Enhancing identification of early-stage lung adenocarcinomas through solid component analysis of three-dimensional computed tomography images.

OBJECTIVES: As the role of segmentectomy expands in managing early-stage lung adenocarcinoma, precise preoperative assessments of tumor invasiveness via computed tomography become crucial. This study aimed to evaluate the effectiveness of solid component analysis of three-dimensional (3D) computed tomography images and establish segmentectomy criteria for early-stage lung adenocarcinomas. METHODS: This retrospective study included 101 cases with adenocarcinoma diagnoses, with patients undergoing segmentectomy for clinical stage 0 or IA between 2012 and 2017. The solid component volume (3D-volume) and solid component ratio (3D-ratio) of tumors were calculated using 3D computed tomography. Additionally, based on two-dimensional (2D) computed tomography, the solid component diameter (2D-diameter) and solid component ratio (2D-ratio) were calculated. The area under the receiver-operating characteristic curve (AUC) was calculated for each method, facilitating predictions of mortality and recurrence within 5 years. The AUC of each measurement was compared with those of invasive component diameter (path-diameter) and invasive component ratio (path-ratio) obtained through pathology analysis. RESULTS: The predictive performance of 3D-volume did not differ significantly from that of path-diameter, whereas 2D-diameter exhibited less predictive accuracy (AUC: 3D-volume, 2D-diameter, and path-diameter: 0.772, 0.624, and 0.747, respectively; 3D-volume vs. path-diameter: p = 0.697; 2D-diameter vs. path-diameter: p = 0.048). Results were similar for the solid component ratio (AUC: 3D-ratio, 2D-ratio, path-ratio: 0.707, 0.534, and 0.698, respectively; 3D-ratio vs. path-ratio: p = 0.882; 2D-ratio vs. path-ratio: p = 0.038). CONCLUSION: Solid component analysis using 3D computed tomography offers advantages in prognostic prediction for early-stage lung adenocarcinomas.

The effect of epidermal growth factor receptor mutation on adjuvant chemotherapy with tegafur/uracil for patients with completely resected, non-lymph node metastatic non-small cell lung cancer (> 2 cm): a multicenter, retrospective, observational study as exploratory analysis of the CSPOR-LC03 study.

BACKGROUND: The use of adjuvant osimertinib for epidermal growth factor receptor (EGFR) mutants is expected to expand to earlier stage I in the future, potentially competing with the current standard of care, oral tegafur/uracil (UFT), in Japan. However, the effect of EGFR mutation status on the therapeutic effect of UFT remains unclear. This study was conducted as an exploratory analysis of a retrospective observational study that investigated the real-world data of postoperative adjuvant chemotherapy in Japan (CSPOR-LC03). METHODS: Between 2008 and 2013, 1812 patients with completely resected adenocarcinoma diagnosed as pathologic stage I (T1 > 2 cm, TNM classification, sixth edition) who have maintained organ function, and no history of other cancers were included. The primary endpoint was the 5-year disease-free survival (DFS) rate, and we compared this rate between four groups classified based on the administration of adjuvant UFT and EGFR mutation status. RESULTS: Of the 933 (51%) patients with EGFR mutations, 394 underwent adjuvant UFT therapy. Of the 879 (49%) patients without EGFR mutations, 393 underwent adjuvant UFT therapy. The 5-year DFS of UFT+/EGFR+ and UFT-/EGFR+ patients were 82.0 and 87.1%, respectively, and those of UFT+/EGFR- and UFT-/EGFR- patients were 80.0 and 86.9%, respectively. DFS was significantly worse in the UFT+ group than in the UFT- group (P = 0.015). Adjuvant UFT therapy was not an independent prognostic factor for DFS, regardless of the EGFR mutation status. CONCLUSION: In pathologic stage I (>2 cm) lung adenocarcinomas with EGFR mutation, the survival benefit of adjuvant UFT was not observed.

The effect of lobar shifting following right upper lobectomy on postoperative pulmonary function.

