Outcomes of initial surgery in patients with clinical N2 non-small cell lung cancer who met 4 specific criteria.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Thoracic Paravertebral Block in Patients Ineligible for Epidural Block].

We retrospectively assessed the effectiveness and the safety of thoracic paravertebral block(PVB) in patients ineligible for epidural block (EP). Eleven PVB patients and 33 EP patients were enrolled. Postoperative pain was evaluated using a numerical rating scale (NRS). The mean NRS ± standard deviation at rest 24 and 48 hours after surgery were 1.36 ± 1.63 and 0.55 ± 1.03 in the PVB group and 1.07 ± 1.47 and 1.38 ± 1.31 in the EP group, respectively. There were no statistically significant differences in the NRS scores. Approximately 10% of the EP patients had complications such as hypotension, nausea and vomiting, or urinary retention. On the other hand, there were no adverse events in the PVB group. PVB can provide pain relief comparable to EP with a better side-effect profile. There were no technical complications associated with PVB. Thoracic PVB is an effective and safe method of postoperative analgesia for patients undergoing thoracic surgery with ineligibilities for EP.

Prospective genetic profiling of squamous cell lung cancer and adenosquamous carcinoma in Japanese patients by multitarget assays.

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.

Results of surgical treatment for non-small cell lung cancer with positive sputum cytology: experience from a single institution.

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.

Enzymatic assay for D-aspartic acid using D-aspartate oxidase and oxaloacetate decarboxylase.

An enzymatic assay system for D-Asp was established using D-aspartate oxidase and oxaloacetate decarboxylase. In this system, D-Asp is converted to pyruvate, which is determined fluorometrically with 1,2-diamino-4,5-methylenedioxybenzene. This method makes possible D-Asp measurement at the micromolar level. The D-Asp contents of an edible brown alga, Hijika fusiforme, a lactic acid bacteria beverage, and pig testis were determined by the method.

Long-term survival after pulmonary resections for multiple metastases from gastric cancer: A case report.

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.

Risk factors for local recurrence after lobectomy and lymph node dissection in patients with non-small cell lung cancer: Implications for adjuvant therapy.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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, p<0.0001). 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, p<0.0001) 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 (p<0.0001). CONCLUSION: 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.

Can 18F-FDG PET predict the grade of malignancy in thymic epithelial tumors? An evaluation of only resected tumors.

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.

Continuous paravertebral block using a thoracoscopic catheter-insertion technique for postoperative pain after thoracotomy: a retrospective case-control study.

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.

Survival data for postoperative adjuvant chemotherapy comprising cisplatin plus vinorelbine after complete resection of non-small cell lung cancer.

PURPOSE: 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. METHODS: We retrospectively evaluated patients with NSCLC who received adjuvant chemotherapy comprising CDDP + VNR at the Shizuoka Cancer Center between February 2006 and October 2011. RESULTS: 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. CONCLUSIONS: 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.

Comparison of Clinically Relevant Mutation Profiles Between Preoperative Biopsy and Corresponding Surgically Resected Specimens in Japanese Patients With Non-Small-cell Lung Cancer by Amplicon-based Massively Parallel Sequencing.

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.

A CaVbeta SH3/guanylate kinase domain interaction regulates multiple properties of voltage-gated Ca2+ channels.

Auxiliary Ca(2+) channel beta subunits (Ca(V)beta) regulate cellular Ca(2+) signaling by trafficking pore-forming alpha(1) subunits to the membrane and normalizing channel gating. These effects are mediated through a characteristic src homology 3/guanylate kinase (SH3-GK) structural module, a design feature shared in common with the membrane-associated guanylate kinase (MAGUK) family of scaffold proteins. However, the mechanisms by which the Ca(V)beta SH3-GK module regulates multiple Ca(2+) channel functions are not well understood. Here, using a split-domain approach, we investigated the role of the interrelationship between Ca(V)beta SH3 and GK domains in defining channel properties. The studies build upon a previously identified split-domain pair that displays a trans SH3-GK interaction, and fully reconstitutes Ca(V)beta effects on channel trafficking, activation gating, and increased open probability (P(o)). Here, by varying the precise locations used to separate SH3 and GK domains and monitoring subsequent SH3-GK interactions by fluorescence resonance energy transfer (FRET), we identified a particular split-domain pair that displayed a subtly altered configuration of the trans SH3-GK interaction. Remarkably, this pair discriminated between Ca(V)beta trafficking and gating properties: alpha(1C) targeting to the membrane was fully reconstituted, whereas shifts in activation gating and increased P(o) functions were selectively lost. A more extreme case, in which the trans SH3-GK interaction was selectively ablated, yielded a split-domain pair that could reconstitute neither the trafficking nor gating-modulation functions, even though both moieties could independently engage their respective binding sites on the alpha(1C) (Ca(V)1.2) subunit. The results reveal that Ca(V)beta SH3 and GK domains function codependently to tune Ca(2+) channel trafficking and gating properties, and suggest new paradigms for physiological and therapeutic regulation of Ca(2+) channel activity.

Boundary between N1 and N2 Lymph Node Descriptors in the Subcarinal Zone in Lower Lobe Lung Cancer: A Brief Report.

INTRODUCTION: In the International Association for the Study of Lung Cancer (IASLC) lymph node (LN) map, some LNs in the subcarinal space defined as #10 (N1) in the Naruke map were changed to #7 (N2). We aimed to validate the boundary between N1 and N2 in the subcarinal zone. METHODS: We reviewed the records of 399 consecutive patients who had undergone complete resection for lower lobe non-small cell lung cancer. Involved lymph node stations were classified as N1 by both maps (N1 group), N1 by the Naruke map but reclassified as N2 by the IASLC map (#10 [subcarinal] group), and N2 by both maps (N2 group). The survival rates among these groups were compared using Kaplan-Meier and log-rank analyses. RESULTS: LNs were classified as N0, N1, and N2 in 268, 67, and 64 patients, respectively, on the IASLC map and as N1 and N2 in 82 and 49 patients, respectively, on the Naruke map. The 5-year disease-free survival rates were 81.7% for N0, 50.9% for N1, 33.3% for the #10 (subcarinal) group, and 24.4% for N2. The rates of the N1 and #10 (subcarinal) groups were significantly different (p = 0.027), but those of the N2 and #10 (subcarinal) groups were not (p = 0.78). On multivariate analysis, metastatic disease in the LNs of #10 in the subcarinal space was an independent prognostic factor for patients classified as N1 on the Naruke map (hazard ratio = 2.47, 95% confidence interval: 1.17-4.85, p = 0.019). CONCLUSION: All lymph nodes in the subcarinal space should be defined as #7 (N2) for prognosis.

Continuous infusion of recombinant activated factor VII for bleeding control after lobectomy in a patient with inherited factor VII deficiency.

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.

Retrocardiac lung hernia after thoracic esophagectomy: report of a rare case.

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.

Variation in (18)F-FDG PET findings in a patient with synchronous multiple thymoma.

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.

High-Grade Neuroendocrine Carcinoma with Bronchial Intraepithelial Tumor Spread: Possibly a New Histologic Feature of Large-Cell Neuroendocrine Carcinoma.

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.

High-resolution computed tomography findings of early mucinous adenocarcinomas and their pathologic characteristics in 22 surgically resected cases.

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.

Pulmonary adenosquamous carcinoma with mucoepidermoid carcinoma-like component with characteristic p63 staining pattern: either a novel subtype originating from bronchial epithelium or variant mucoepidermoid carcinoma.

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.

Molecular profiling of small cell lung cancer in a Japanese cohort.

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.