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Highlights • We report a case of long-term survival after pulmonary resections for multiple metastases from gastric cancer. • The prognosis of pulmonary resection for metastatic gastric cancer is poor even though solitary metastasis. • Recently, however, cases of long-term survival have been reported. • By contrast, long-term survival after pulmonary resections for multiple pulmonary metastases from gastric cancer is extremely rare. • Our case suggests that pulmonary metastasectomy could be a therapeutic option even in patients involving multiple pulmonary metastases., Introduction The prognosis of pulmonary resection for metastatic gastric cancer is poor even though solitary metastasis. Long-term survival after pulmonary resections for multiple pulmonary metastases from gastric cancer is extremely rare. Case presentation The patient was 67-year old man who underwent a distal gastrectomy for early gastric cancer. Wedge resections of the right upper and lower lobes and right lower lobectomy were performed for metastases from gastric cancer at 29 months and 55 months after the gastrectomy, respectively. As of 96 months after the first pulmonary metastasectomy, this patient continues to be recurrence-free. Discussion Multiple pulmonary metastases after gastrectomy are not considered candidates for surgery. Although systemic chemotherapy is the standard therapy for metastatic gastric cancer, the prognosis is extremely poor. In this case with favorable prognostic factors, such as long disease-free intervals or absence of extrapulmonary metastasis, pulmonary metastasectomy could be a therapeutic option in patients despite the presence of multiple pulmonary metastases. Conclusions Our case suggests that even in cases involving multiple pulmonary metastases, pulmonary metastasectomy might be an effective therapeutic option that can improve survival.

The objective of this study was to investigate clinicopathological risk factors for local recurrence in patients who underwent either complete resection with lobectomy or more extensive resection with hilar and mediastinal lymph node dissection for non-small cell lung cancer (NSCLC). The role of adjuvant therapy was also explored.We reviewed the records of 1012 consecutive stage I-III NSCLC patients who underwent complete resection. The median follow-up time was 59 months. The risk factors for local recurrence were investigated by multivariate analysis using Cox's proportional hazards regression model.Local recurrence was identified in 9.4% of the patients. The most significant risk factor for local recurrence was lymph node metastasis (N1: hazard ratio [HR]=2.27, p=0.009; N2: HR=6.85, p0.0001). For the subgroup of patients with lymph node metastasis (n=289), the independent risk factors for local recurrence were N2 disease with N1 metastasis (N2 with N1; HR=3.46, p0.0001) and non-receipt of adjuvant platinum-based chemotherapy (HR=1.91, p=0.018). The 5-year freedom from local recurrence rates were 96.1%, 84.1%, 85.0%, and 53.5% for N0, N1, skip N2, and N2 with N1 stages (p0.0001).Local recurrence is significantly associated with poor overall survival. Therefore, local control is essential for radical cure of NSCLC. N2 with N1 status was the primary risk factor for local recurrence, while adjuvant chemotherapy improved local control. These data have important implications for postoperative radiotherapy and highlight the need to devise more effective eligibility criteria for this modality in patients with lymph node metastasis.

Objective Although 18-fluorine fluorodeoxyglucose positron emission tomography (18F-FDG PET) is thought to be useful for predicting the histological grade of thymic epithelial tumors (TETs), it remains controversial. To date, just a few of many previous studies have included only resected cases. Therefore, we investigated 18F-FDG PET findings only in patients with resected TETs. Patients and methods A total of 112 patients with TETs consisting of 92 thymomas and 20 thymic carcinomas (TCs), resected at two institutes (Shizuoka Cancer Center [Shizuoka] and National Cancer Center Hospital [Tokyo]) between October 2002 and December 2015, were evaluated. Spearman rank correlation coefficient was used to assess the association between the maximum standardized uptake value (SUVmax) in the tumor and both the histological subtype and tumor stage. The cutoff value of SUVmax for differentiating thymoma from TC was calculated. Results The SUVmax was strongly related to both the World Health Organization (WHO) histological subtype and tumor stage based on the eighth edition of the tumor-node-metastasis (TNM) classification (Spearman rank correlation coefficient =0.485 and 0.432; p = 0.000 and 0.000, respectively). There was a significant difference between thymoma and TC. The optimal SUVmax cutoff value for differentiating thymoma from TC was 4.58 (sensitivity: 80% and specificity: 78.3%). In contrast, there was no significant difference between low-risk (type A, AB, and B1) and high-risk (type B2 and B3) thymoma, or between type B3 thymoma and the other subtypes. Conclusion Our results suggest that 18F-FDG PET is useful for differentiating thymoma from TC, but not for predicting the histologic grade of thymoma.