OBJECTIVES: Lobes occasionally displace after lobectomy, referred to as "lobar shifting". However, the benefits, especially in postoperative pulmonary function, remain controversial. This study aimed to measure the effect of lobar shifting on postoperative pulmonary function especially in the right upper lobe. METHODS: This retrospective study includes 273 right upper lobectomy patients (lobectomy group) and 24 right upper segmentectomy patients (segmentectomy group) from 2012 to 2021. The lobectomy group was further subdivided based on their Synapse Vincent® image: with their postoperative middle lobe bronchus shifted toward the head (shift group: 176 cases) and without (non-shift group: 97 cases). Several factors were examined to determine the cause of lobar shifting. The rate of measured actual postoperative forced expiratory volume in 1 s (FEV1.0) to predicted postoperative FEV1.0 was analyzed and compared among the three groups. RESULTS: Factors that correlated with lobar shifting included age (p < 0.001), a relatively small middle lobe volume (p = 0.03), no adhesions (p < 0.001), and good upper/middle and middle/lower lobulation (p = 0.04, p = 0.02). The rate of measured actual postoperative FEV1.0 to predicted postoperative FEV1 for the shift, non-shift, and segmentectomy groups were 112.5%, 107.9%, and 103.1% (shift vs non-shift: p = 0.04, shift vs segmentectomy: p = 0.02, non-shift vs segmentectomy: p = 0.19). CONCLUSIONS: Lobar shifting after right upper lobectomy is influenced by morphological factors and may have a beneficial impact on postoperative pulmonary function.

Asia expert consensus on segmentectomy in non-small cell lung cancer: A modified Delphi study.

Objective: Segmentectomy as a parenchymal-sparing surgical approach has been recommended over lobectomy in select patients with early-stage non-small cell lung cancer. This study aimed to address 3 aspects of segmentectomy ("patient indication"; "segmentectomy approaches"; "lymph node assessment") where there is limited clinical guidance. Methods: A modified Delphi approach comprising 3 anonymous surveys and 2 expert discussions was used to establish consensus on the aforementioned topics among 15 thoracic surgeons (2 Steering Committee; 2 Task Force; 11 Voting Experts) from Asia who have extensive segmentectomy experience. Statements were developed by the Steering Committee and Task Force based on their clinical experience, published literature (rounds 1-3), and comments received from Voting Experts through surveys (rounds 2-3). Voting Experts indicated their agreement with each statement on a 5-point Likert scale. Consensus was defined as ≥70% of Voting Experts selecting either "Agree"/"Strongly Agree" or "Disagree"/"Strongly Disagree." Results: Consensus from the 11 Voting Experts was reached on 36 statements (11 "patient indication" statements; 19 "segmentation approaches" statements; 6 "lymph node assessment" statements). In rounds 1, 2, and 3, consensus was reached on 48%, 81%, and 100% of drafted statements, respectively. Conclusions: A recent phase 3 trial reported significantly improved 5-year overall survival rates for segmentectomy compared with lobectomy, proposing thoracic surgeons to consider segmentectomy as a surgical option in suitable patients. This consensus serves as a guidance to thoracic surgeons considering segmentectomy in patients with early non-small cell lung cancer, outlining key principles that surgeons should consider in surgical decision-making.

Uniportal left S1 + 2 segmentectomy.

The left upper lobe is one of the largest lobes of the lung; left upper segmentectomy is well established among thoracic surgeons. In uniportal left S1 + 2 segmentectomy, dissection of the vasculature, bronchus, and intersegmental plane can be performed anteriorly. Given that the fissureless technique is commonly used in uniportal video-assisted thoracoscopic surgery, S1 + 2 segmentectomy exhibits high affinity with the unidirectional approach. We have frequently performed left S1 + 2 segmentectomy for early non-small cell lung cancer located in the apical segment, since this procedure has the potential to preserve pulmonary function over tri-segmentectomy. Herein, we introduce our approach to uniportal left S1 + 2 segmentectomy as a minimally invasive alternative for preserving lung function.

The dynamic pulmonary functional change after thoracoscopic lower lobe segmentectomy.

