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Background: This study aimed to investigate the efficacy of adjuvant chemotherapy for pathologic stage I non-small cell lung cancer (NSCLC) with high risk for recurrence., Methods: Prospectively collected data from 1278 patients with pathologic stage I NSCLC according to eighth edition staging guidelines who were undergoing lobectomy were retrospectively analyzed. Factors associated with high risk for recurrence were determined using the multivariable Cox proportional hazards model for recurrence-free survival (RFS). Survival was compared between patients who received adjuvant chemotherapy and those who did not., Results: In multivariable analysis, age (≥70 years), invasive component size (>2 cm), visceral pleural invasion, lymphatic invasion, and vascular invasion were identified as independent factors for RFS. In patients with high-risk factors for recurrence such as pathologic T1c or T2a or lymphovascular invasion (high-risk group; n = 641), adjuvant chemotherapy resulted in significantly longer RFS and overall survival (n = 222; 5-year RFS, 81.4%; 5-year overall survival, 92.7%) than in patients who did not receive adjuvant chemotherapy (n = 418; 5-year RFS, 73.8%; P = .023; 5-year overall survival, 81.7%; P < .0001). In patients without any high-risk factors for recurrence (low-risk group; n = 637), RFS was not significantly different between those who received adjuvant chemotherapy (n = 83; 5-yeat RFS, 98.1%) and those who did not (n = 554; 5-year RFS, 95.7%; P = .30)., Conclusions: Adjuvant chemotherapy may improve survival in patients with pathologic stage I NSCLC who have factors associated with high risk for recurrence, such as pathologic T1c or T2a or lymphovascular invasion., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: We aimed to determine the influences of surgical procedures on the postoperative death of octogenarians with clinical Stage IA non-small cell lung cancer excluding cT1mi., Methods: We compared overall survival and the cumulative incidence of death due to all and other causes among 1 130 279, and 191 consecutive patients aged ≤79 and ≥80 years after lobectomy, segmentectomy and wedge resection at three institutions. Death due to other causes was defined as death due to any cause except non-small cell lung cancer., Results: The median followup was 53 months. The 5-year overall survival rates for patients aged ≥ 80 and ≤ 79 years after lobectomy, segmentectomy and wedge resection were respectively, 78.0% (95% confidence interval, 63.8%-87.2%) versus 91.2% (95% confidence interval, 89.0%-92.9%), 68.1% (95% confidence interval, 45.2%-83.1%) versus 90.0% (95% confidence interval, 84.6%-93.5%), and 62.7% (95% confidence interval, 44.0-76.7%) versus 84.4% (95% confidence interval, 76.3%-89.9%) (P < 0.01 for all). The cumulative incidence of death due to other causes after wedge resection was similar between patients aged ≥ 80 and ≤ 79 years (P = 0.45), but significantly higher in those aged ≥ 80, than ≤ 79 years after lobectomy or segmentectomy (P = 0.00015 and 0.00091, respectively)., Conclusions: The influence of wedge resection on death due to other causes was lower than that of lobectomy or segmentectomy in patients with non-small cell lung cancer aged ≥ 80 years. Wedge resection might be a useful option for octogenarians even if they can tolerate lobectomy/segmentectomy to avoid postoperative death due to causes other than non-small cell lung cancer., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Complex segmentectomy creates several intricate intersegmental planes; however, it has not been fully established in lung cancer treatment. We compared the oncologic outcomes of complex segmentectomy and lobectomy through a large cohort, multicenter database using propensity score-matched analysis., Methods: We retrospectively analyzed data from 1517 patients with clinical stage I lung cancer with a solid component size 2.0 cm or less, who underwent surgical resection at 3 institutions between 2010 and 2018. Complex segmentectomy (n = 240) and location-adjusted lobectomy (n = 