Despite the efficacy of postoperative adjuvant cisplatin (CDDP)-based chemotherapy for patients who have undergone surgical resection of non-small cell lung cancer (NSCLC), few reports have presented survival data for Asian patients treated with adjuvant chemotherapy involving a combination of CDDP and vinorelbine (VNR). This study was performed to evaluate the survival of patients with NSCLC who received postoperative adjuvant chemotherapy comprising CDDP + VNR. We retrospectively evaluated patients with NSCLC who received adjuvant chemotherapy comprising CDDP + VNR at the Shizuoka Cancer Center between February 2006 and October 2011. One hundred patients who underwent surgical resection of NSCLC were included in this study. The patients’ characteristics were as follows: median age 63 years (range 36–74 years), female 34%, never-smokers 20%, and non-squamous NSCLC 73%. Pathological stages IIA, IIB, and IIIA were observed in 31, 22, and 47% of patients, respectively. The 5- and 2-year overall survival rates were 73 and 93%, respectively. The 5- and 2-year relapse-free survival rates were 53 and 62%, respectively. Univariate analysis of prognostic factors showed that patient characteristics (sex, histology, and pathological stage) and CDDP dose intensity were not significantly associated with survival. In 48 patients who developed NSCLC recurrence, the 5-year survival rate after recurrence was 29%, and the median survival time after recurrence was 37 months. Our results suggest that the prognosis after surgical resection of NSCLC and adjuvant chemotherapy comprising CDDP + VNR might be improving compared with previous survival data of adjuvant chemotherapy for NSCLC.

The role of surgery for patients with non-small cell lung cancer (NSCLC) with clinical mediastinal lymph node metastasis (N2) remains controversial. We specified 4 criteria for performing initial surgery in these patients (single-station N2, non-bulky N2, N2 with regional mode of spread, and N2 without N1) and examined the outcomes to validate the treatment options.Between September 2002 and December 2010, of 1290 patients who underwent complete resection for NSCLC, 808 patients underwent initial standard resection, including 779 patients with cN0-1 and 29 with cN2. We compared the outcomes, and evaluated patients with cN2-pN2.The median follow-up was 45.5 months (3-119 months). Seventy (9.0 %) and 24 (82.8 %) patients had p-N2 in the cN0-1 and cN2 groups, respectively (p 0.0001). The 5-year disease-free survival (DFS) rates in the cN0-1 and cN2 groups were 73.3 and 50.6 %, respectively (p = 0.0053), and the 5-year overall survival (OS) rates were 81.3 and 71.1 %, respectively (p = 0.051). The 5-year DFS and OS of patients with cN2-pN2 were 52.5 and 72.6 %, respectively.Patients with clinical N2 disease based on our criteria represent a highly specific group with a favorable prognosis. Resection should therefore be the initial treatment for these patients.

Introduction During surgical resection of a peripherally located high-grade neuroendocrine carcinoma (HGNEC), we unexpectedly discovered prominent bronchial intraepithelial tumor spread up to the surgical end of the bronchus. Because bronchial intraepithelial tumor spread of peripherally located HGNEC has been rarely reported, we conducted a retrospective analysis at our hospital. Methods We histologically reviewed surgically resected HGNEC cases to assess bronchial intraepithelial spread of tumor cells. HGNECs with bronchial intraepithelial tumor spread were further studied by immunohistochemistry for neuroendocrine markers, and their clinicopathological characteristics were evaluated. Results Of 1778 cases of surgically resected lung cancer in our hospital, 47 cases of HGNEC were evaluated. Bronchial intraepithelial tumor spread was observed in nine cases (19.1%); eight of these cases were large-cell neuroendocrine carcinoma (LCNEC) or small-cell lung carcinoma with an LCNEC component. Moreover, bronchial intraepithelial tumor spread was continuous from the primary tumor to the resected end of the bronchus in four cases, and all these cases had an LCNEC component. Furthermore, HGNEC with bronchial intraepithelial tumor spread was associated with a higher recurrence rate than no bronchial intraepithelial tumor spread. Conclusion The results of this study suggest that bronchial intraepithelial tumor spread is commonly observed in cases of peripherally located HGNEC and may be a unique form of tumor invasion, especially tumors with LCNEC morphology. Therefore, surgeons and pathologists should be cognizant of bronchial intraepithelial tumor spread in peripherally located HGNEC, as well as its potential role as an indicator of HGNEC aggressiveness.

Background The pathological criteria of early-stage mucinous adenocarcinoma of the lung have recently been defined; however, its characteristic radiologic imaging findings are still poorly understood. Thus, this study aimed to clarify the radiologic and pathological findings of early-stage mucinous adenocarcinoma. Materials and methods In this study, we clinicopathologically reviewed 22 cases of surgically resected mucinous adenocarcinoma in situ (AIS) and minimal invasive adenocarcinoma (MIA), and attempted to elucidate the characteristic radiologic features of early mucinous adenocarcinomas using high-resolution computed tomography (HRCT). Results Radiologically, the mean value of the maximum diameter of 22 tumours was 2.1 cm (range, 1.0–2.9 cm). Based on the HRCT findings, the tumours were divided into part-solid ground glass nodules (n = 11) and solid nodules (n = 11). The mean CT attenuation value was 25.7 HU (range, 17–35 HU). All tumours, except 3 tumours pathologically diagnosed as AIS, showed air-containing features. According to the preoperative CT findings, 7 (35%) cases were diagnosed as inflammatory nodules. Of these, 4 cases had lobular-bounded margins, and 3 showed vaguely outlined ground glass shadows. Conclusion The characteristic HRCT findings of mucinous AIS and MIA were solid or part-solid nodules with air-containing spaces. However, some AIS and MIA nodules showed lobular-bounded margins or marginally vaguely outlined ground glass shadows, and were difficult to differentiate from inflammatory nodules.