BACKGROUND: The advantages of segmentectomy over lobectomy in sparing pulmonary function remain controversial. Lower lobe segmentectomy is divided into simple segmentectomy, such as segment 6; and complex segmentectomy that includes the basal segments. Here, we compared residual lung function after thoracoscopic segmentectomy versus lobectomy in the lower lobe using the three-dimensional computed tomography volumetric method. METHODS: Between January 2012 and October 2020, 67 patients who underwent thoracoscopic segmentectomy of the lower lobe were matched to 67 patients who underwent thoracoscopic lower lobectomy during the same period using propensity score matching analysis. The postoperative decrease in the rate of forced expiratory volume in 1 s was compared between methods. The regional forced expiratory volume in 1 s of the residual lobe rescued by segmentectomy was measured using volumetric and spirometric analyses and compared to lower lobectomy. The ratio of the actual to predicted postoperative forced expiratory volume in 1 s in the residual lobe was defined as the preservation rate. RESULTS: Of the 67 thoracoscopic segmentectomies, 43 were S6, seven were S8, three were S8 + 9, seven were S10, and seven were S9 + 10. The percentage of postoperative/preoperative forced expiratory volume in 1 s was significantly higher in the segmentectomy versus lobectomy group (90.7% vs. 85.7%, p = 0.001). The preservation rates after simple segmentectomy (n = 43) and complex segmentectomy (n = 24) did not differ significantly (82.2% vs. 80.2%, p = 0.709). CONCLUSIONS: Thoracoscopic lower lobe segmentectomy versus lobectomy preserves postoperative lung function. Even complex segmentectomy exhibited outcomes relevant to simple segmentectomy by sparing the residual lobe.

Segmental volumetric analysis with a ventilated or perfused area: identifying the intersegmental plane.

OBJECTIVES: Two methods are available to identify the intersegmental plane during segmentectomy: the inflation-deflation method, based on the ventilation area, and injection of indocyanine green, based on the pulmonary arterial distribution. However, whether the intersegmental plane created by these 2 methods matches remains unknown. Our goal was to identify the demarcation lines based on bronchial and arterial territories using 3-dimensional computed tomography-based volumetry. METHODS: We collected data from patients who underwent thoracoscopic segmentectomy in our hospital between April 2012 and May 2021. Three-dimensional images were reconstructed from the preoperative contrast-enhanced computed tomography data using the SYNAPSE VINCENT software program. The volume of the affected area and the distance of the tumour from the intersegmental plane were calculated based on each affected artery and bronchus. Each calculated volume was compared to each affected segment using a paired t-test. RESULTS: Of 195 patients, 114 underwent upper lobe segmentectomy, and 81 underwent lower lobe segmentectomy. In upper lobe segmentectomy, the affected arterial segmental volume was smaller than the bronchial volume (505.0 ml vs 539.4 ml, P < 0.001). In lower lobe segmentectomy, there was no significant difference between arterial and bronchial volumes (234.6 ml vs 236.9 ml, P = 0.607). The volume of the affected arterial segmental lung and the distance of the tumour from the intersegmental plane were significantly smaller than the bronchial volume in upper lobe segmentectomies. CONCLUSIONS: As per the results, the affected segmental volume delineated by the indocyanine green method would be underestimated in upper lobe segmentectomy.

Adjuvant atezolizumab in Japanese patients with resected stage IB-IIIA non-small cell lung cancer (IMpower010).

The global phase 3 IMpower010 study evaluated adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in patients with resected stage IB-IIIA non-small cell lung cancer (NSCLC). Here, we report a subgroup analysis in patients enrolled in Japan. Eligible patients had complete resection of histologically or cytologically confirmed stage IB (tumors ≥4 cm)-IIIA NSCLC. Upon completing 1-4 cycles of adjuvant cisplatin-based chemotherapy, patients were randomized 1:1 to receive atezolizumab (fixed dose of 1200 mg every 21 days; 16 cycles or 1 year) or BSC. The primary endpoint of the global IMpower010 study was investigator-assessed disease-free survival, tested hierarchically first in patients with stage II-IIIA NSCLC whose tumors expressed programmed death-ligand 1 (PD-L1) on ≥1% of tumor cells, then in all randomized patients with stage II-IIIA NSCLC, and finally in the intention-to-treat (ITT) population (stage IB-IIIA NSCLC). Safety was evaluated in all patients who received atezolizumab or BSC. The study comprised 149 enrolled patients in three populations: ITT (n = 117; atezolizumab, n = 59; BSC, n = 58), all-randomized stage II-IIIA (n = 113; atezolizumab, n = 56; BSC, n = 57), and PD-L1 tumor cells ≥1% stage II-IIIA (n = 74; atezolizumab, n = 41; BSC, n = 33). At the data cutoff date (January 21, 2021), a trend toward disease-free survival improvement with atezolizumab vs BSC was observed in the PD-L1 tumor cells ≥1% stage II-IIIA (unstratified hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.25-1.08), all-randomized stage II-IIIA (unstratified HR, 0.62; 95% CI, 0.35-1.11), and ITT (unstratified HR, 0.61; 95% CI, 0.34-1.10) populations. Atezolizumab-related grade 3/4 adverse events occurred in 16% of patients; no treatment-related grade 5 events occurred. Adjuvant atezolizumab showed disease-free survival improvement and a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.