851) as well as surgical results were analyzed for all patients and their propensity score-matched pairs., Results: The prognosis of patients undergoing complex segmentectomy was not significantly different from that of patients undergoing lobectomy (5-year cancer-specific survival [CSS] rate, 96.4% versus 97.2%, P = .69; and 5-year recurrence-free interval [RFI] rate, 95.8% versus 93.4%, P = .19). This trend was also identified in subanalyses for pure solid tumors. However, there were major differences in clinicopathologic features between the 2 groups. After propensity score-matched analysis, proper matching of patients was ascertained. In 219 propensity score-matched pairs, long-term outcomes were similar between patients undergoing complex segmentectomy (5-year CSS, 96.0%; 5-year RFI, 95.5%) and lobectomy (5-year CSS, 97.8%; 5-year RFI, 95.9%). Propensity score-adjusted multivariable analysis for RFI revealed that prognosis associated with complex segmentectomy was comparable to the prognosis obtained with lobectomy (hazard ratio = 0.98; 95% confidence interval, 0.33-2.40; P = .98)., Conclusions: Complex segmentectomy provides acceptable oncologic outcomes in clinical stage I lung cancer treatment., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Anatomical resection with lymph node dissection is the standard treatment for early non-small cell lung cancer, whereas wedge resection is considered as a compromise. We aimed to determine whether wedge resection without lymph node dissection could be a treatment option for patients aged ≥80 years., Methods: We assessed 669 patients with clinical stage IA non-small cell lung cancer, whole tumour sizes ≤2 cm and a consolidation to tumour ratio of >0.5 who underwent R0 resection at three institutions between 2010 and 2016. We selected 58 of them who were aged ≥80 years and analysed their clinicopathological findings and prognosis after surgical procedures over a median follow-up of 38 months. Propensity scores for surgical procedures were calculated using age, gender, smoking status and solid tumour size on computed tomography., Results: Three-year overall and recurrence-free survival rates after wedge resection and after segmentectomy + lobectomy for patients aged ≥80 years did not significantly differ (overall survival: 88.9% [95% confidence interval, 69.4-96.3%] vs. 75.5% [95% confidence interval, 51.5-88.8%], P = 0.95; recurrence-free survival: 85.2% [95% confidence interval: 65.2-94.2%] vs. 68.0% [95% confidence interval, 44.4-83.2], P = 0.57). Multivariable Cox regression analysis of overall survival with propensity scores revealed that surgical procedure was not an independent predictor of a poor prognosis (hazard ratio: 0.86 (0.28-2.6), P = 0.78) in patients aged ≥80 years., Conclusions: Wedge resection might be an alternative to lobectomy or segmentectomy with lymph node dissection for patients aged ≥80 years with early non-small cell lung cancer., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: The prognosis of patients with cT1N0 lung adenocarcinoma is better when tumors include mixed ground glass opacity (GGO), compared with pure solid tumors. However, whether the prognosis of patients with mixed GGO tumors is favorable regardless of the solid component size remains unknown. Therefore, we aimed to determine the prognostic role of the solid component size in mixed GGO., Methods: We retrospectively analyzed the clinicopathological findings and prognoses of 856 patients with mixed GGO tumors based on solid component size during a median follow-up of 45 months, among 1215 patients with cT1N0 lung adenocarcinoma according to the TNM Classification of Malignant Tumors, Eighth Edition, who underwent R0 resection at 3 institutions between 2010 and 2015., Results: Four-year recurrence-free survival rates were significantly worse for patients with mixed GGO cT1c tumors (solid component size: 2-3 cm; 81.5%; 95% confidence interval [CI], 72.8%-87.7%) than for those with cT1mi+1a tumors (0-1 cm; 96.8%; 95% CI, 94.2%-98.2%) and cT1b (1-2 cm; 95.3%; 95% CI, 92.1%-97.2%) (both P < .001), although that for cT1b