Yosuke Matsuura

High expression of programmed cell death 1 ligand 1 in lung adenocarcinoma is a poor prognostic factor particularly in smokers and wild-type epidermal growth-factor receptor cases

A clinical implication of programmed cell death 1 ligand 1 (PD‐L1) expression in lung adenocarcinoma has not been well established. We evaluated PD‐L1 expression immunohistochemically on 296 surgically resected lung adenocarcinomas to investigate a clinical implication of PD‐L1 expression especially in terms of smoking history and epidermal growth‐factor receptor (EGFR) mutation status. Patients were classified into high‐ and low‐PD‐L1 expression groups. The high‐expression group (n = 107) showed a significantly higher proportion of smokers and poor differentiation compared with the low‐expression group (n = 189). Survival analysis showed that the prognosis of the high‐expression group was worse in overall survival than that of the low‐expression group (3‐year overall survival 85 vs. 94%, P = 0.005). Stratified survival analyses showed that the prognoses of the high‐expression group were worse than those of the low‐expression group in both strata of smokers and wild‐type EGFR (P = 0.009 and P = 0.007, respectively). We found that high PD‐L1 expression was a poor prognostic factor in the smokers or the patients with wild‐type EGFR, whereas it was not the case in those who never smoked or those with EGFR mutation, implying the importance of adenocarcinoma driver mutations and etiology.

Efficacy and feasibility of a novel and noninvasive computed tomography-guided marking technique for peripheral pulmonary nodules

Thoracoscopic surgery is an option to diagnose small peripheral pulmonary nodules (SPPNs). In some cases, intraoperative localization is difficult because of lesion size or distance from the pleura, and the time required for intraoperative localization is prolonged. In such cases, preoperative marking is useful. Percutaneous computed tomography (CT)–guided hookwire placement is the most commonmethod of preoperative marking. It is a relatively easy technique but it is sometimes accompanied by critical complications, especially air embolism, resulting from puncture of the visceral pleura (VP). To avoid catastrophic complications, several marking techniques without puncture of the VP can be performed.

Prognosis of non-small-cell lung cancer patients with positive pleural lavage cytology

OBJECTIVES Positive pleural lavage cytology (PLC) is considered as a precursor condition of pleural dissemination (PD) or malignant pleural effusion (PE), and one of the poor prognostic factors in surgically resected non-small-cell lung cancer (NSCLC) patients. Although PD and PE are classified as M1a, PLC does not contribute to the tumour, node and metastasis (TNM) classification of the Union Internationale Contre le Cancer. This study aimed to evaluate the prognostic effect of positive PLC status in surgically resected NSCLC patients compared with PD and/or PE. We also aimed to consider the contribution of positive PLC status to the TNM classification. METHODS We reviewed 1572 consecutive patients with completely resected NSCLC, and analysed the relationship between PLC status, other clinicopathological factors and prognosis. The survival rates of 45 patients with PD and/or PE were also investigated. RESULTS Positive preresection PLC (pre-PLC) status was observed in 56 patients. Pre-PLC status was significantly associated with other clinicopathological factors. Positive pre-PLC patients exhibited a worse 5-year overall survival (50.6%) compared with negative pre-PLC patients (78.0%), but better survival than PD and/or PE patients (21.0%). Prognosis of positive pre-PLC patients was equal to that of pT3, negative pre-PLC patients; survival equality was observed when patients were stratified according to pN0, pN1 and pN2. CONCLUSIONS Positive pre-PLC had the significant prognostic effect in surgically resected NSCLC patients. However, it is not a contraindication for surgical resection, unlike PD and/or PE. Our data suggest that positive pre-PLC should be classified as pT3 in next TNM classification.