Segmentectomy versus lobectomy for inner-located small-sized early non-small-cell lung cancer.

OBJECTIVES: Although segmentectomy is an acceptable alternative to lobectomy for peripheral small-sized non-small-cell lung cancer, the effectiveness of segmentectomy for inner lesions remains unknown. The aim of this study was to examine the feasibility of segmentectomy in comparison with lobectomy for inner lesions. METHODS: We retrospectively analysed 570 patients with small (≤2 cm) cN0 non-small-cell lung cancer who underwent segmentectomy or lobectomy between January 2007 and March 2021. We focused on patients with lesions located in the inner two-thirds, which were determined using three-dimensional computed tomography (n = 227). After propensity score matching analysis based on sex, age, pulmonary function, serum carcinoembryonic antigen level, radiographic tumour findings and tumour location, we compared the surgical and oncological outcomes in patients who underwent segmentectomy (n = 66) and lobectomy (n = 66). RESULTS: Postoperative mortality or morbidity did not differ significantly between the 2 groups. The 5-year recurrence-free and overall survival rates in the segmentectomy and lobectomy groups were 93.6% vs 84.1% and 95.8% vs 87.9%, respectively. The differences between 2 groups were not significant (P = 0.62 and P = 0.23, respectively). The 2 groups also showed no differences in loco-regional recurrence. Multivariable Cox regression analysis revealed that segmentectomy had a comparable impact on recurrence-free survival (hazard ratio, 0.61; 95% confidence interval, 0.17-2.03; P = 0.43). CONCLUSIONS: Segmentectomy for inner-located small-sized non-small-cell lung tumours could be an acceptable treatment in comparison with lobectomy.

Resected stage I anaplastic lymphoma kinase-positive lung adenocarcinoma has a negative impact on recurrence-free survival.

BACKGROUND: The clinical and prognostic implications of anaplastic lymphoma kinase (ALK) status in resected lung cancers remain unclear. In this study we analyzed the prognostic and predictive significance of ALK-positive among patients with completely resected lung adenocarcinoma. METHODS: We retrospectively reviewed 197 patients with lung adenocarcinoma who underwent complete surgical resection and had been tested for their ALK status. We investigated the impact of an ALK-positive status on the recurrence-free survival (RFS) and overall survival (OS) and examined the predictive factors for an ALK-positive status. RESULTS: ALK positivity was noted in 36 (18%) out of 197 patients, and when limited to stage I patients, in 24 (19%) out of 124. In the pathological-stage I population, while the OS exhibited no significant difference between ALK-positive and ALK-negative patients (5-year OS rate, 81.2% vs. 89.8%, p = 0.226), the RFS of ALK-positive patients was significantly worse than that of ALK-negative patients (5-year RFS rate, 55.9% vs. 78.8%, p = 0.018). A multivariate analysis showed that ALK-positive status (hazard ratio [HR] 3.431, p = 0.009) was an independent prognostic factor for the RFS. Regarding the relationship between clinicopathological factors and an ALK-positive status, a high-grade histological subtype, including solid and micropapillary subtypes (odds ratio [OR] 5.464, p < 0.001), and never-smokers (OR 4.292, p = 0.018) were associated with ALK-positive. CONCLUSION: A high-grade histological subtype and never-smokers were associated with ALK positivity, and the RFS of ALK-positive patients was worse than that of ALK-negative patients among patients with completely resected stage I lung adenocarcinoma.

Segmentectomy for Inner Location Small-Sized Non-Small Cell Lung Cancer: Is It Feasible?

