Semipinacol rearrangement of a bicyclo[7.2.0]undecane framework into a bicyclo[6.3.0]undecane skeleton: a model study on the biosynthesis of seiridiasteriscane A.

Seiridiasteriscane A is an asteriscane-type sesquiterpenoid bearing a trans-fused bicyclo[6.3.0]undecane skeleton. Although its biosynthesis has been proposed to involve a semipinacol rearrangement of a putative intermediary acetate bearing a bicyclo[7.2.0]undecane ring system (presumably derived from coisolated pestalotiopsin M) followed by epimerization of the resulting cis-fused seiridiasteriscane B, such a type of semipinacol rearrangement has never been reported so far. Our model study revealed that a 1-hydroxybicyclo[7.2.0]undecan-2-yl acetate underwent a smooth and stereospecific semipinacol rearrangement with the assistance of Et2AlCl to give the corresponding bicyclo[6.3.0]undecane-9-one. In addition, the resulting cis-fused 5,8-bicyclic ketone was partially epimerized to the corresponding trans-fused ketone by prolonged adsorption onto a silica gel plate. These results may support a recently proposed biosynthetic pathway of seiridiasteriscane A.

Gpr137b is an orphan G-protein-coupled receptor associated with M2 macrophage polarization.

Macrophages are classified mainly into two subtypes, M1 and M2, which exhibit distinct phenotypes, based on their microenvironment. Although recent studies have suggested that G-protein-coupled receptors (GPCRs) are associated with M1/M2 macrophage polarization, available information on GPCR-mediated macrophage polarization is still limited. In the present study, we identified Gpr137b as an orphan GPCR abundantly expressed in RAW264, a mouse macrophage cell line, and illuminated its role in M2 macrophage polarization. We generated Gpr137b-knockout (Gpr137b-KO) clones of RAW264 cells using the CRISPR/Cas9 genome editing system. Two independent Gpr137b-KO clones were isolated, which were demonstrated to have frameshifting 188-nucleotide deletions at a region containing the ATG start codon of Gpr137b. Consistently, qRT-PCR analysis revealed that the deleted region is not transcribed. We then treated the Gpr137b-KO and wildtype RAW264 cells with interleukin-4 (IL-4) to induce M2 macrophage polarization. Microarray analysis revealed that the IL-4-induced gene expression of representative M2 macrophage markers was significantly reduced in the Gpr137b-KO cells, and this was validated by qRT-PCR analysis. By contrast, M1 macrophage marker gene expression induced by lipopolysaccharide was unaffected by Gpr137b-KO. Collectively, the current study shows that Gpr137b is a possible regulator of M2 macrophage polarization.

MiR-141-3p is upregulated in esophageal squamous cell carcinoma and targets pleckstrin homology domain leucine-rich repeat protein phosphatase-2, a negative regulator of the PI3K/AKT pathway.

The phosphatidylinositol-3-kinase (PI3K)/AKT pathway is frequently activated in various human cancers and plays essential roles in their development and progression. Accumulating evidence suggests that dysregulated expression of microRNAs (miRNAs) is closely associated with cancer progression and metastasis. Here, we focused on miRNAs that could regulate genes related to the PI3K/AKT pathway in esophageal squamous cell carcinoma (ESCC). To identify upregulated miRNAs and their possible target genes in ESCC, we performed microarray-based integrative analyses of miRNA and mRNA expression levels in three human ESCC cell lines and a normal esophageal epithelial cell line. The miRNA microarray analysis revealed that miR-31-5p, miR-141-3p, miR-200b-3p, miR-200c-3p, and miR-205-5p were expressed at higher levels in the ESCC cell lines than the normal esophageal epithelial cell line. Bioinformatical analyses of mRNA microarray data identified several AKT/PI3K pathway-related genes as candidate targets of these miRNAs, which include tumor suppressors such as DNA-damage-inducible transcript 4 and pleckstrin homology domain leucine-rich repeat protein phosphatase-2 (PHLPP2). To validate the targets of relevant miRNAs experimentally, synthetic mimics of the miRNAs were transfected into the esophageal epithelial cell line. Here, we report that miR-141-3p suppress the expression of PHLPP2, a negative regulators of the AKT/PI3K pathway, as a target in ESCC.

Interactions between the non-seed region of siRNA and RNA-binding RLC/RISC proteins, Ago and TRBP, in mammalian cells.

Small interfering RNA (siRNA)-based RNA interference (RNAi) is widely used for target gene silencing in various organisms. We previously showed that 8-nt-long 5' proximal nucleotides, which include seed sequence (positions 2-8 from the 5' end of guide strand), and the complementary sequence of the passenger strand are capable of being simultaneously replaced with cognate deoxyribonucleotides without any substantial loss of gene silencing. In the present study, examination was made of RNA requirements in the non-seed region of siRNA. The non-seed region of siRNA was found to be subdivided into four domains, in which two nucleotide pairs (positions 13 and 14) were replaceable with cognate deoxyribonucleotides without reducing RNAi activity. However, RNA sequences at positions 9-12 and 15-18 were essential for effective gene silencing, and these two double-stranded RNA cores are required for binding of the trans-activation response RNA-binding protein (TRBP). The terminal RNA (positions 19-21) provided Argonaute protein binding sites. Argonaute binding was enhanced by the presence of RNAs at positions 15-18. Knockdown experiments showed that, unlike Argonaute and TRBP, Dicer was dispensable for RNAi. Based on these observations, we discuss possible RNA/protein and protein/protein interactions in RNA-induced silencing complex formation.