Inherited factor VII (FVII) deficiency is a rare recessive inherited coagulation disorder with limited available information, especially in patients undergoing major thoracic surgery. In addition, an optimal management strategy for the disease has not been defined. We herein report a case involving a 61-year-old man with asymptomatic FVII deficiency who underwent a right middle and lower lobectomy to treat lung cancer. To the best of our knowledge, the present report is the first to describe the use of recombinant activated FVII continuous infusion for bleeding control after a major thoracic surgery in a patient with inherited FVII deficiency.

Background Little is known about the prognostic value of positive sputum cytology in patients with non-small cell lung cancer (NSCLC). Patients and Methods We retrospectively examined the clinicopathological data of 30 patients who had undergone complete resection for NSCLC with positive sputum cytology between September 2002 and June 2011. Results Distant recurrence occurred significantly more frequently in the patients with adenocarcinoma (Ad) than in those with squamous cell carcinoma ( p = 0.01). The most frequent metastatic site after surgery was the brain, occurring in five patients with Ad. The 5-year disease-free survival (DFS) and overall survival (OS) rates of the 30 patients were 53 and 49%, respectively. In multivariate analyses, radiographic feature of pneumonic-type shadow and pathological N (pN) 1–2 status were the independent factors significantly correlated with poor DFS ( p = 0.009, 0.001, respectively), whereas pN 1–2 status was the only independent factor significantly correlated with poor OS ( p = 0.009). Conclusion Surgical outcome for NSCLC with positive sputum cytology was unfavorable at our institution. Close surveillance after a curative resection is mandatory for those patients presenting with radiographic feature of pneumonic-type shadow as those with lymph node metastases because they are at high risk for recurrence.

We herein present a case of synchronous multiple thymoma that was suspected based on the findings of positron emission tomography with fluorine-18-labeled-fluorodeoxyglucose ((18)F-FDG PET). The patient was a 70-year-old male with two similarly sized and heterogeneously enhanced masses on the right side of the anterior mediastinum on chest computed tomography. (18)F-FDG PET revealed variation in FDG accumulation between the masses, in which the maximum standardized uptake value was 4.4 in Tumor 1 and 8.7 in Tumor 2. Based on these imaging findings, the masses were suspected to be independent, likely synchronous double primary thymoma. Total thymectomy with removal of the two tumors was performed via median sternotomy. A pathological examination identified Tumor 1 as type AB thymoma and Tumor 2 as type A thymoma. This is the first reported case of synchronous multiple thymoma which was suspected based on a variation in the (18)F-FDG PET findings between the tumors.

Mediastinal cystic seminoma is uncommon; only 17 cases have been reported, most diagnosed postoperatively, without recurrence on follow-up, even without radiotherapy. Here, we report a mediastinal seminoma showing a unilocular cyst with enhancing thickened wall in computed tomography (CT) and septal structures in magnetic resonance imaging (MRI) in a 24-year-old man. Fluorodeoxyglucose (FDG) uptake was not significant. Histopathologically, seminoma cells were found scattered in the cyst wall. Twenty months after resection, the patient's quality of life is good, without chemotherapy or radiation. Cystic seminoma has a good prognosis and complete resection without adjuvant therapy might be sufficient for young patients of reproductive age.

Background Thoracic epidural analgesia (EDA) is the gold standard for pain control after thoracotomy. However, because of its severe side effects, it is contraindicated in patients taking anticoagulant or antiplatelet drugs. In addition, some patients’ anatomy can make epidural catheter insertion challenging. We therefore investigated the safety and efficacy of paravertebral block (PVB) using a thoracoscopic insertion technique, which avoids damage to the parietal pleura, for postoperative pain after thoracotomy. Methods Patients who underwent thoracotomy with thoracic PVB in our hospital between March 2013 and March 2014 were examined retrospectively. Prior to creating the thoracotomy incision, a catheter for PVB was inserted percutaneously into the paravertebral space under thoracoscopic guidance. A matched-pair control group was selected at a 1:2 ratio from patients who underwent thoracotomy with thoracic EDA in our hospital from April 2011 to February 2013. Pain control and side effects were compared between groups and the results statistically analyzed. Results Thoracic PVB was performed in 56 patients during this period, and 112 patients were selected as matched controls. Numeric Rating Scale scores on postoperative day 2 did not differ significantly between the PVB group (3.25 ± 1.80) and the EDA group (3.56 ± 2.05) (p = 0.334). In terms of side effects, urinary retention occurred less frequently in thoracic PVB patients (p = 0.03). Conclusion Under the conditions of the present study, continuous thoracic PVB was at least as effective as epidural analgesia for postoperative pain control after thoracotomy with lung resection. Electronic supplementary material The online version of this article (doi:10.1186/s13019-017-0566-8) contains supplementary material, which is available to authorized users.