BACKGROUND: The efficacy of segmentectomy for inner small-sized non-small-cell lung cancer (NSCLC) remains unknown. We aimed to elucidate whether segmentectomy for inner small-sized NSCLC, defined using a novel 3-dimensional measuring method, yields feasible oncologic outcomes compared with segmentectomy for outer lesions. METHODS: We retrospectively analyzed patients with small-sized (<2 cm) cN0 NSCLC who underwent segmentectomy between January 2007 and December 2020. The tumor centrality ratio, which was measured by using 3-dimensional reconstruction software, was evaluated. The location of tumor origin was confirmed pathologically. Cases with a ratio <2:3 and >2:3 were allocated to the inner group and outer group, respectively. Oncologic outcomes were compared between the 2 groups. RESULTS: Our cohort was divided into the inner group (n = 75) and outer group (n = 127). The proximal distance from a tumor was >20 mm in all cases. The tumor centrality ratio was associated with the pathologic origin of a tumor. The rate of unforeseen positive lymph node metastasis was significantly higher in the inner group (P = .04). There were no significant differences in the 5-year recurrence-free survival (91% vs 87%, P = .67). Univariate analysis identified age, consolidation/tumor ratio, the presence of ground-glass opacity, and lymphovascular invasion, but not tumor centrality, as significant prognostic factors for recurrence-free survival. In the multivariate analysis, the presence of ground-glass opacity and lymphovascular invasion remained significant. CONCLUSIONS: Regarding oncologic outcomes, segmentectomy with a safety proximal distance could be feasible, even for inner small-sized NSCLC. Tumor invasiveness, not tumor centrality, may influence tumor recurrence.

The difference in postoperative pulmonary functional change between upper and lower thoracoscopic lobectomy.

OBJECTIVES: Through 3-dimensional lung volumetric and morphological analyses, we aimed to evaluate the difference in postoperative functional changes between upper and lower thoracoscopic lobectomy. METHODS: A total of 145 lung cancer patients who underwent thoracoscopic upper lobectomy (UL) were matched with 145 patients with lung cancer who underwent thoracoscopic lower lobectomy (LL) between April 2012 and December 2018, based on their sex, age, smoking history, operation side, and pulmonary function. Spirometry and computed tomography were performed before and 6 months after the operation. In addition, the postoperative pulmonary function, volume and morphological changes between the 2 groups were compared. RESULTS: The rate of postoperative decreased and the ratio of actual to predicted postoperative forced expiratory volume in 1 s were significantly higher after LL than after UL (P < 0.001 for both). The tendency above was similar irrespective of the resected side. The postoperative actual volumes of the ipsilateral residual lobe and contralateral lung were larger than the preoperatively measured volumes in each side lobectomy. Moreover, the increased change was particularly remarkable in the middle lobe after right LL. The change in the D-value, representing the structural complexity of the lung, was better maintained in the left lung after LL than after UL (P = 0.042). CONCLUSIONS: Pulmonary function after thoracoscopic LL was superior to that after UL because the upward displacement and the pulmonary reserves of the remaining lobe appeared more robust after LL.

Comparison of oncological outcomes between trisegmentectomy and lobectomy for non-small cell lung cancer in the left upper division.

Background: The left upper lobe is one of the largest lobes in the lungs and is divided into two anatomical units: the upper division (segments 1+2 and segment 3) and lingula (segments 4 and 5). This anatomical classification is similar to that used for the right upper and middle lobes. Although bilobectomy is not recommended for right upper or middle lobe tumors close to the interlobar plane, lobectomy is often performed for tumors located close to the intersegmental plane in the left upper division. To aid in establishing trisegmentectomy as a standard treatment for clinical N0 non-small cell lung cancer (NSCLC) in the left upper lobe, we aimed to re-assess its feasibility based on oncological outcomes according to tumor location. Methods: We retrospectively analyzed the data of patients with clinical N0 NSCLC in the left upper division who underwent left upper lobectomy or trisegmentectomy between April 2006 and December 2020. After propensity score matching, oncological outcomes were compared between the trisegmentectomy and lobectomy groups. To verify whether trisegmentectomy was indicated regardless of tumor distance from the intersegmental plane, we compared the recurrence-free survival (RFS) rates following trisegmentectomy between patients with tumors ≤20 and >20 mm from the intersegmental plane. Results: After propensity score matching, 46 patients were included in each group. There was no significant difference in the 5-year RFS rate between the lobectomy and trisegmentectomy groups (75.5% vs. 84.0%, P=0.41). In the trisegmentectomy cohort, the 5-year RFS rate did not significantly differ according to tumor distance from the intersegmental plane (≤20 or >20 mm) measured using three-dimensional computed tomography (79.4% vs. 81.2%, P=0.69). Multivariate analysis indicated that tumor distance from the intersegmental plane was not a significant predictor of RFS (hazard ratio: 1.75, 95% confidence interval: 0.52-5.91, P=0.37). Conclusions: Our analysis suggests that oncological outcomes (i.e., RFS rates) following trisegmentectomy for clinical N0 NSCLC in the left upper division are not significantly inferior to those following lobectomy, even if the tumor is located close to the intersegmental plane.

