Abstract Objects Pulmonary adenocarcinoma with a micropapillary component (MPC) has aggressive malignant behavior even if resectable. The aim of this study was to determine clinicopathological ...features of patients who underwent surgery for pulmonary adenocarcinoma harboring MPCs, with particular focus on coexistent free tumor clusters (FTCs). Methods We retrospectively reviewed 444 pulmonary adenocarcinoma patients who underwent surgery from March 2007 to July 2013. A MPC was defined as a >5% micropapillary pattern 9. We also defined FTCs to be a group of more than three small clusters containing <20 nonintegrated micropapillary tumor cells that were spreading within air spaces, >3 mm apart from the main tumor. The clinicopathological characteristics of patients with and without FTCs were retrospectively investigated in MPC-positive patients. Results MPCs were identified in 67 patients (15.1%), of whom 31 patients (46.3%) were positive for FTCs. The distance between the furthest edge of FTCs and main tumors did not exceed the diameter of the main tumor in each case (average, 7.3 mm). Loco-regional recurrences were frequently observed in FTC-positive patients. FTC-positive patients experienced a significantly lower 5-year recurrence-free survival rate compared to FTC-negative/MPC-positive patients (20.4% vs 52.2%, p<0.001). Recurrence-free survival of FTCs-negative and positive patients were equivalent to that of patients with p-T2 and p-T3 MPC-negative adenocarcinoma, respectively. Conclusions Coexistence of FTCs resulted in a further negative impact on postoperative prognosis among MPC-positive adenocarcinomas, and should be considered for upstaging the p-T factor and during evaluation of surgical margins.
Background Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a life-threatening complication of lung cancer operation for patients with IPF, and no effective prophylaxis has ever been ...reported. In this study, we investigate the effect of perioperative treatment with an anti-IPF agent on reduction of the risk of developing AE-IPF. Methods A consecutive series of 50 lung cancer patients with IPF who underwent operations at our institution from October 2006 to October 2014 was retrospectively investigated. Since September 2009, pirfenidone was orally administered to patients from 4 weeks before operation to 4 weeks after operation. Thirty-one patients received the perioperative pirfenidone treatment (PPT), and their clinical outcome was retrospectively compared with that of 19 patients who did not receive PPT. Results No differences were found in age, smoking history, sex, vital capacity, KL-6, procedure, or risk score (10.5 ± 2.2 versus 11.2 ± 1.5) between the PPT and non-PPT groups. The incidence of AE-IPF for the PPT/non-PPT groups was 0.0%/10.5% within 30 postoperative days ( p = 0.07) and 3.2%/21.1% within 90 postoperative days ( p = 0.04), respectively. Logistic regression analysis showed a significant association between PPT and the incidence of AE-IPF within 30 ( p = 0.045) and 90 ( p = 0.04) postoperative days. Conclusions A prophylactic effect of PPT for postoperative AE-IPF in patients with lung cancer was suggested. Further confirmatory prospective studies should be considered for PPT.
Background Integrated positron emission tomography (PET) with computed tomography (CT) is a useful modality to investigate lymph node metastases for non-small cell lung cancer, but is less sensitive ...for normal-sized lymph nodes. We sometimes encounter cases with radiologically normal lymph nodes and unsuspected mediastinal metastases detected by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). However, few studies have investigated staging in patients with radiologically normal mediastina, and the accuracy of EBUS-TBNA staging for radiologically normal mediastina and hila is unclear. Methods This study was a retrospective, single-institution review of a prospectively maintained database at Chiba Cancer Center between May 1, 2008, and September 1, 2013. We analyzed 113 non-small cell lung cancer patients with both CT-negative and PET/CT-negative lymph nodes (N0) in preoperative nodal staging performed by EBUS-TBNA. After preoperative staging was performed, patients with either N0 or N1 clinical staging underwent surgery. Final N factors were determined by mediastinal lymphadenectomy. Results In our study, the overall rate of N2 disease was 17.6% (20 of 113). For nodal staging by EBUS-TBNA, the sensitivity, specificity, negative predictive value, and diagnostic accuracy were 35.0% (7 of 20), 100% (93 of 93), 87.7% (93 of 106), and 88.4% (100 of 113), respectively. There were no severe complications from EBUS-TBNA staging. Conclusions The overall rate of unsuspected N2 was not low. EBUS-TBNA was accurate and feasible for preoperative mediastinal nodal staging of non-small cell lung cancer with both CT-negative and PET/CT-negative lymph nodes. The sensitivity of EBUS-TBNA for radiologically normal mediastina and hila was low. Further investigations are required.
