Complete thoracoscopic lobectomy versus hybrid video-assisted thoracoscopic lobectomy for non-small cell lung cancer.

OBJECTIVE: Video-assisted thoracoscopic surgery (VATS) is the standard approach to lobectomy for early-stage non-small cell lung cancer (NSCLC). However, there are many different types. One of its approaches is complete thoracoscopic surgery (CTS), which may be less invasive because of low chest wall stress. This study compared the treatment outcomes of CTS and hybrid VATS lobectomy for NSCLC. METHODS: In total, 442 eligible patients with clinical N0 NSCLC underwent lobectomy between 2007 and 2016. Patients were classified into a group of patients who underwent CTS and a group of those who underwent hybrid VATS. Propensity score matching was performed between the two groups. RESULTS: There were 175 patients after matching. The median follow-up period in the CTS and hybrid VATS groups was 60 and 63 months, respectively. The CTS group showed less blood loss (CTS, 50 mL vs. 100 mL, p = 0.005), fewer complications (CTS, 25.7% vs. 36.6%, p = 0.037), and shorter postoperative hospital stays (CTS, 8 days vs. 12 days, p < 0.001). There was no significant difference in the postoperative 30-day mortality rates. Between the patients who underwent CTS and hybrid VATS groups, the 5-year overall survival rates were 85.4% and 86.0% (p = 0.701), the relapse-free survival rates were 76.5% and 74.9% (p = 0.435), and the lung cancer-specific survival rates were 91.5% and 91.7% (p = 0.90), respectively. CONCLUSIONS: CTS is less invasive and has superior short-term outcomes as an approach to lobectomy for early-stage NSCLC.

Treatment outcomes of lobectomy with and without mediastinal lymph node dissection in older patients with clinical N0 non-small cell lung cancer.

BACKGROUND: To reduce surgical stress, we omit mediastinal lymph node dissection (MLND) in patients with non-small cell lung cancer aged ≥80 years without N1 metastasis, as confirmed via surgery. This study examined the effect of MLND omission on prognosis. METHODS: Altogether, 212 eligible patients with clinical N0 non-small cell lung cancer underwent video-assisted thoracoscopic lobectomy between 2007 and 2017. Patients were classified into two groups as follows: patients aged 75-79 years who underwent MLND group, and patients aged ≥80 years in whom MLND was omitted (non-MLND group). Propensity score matching was performed between the two groups. RESULTS: There were 86 patients after matching. The non-MLND group showed shorter operative time (237.5 min vs. 207.5 min, p = 0.018). No differences in postoperative complications were noted between the two groups. Between the MLND group and non-MLND group, the 5-year overall survival rates were 84.0% and 84.7% (p = 0.989), relapse-free survival rates were 69.8% and 74.7% (p = 0.855), and cancer-specific survival rates were 91.4% and 91.6% (p = 0.700), respectively. These results did not differ significantly. CONCLUSION: This study demonstrated that MLND does not affect the prognosis of patients with non-small cell lung cancer aged ≥80 years. Lobectomy without MLND is one of the surgical treatment options in older patients with clinical N0 non-small cell lung cancer. Naturally, the clinical stage of patients must be carefully evaluated before surgery.

Older age is not a negative factor for video-assisted thoracoscopic lobectomy for pathological stage I non-small cell lung cancer: a single-center, retrospective, propensity score-matching study.

PURPOSE: Video-assisted thoracoscopic surgery (VATS) has changed the surgical approach to non-small cell lung cancer (NSCLC) dramatically. The current study compares the outcomes of older and younger patients who underwent VATS lobectomy for NSCLC. METHODS: In total, 424 eligible patients with pathological stage I NSCLC underwent VATS lobectomy between 2007 and 2017. Patients were classified into two groups (< 75 and ≥ 75 years old), after which propensity score-matching was performed. RESULTS: After matching, 143 patients were identified. No significant difference in postoperative complication rates was observed; however, the ≥ 75-year-old group had a longer postoperative hospital stay (p = 0.001). The 5-year overall survival, relapse-free survival, and lung cancer-specific survival rates of the < 75- and ≥ 75-year-old groups were 87.1% vs. 85.6% (p = 0.537), 82.1% vs. 79.0% (p = 0.531), and 93.5% vs. 92.7% (p = 0.832), respectively. CONCLUSION: Despite the longer postoperative recovery following VATS lobectomy, the short- and long-term outcomes of older patients did not differ from those of younger patients. Thus, for early-stage NSCLC, older age alone was not a negative factor for lobectomy performed via minimally invasive surgery. Naturally, the systemic condition of this population must be evaluated carefully before surgery.

Protective roles of cytoplasmic p21Cip1 /Waf1 in senolysis and ferroptosis of lung cancer cells.