Cellular cannibalism and consequent thrombocytopenia in a patient with bone marrow metastasis of malignant pleural mesothelioma: A case report.

Cellular cannibalism is a tumor activity where a cell is engulfed by another cell. This process promotes tumor cell survival under unfavorable conditions. The current report describes an extremely rare case of thrombocytopenia resulting from cellular cannibalism in a patient with bone marrow metastasis due to malignant pleural mesothelioma (MPM). A 77-year-old male presented with hemothorax and thrombocytopenia. He was diagnosed with MPM of the sarcomatoid cell type. However, his disease progressed rapidly and he died 11 days after admission. Bone marrow aspiration revealed metastatic MPM cells that had engulfed other blood cells. Accordingly, the observed thrombocytopenia was attributed to cellular cannibalism by metastatic MPM tumor cells. To the best of our knowledge, this is the first reported case of thrombocytopenia due to cellular cannibalism in a patient with this type of malignancy (MPM). The results suggested that although MPM rarely metastasizes to the bone marrow, bone marrow aspiration could be useful in such cases.

Prognostic significance of preoperative haemoglobin A1c level in patients with lung adenocarcinoma.

OBJECTIVES: We investigated the influence of the preoperative haemoglobin A1c (HbA1c) value on the prognosis and pathology of patients with lung adenocarcinoma who underwent surgery. METHODS: We reviewed the medical records of 400 lung adenocarcinoma patients who underwent lobectomy with mediastinal lymph node dissection between 2009 and 2013 using a prospectively maintained database. We stratified 400 patients into 4 groups according to the preoperative HbA1c value as follows: HbA1c ≤ 5.9 (n = 296), 6.0 ≤ HbA1c ≤ 6.9 (n = 70), 7.0 ≤ HbA1c ≤ 7.9 (n = 21) and HbA1c ≥ 8.0 (n = 12). We compared the recurrence-free survival and overall survival (OS) among these 4 groups. Univariate and multivariate analyses were performed to identify the risk factors for recurrence. RESULTS: The median follow-up period was 61.2 months. On comparing the recurrence-free survival and OS rates among these 4 groups, we found that these rates among patients in the HbA1c ≥ 8.0 group were significantly poorer compared with the other 3 groups (5-year recurrence-free survival: HbA1c ≤ 5.9, 70.4%; 6.0 ≤ HbA1c ≤ 6.9, 69.7%; 7.0 ≤ HbA1c ≤ 7.9, 70.7%; ≥8.0 HbA1c, 18.8%; P = 0.002; and 5-year OS: HbA1c ≤ 5.9, 88.7%; 6.0 ≤ HbA1c ≤ 6.9, 80.6%; 7.0 ≤ HbA1c ≤ 7.9, 90.2%; ≥8.0 HbA1c, 66.7%; P = 0.046). Patients in the HbA1c ≥ 8.0 group had significantly more tumours with vascular invasion (P = 0.041) and experienced distant metastasis significantly more often (P = 0.028) than those with other values. A multivariate analysis revealed that preoperative HbA1c ≥ 8.0 [hazard ratio (HR) 2.33; P = 0.026] and lymph node metastasis (HR 3.94; P < 0.001) were significant independent prognostic factors for recurrence. CONCLUSIONS: Our results revealed that preoperative HbA1c ≥ 8.0 is associated to poor prognosis due to the occurrence of distant metastasis and we should carefully follow these patients after surgery. CLINICAL REGISTRATION NUMBER: Hyogo Cancer Center, G-57.

Cluster analysis of emphysema for predicting pulmonary complications after thoracoscopic lobectomy.