Background A sessile serrated adenoma/polyp (SSA/P) is a common type of colorectal polyp that possesses malignant potential. Although narrow-band imaging (NBI) can easily differentiate neoplastic ...lesions from hyperplastic polyps (HPs), SSA/Ps can be a challenge to distinguish from HPs. Objective To investigate specific endoscopic features of SSA/Ps by using NBI with optical magnification. Design Retrospective study. Setting Single high-volume referral center. Patients A total of 289 patients with histopathologically proven SSA/Ps or HPs obtained from colonoscopic polypectomy. Intervention Endoscopic images obtained by using NBI with optical magnification of 242 lesions (124 HPs, 118 SSA/Ps) removed between January 2010 and December 2012 were independently evaluated by 2 experienced endoscopists. Three external experienced endoscopists systematically validated the diagnostic accuracies by using 40 lesions (21 HPs and 19 SSA/Ps) removed between January and March 2013. Main Outcome Measurements Specific endoscopic features of SSA/Ps by using 5 potential characteristics: dilated and branching vessels (DBVs), irregular dark spots, a regular network pattern, a disorganized network pattern, and a dense pattern. Results Multivariate analysis demonstrated that DBV had a 2.3-fold odds ratio (95% confidence interval, 0.96-5.69) among SSA/Ps compared with HPs (sensitivity, 56%; specificity, 75%; accuracy, 65%). Interobserver and intraobserver agreement indicated almost perfect agreement for DBVs in both the evaluation and validation studies. When DBVs, proximal location, and tumor size (≥10 mm) were combined, the positive predictive value was 92% and the area under the curve was 0.783 in the receiver-operating characteristics by using the validation group. Limitations Retrospective study. Conclusions The current study suggests that a DBV is a potentially unique endoscopic feature of a colorectal SSA/P.
Background Video-assisted thoracoscopic wedge resection of multiple small, non-visible, and nonpalpable pulmonary nodules is a clinical challenge. We propose an ultra-minimally invasive technique for ...localization of pulmonary nodules using the electromagnetic navigation bronchoscope (ENB)-guided transbronchial indocyanine green (ICG) injection and intraoperative fluorescence detection with a near-infrared (NIR) fluorescence thoracoscope. Methods Fluorescence properties of ICG topically injected into the lung parenchyma were determined using a resected porcine lung. The combination of ENB-guided ICG injection and NIR fluorescence detection was tested using a live porcine model. An electromagnetic sensor integrated flexible bronchoscope was geometrically registered to the three-dimensional chest computed tomographic image data by way of a real-time electromagnetic tracking system. The ICG mixed with iopamidol was injected into the pulmonary nodules by ENB guidance; ICG fluorescence was visualized by a near-infrared (NIR) thoracoscope. Results The ICG existing under 24-mm depth of inflated lung was detectable by the NIR fluorescence thoracoscope. The size of the fluorescence spot made by 0.1 mL of ICG was 10.4 ± 2.2 mm. An ICG or iopamidol spot remained at the injected point of the lung for more than 6 hours in vivo. The ICG fluorescence spot injected into the pulmonary nodule with ENB guidance was identified at the pulmonary nodule with the NIR thoracoscope. Conclusions The ENB-guided transbronchial ICG injection and intraoperative NIR thoracoscopic detection is a feasible method to localize multiple pulmonary nodules.
Background The utility of rapid on-site evaluation (ROSE) during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for lymph node staging in lung cancer is still ...controversial. The aim of this study was to assess the role of ROSE during EBUS-TBNA and the interpretation of its results. Methods We performed a retrospective chart review of patients with suspected or diagnosed lung cancer who underwent EBUS-TBNA for lymph node staging. The slides were air-dried and Diff-Quik (American Scientific Products, McGaw Park, IL) staining was used for ROSE. Additional smears were prepared for Papanicolaou staining and any remaining sample was placed in 10% formalin for histologic evaluation. The results of ROSE were compared with the results of the final pathologic diagnosis. Results EBUS-TBNA was performed in 438 patients on 965 lymph nodes. Eighty-four lymph nodes (8.7%) were determined insufficient for definitive diagnosis by final cytologic evaluation. However 45 of the 84 lymph nodes were able to be diagnosed by histologic examination. The non-diagnostic sampling rate was 4.0%. There were no false-positive results on ROSE; however 25 cases (5.7%) were falsely evaluated as negative on ROSE. The concordance rate for staging between ROSE and final pathologic diagnosis was 94.3%. The sensitivity, specificity, negative predictive value, and diagnostic accuracy rate of EBUS-TBNA for correct lymph node staging was 96.5%, 100%, 89.8%, and 98.2%, respectively. Conclusions ROSE during EBUS-TBNA for material adequacy showed a low rate of non-diagnostic sampling. There was a high agreement between the on-site and final pathologic evaluation during EBUS-TBNA; however immediate diagnosis should be approached with caution.