Aim: The aim of this study was to clarify the relationship between pathological effects and the prognosis of patients with stage III non-small cell lung cancer (NSCLC) treated with induction chemoradiation. Methods: Patients who were untreated and potentially resectable with stage III NSCLC were enrolled. They received carboplatin and docetaxel with concurrent radiotherapy (5 × 2 Gy/week with a total dose of 40 Gy) followed by surgery. We assessed the relationship between the pathological effect (Ef) (Ef 1: slight pathological response, Ef 2: moderate pathological response, Ef 3: complete pathological response) and prognosis. Results: In all, 30 patients with stage III NSCLC (24 men and 6 women, mean age 60.7 years, 17 with adenocarcinomas and 13 with squamous cell carcinomas, 21 with clinical stage IIIA and nine with stage IIIB) participated in the trial and underwent induction chemoradiation. A total of 27 patients (90%) with complete response, partial response and stable disease had surgical resection. The pathological effect was Ef 1 and Ef 2 in 10 patients each, and Ef 3 in seven patients. Median survival was 10.9 months in patients with Ef 1 and 49.6 months in patients with Ef 2. Six out of seven Ef 3 patients are alive at the time of writing with a mean survival of 77.1 months (14–104 months). There was a significant difference in overall survival based on pathological effect rating (P = 0.0036). Conclusion: The Ef rating was well correlated with prognosis after induction chemoradiation.

This study assessed the repair strategies used by verbal students with autism (N = 12) when faced with verbal requests for clarification, gestural requests, not attending and not responding, and wrong responses. Data were collected in request contexts contrived by the communication partner during free play. The results indicated that most of the students repaired more than 80% of the communication breakdowns. In addition, they tended to choose communication forms that reflected the social meaning of the breakdown. However, they were likely to rely on unconventional forms when they faced wrong response breakdowns.

The substances that cause physiological halitosis have been found to be mainly volatile sulfur compounds (VSCs) [hydrogen sulfide (H 2 S), methylmercaptan (CH 3 SH) and dimethylsulfide (CH 3 ) 2 S] produced by putrefaction of anaerobic bacteria. In order to clarify the role of these periodontopathic bacteria in halitosis, we investigated the amounts of four species of bacteria, Prevotella intermedia , Fusobacterium nucleatum , Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans in 10 μl of the tongue coats of healthy people using quantitative PCR and examined the correlation with the concentrations of VSCs present in the subject's breath (physiological halitosis). The following results were obtained. 1.H 2 S in the oral breath of the subjects showed a positive correlation with the detected counts of A. actinomycetemcomitans, P. intermedia, P. gingivalis, F. nucleatum and the total bacteria. 2.CH 3 SH in the oral breath of the subjects showed a positive correlation with the detected count of P. gingivalis. 3.(CH 3 ) 2 S in the oral breath of the subjects showed a positive correlation with the detected counts of A. actinomycetemcomitans, P. intermedia and total bacteria. 4.The concentrations of VSCs in the oral breath of the subjects showed a positive correlation with the total count of bacteria. These results suggest that periodontopathic bacteria present in the tongue coat of healthy people might be the cause of physiological halitosis.

主気管支腔内を中枢側進展し，一側無気肺による急性呼吸不全を来たした右上葉肺癌に対し，全身麻酔硬性気管支鏡下腫瘍debulkingを施行し，その後待機的根治切除を行った2例を経験した．いずれも低分化型腺癌で，右主気管支の腫瘍を硬性外筒でcore outし，無気肺を改善させてから，待機的に右上葉管状切除術を施行した．症例1は46歳，男性，病理病期III b期（p-T4N2M0）で，現在術後39ヵ月で無再発生存中であり，症例2は79歳男性，病理病期II b期（p-T3N0M0）で，術後日常生活に復したが術後5ヵ月で腫瘍死となった．硬性気管支鏡下腫瘍debulkingは，QOLの一時的な改善のみならず，肺癌に対するその後の集学的治療をすすめる上で有用であった．