tumors was comparably favorable to those of T1mi+1a tumors. Multivariable Cox regression analysis of recurrence-free survival revealed that a solid component size of 2 cm to 3 cm (cT1c) vs less than or equal to 2 cm (cT1mi+1a+1b) was an independent prognostic factor (hazard ratio, 4.16; 95% CI, 2.24-7.72; P < .001)., Conclusions: The prognostic impact of a solid component size less than or equal to 2 cm and greater than 2 cm significantly differs after complete resection of GGO-mixed T1N0 lung adenocarcinoma. The prognosis of patients with solid components less than or equal to 2 cm is favorable, whereas the behavior of those solid components greater than 2 cm is more aggressive., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Recurrence risk of resected lung adenocarcinoma is represented by pathological stage (pStage), histological subtype, and potentially by EGFR mutation. However, the relationship among these factors and their combined impact on prognosis are unclear., Materials and Methods: Using a multicenter database, we retrospectively investigated the prognostic impact of EGFR mutation status in relation to pStage and histological subtype in resected pN0-1M0 lung adenocarcinoma., Results: Among 1155 pN0-1M0 adenocarcinoma cases, pStage 0 and IA1-IB were confirmed predominantly in EGFR-positive cases. AIS, MIA, and lepidic predominant adenocarcinoma were also more frequently found in EGFR-positive cases and showed no/little recurrence regardless of EGFR mutation status. The 5-year recurrence-free survival (RFS) of papillary, acinar, solid, and micropapillary predominant adenocarcinoma was stratified by pStage (IA1-IB, IIA-IIIA) or histological malignant subtype (intermediate or high malignant subtype), and more finely subdivided by EGFR mutation status. Positive EGFR mutation cases showed worse RFS in both classifications. Low malignant subtype and pStage IA1-IB intermediate malignant subtype showed low frequency of recurrence. Whereas, in pStage IA1-IB high malignant subtype and pStage IIA-IIIA cases, EGFR-positive cases showed poorer 5-year RFS than EGFR-negative (49.6% and 75.6%, respectively, hazard ratio [HR] = 1.84, 95% CI = 1.38-7.42, p <  0.01) and multivariate analysis indicated positive EGFR mutation status was significantly related to poorer PRF (HR = 2.005, 95% CI = 1.029-3.906, p =  0.041)., Conclusion: EGFR mutation harbored primarily in early-stage or low-malignant histological subtypes with no/little recurrence. In pN0-1M0 adenocarcinoma with higher risk of recurrence, positive EGFR mutation cases showed worse RFS. EGFR mutation status enables better stratification of recurrence risk when considering pStage and histological malignant subtype., Competing Interests: Declaration of Competing Interest None. Financial/nonfinancial disclosures: None Other contributions: The authors would like to thank Editage (www.editage.jp) for English language editing., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Quantitative computed tomography (CT) histogram analysis of tumors is reported to help distinguish between invasive and less invasive lung cancers. This study aimed to clarify whether CT histogram analysis of tumors can be used to classify patients with clinical stage 0 to IA non-small cell lung cancer according to pathologic lymph node (pN) status., Methods: Predictive factors associated with pN metastasis were identified from the derivation dataset including 629 patients with clinical stage 0 to IA non-small cell lung cancer who underwent complete resection with lymph node dissection (surgeries between 2008 and 2013). The validation dataset including 238 patients (surgeries between 2014 and 2015) were subsequently reevaluated. Clinicosurgical factors, including CT histogram analysis of tumors (CT value percentiles 2.5, 25, 50, 75, and 97.5, skewness, and kurtosis) were assessed., Results: Seventy-three patients (12%) in the derivation cohort and 35 patients (15%) in the validation cohort had positive nodes. The pN status significantly affected survival in the entire population: 5-year overall survival of 93.1% vs 71.1% and 5-year disease-free