OBJECTIVE: Therapy-induced senescent cancer cells increase the expression of the cyclin-dependent kinase inhibitors p16Ink4a and p21Cip1/Waf1 . Given that p21 regulates not only the cell cycle but also cell death, we investigated the roles of p21 in cell death using a p16-negative A549 human lung adenocarcinoma cell line. METHODS: Senescence was induced by doxorubicin (DXR) or pemetrexed (PEM). The protein expression of p21 was examined by immunoblot. Cell death, reactive oxygen species (ROS) and lipid peroxidation were determined by flow cytometry. ABT-263 and ABT-737 were used as senolytic drugs. In vivo growth of A549 cells with different levels of p21 and their sensitivity to PEM were examined in xenograft models. RESULTS: DXR-induced senescent A549 cells increased the expression of cytoplasmic p21, and the sensitivity to ABT-263 was augmented in p21-knockout A549 (A549-KOp21) cells. A similar senolytic effect was observed when PEM was combined with ABT-737. PEM alone induced a higher level of non-apoptotic cell death, ferroptosis, in A549-KOp21 cells than in A549 cells. Although there was no difference in the level of lipid peroxidation, ROS levels were higher in PEM-treated A549-KOp21 cells than in PEM-treated A549 cells. A loss of p21 increased the sensitivity of A549 cells to PEM both in vitro and in vivo. A clinical database analysis showed that CDKN1Ahigh lung adenocarcinoma patients had a poorer prognosis compared to CDKN1Alow patients. CONCLUSION: Cytoplasmic p21, which was increased in therapy-induced senescent lung cancer cells, plays protective roles in senolysis and ferroptosis.

Protective role of cytoplasmic p21Cip1/Waf1 in apoptosis of CDK4/6 inhibitor-induced senescence in breast cancer cells.

Inhibition of CDK4/6 slows the cell cycle and induces senescence in breast cancer cells. However, senescent cancer cells promote invasion and metastasis. Several drugs reportedly target senescent cells, including ABT-263 (navitoclax). We examined the effects of the CDK4/6 inhibitor abemaciclib and ABT-263 on two human breast cancer cell lines. The abemaciclib and ABT-263 combination additively decreased the viability of MDA-MB-231 cells, but not MCF-7 cells. Also, the combination therapy-induced caspase-dependent apoptosis in MDA-MB-231 cells. Combination therapy with abemaciclib and ABT-737, an ABT-263 analog, significantly suppressed the in vivo growth of MDA-MB-231 with transient body-weight loss. Given that p16Ink4a and p21Cip1/Waf1 are key factors in senescence and that both cell lines were negative for p16, the role of p21 in apoptosis of treated breast cancer cells was investigated. Although abemaciclib increased the cytoplasmic p21 level in both cell lines as a hallmark of senescence, the abemaciclib and ABT-263 combination decreased it only in MDA-MB-231 cells. This decrease of p21 expression was relieved by caspase inhibition, and p21 was colocalized with caspase-3 in the cytoplasm of MDA-MB-231 cells. Alternatively, small interfering RNA-mediated knockdown of p21 rendered caspase-3-negative MCF-7 cells susceptible to abemaciclib and ABT-263, as well as TNF-related apoptosis-inducing ligand. Furthermore, a clinical database analysis showed that p21high breast cancer patients had a poorer prognosis compared to p21low patients. These results suggest that cytoplasmic p21 plays a protective role in apoptosis of CDK4/6 inhibitor-induced senescent breast cancer cells.

[Experience of Complete Video-assisted Thoracoscopic Pneumonectomy].

Thoracotomy has been preferred to video-assisted thoracoscopic surgery( VATS) for performing pulmonary pneumonectomy, and there have been no reports of complete video-assisted thoracoscopic surgery (cVATS) for such a case. We present three cases of cVATS pneumonectomy. The operation method was based on four ports, and ports were added in difficult cases. In these cases, the blood loss and length of surgery were similar to results of VATS reported previously. We experienced bleeding complications in one case but were able to manage appropriately. There were no serious postoperative complications in our cases. In addition, it was considered acceptable in terms of safety because there were no deaths within 30 days after operation in all cases. The cVATS pneumonectomy for lung cancer is one of the useful treatment option because of safety and many benefits although the long-term results are unknown at present.

Pemetrexed sensitizes human lung cancer cells to cytotoxic immune cells.

Pemetrexed (PEM) is a useful drug that can be combined with immune checkpoint blockade therapy for treatment of patients with advanced non-small-cell lung cancer (NSCLC). However, its effects on anti-cancer immunity, especially the sensitivity of NSCLC cells to cytotoxic immune cells, have not been fully investigated. In this study, we examined the effects of PEM on the sensitivity of human NSCLC cells to two different types of cytotoxic immune cells. Pre-treatment with PEM increased the sensitivity of two NSCLC cell lines, PC9 and A549, to activated T cells and natural killer (NK) cells, and decreased the expression of anti-apoptotic proteins, including XIAP and Mcl-1. In addition, PEM treatment increased the cell surface expression of programmed death-ligand 1 (PD-L1) on PC9 cells. PEM-induced upregulation of PD-L1 on PC9 cells was at least partially ascribed to activation of ERK and the NFκB pathway. In contrast, PEM treatment increased the expression of UL16-binding proteins (ULBP), ligands for the NKG2D NK receptor, on PC9 and A549 cells, as well as the induction of senescence. Although the addition of anti-programmed cell death 1 antibody showed no effect on the sensitivity of PEM-treated PC9 and A549 cells to activated T cells, that of anti-NKG2D antibody decreased the enhanced sensitivity of PEM-treated A549 cells to NK cells. These results indicate that PEM can effectively sensitize human NSCLC cells to cytotoxic immune cells while modulating the expression of immune-regulatory molecules.