A retrocardiac lung hernia is an extremely rare complication after esophagectomy. A 56-year-old man was admitted to our hospital with advanced middle thoracic esophageal cancer and a giant bulla at the apical portion of the right lung. Since it appeared that dissection of the upper mediastinum would most likely require resection of the right bulla, a two-stage operation for esophageal cancer was planned. During the first-stage operation, thoracic esophagectomy and resection of the right giant bulla were performed. Fourteen days after the first-stage operation, the patient underwent laparotomy as the second-stage operation to reconstruct a narrow gastric tube via a retrosternal route. After the second-stage operation, the inflammatory reaction was prolonged. Therefore, a thoracoabdominal computed tomography scan was performed, showing retrocardiac pulmonary atelectasis. The patient was diagnosed with a retrocardiac left lung hernia in which the left lower lobe was displaced into the right thoracic cavity. Because the inflammatory reaction was due to effects of the lung hernia, a repair operation was performed via a left seventh intercostal thoracotomy. At thoracotomy, the left basal segment of the lung was atelectatic and reddish and had herniated into the right thoracic cavity through an opening between the aorta and pericardium. The herniated lung tip adhered strongly to the subcarina, and synechiotomy was performed. We believe that simultaneous removal of the right giant bulla with esophagectomy was the important cause of this complication.

This descriptive study extends previous studies on communication repairs by (a) involving elementary-age children With autism Who are prelinguistic to emergent one-Word communicators and (b) examining repair strategies in terms of the relationships betWeen the conventionality and functionality of communication forms and the type of breakdoWn. Communication initiations and repairs emitted by three students With autism Were observed in natural settings in Which communication breakdoWns Were intentionally introduced. The students repaired almost all the breakdoWns regardless of type. Furthermore, they repaired communication breakdoWns effectively by adding semantic categories. They Were likely to adjust their repair strategies according to the social meaning of “Without attention.” When they repaired communication breakdoWns by modifications, they Were more likely to use less-conventional forms. The results are discussed in relation to interventions in communication competence.

Background Amplicon-based massively parallel sequencing (MPS) is an effective platform for identifying clinically actionable mutations across many genes in limited amounts of tissue. Most lung cancers are diagnosed and staged using small tissue samples obtained by transbronchial biopsy (TBB). To determine whether the mutations in TBB specimens detected by amplicon-based MPS reflect those present in the tumors, we compared the mutational profiles of preoperative TBB specimens and corresponding surgically resected specimens. Patients and Methods Fresh-frozen primary tumor specimens from non–small-cell lung cancer patients (n = 46) obtained preoperatively by TBB and during surgical resection were analyzed. The concordance of mutations detected by amplicon-based MPS in the 2 sample types was investigated, and the allele frequency of the mutations common to both specimens from the same patient was determined. Results An initial assessment of DNA quantity revealed that 46% of the TBB specimens (21 of 46) had less than the lower limit for amplicon-based MPS. These 21 TBB specimens were consequently omitted from the analysis. Of the 29 mutations detected in the TBB and/or surgically resected specimens from 25 patients, 23 were present in both samples, for a concordance rate of 79%. Conclusion Amplicon-based MPS with TBB specimens approximately reflects clinically relevant tumor mutation profiles. However, the rate of TBB specimens with sufficient DNA quantity for amplicon-based MPS was only around 50%. Therefore, surgically resected specimens have a valuable role in exploratory and comprehensive genomic profiling.

Background Despite considerable recent progress in the treatment of lung adenocarcinoma, there has been little progress in the development of efficacious molecular targeted therapies for squamous cell lung cancer. In addition to the recent comprehensive genome-wide characterization of squamous cell lung cancer, it is also important to genotype this form of cancer. We therefore conducted the Shizuoka Lung Cancer Mutation Study to analyze driver mutations in patients with thoracic malignancies. Here we report the results of genotyping in patients with squamous cell lung cancer. Methods Based on the biobanking system, in conjunction with the clinic and pathology lab, we developed a genotyping panel designed to assess 24 mutations in 10 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, HER2 and DDR2), EGFR, MET, PIK3CA, FGFR1 and FGFR2 copy numbers, and EML4-ALK and ROS1 translocations, using pyrosequencing plus capillary electrophoresis, quantitative polymerase chain reaction (PCR) and reverse-transcription PCR, respectively. Results A total of 129 patients with squamous cell lung cancer and adenosquamous carcinoma were enrolled in this study between July 2011 and November 2012. We detected genetic alterations in 40% of all cases. Gene alterations included: EGFR mutations, 6%; KRAS mutations, 4%; PIK3CA mutations, 13%; NRAS mutations, 1%; KIF5b-RET fusion gene, 1%; EGFR copy number gain, 5%; PIK3CA copy number gain, 15%; and FGFR1 copy number gain, 5%. Twelve patients (9%) harbored simultaneous genetic alterations. Genetic alterations were detected more frequently in surgically-resected, snap-frozen samples than in formalin-fixed, paraffin-embedded samples (50% vs. 29%). In addition, patients aged ≤70 years old and never-smokers showed high frequencies of genetic alterations. Conclusions This study represents one of the largest prospective tumor-genotyping studies to be performed in Asian patients with squamous cell lung cancer. These results suggest that incorporation of genetic profiling into lung cancer clinical practice may facilitate the administration of personalized cancer treatments in patients with squamous cell lung cancer. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-786) contains supplementary material, which is available to authorized users.