survival of 85.9% vs 43.1% for negative vs positive (both P < .001). On multivariate analysis in the derivation cohort, the 75th percentile CT value (P < .001), age (P = .003), and comorbidities (P = .006) were significantly associated with pN metastasis. The area under the curve and the cutoff level of the 75th percentile CT value relevant to pN metastasis were 0.729 and 1.5 HU, respectively, and the threshold value provided accuracy of 71% for the validation cohort., Conclusions: Histogram analysis of CT imaging metrics of tumors contributes to noninvasive prediction of pN metastasis in patients with clinical stage 0 to IA non-small cell lung cancer., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to analyze the accuracy of computed tomography (CT) and F-18 fluorodeoxyglucose-positron emission tomography/CT (FDG-PET/CT) to distinguish lepidic growth adenocarcinoma (LGA), including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic-predominant adenocarcinoma, all of which have favorable survival outcomes, from the more aggressive and invasive non-LGA subtypes., Materials and Methods: We identified 225 patients with c-0/I adenocarcinoma of the lung who underwent PET/CT and 3DCT followed by complete resection. Maximum standardized uptake values (SUVmax) of FDG and several histogram parameters were analyzed. Histological grades were classified according to the predominant subtype (G1: lepidic; G3: micropapillary or solid; and G2: subtypes other than G1/G3)., Results: The proportion of pathological invasive factors (lymphatic vessel involvement/blood vessel invasion/pleural invasion/lymph node metastasis) of patients with preinvasive adenocarcinoma, G1, G2, and G3 tumors were 0%, 3.6%, 48.0%, and 100%, respectively; p <  0.001). Multivariate analysis with CT-related parameters demonstrated that 75 th percentile CT attenuation value (75 th %, p <  0.001) and maximum CT attenuation value (maxCT, p =  0.009) were associated with incidence of non-LGA, whereas the value of SUVmax demonstrated a significant correlation (p <  0.001). When all patients were dichotomized according to ground-glass opacities (GGO)/solid-dominancy for CT maximum diameter, a significant correlation with non-LGA was shown in patients with solid-dominant tumor on SUVmax (p <  0.001) and with GGO-dominant tumor on 75 th % (p =  0.006) and maxCT (p =  0.007). The combination of one of the two significant histogram parameters and SUVmax revealed higher predictive performance for pathological high malignant features (positive pathological invasive factors, non-LGA, and the highly malignant subtype covering G2 with moderately or poorly-differentiated carcinoma and G3) than the individual use of either factor., Conclusion: The 75 th %, maxCT, and SUVmax were highly useful in distinguishing LGA from non-LGA in c-0/I adenocarcinoma., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to conduct comparative analyses of the biological malignant potential of clinical stage IA adenocarcinoma using positron emission tomography/computed tomography (PET/CT), high-resolution CT (HRCT), and three-dimensional CT (3DCT). The predictive performance of these parameters was evaluated in terms of clinical outcomes and pathological invasiveness (positive lymphatic permeation, blood-vessel invasion, pleural invasion, and lymph-node metastasis)., Materials and Methods: We enrolled 170 patients with c-IA adenocarcinoma who underwent PET/CT, HRCT, and 3D reconstruction of lung structures using the Synapse Vincent system (Fujifilm Corporation, Tokyo, Japan) followed by complete resection. Maximum standardized uptake values (SUV max ) of F 18 -fluorodeoxyglucose and the size and volume of the solid part of the tumor were quantified and analyzed in relation to surgical outcomes., Results: Univariate analysis demonstrated that all the three parameters and whole-tumor volume were associated with unfavorable disease-free survival (DFS), while the volume of the solid part was the independent predictor on multivariate analysis (p < .001). The receiver operating characteristic curves for pathological invasiveness, determined