[A Case of Gastrointestinal Metastases of Breast Cancer Effectively Treated with Gemcitabine and Paclitaxel Combination Chemotherapy].

A 55-year-old woman was admitted to our hospital complaining of constipation and abdominal distention. She had a history of right breast surgery for cancer at the age of 48 years. An abdominalCT scan revealed tumors at the antrum of the stomach and the ascending colon, and the tumor at the ascending colon caused obstruction of the colon. She was diagnosed with breast cancer recurrence and was administered combination chemotherapy consisting of gemcitabine and paclitaxel. Ileus improved after this treatment, and she was discharged from the hospital and was able to receive outpatient chemotherapy. After 8 months, she experienced symptoms of ileus again, and conservative treatment was considered impossible. Therefore, she underwent distal gastrectomy and right hemicolectomy. Histological and immunohistological analyses confirmed that the tumors were breast cancer metastases. Chemotherapy with gemcitabine and paclitaxel helped our patient to return to daily life and improved her prognosis.

Ultrasonographic Detective Flow Imaging for Evaluating Parathyroid Adenoma in Patients with Primary Hyperparathyroidism.

BACKGROUND: Detective flow imaging (DFI) is a new imaging technology that displays low-velocity blood flow, which is difficult to visualize on conventional color Doppler ultrasonography (CDU). In this study, we compared the usefulness of DFI with that of CDU and methoxy-isobutyl-isonitrile (MIBI) scintigraphy for detecting parathyroid adenoma (PA) in patients with primary hyperparathyroidism (PHPT). METHODS: From March 2021 to March 2023, 87 PHPT patients underwent surgery, and 66 had a single PA. We performed preoperative conventional ultrasonography with CDU, MIBI scintigraphy, and DFI for 42 patients (5 males and 37 females; mean age: 61.6 ± 15.4 years). RESULTS: MIBI scintigraphy detected PA in 85.7% (36/42) patients, and both CDU and DFI detected PA in all patients. The rates of vascularity in PA detected by CDU and DFI were 71.4% (30/42) and 85.7% (36/42), respectively. Vascularity was detected by DFI in 6 patients who were negative for vascularity on MIBI scintigraphy. Furthermore, DFI detected blood supply in 6 of the 12 patients with undetectable blood supply on CDU. Fisher's exact test revealed that high or low blood flow, as determined by DFI, was significantly associated with detection of feeding vessels in PA by CDU (P < 0.001). CONCLUSIONS: DFI was useful for preoperative detection of PA blood flow.

Regulation of Macrophage Polarization in Allergy by Noncoding RNAs.

Allergy is a type 2 immune reaction triggered by antigens known as allergens, including food and environmental substances such as peanuts, plant pollen, fungal spores, and the feces and debris of mites and insects. Macrophages are myeloid immune cells with phagocytic abilities that process exogenous and endogenous antigens. Upon activation, they can produce effector molecules such as cytokines as well as anti-inflammatory molecules. The dysregulation of macrophage function can lead to excessive type 1 inflammation as well as type 2 inflammation, which includes allergic reactions. Thus, it is important to better understand how macrophages are regulated in the pathogenesis of allergies. Emerging evidence highlights the role of noncoding RNAs (ncRNAs) in macrophage polarization, which in turn can modify the pathogenesis of various immune-mediated diseases, including allergies. This review summarizes the current knowledge regarding this topic and considers three classes of ncRNAs: microRNAs, long ncRNAs, and circular ncRNAs. Understanding the roles of these ncRNAs in macrophage polarization will provide new insights into the pathogenesis of allergies and identify potential novel therapeutic targets.

Retrospective single-arm cohort study of video-assisted thoracic surgery for treatment of idiopathic peripherally located simple type pulmonary arteriovenous malformation in 23 consecutive patients.