OBJECTIVES: Despite significant advances in surgical techniques, including thoracoscopic approaches and perioperative care, the morbidity rate remains high after lung resection. This study focused on a low attenuation cluster analysis, which represented the size distribution of pulmonary emphysema and assessed its utility for predicting postoperative pulmonary complications after thoracoscopic lobectomy. METHODS: From April 2013 to September 2018, lung cancer patients who received spirometry and computed tomography (CT) before surgery and underwent thoracoscopic lobectomy were included. The cumulative size distribution of the low attenuation area (LAA, defined as ≤-950 Hounsfield unit on CT) clusters followed a power-law characterized by an exponent D-value, a measure of the complexity of the alveolar structure. D-value and LAA% (LAA/total lung volume) were calculated using preoperative 3-dimensional CT software. The relationship between pulmonary complications and patient characteristics, including D-value and LAA%, was investigated. RESULTS: Among 471 patients, there were 61 respiratory complication cases (12.9%). Receiver operation characteristic curve analysis revealed that the best predictive cut-off value of D-value and LAA% for pulmonary complications was 2.27 and 16.5, respectively, with an area under the curve of 0.72 and 0.58, respectively. D-value was significantly correlated with % forced expiratory volume in 1 s. Per univariate analysis, gender, smoking history, forced expiratory volume in 1 s/forced vital capacity, LAA% and D-value were risk factors for predicting postoperative pulmonary complications. In the multivariate analysis, D-value remained a significant predictive factor. CONCLUSION: Preoperative assessment of emphysema cluster analysis may represent the vulnerability of the operated lung and could be the novel predictor for pulmonary complications after thoracoscopic lobectomy.

Pleural invasion, epidermal growth factor receptor mutation and carcinoembryonic antigen level affect pleural lavage cytology-positive status in non-small-cell lung cancer.

OBJECTIVES: Pleural invasion (pl) is strongly associated with the pleural lavage cytology (PLC) status. We analysed tumours with pl and evaluated the relationship between the PLC status and pl. METHODS: We retrospectively reviewed 428 surgically treated patients who had been diagnosed with non-small-cell lung cancer with pl and had their PLC status examined between 2000 and 2016. We investigated the influence of a PLC-positive status on the prognosis and searched for the factors predictive of a PLC-positive status. RESULTS: Seventy-eight (18%) patients were PLC positive. The recurrence-free survival of PLC-positive patients was significantly worse than that of PLC-negative patients in pl1 and pl2, but not in pl3 (5-year recurrence-free survival rate, PLC positive versus PLC negative: pl1, 22.0% vs 60.0%, P = 0.002; pl2, 30.4% vs 59.7%, P = 0.015; pl3, 50.0% vs 59.6%, P = 0.427). A multivariable analysis showed that the degree of pl (pl2-3 versus pl1) [odds ratio (OR) 5.34, P < 0.001] was an independent predictive factor for PLC positivity. Epidermal growth factor receptor (EGFR) mutation positivity (OR 5.48, P = 0.042) and carcinoembryonic antigen (CEA) ≥5 ng/ml (OR 3.78, P = 0.042) were associated with a PLC-positive status in patients with pl2-3. We found that the PLC-positive rate in patients with pl2-3 was 35.6%; however, if the tumour was EGFR mutation positive and had CEA ≥5 ng/ml, the PLC-positive rate increased to 77%. CONCLUSIONS: If a tumour was suspected of being pl2-3 and had EGFR mutation positivity and CEA ≥5 ng/ml, the PLC-positive rate was extremely high. CLINICAL TRIAL REGISTRATION NUMBER: Hyogo Cancer Center, G-138.

EWSR1-CREM fusion in pulmonary mesenchymal neoplasm showing distinctive clear cell morphology.

EWSR1-CREM gene fusions were recently discovered in several mesenchymal and epithelial tumors, including myxoid mesenchymal tumors of the central nervous system, rare cases of soft tissue clear cell sarcoma and angiomatoid fibrous histiocytoma, and hyalinizing clear cell carcinoma, which implicates the potential phenotypic diversities of tumors harboring an EWSR1-CREM fusion. We herein present an exceedingly indolent pulmonary mesenchymal tumor showing distinctive clinicopathological features. This tumor histologically displayed a small nest and alveolar pattern consisting of monomorphic clear cells intermingled with dilated anastomosing vasculature. Immunophenotypically, tumor cells were positive for vimentin and focally positive for synaptophysin, but negative for many immunohistochemical panels including keratins, EMA, desmin, mesothelial markers, melanotic markers, smooth muscle actin, inhibin and S-100 protein. Interestingly, RNA sequencing identified an in-frame EWSR1-CREM fusion, which was confirmed by subsequent real-time/reverse transcription polymerase chain reaction and fluorescence in situ hybridization assay. Clinical follow-up showed no evidence of recurrence and metastasis. Our pathological findings further expand the phenotypic spectrum of tumors associated with EWSR1-CREM fusions, implying the emergence of a possible novel tumor entity.

Thoracoscopic left S1 + 2 segmentectomy as a good resolution for preserving pulmonary function.