using the variables dichotomized at each cut-off level (SUV max 2.4; solid-part size 1.23 cm; solid-part volume 779 mm 3 ), showed that all were significantly correlated with pathological invasiveness and prognosis, whereas the combination of SUV max and the solid-part volume was the most powerful predictor of survival and pathological invasiveness compared to any other parameters: the 4-year DFS and proportion of pathological invasiveness in patients with SUV max  > 2.4 and solid-part volume > 779 mm 3 versus those with SUV max  ≤ 2.4 or solid-part volume ≤779 mm 3 were 81.2% versus 98.3% (p < .001) and 84.3% versus 15.1% (p < .001), respectively., Conclusion: In c-IA adenocarcinoma, the volume of the solid part of the tumor was the independent predictor for unfavorable DFS, and the integration of the volume of the solid part and SUV max was highly beneficial for the prediction of survival and pathological invasiveness., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We report a case of metachronous multiple lung adenocarcinoma at the cut-end, diagnosed 4 years after sublobar resection for adenocarcinoma in situ (AIS), on the basis of discordance of epidermal growth factor receptor (EGFR) mutation status between the first and second tumor. The patient was an 81-year-old Japanese man, whose chest computer tomography (CT) scan showed mixed ground-glass opacity in the right upper lobe of the lung. Wedge resection was performed and a diagnosis of AIS, non-mucinous (18 × 14 mm), with a margin of 6 mm, was made. A tumor at the cut-end was seen on a CT scan 4 years later, and abnormal uptake was identified by fluorine-18 fluorodeoxyglucose-positron emission tomography. Right upper lobectomy and lymph node dissection were performed and the tumor was diagnosed as invasive adenocarcinoma, acinar predominant. Discordance of EGFR mutation status between the first tumor, harboring exon 19 deletion, and the second tumor, having an L858R point mutation in exon 21, revealed that the second tumor was metachronous multiple lung cancer. This case demonstrates the necessity of comparing EGFR mutation status between the first tumor and the second tumor at the cut-end.

To identify a possible new treatment modality for malignant pleural mesothelioma (MPM), we examined whether combination treatment consisting of pemetrexed chemotherapy and photodynamic therapy (PDT) using the photosensitizer NPe6, enhanced the antitumor effect in both in vitro and in vivo models. We also investigated preclinical treatment schedules. Four human malignant mesothelioma cell lines (MSTO‑211H, H2052, H2452 and H28) were assayed using the WST assay after treatment with pemetrexed and NPe6‑PDT. The treatment schedule for the combination treatment was examined using nude mice. Pemetrexed pre‑treatment enhanced the lethal effect of NPe6‑PDT in the four malignant mesothelioma cell lines, but NPe6‑PDT followed by pemetrexed treatment did not enhance cell lethality in the in vitro assay. Pemetrexed pre‑treatment did not enhance the intracellular accumulation of NPe6, which is one of the determinants of the antitumor effect of PDT. In nude mice injected with MSTO‑211H cells and then treated using a combination of pemetrexed and NPe6‑PDT (10 mg/kg NPe6, 10 J/cm(2) laser irradiation), the tumor volume decreased by 50% but subsequently increased, reaching the pre‑treatment value after 14 days. Pemetrexed treatment followed by NPe6‑PDT resulted in an 80% reduction in the tumor size and inhibited re‑growth. NPe6‑PDT followed by pemetrexed treatment resulted in a 60% reduction in tumor size but did not inhibit re‑growth. NPe6‑PDT induced the expression of thymidylate synthase (TS), which confers resistance to pemetrexed, and NPe6‑PDT followed by pemetrexed treatment did not enhance the treatment outcome in vivo. In conclusion, combination treatment, consisting of pemetrexed followed by NPe6‑PDT, should be further investigated as a new treatment modality for MPM. In the future, this combination treatment may contribute to a reduction in local recurrence and a prolonged survival period in patients with MPM.