[Bronchial Artery Aneurysm with Hoarseness;Report of a Case].

The patient was a 72-year-old man with a history of bronchiectasis. He was admitted to our hospital for an examination of hoarseness. Chest computed tomography (CT) showed bronchiectasis in the bilateral lungs and bronchial artery aneurysm in the mediastinum. To prevent rupture of the aneurysm, we imaged the bronchial artery aneurysm by selective bronchial artery angiography and performed bronchial artery embolization (BAE) with 19 platinum coils. Three months after successful BAE, his hoarseness had improved, and the bronchial artery aneurysm was reduced in size after 12 months. To our knowledge, this is the 1st report of BAE improving hoarseness due to bronchial artery aneurysm.

[Idiopathic Bilateral Chylothorax which Presented Difficulty in Treatment].

A 57-year-old woman was referred to our hospital because of bilateral chylothorax. She was previously treated with dietary restriction and pleurodesis resulting in failure. She did not have diseases causing chylothorax, and was diagnosed as having idiopathic chylothorax. To control chylothorax, 2 surgical operations to ligate bilateral thoracic ducts, right pleurodesis, and 2 times of left pleurodeses was necessary.

[Giant Solitary Fibrous Tumor Associated with Loss of Consciousness by Hypoglycemic Attack].

We herein report a rare case of solitary fibrous tumor (SFT) producing high-molecular-weight insulin-like growth factor Ⅱ(big IGF-Ⅱ). A 51-year-old woman with a large mass in the right thorax suffered from repeated loss of consciousness due to hypoglycemic attack. A hematological examination revealed low values of serum insulin and C-peptide despite her hypoglycemia. We therefore regarded her giant thoracic tumor as the cause of the hypoglycemic attack. She underwent resection of the tumor and was diagnosed with SFT pathologically. After the surgery, her blood sugar level stabilized immediately, and she has had no hypoglycemic attacks since. Although we identified big IGF-Ⅱ in a preoperative serum sample by a Western immunoblot analysis, it was not detected after surgical resection. Positivity for big IGF-Ⅱ was observed in the tumor cells by immunohistochemical staining. We therefore concluded that big IGF-Ⅱ produced by the SFT caused the hypoglycemic attack in this patient.

[Clinical Assessment of Fourteen Cases of Thoracic Endometriosis].

We retrospectively assessed the clinical and pathological features of 14 patients with thoracic endometriosis who were treated at our hospital from 2007 to 2017. Thirteen patients presented pneumothorax and 1 patient presented bloody sputum. All were treated surgically. Pneumothorax occurs on the right side in all 13 cases and bloody sputum was from left side lesion. Ten patients presented symptoms closely related with their menstrual cycle (days -2 to 5). At surgery, dark red or dark brown spots, small hiatus and scar-like findings on the surface of the visceral pleura or diaphragm were identified in all cases. Pathological or immunohistochemical examinations of diaphragm or lung tissue specimens revealed endometrial tissue in 6 cases of pneumothorax and a case of bloody sputum. Nine patients received hormonal therapy(8:pneumothorax, 1:bloody sputum). Pleurodesis was performed for 1 pneumothorax patient with recurrent pneumothorax after hormonal therapy. In case of young female with repeated pneumothorax, catamenial pneumothorax must be kept in mind as a differential diagnosis and appropriate timing for surgical treatment should be considered to establish pathologically correct diagnosis.

Efficacy of low-dose computed tomography screening for lung cancer: the current state of evidence of mortality reduction.

The interim and final results of randomized controlled trials on the efficacy of lung cancer computed tomography (CT) screening have been reported recently from Western countries. The outcome of the National Lung Screening Trial (NLST) demonstrated the efficacy of low-dose thoracic CT screening for heavy smokers; however, other studies have found no apparent reduction in the mortality rate, and the outcome of the NELSON study is awaited. To date, a few studies have reported on the efficacy of lung cancer CT screening for non-/light smokers. A report from the Hitachi district, which is an ecological/time series study where non-/light smokers account for approximately half of the CT screening examinees, was published in 2012, with an outcome suggesting efficacy. Currently, a randomized controlled trial (JECS Study) is underway in Japan with non-/light smokers as the subjects, and this trial is very important in terms of cancer prevention.