Prognostic Effect of Lymphovascular Invasion on TNM Staging in Stage I Non–Small-cell Lung Cancer

Introduction Lymphovascular invasion (LVI) is a known adverse prognostic factor for early‐stage non–small‐cell lung cancer (NSCLC). Nonetheless, the prognostic effect of LVI on TNM staging of stage I NSCLC remains inconclusive. We thus hypothesized that it might be better to upstage pathologic stage IA NSCLC with LVI to pathologic stage IB NSCLC. Patients and Methods Using a Cox proportional hazards model, we examined the effect of LVI on disease‐specific survival (DSS) in stage IA versus stage IB disease in 660 consecutive patients with stage I NSCLC (598 with adenocarcinoma, 62 with squamous cell carcinoma) who had undergone complete resection. Results On univariable analysis of stage IA cases, vascular invasion (VI) was significantly associated with inferior DSS (univariable hazard ratio [HR], 3.39; 95% confidence interval [CI], 1.46‐7.89; P = .005). In contrast, lymphatic invasion exhibited a tendency toward inferior DSS (univariable HR, 2.90; 95% CI, 0.97‐8.66; P = .056). Multivariable analysis of DSS in stage IA cases identified VI as an independent significant prognostic factor (multivariable HR, 2.86; 95% CI, 1.58‐5.18; P = .007). With VI, DSS was significantly poorer for stage IB than for stage IA patients without VI (univariable HR, 3.44; 95% CI, 1.67‐7.09; P < .001). In contrast, no difference was observed between patients with stage IA and VI and stage IB patients (P = .97). Conclusion The presence of VI independently and significantly affects DSS in patients with stage IA NSCLC. We found that stage IA with VI and stage IB disease had equivalent prognostic outcomes. Our results suggest that stage IA with VI should be upstaged to IB in the TNM classification of NSCLC. Micro‐Abstract Using 660 consecutive patients with stage I non–small‐cell lung cancer (NSCLC) and a Cox proportional hazards model, we examined the prognostic association of lymphovascular invasion in TNM staging of stage I NSCLC. We found that stage IA with vascular invasion and stage IB disease have equivalent prognostic outcomes, suggesting that stage IA with vascular invasion should be upstaged to stage IB in the TNM classification of NSCLC.

Indocyanine green fluorescence-navigated thoracoscopic anatomical segmentectomy

BACKGROUND To evaluate the feasibility and efficacy of thoracoscopic anatomical segmentectomy (TS-S) using three-dimensional computed tomography (3D-CT) reconstruction and indocyanine green-fluorescence (ICGF) navigation. METHODS Twenty TS-S procedures were performed for 15 primary lung cancers and 5 metastatic lung tumors. Preoperatively we evaluated the target segmental pulmonary artery and created a virtual intersegmental plane using 3D-CT reconstruction. Intraoperatively, the target segmental artery and bronchus were divided, and after intravenous systemic injection of indocyanine green (ICG, 0.25 mg/kg), ICGF of the non-target segments (NTS) was observed using infrared thoracoscopy (KARL STORZ Endoskope Japan K.K., Tokyo, Japan). We marked the border between target and NTS with electrocautery and divided the lung parenchyma along this border using electrocautery or staples. Strength of contrast between target and NTS was quantified as contrast index (CI) and compared over time. RESULTS ICGF provided demarcation of sufficient clarity and duration to mark the lung surface in 19 patients (95%). TS-S was successfully performed in all patients. Mean operative duration was 186 min (90-310 min) and mean blood loss was 30 mL (0-107 mL). Demarcation appeared 20 s (10-100 s) after injection of ICG, and ICGF lasted 180 s (90-300 s). CI peaked 30 s after the appearance of ICGF and decreased over time. Effective contrast continued for 70 s (30-116 s), which was sufficient to mark the line of demarcation. There were no complications attributable to this method. CONCLUSIONS ICGF navigation is a safe and effective technique for TS-S.

Video-assisted thoracoscopic surgery lobectomy for non-small cell lung cancer

Since 1990s, video-assisted thoracoscopic surgery (VATS) lobectomy has become a standard procedure for early-stage non-small cell lung cancer. However, VATS lobectomies are less common, and no randomized controlled trial of VATS versus conventional open lobectomy for early-stage lung cancer has been performed in Japan. Furthermore, VATS lobectomy procedures are not standardized in Japan, and may vary by institution or by practitioner, which complicates their evaluation. Although VATS procedures (such as pneumonectomy, bronchoplasty, and chest wall resection) have been reportedly performed for patients with advanced disease, whether VATS could be a standard modality for advanced lung cancer is unclear from an oncological perspective. Until recently, VATS lobectomies commonly used three or four ports to conduct systemic lymph node dissection; however, VATS lobectomies with reduced port have been recently reported. This article reviews current trends in VATS lobectomy procedures.