Background: The rapid aging of the population in Japan has been accompanied by an increased rate of surgery for lung cancer among elderly patients. It is thus an urgent priority to map out a treatment strategy for elderly patients with primary lung cancer. Although surgical resection remains standard treatment for early stage non-small-cell lung cancer (NSCLC), it is now essential to confirm the status of epidermal growth factor receptor (EGFR) gene mutations when planning treatment strategies. Furthermore, several studies have reported that EGFR mutations are an independent prognostic marker in NSCLC. However, the relations between age group and the molecular and pathological characteristics of NSCLC remain unclear. We studied the status of EGFR mutations in elderly patients with NSCLC and examined the relations of EGFR mutations to clinicopathological factors and outcomes according to age group., Methods: A total of 388 consecutive patients with NSCLC who underwent complete tumor resection in our hospital from 2006 through 2008 were studied retrospectively. Formalin-fixed, paraffin-embedded tissue sections were used to isolate DNA from carcinoma lesions. Mutational analyses of EGFR gene exons 19, 20, and 21 and KRAS gene exons 12 and 13 were performed by loop-hybrid mobility shift assay, a highly sensitive polymerase chain reaction-based method., Results: EGFR mutations were detected in 185 (47.7%) and KRAS mutations were detected in 33 (8.5%) of the 388 patients. EGFR mutations were found in a significantly higher proportion of patients younger than 80 years (younger group; 178/359, 49.6%) than in patients 80 years or older (older group; 7/29, 24.1%) (P = 0.008). In contrast, KRAS mutations were more common in the older group (6/29, 20.7%) than in the younger group (27/359, 7.5%) (P = 0.014). The older group showed a trend toward a higher rate of 5-year overall survival among elderly patients with EGFR mutations (100%) than among those with wild-type EGFR (66.2%), but the difference was not significant., Conclusions: Our results suggest that the EGFR status of patients with NSCLC differs between patients 80 years or older and those younger than 80 years. EGFR mutation status might be a prognostic marker in elderly patients with completely resected NSCLC.

Objective: We examined the appropriate measurement for pathological tumor size by comparing radiological and pathological tumor size of resected lung adenocarcinoma in FSE., Materials and Methods: We reviewed records of 59 resected specimens of lung adenocarcinoma for FSE from January to December 2008. Specimens were well-inflated with saline by using an injector before cutting into segments. After selecting the tumor segment of maximal diameter, we compared three ways of measuring pathological tumor size by using paired t-test: (I) macroscopic tumor size (MTS), measured with a metal straight ruler, (II) microscopic frozen section tumor size (FSTS), and (III) microscopic paraffin section tumor size (PSTS). We compared each discrepancy rate (DR) [DR=(CT tumor size-pathological tumor size)/CT tumor size×100] (%) between tumors that were air-containing type and solid-density type on CT scans, and also compared the tumors with lepidic component rates (LCR) ≥50% and LCR <50%, by using Mann-Whitney U-tests., Results: FSE could diagnose malignancy with 100% accuracy. The mean CT tumor size was 18.36mm, and the mean pathological tumor sizes (MTS, FSTS, and PSTS) were 17.81, 14.29, and 14.23mm, respectively. FSTS and PSTS were significantly smaller than CT tumor size (p<0.001). The DR calculated with PSTS was significantly larger in air-containing than in solid-density tumors, and also larger in LCR ≥50% than in LCR <50% tumors., Conclusion: FSE with the inflation method diagnosed malignancy with 100% accuracy. The lung specimen must be sufficiently inflated to prevent tissue shrinking, and we propose MTS as the definition for pathological tumor size in FSE. The greater discordance observed between CT tumor size and microscopic tumor size was assumed to be due to shrinkage of the lepidic component in the tumor., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Solitary pulmonary capillary hemangioma (SPCH) is a rare benign lung tumor that must be distinguished from small and early lung cancers. Here, we report a case of SPCH for which we performed frozen section diagnosis. The patient was a 55-year-old Japanese woman. Five years before the operation, mixed ground-glass opacity was detected by computed tomography in the left posterior basal segment of the lower lobe (S10). Because the interior tumor density of the ground-glass opacity increased slightly, video-assisted thoracic surgery wedge resection was performed. Frozen section diagnosis revealed a benign tumor without proliferation of atypical epithelial cells. The tumor had narrow alveolar lumens, thickened alveolar septa and a clear boundary separating it from normal lung tissue. The proliferated lumens varied in size and were lined with single layers of flat cells. After the operation, immunohistochemical staining of a paraffin section revealed that the thickened alveolar septa resulted from the proliferation of capillary vessels, the flat cells of which were positive for CD31 and CD34 and negative for podoplanin; the tumor was diagnosed as SPCH. Here, we discuss the pathological features of SPCH on frozen sections with reference to this case and review previous related reports., (© 2013 The Authors. Pathology International © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.)