Objectives Advances in the molecular profiling of lung adenocarcinoma over the past decade have led to a paradigm shift in its diagnosis and treatment. However, there are very few reports on the molecular profiles of small cell lung cancers (SCLCs). We therefore conducted the present Shizuoka Lung Cancer Mutation Study to analyze genomic aberrations in patients with thoracic malignancies. Materials and methods We collected samples of SCLC from a biobank system and analyzed their molecular profiles. We assessed 23 mutations in nine genes ( EGFR , KRAS , BRAF , PIK3CA , NRAS , MEK1 , AKT1 , PTEN , and HER2 ) using pyrosequencing plus capillary electrophoresis. We also amplified EGFR , MET , PIK3CA , FGFR1 , and FGFR2 using quantitative real-time polymerase chain reaction (PCR) and the fusion genes ALK , ROS1 , and RET using reverse transcription PCR. Results Between July 2011 and January 2013, 60 SCLC patients were enrolled in the study. Samples included eight surgically resected snap-frozen samples, 50 formalin-fixed paraffin-embedded samples, and seven pleural effusion samples. We detected 13 genomic aberrations in nine cases (15%), including an EGFR mutation ( n = 1, G719A), a KRAS mutation ( n = 1, G12D), PIK3CA mutations ( n = 3, E542K, E545K, E545Q), an AKT1 mutation ( n = 1, E17K), a MET amplification ( n = 1), and PIK3CA amplifications ( n = 6). EGFR and KRAS mutations were found in patients with combined SCLC and adenocarcinoma. No significant differences were detected in the characteristics of patients with and without genomic aberrations. However, serum neuron-specific enolase and progastrin-releasing peptide levels were significantly higher in patients without genomic aberrations than in those with aberrations ( p = 0.01 and 0.04, respectively). Conclusion Genomic aberrations were found in 15% SCLC patients, with PIK3CA amplifications most frequently observed. To further our understanding of the molecular profiles of SCLC, comprehensive mutational analyses should be conducted using massive parallel sequencing.

Background Our previous study found unique adenosquamous carcinomas (ADSQs) containing a mucoepidermoid carcinoma (MEC)-like component and a characteristic p63 staining pattern. This study focused on these unique ADSQs. Methods Thirty ADSQ cases were studied histologically and by immunohistochemistry for TTF-1 and p63. Of these 30 ADSQs, eight were selected as unique ADSQs. The clinicopathological characteristics of these ADSQs were further studied, and the gene rearrangement of mammalian mastermind-like 2 (MAML2) was investigated by fluorescence in situ hybridization (FISH) for differentiation from pulmonary MEC. Results The clinicopathological characteristics between the eight ADSQs and the other ADSQ cases showed no statistically significant differences, except for serum CEA level. Histologically, the eight ADSQs contained varying degrees of the MEC-like component, which consisted of solid nests with mucin-filled cysts or a cribriform-like structure. Immunohistochemically, p63-positive nuclei characteristically encircled the tumor nests, although TTF-1 was completely negative. All unique ADSQs not only had a variable degree of squamous cell carcinoma component in addition to the MEC-like component, but also contained a small tubular adenocarcinoma component in three tumors. FISH analysis revealed no MAML2 gene rearrangement in the eight ADSQs. Conclusions Of the 30 ADSQs investigated in this study, eight contained a MEC-like component with a characteristic p63 basilar staining pattern similar to that of bronchial basal cells. These unique ADSQs shared clinical characteristics with ordinary ADSQs, but clinicopathologically differed from pulmonary ordinary MEC. Therefore, these unique ADSQs may be either a novel ADSQ subtype originating from bronchial epithelium or variant-type MEC.

Background Until date, there are no clear recommendations for regular perioperative measurements of serum CEA levels for lung cancer in any guidelines. The purpose in the present study is to evaluate the prognostic significance of perioperative serum carcinoembryonic antigen (CEA) levels in patients with pathological-stage I non-small cell lung cancer (NSCLC). Methods We retrospectively reviewed 263 completely resected pathological-stage I NSCLC patients whose preoperative and postoperative serum CEA levels were measured. Patients were subdivided according to the perioperative change of CEA levels: continuously normal CEA levels (NN group), continuously high CEA levels (HH group), and high preoperative CEA levels that returned to normal levels post-operation (HN group). The clinicopathological factors and overall survival (OS) among these 3 groups were compared. Univariate and multivariate analyses of the correlation between clinicopathological factors and OS were performed. Results High preoperative CEA levels significantly correlated with men aged >70 years with smoking history, high serum CYFRA 21–1 levels, greater tumor diameter, presence of visceral pleural invasion (VPI), and moderate-to-poor differentiation. Five-year OS rates in the NN and HH groups were 95.5% and 59.3%, respectively. Four-year OS rate in the HN group was 85.5%. Multivariate analyses indicated tumor diameter of more than 30 mm, presence of VPI, and the HH group were independent unfavorable prognostic factors. Conclusions A high postoperative CEA level was an independent unfavorable prognostic factor in pathological-stage I NSCLC patients. Patients with high postoperative CEA levels may benefit from adjuvant chemotherapy.