Novel techniques for video-assisted thoracoscopic surgery segmentectomy

Small lung cancers are being increasing diagnosed because of advances in computed tomography (CT) and low-dose CT screening. Sublobar resection of peripheral, small lung nodules, such as ground-glass nodules, is a useful therapeutic option that obtains both a pathological diagnosis and radical cure. Lung segmentectomy is a better option than wedge resection for securing a sufficient surgical margin and can also be used to assess hilar nodes. Anatomical segmentectomy, however, is a technically more complicated operative procedure than standard lobectomy. We describe the issues and novel techniques of video-assisted thoracoscopic segmentectomy.

Thoracoscopic segmentectomy for small-sized peripheral lung cancer

Background Lung segmentectomy is a therapeutic option in containing pathological diagnosis and radical cure for small-sized peripheral lung cancer. We retrospectively investigated the results of thoracoscopic segmentectomy (TS-S). Methods From April 2008 to December 2016, 191 patients who underwent TS-S for small-sized peripheral lung cancer were reviewed retrospectively. Intentional indication of TS-S is peripheral radiologically noninvasive lung cancer whose tumor size is less than 2 cm in size with consolidation to tumor (C/T) ratio less than 0.5. Compromised indication is radiologically invasive lung cancer (C/T ration more than 0.5) which we can keep sufficient surgical margin. Results We performed TS-S in 191 patients (81 males and 110 females, median age 66 years). The mean diameter of the nodules was 15 mm (range, 6-46 mm), and clinical IA/IB was 184/7, respectively. Intentional indication was 145 (76%) and compromised one was 46 (24%). The mean operation time was 169 min (range, 73-319 min) and the mean blood loss was 42 g (range, 0-2,900 g). One procedure was converted to open thoracotomy due to bleeding of pulmonary artery (conversion rate, 0.5%). The median chest drainage duration was 1 day (range, 1-9 days), and the median postoperative hospital stay was 7 days (range, 3-30 days). Postoperative complications occurred in 19 patients (10%), including air leak lasting more than 7 days in 3 patients, and late phase air leak in 1 patient. There was no 30-day mortality. Median follow-up was 52 months. The 5-year overall survival (OS) rates and relapse free survival rates, including deaths from all causes, were 93.4% and 90.8%, respectively. During this period, there were 4 distal recurrences after TS-S. However, there was no local recurrence. Conclusions Our result of TS-S was an acceptable. Appropriate selection of patient and surgical procedure in TS-S is important issue.

Video-assisted thoracoscopic surgery lobectomy via confronting upside-down monitor setting

Video-assisted thoracoscopic surgery (VATS) has been widely accepted as a minimally invasive surgery for treatment of early-stage lung cancer. However, various VATS approaches are available. In patients with lung cancer, VATS should achieve not only minimal invasiveness but also safety and oncological clearance. In this article, we introduce our method of VATS lobectomy.

Development of indication criteria for preoperative examination in lung cancer

Background Systemic examination for distant metastases is generally recommended for all lung cancer patients. However, this approach rarely detects distant metastases in typically resectable cT1-2N0 non-small-cell lung cancer. The aim of this study was to identify factors associated with distant metastases and develop indication criteria for preoperative systemic examination in patients with cT1-2N0 non-small-cell lung cancer, with a particular focus on computed tomography imaging of primary lesions. Methods We retrospectively reviewed non-small-cell lung cancer patients treated at our institute between 2005 and 2013. Data were extracted and compared between two groups: patients diagnosed as cT1-2N0M0 who underwent complete resection (M0 group, n = 1530) and those diagnosed as cT1-2N0M1b who received systemic chemotherapy (M1 group, n = 26). Results The median age at diagnosis was significantly lower in the M1 group (p = 0.015). Although carcinoembryonic antigen levels were significantly higher in the M1 group (p < 0.001), 42% had normal levels. Tumor diameters in lung and mediastinal windows on chest computed tomography were significantly larger, and the proportion (mediastinal/lung window tumor diameter ratio) was higher in the M1 group (p < 0.001). All 26 patients in the M1 group had a tumor diameter >15 mm and mediastinal/lung window ratio >0.75. Conclusions Preoperative systemic examination is not necessary in cT1-2N0 non-small-cell lung cancer patients when tumor diameters are ≤15 mm and mediastinal/lung window ratios are ≤0.75. According to these criteria, systemic examinations would have been reduced by 40% in our cohort.