We report a rare case of lung adenocarcinoma in which micropapillary components were considered to cause stump recurrence. A woman in her fifties was diagnosed with lung cancer in the right middle lobe with invasion to the upper lobe, which was treated by a right middle lobectomy together with upper lobe partial resection. The cancer was pathologically diagnosed as adenocarcinoma and had a free surgical margin. There was no recurrence during the following 5 years and 8 months, and thus periodical surveillance, including computed tomography, was stopped. However, 2 years and 7 months after this, she was discovered to have an abnormal shadow on chest radiography, and a thorough examination revealed a 3-cm-sized tumor involving the previous surgical margin. Therefore, she underwent right upper lobectomy. We pathologically re-evaluated the first tumor and found that it was an adenocarcinoma with a micropapillary component in the periphery, 6mm away from the surgical margin. In addition, a few tiny clusters of tumor cells were found to be floating within the alveolar spaces near the margin. The first and second tumors showed almost the same histological mixture of components of adenocarcinoma and the same EGFR mutation. From these results, we concluded the second tumor was a stump recurrence originating from the first tumor resection. This case illustrates the importance of careful pathological investigation when an autosuture instrument is used for a partial resection in a case of lung adenocarcinoma with micropapillary components. In such cases, it is particularly important to clarify if micropapillary components are floating near a stump., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Patients with large cell neuroendocrine carcinoma (LCNEC) of the lung are considered to have poor prognosis. However, the benefit of adjuvant chemotherapy for these patients has not been established. In this study, we retrospectively evaluated the efficacy of perioperative chemotherapy for patients with completely resected LCNEC in a single-center setting. From 1999 through 2007, 45 patients with surgically resected LCNEC or mixed LCNEC containing at least one portion of the neuroendocrine differentiation or morphology in non-small cell lung carcinoma were enrolled as participants of this study. Survival rates were calculated by the Kaplan-Meier method. Differences between survival curves were computed with the log-rank test. For multivariate analysis, the Cox's proportional hazards regression model was used to evaluate variables that were significant predictors of survival. Of 1397 patients undergoing surgical resection for primary lung cancer from 1999 to 2007, 45 (3.2%) were classified as LCNEC. Thirty-six (80%) patients were men, and nine (20%) were women. Twenty-four (92%) of 26 patients were present or past smokers. Twenty-three (41%) of 45 patients received perioperative chemotherapy, including seven induction chemotherapies and 16 adjuvant chemotherapies. Survival of patients who underwent perioperative adjuvant chemotherapy was significantly higher than that of those who received surgery alone (P = 0.04). The 5-year survival rate of patients who underwent perioperative adjuvant chemotherapy was 87.5%, whereas that of patients who underwent surgery alone was 58.5%. Even in stage I cases, perioperative adjuvant chemotherapy still favors survival compared with surgery alone. In the Cox proportional hazard multivariate analysis, surgery with or without chemotherapy showed an independent prognostic influence on overall survival (P = 0.0457). Patients who received surgery alone were 9.5 times more likely to die than patients who underwent surgery plus chemotherapy. In conclusion, perioperative chemotherapy will be needed to improve survival in patients with LCNEC. As the population of LCNEC is small, it has been difficult to conduct randomized controlled trials to show the survival benefit of adjuvant chemotherapy. This should be, therefore, evaluated further in prospective multi-institutional phase II trials.