OBJECTIVES: Segmentectomies such as S1 + 2, S1 + 2+3 and S4 + 5 segmentectomy are used to treat patients with non-small-cell lung cancer (NSCLC) in the left upper lobe. However, the preservable lung volume and changes after such segmentectomies remain unknown. We compared the residual pulmonary function after thoracoscopic segmentectomy or lobectomy in the left upper lobe and examined the efficacy of S1 + 2 segmentectomy regarding postoperative pulmonary function. METHODS: Patients with left upper lobe NSCLC who underwent thoracoscopic segmentectomy or lobectomy were included. Spirometry and computed tomography were performed before and 6 months after resection, and the ipsilateral preserved lobe volume was calculated using 3-dimensional computer tomography. The percentage of postoperative/preoperative forced expiratory volume in 1 s and actual/predicted regional forced expiratory volume in 1 s (preservation rate) in the residual lobe were compared. RESULTS: Eighty-eight patients underwent lobectomy and 70 patients underwent segmentectomy (23 S1 + 2, 35 S1 + 2+3 and 12 S4 + 5 segmentectomies). The percentage of postoperative/preoperative forced expiratory volume in 1 s was 97 in S1 + 2, 82 in S1 + 2+3, 86 in S4 + 5 segmentectomy and 73 in left upper lobectomy, indicating that segmentectomy could be a meaningful approach to preserve pulmonary function. The preservation rate was 83% in S1 + 2 and 62% in S1 + 2+3 segmentectomy and was significantly higher in S1 + 2 than in S1 + 2+3 segmentectomy (P < 0.001). CONCLUSIONS: Postoperative pulmonary function and the preservable lung volume of the residual lobe after thoracoscopic S1 + 2 segmentectomy were well-preserved among other segmentectomies and lobectomy. Thoracoscopic S1 + 2 segmentectomy is a good alternative for preserving postoperative function.

DLL3 expression is a predictive marker of sensitivity to adjuvant chemotherapy for pulmonary LCNEC.

BACKGROUND: The mammalian Notch family ligands delta-like 3 (DLL3) is reported to be a potential therapeutic target for large cell neuroendocrine carcinomas (LCNEC). The effect of DLL3 expression on LCNEC prognosis has not yet been elucidated. METHODS: We reviewed the medical records of 70 LCNEC patients undergoing surgical resection between 2001 and 2015 using a prospectively maintained database. We performed immunohistochemistry for DLL3 and investigated the correlation between the sensitivity of LCNEC to platinum-based adjuvant chemotherapy. RESULTS: DLL3 expression was positive in 26 (37.1%) LCNEC patients. A total of 23 patients (32.9%) received platinum-based adjuvant chemotherapy. Among patients with DLL3 expression-positive tumors, no difference was found in the five-year overall survival (OS) or recurrence-free survival (RFS) between patients with and without adjuvant chemotherapy (surgery + chemotherapy vs. surgery alone, five-year OS: 58.3% vs. 35.7% P = 0.36, five-year RFS: 41.7% vs. 35.7% P = 0.74). In contrast, among patients with DLL3-negative tumors, significantly greater five-year OS and RFS rates were observed for patients with adjuvant chemotherapy than for those without it (surgery + chemotherapy vs. surgery alone: five-year OS: 90.0% vs. 26.9% P<0.01, five-year RFS: 80.0% vs. 21.7% P < 0.01). A multivariate analysis for the RFS revealed that adjuvant chemotherapy was a significant independent prognostic factor among patients with DLL3-negative tumors (hazard ratio [HR]: 0.05, 95% confidence interval [CI]: 0.01-0.41, P < 0.01), although it was not a factor among patients with DLL3-positive tumors (HR: 0.73, 95% CI: 0.23-2.27, P = 0.58). CONCLUSIONS: Our results revealed that DLL3 is a predictive marker of sensitivity to platinum-based adjuvant chemotherapy for LCNEC. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: DLL3 was a predictive marker of sensitivity to platinum-based adjuvant chemotherapy for LCNEC. Among patients with DLL3 expression-negative LCNEC, platinum-based adjuvant chemotherapy significantly improved the OS and RFS, although it did not do so among patients with DLL3 expression-positive LCNEC. WHAT THIS STUDY ADDS: Our results suggest that DLL3 expression-positive LCNEC may be better treated with other types of adjuvant chemotherapy, such as the anti-DLL3 therapies if these effects are confirmed by ongoing clinical research.