Background The importance of biomarker analysis in patients with non-small cell lung cancer (NSCLC) is well known. The purpose of this study was to analyze the mutation status of multiple genes in ...metastatic lymph nodes obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and to examine the correlation between treatments and outcomes. Methods Genetic alterations were analyzed in metastatic hilar or mediastinal lymph nodes diagnosed by EBUS-TBNA in 156 patients with NSCLC. Epidermal growth factor receptor ( EGFR ) was analyzed using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method (n = 156). V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( K-ras ) (exons 2-3) and tumor protein 53 ( p53 ) (exons 4-8) were analyzed by direct sequencing (n = 113). In addition, retrospective chart review was performed for clinical data analysis. Results EGFR gene mutations were detected in 42 cases (26.9%). Twenty-three patients with EGFR mutations received gefitinib, with an overall response rate (partial response PR) of 54.5% and disease control rate (PR + stable disease) of 86.4% (Response Evaluation Criteria in Solid Tumors). K-ras gene mutations were detected in four cases (3.5%), and p53 gene mutations were detected in 47 cases (41.6%). Fifty-two patients underwent conventional chemotherapy (46 patients underwent platinum-based chemotherapy). Patients with p53 gene mutations showed chemoresistance (progressive disease of 42.9%, P = .0339) and a relatively poor prognosis after chemotherapy ( P = .1391). Conclusions Multigene mutation analysis can be performed in EBUS-TBNA samples of metastatic lymph nodes from patients with NSCLC. EBUS-TBNA allows genetic evaluation of tumor cells within the metastatic node, which may allow physicians to better select treatments, particularly EGFR tyrosine kinase inhibitors.
Background Lung carcinoma is often associated with interstitial lung disease (ILD), and the prognosis of lung cancer accompanied by ILD is unfavorable. In this study, cases of patients with primary ...lung cancer with or without ILD were reviewed to analyze surgical outcome, with special interest in the conformity of clinical and pathologic stages, pathologic findings of pleural invasion, malignant pleurisy first detected at the time of thoracotomy, and survival. Methods Retrospective chart review was performed for 1,264 primary lung cancer patients who underwent surgery from 2004 to 2015. Concomitant ILD was diagnosed by pathological examination or preoperative chest computed tomography findings. Results ILD was found in 104 patients (8.2%) with primary lung cancer. Conformity of clinical and pathological stages in the ILD-positive patients was poor, with a lower kappa value than that for the 1,160 ILD-negative patients (0.34 versus 0.51). The ILD group had significantly higher incidences of pleural invasion and unexpected malignant pleurisy than did the non-ILD group (for pleural invasion, 49.0% versus 24.5%, p < 0.0001; for malignant pleurisy, 7.69% versus 1.47%, p < 0.0001). The 5-year overall survival rates of the ILD group showed significantly lower than those of the non-ILD group (45.2% versus 70.1%; p = 0.0014) after propensity score matching. Conclusions In lung cancer, the concomitant existence of ILD is a risk factor for pleural invasion. Concomitant ILD might cause underestimation of clinical staging, increase the chance of unexpected malignant pleurisy during surgery, and shorten survival time.
Background The aim of this study was to assess the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for differentiating cN0 versus cN1 non-small cell lung cancer. ...Methods A retrospective review of EBUS-TBNA results in patients with potentially resectable clinical N0 or N1 non-small cell lung cancer based on computed tomography and positron emission tomography was performed. Systematic mediastinal and hilar lymph node sampling was performed by EBUS-TBNA. Lymph nodes larger than 5 mm in short axis or suspicious nodes were targeted. In the absence of N2 or N3 disease, patients underwent resection with lymph node dissection. Results A total of 981 patients underwent EBUS-TBNA during the study period, of which 163 patients met the study criteria. There were 94 cN0 and 69 cN1 patients. A total of 453 lymph nodes (338 mediastinal and 115 N1 lymph nodes, average 2.8 nodes/patient) were sampled. Endobronchial ultrasound upstaged 9 (5.5%) patients to N2 disease, but was falsely negative in the mediastinum in 7 (4.3%) patients. In cN0 patients, EBUS confirmed N0 in 87 (53.4%) and upstaged in 7 (4.3%, N1 in 1, N2 in 6). In cN1 patients, EBUS confirmed N1 in 19 (11.7%), downstaged in 47 (28.8%), and upstaged in 3 (1.8%). The sensitivity, specificity, diagnostic accuracy, and negative predictive value of EBUS-TBNA to accurately differentiate between N0 and N1 disease was 76.2%, 100%, 96.6%, and 96.2%, respectively. The accuracy of mediastinal staging was 95.7%. Conclusions Endobronchial ultrasound-guided transbronchial needle aspiration can accurately access the hilar and interlobar lymph nodes in patients with potentially resectable lung cancer. Accurate assessment of cN0 versus cN1 by EBUS-TBNA may be used to guide induction therapy before surgery.
We analyzed an EGFR-mutated lung cancer with a pathologic diagnosis of combined large cell neuroendocrine carcinoma with mixed adenocarcinoma subtypes. Targeted next-generation sequencing of each ...component suggested that mutations in RB1, TP53, and SMAD4 and apparent loss of heterozygosity of TP53 and SMAD4 accompanied the transition of different adenocarcinoma subtypes. Additional gene mutations including PTEN, MST1R, and PIK3CA were noted during transdifferentiation from acinar adenocarcinoma to large cell neuroendocrine carcinoma. Combined DNA and RNA analysis using Todai OncoPanel revealed that transdifferentiation to different pathologic subtypes occurred in a single tumor through the accumulation of gene mutations.
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