle index as a clinical measurement of sarcopenia, and divided patients into the sarcopenic (n = 21) and the non-sarcopenic group (n = 48). We then investigated the effect of sarcopenia on postoperative prognosis, and evaluated the correlation between sarcopenia and neutrophil/lymphocyte ratio.ResultsThis study included 47 males and 22 females. Univariate analysis revealed that sarcopenia, performance status, and serum cytokeratin-19 fragment level were predictors of poor prognosis; multivariate analysis revealed that performance status and sarcopenia were independent predictors of poor prognosis. The presence of sarcopenia was significantly correlated with neutrophil/lymphocyte ratio elevation.ConclusionsSarcopenia is a novel predictor of poor prognosis in patients with stage IIIA (N2) non-small cell lung cancer. Neutrophil/lymphocyte ratio elevation might be the reason for poor prognosis in sarcopenic patients.

Relationship between Perioperative N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) and Complications in Thoracic Surgery

Background: In cardiac surgery, the N-terminal pro-brain natriuretic peptide (NT-proBNP) level is reportedly correlated with the onset of postoperative complications. We examined the relationship between the NT-proBNP level and perioperative complications in thoracic surgery and elucidated the significance of NT-proBNP measurement. Methods: We evaluated 48 patients excluding hemodialysis patients who underwent lung resection from November 2015 to February 2016. NT-proBNP measurement was performed three times preoperatively on postoperative days 2 and 5. We examined the relationship between clinical background factors such as preoperative comorbidity and the development of postoperative complications. Based on established criteria for surgical complications (Clavien-Dindo classification), grade ≥ II was defined as a complications. We classified the patients into two groups (with or without complications) and compared and examined the background factors between the groups. Results: The study included 48 patients (33 male, 15 female) with an average age of 72 years (range, 35 - 86 years). Preoperative comorbidities included cardiovascular disease in five patients, diabetes mellitus in four, and chronic obstructive pulmonary disease in six. The average operation time was 163 (29 - 308) minutes, and the bleeding volume was 30 (10 - 620) ml. Early complications were confirmed in 11 patients, and late complications were confirmed in 7 patients. A high NT-proBNP level on postoperative day 5 was an independent risk factor for late complications. Conclusion: The perioperative NT-proBNP level is considered to be a predictor of complications. Its measurement is useful for predicting postoperative complications, and careful perioperative management is required for patients with high levels.

Pirfenidone suppresses polarization to M2 phenotype macrophages and the fibrogenic activity of rat lung fibroblasts

Pirfenidone is a representative medication to treat interstitial pulmonary fibrosis. Researchers reported pirfenidone (>100 µg/ml) significantly suppressed fibroblast growth in vitro. However, clinically, the maximum concentration of pirfenidone in the blood is approximately 10 µg/ml. We hypothesized there might be an additional mechanism of pirfenidone to fibroblasts indirectly. Macrophages are known to control the activation of fibroblasts via the regulation of inflammatory M1 and suppressive M2 polarization. The aim of this study was to investigate the effects of pirfenidone on alveolar macrophage polarization. Rat alveolar macrophages (NR8383) were stimulated in vitro with lipopolysaccharide (LPS) + interferon (IFN)-γ, or interleukin (IL)-4 + IL-13. Expression of M1 and M2 markers and supernatant’s levels of TGF-β1 were assessed after pirfenidone treatment (0–100 µg/ml). Treatment with LPS + INF-γ or IL-4 + IL-13 significantly increased the expression of M1 and M2 markers, respectively. In macrophage polarization assays, pirfenidone significantly reduced the expression of M2 markers at concentrations greater than 10 µg/ml but had no effect on the expression of M1 markers. At these concentrations, pirfenidone significantly reduced TGF-β1 levels in NR8383 culture supernatants. In rat lung fibroblasts treated with NR8383 culture supernatants, pirfenidone significantly suppressed proliferation, and the collagen mRNA and protein levels. In conclusion, our results demonstrated that pirfenidone suppressed polarization to M2 macrophages at clinically relevant concentrations and suppressed the rat lung fibroblasts fibrogenic activity.

Pulmonary Resection for Lung Cancer Following Transcatheter Aortic Valve Implantation for Severe Aortic Valve Stenosis: A Case Report

An 82-year-old woman was referred to our hospital because of dyspnea on effort. Echocardiography revealed severe aortic valve stenosis (AS). Simultaneously, chest computed tomography (CT) revealed a 19-mm nodule in the lower lobe of the right lung, and bronchoscopic biopsy revealed adenocarcinoma. She underwent transcatheter aortic valve implantation (TAVI) for severe AS. Three weeks later, she underwent lower lobectomy of the right lung and mediastinal dissection for the lung cancer. Her postoperative course was good, and she was discharged 8 days postoperatively. In conclusion, we encountered a patient who successfully underwent pulmonary resection for lung cancer following TAVI for severe AS. We suggest that pulmonary resection following TAVI is an acceptable choice for lung cancer in patients with severe AS because of the lack of a need for cardiopulmonary bypass, the high safety and efficacy of two-stage therapy, and the short period between the two therapies.

Solitary splenic metastasis from lung adenocarcinoma: A case report

Solitary splenic metastasis is extremely rare, with only 27 reported cases in the literature. An 81‐year‐old woman was referred to our hospital for treatment of pulmonary and splenic lesions. Chest computed tomography showed a small lung nodule in the right upper lobe, abdominal computed tomography showed an 8 cm splenic mass with abnormal accumulation, and positron emission tomography revealed a maximum standardized uptake value of 7.9. She had elevated serum cancer antigen 19‐9 (1847 U/mL) and carcinoembryonic antigen concentrations (17.9 ng/mL). She underwent laparoscopic splenectomy. Pathological examination revealed poorly differentiated adenocarcinoma. We performed partial lung resection and diagnosed the small lung lesion as lung adenocarcinoma. Both lesions were positive for thyroid transcription factor 1. Thus, primary lung adenocarcinoma and solitary splenic metastasis were diagnosed. The patient was still alive without recurrence four years postoperatively. Herein, we report a rare case of lung adenocarcinoma with solitary splenic metastasis and review the literature.

Elevation of Serum Carcinoembryonic Antigen Concentration Caused by Everolimus-Induced Lung Injury: A Case Report

A 66-year-old woman underwent right nephrectomy for treatment of renal cell carcinoma (RCC). Two years later, she underwent wedge resection of the right lung for treatment of metastatic RCC and primary adenocarcinoma of the lung. She began oral sorafenib for the remaining nodules of the left lung, which were suspected to be metastatic RCC. Two years later, the sorafenib was changed to everolimus because of slight enlargement of the left pulmonary nodules. The carcinoembryonic antigen (CEA) concentration then increased to 25.7 ng/mL, and chest computed tomography (CT) revealed ground-glass opacities (GGO) in the bilateral lungs. Everolimus-induced lung injury was suspected, and she discontinued the everolimus. Two months later, the serum CEA concentration decreased to almost within the reference range at 5.9 ng/mL, and the GGO disappeared on chest CT. In conclusion, we encountered a patient who developed an elevated serum CEA concentration caused by everolimus-induced lung injury.