OBJECTIVES: Even after curative resection, a significant fraction of patients with stage I non-small-cell lung cancer (NSCLC) die primarily because of systemic relapse. The purpose of the present study was to investigate the risk factors for both recurrence and poor survival in patients with pathological (p-) stage I NSCLC. METHODS: We retrospectively reviewed 467 consecutive patients from a single institution with completely resected p-stage I NSCLC. Patients with multiple lung tumours or malignancies from other organs and those who had undergone preoperative therapies were excluded. The correlation between clinicopathological factors and surgical outcomes, including disease-free survival (DFS) and overall survival (OS), was analysed. The clinicopathological factors examined were age, gender, smoking history, serum carcinoembryonic antigen (CEA) levels, serum cytokeratin 19 fragment levels, surgical procedure, tumour histology, p-stage, angiolymphatic invasion and differentiation grade. RESULTS: The 5-year DFS and OS rates of the total study population were 91.4 and 92.8%, respectively. Multivariate analysis results indicated that high serum CEA levels (>5.0 ng/ml) and p-stage IB were independent factors for recurrence, whereas older age (>70 years), high serum CEA levels and p-stage IB were independent factors for poor survival. The risks of recurrence and death in patients with both high serum CEA levels and p-stage IB was 10.3 and 5.2 times higher than those observed in patients with both normal serum CEA levels and p-stage IA, respectively. CONCLUSIONS: High serum CEA levels and p-stage IB were independent factors for both recurrence and poor survival in p-stage I NSCLC patients.

Parenchyma-sparing main bronchial sleeve resection is a safe and effective procedure to restore impaired lung function. We present a case illustrating recovery of lung perfusion in a 24-year-old woman with dyspnea on exertion because of bronchial tuberculosis. Bronchoscopic examination revealed pin-hole stenosis of the left main bronchial orifice. 99mTc-macroaggregated albumin perfusion scanning revealed essentially absent left lung perfusion. Because of bronchomalacia in the distal portion, six rings of the left main bronchus were resected by carinoplasty. Symptoms abated and perfusion recovered to a large extent 2 months later. She became pregnant and delivered successfully 12 months postoperatively.

Objectives: The aim of this study was to assess the significance of microscopic vascular invasion (MVI) in a population of completely resected patients with non-small-cell lung cancer (NSCLC), along with an analysis of impact of the MVI and clinicopathological factors on recurrence and survival. Methods: From September 2002 to December 2010, 1230 patients with NSCLC received complete resection at our institution. MVI was ascertained using histopathological and immunohistochemical techniques. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan–Meier method. We performed multivariate analyses to determine the independent prognostic factors. Results: MVI was observed in 448 patients (36.4%). Prevalence of MVI was lower in Stage I cases than in higher stage cases (P < 0.001). The presence of MVI was associated with DFS (P< 0.001, 3-year DFS: 87.1% in MVI-positive vs 64.3% in MVI-negative) and with OS (P< 0.001). Especially in Stage IB patients, who often receive oral anticancer agents as adjuvant chemotherapy in our institution, the presence of MVI was associated with DFS (P < 0.001, 3-year DFS: 85.4% in MVI-positive vs 69.3% in MVI-negative) and with OS (P = 0.039). In a multivariate survival analysis, The significant indicator of poor DFS was MVI (P< 0.001, CI 1.61-2.96), pulmonary metastases (P < 0.001, CI 1.49-2.98), pleural invasion (P = 0.007, CI 1.04-1.27), tumour size (P < 0.001, CI 1.01-1.02), and CEA level (P= 0.002, CI 1.00-1.01), although adjuvant chemotherapy has no significant relationship with DFS (P = 0.60). Conclusions: The finding of MVI in NSCLC is frequent. MVI correlates with tumour stages. The presence of MVI is an independent negative prognostic factor on both DFS and OS. Patients with these predictive factors of recurrence may be good candidates for intensive adjuvant chemotherapy. Disclosure: No significant relationships.

Objectives The levels of trace elements in mixed saliva were not well-defined. This study was performed to determine Al and Fe concentrations in mixed saliva of children and to investigate the relationship between these levels and dental caries. Methods Among 562 collected mixed saliva specimens, 514 and 548 samples for analyses of Al and Fe levels were obtained, respectively. The Al and Fe concentrations were determined using flameless atomic absorption spectrometry. Results The Al and Fe concentrations in children without a history of caries were 0.093 ± 0.136 and 0.121 ± 0.128 μg/mL, respectively. The Fe level depended on sex. The Fe level in girls who experienced caries was significantly higher than that without caries history. The Al and Fe levels were significantly higher in children with treated caries than children without caries history. The Fe concentrations were affected by restoration type. Composite resin increased the Fe level significantly especially in girls, and the Fe level was also higher in boys treated with both composite resin and metal restorations. In children without caries history, the Al level was inversely proportional to the number of deciduous teeth and increased with the number of permanent teeth. In contrast, the Fe level showed the reverse tendency. Conclusions The Fe level in mixed saliva of children was influenced by the restoration type. It was suggested that Al was eluted more from sound permanent teeth than sound deciduous teeth, while Fe was eluted in the opposite manner.

A 71-year-old man with a right hilar mass shadow was referred to our department. Chest computed tomography showed a small fatty area inside. Convex probe endobronchial ultrasound (CP-EBUS) images revealed a heterogeneous low-echoic mass, resembling a stone wall and showing a smooth sliding movement along the tracheal wall during respiration. Transbronchial needle aspiration (EBUS-TBNA) was performed and cartilage cells were identified, compatible with the presence of a hamartoma. The patient requested follow-up without surgical intervention. CP-EBUS images are easier to interpret than other methods for monitoring respiratory dynamics. We conclude that CP-EBUS is a useful addition to techniques both for non-invasive imaging as well as guiding pathological examination.

7567 Background: It has been reported that CRKL amplification, associated with overexpression, has induced cell transformation as well as resistance to EGFR inhibitors. We analyzed CRKLamplificatio...

Background: Integration of genotype-based stratification into the lung cancer clinic is essential to implement the personalized medicine for patients with lung adenocarcinoma. Thus we have developed a multiplexed tumor genotyping panel for detecting somatic mutations relevant to molecular targeted therapies for lung cancer. The mutation profile data are communicated to clinicians to assign patients to appropriate therapy and/or clinical trials. Methods: Multiplexed tumor genotyping panel was developed to assess 23 mutations in 9 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN and HER2), 5 genes amplifications (EGFR, MET, PIK3CA, FGFR1 and FGFR2), and 5 fusion genes (EML4-ALK, CD74-ROS1, SLC34A2-ROS1, KIF5B-RET and CCDC6-RET) using pyrosequencing plus capillary electrophoresis, qRT-PCR, and multiplex RT-PCR, respectively. A written informed consent was obtained upfront from all patients enrolled into this study. Surgically resected tissues, tumor biopsies, pleural effusions and/or pericardial effusions from 280 patients were collected between July 2011 and July 2012 and used for tumor genotyping. Results: Somatic mutations were detected in 52.9% (148/280) of all patients. The most common mutation detected in this study was EGFR mutation (35.4%, 99) followed by KRAS mutation (10.4%, 29). EGFR L858R (52.5%) and KRAS G12C (44.8%) was the most frequent among EGFR and KRAS mutations, respectively. Other detected mutations were PIK3CA mutation (2.5%), PIK3CA amplification (2.5%), EGFR amplification (2.5%), MET amplification (2.1%), EML4-ALK fusion gene (1.4%), BRAF mutation (1.1%), NRAS mutation (1.1%), HER2 mutation (1.1%), MEK1 mutation (0.7%), AKT1 mutation (0.7%), KIF5B-RET fusion gene (0.4%), CD74-ROS1 fusion gene (0.4%) and FGFR1 amplification (0.4%). EGFR tyrosine kinase inhibitor (EGFR-TKI) was administered to 71.9% (41/57) of previously untreated patients who harbor EGFR activating mutations. Among those treated with EGFR-TKIs, simultaneous mutations in other genes with EGFR mutations were detected in 21.9% (9/41). Response rate of EGFR-TKIs in patients with simultaneous mutations (44.4%) was lower than that in patients with EGFR mutation alone (68.8%), suggesting that additional mutations may play some role in evading oncogenic signaling blockade. EGFR mutations were detected less frequently in smokers than in never-smokers (25.1% vs 60.5%, p Conclusions: We have established the multiplexed tumor genotyping panel and this should be incorporated into lung cancer clinical practice to facilitate personalized cancer medicine. Citation Format: Masakuni Serizawa, Yasuhiro Koh, Hirotsugu Kenmotsu, Mitsuhiro Isaka, Akane Naruoka, Junko Suzuki, Masaru Watanabe, Masahiro Endo, Takashi Nakajima, Shoji Takahashi, Yasuhisa Ode, Tateaki Naito, Tetsuhiko Taira, Akira Ono, Toshiaki Takahashi, Nobuyuki Yamamoto. Multiplexed mutational profiling of Japanese lung adenocarcinoma patients for personalized cancer therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 37. doi:10.1158/1538-7445.AM2013-37