BACKGROUND: Although case reports of video-assisted thoracic surgery (VATS) for pulmonary arteriovenous malformation (PAVM) have been published, studies analyzing more than 10 cases were limited. A retrospective single-arm cohort study was performed to investigate the efficacy of VATS in 23 consecutive patients with idiopathic peripherally located simple type PAVM. METHODS: VATS was performed for wedge resection of 24 PAVMs in 23 patients, which included 4 males and 19 females with an age range of 25 to 80 years (mean: 59.6 ± 13.0). Two patients underwent simultaneous resection of lung carcinoma, one by wedge resection and another by lobectomy. Each medical record was analyzed according to the resected specimen, bleeding volume, postsurgical hospital stay length, duration of chest tube placement, and VATS time. The distance between pleural surface/fissure and PAVM was measured on CT, and the influence of this distance on identification of PAVM was investigated. RESULTS: In all 23 patients, VATS was successfully performed, and the venous sac was included in each resected specimen. Bleeding volume was less than 10mL in all but one with 1900 mL bleeding volume due to simultaneous lobectomy for carcinoma, not wedge resection of PAVM. Postsurgical hospital stay length, duration of chest tube placement, and VATS time were 5.0 ± 1.4 days, 2.7 ± 0.7 days, and 49.3 ± 39.9 min, respectively. In 21 PAVMs with a distance of 1 mm or less, purple vessel or pleural bulge of PAVM was identified soon after insertion of a thoracoscope. In the remaining 3 PAVMs with a distance of 2.5 mm or more, additional efforts were needed for identification. CONCLUSION: VATS was found to be a safe and effective to treatment for idiopathic peripherally located simple type PAVM. When the distance between pleural surface/fissure and PAVM was 2.5 mm or more, a plan and strategy for identification of PAVM should be prepared before VATS.

Use of Ultrasonographic Shear Wave Measurements to Diagnose Thyroid Metastasis from Breast Carcinoma.

A metastatic thyroid tumor (MTT) arising from breast carcinoma (BC) is rare and sometimes difficult to diagnose. We present a case of MTT from BC; we suspected anaplastic thyroid carcinoma at initial presentation. The patient was a 58-year-old female with a hard nodule in the right anterior neck and a history of breast cancer. Computed tomography indicated tumors on both thyroid lobes, and ultrasonography (US) with shear wave measurement (SWM) showed malignant features. We performed fine needle aspiration cytology (FNAC), the results of which led us to strongly suspect MTT from BC. The surgically resected specimen was evaluated histopathologically, including by immunohistochemistry (IHC), and the diagnosis was confirmed. In addition to FNAC and IHC, SWM is useful to diagnose MTT from BC.

Gastrocolic fistula caused by transverse colon cancer: a case report.

BACKGROUND: A gastrocolic fistula is an unusual communication between the colon and the stomach. Although colon cancer is the most common malignant cause of gastrocolic fistula in the Western world, the incidence of gastrocolic fistula due to colon cancer is 0.3% in operated cases. CASE PRESENTATION: A 68-year-old man presented with anorexia, general malaise, weight loss, and vomiting of fecal matter. Investigations revealed that the patient had a large nonmetastatic splenic flexure tumor that was diagnosed as colon cancer and had invaded the stomach and pancreas. An upper gastrointestinal series confirmed a gastrocolic fistula. Left hemicolectomy, distal gastrectomy, distal pancreatectomy, and splenectomy were performed. Histology revealed transverse colon cancer, which was UICC stage (8th edition) pT4bN1bcM0 pStage IIIC. Adjuvant chemotherapy was not performed. There was no recurrence or metastasis one year after surgery. We reviewed 17 cases including our case of a gastrocolic fistula caused by colon cancer. Neoadjuvant chemotherapy was not given to any of the patients, and en bloc resections were conducted in all cases. Adjuvant chemotherapy was given to almost all of the patients. There was no recurrence or metastasis. CONCLUSIONS: For gastrocolic fistula caused by advanced colon cancer, secure en bloc surgical resection was the initial treatment in all 17 reported cases including the present case, and adjuvant chemotherapy may contribute to a better prognosis.

Associations of AminoIndex Cancer Screening (Breast) Grade with Clinical and Laboratory Variables.

BACKGROUND: Altered metabolism in the blood of cancer patients is closely related to changes in amino acids. Amino acids play an important physiological role as essential metabolites and regulators of metabolism. AminoIndex Cancer Screening (AICS) uses multivariate analysis of plasma-free amino acid profiles to screen for seven cancer types, including breast cancer. METHODS: To determine the clinical utility of AICS (breast), we retrospectively analyzed associations of AICS (breast) score with clinical and laboratory variables in 390 patients who underwent AICS (breast) testing. The mean age of participants was 50.7 years (range: 26-87 years) and all were female. RESULTS: The AICS (breast) grade was A, B, and C for 250 (64.1%), 90 (23.1%), and 50 (12.8%) participants, respectively. AICS (breast) was significantly correlated with AICS (gastric) (r = 0.487, p < 0.0001) and AICS (lung) (r = 0.523, p < 0.0001). Multivariate linear regression analysis showed no significant difference of AICS (breast) grade with age, body mass index, estimated glomerular filtration rate, dyslipidemia, or blood pressure. However, neutrophil-to-lymphocyte ratio significantly differed in relation to AICS (breast) grade (cut-off value, 1.7; p = 0.030), although only data from 72 patients were analyzed. CONCLUSION: To our knowledge, this is the first study to report associations of AICS (breast) grade with clinical variables.

The Role of miR-217-5p in the Puromycin Aminonucleoside-Induced Morphological Change of Podocytes.

Podocytes, alternatively called glomerular epithelial cells, are terminally differentiated cells that wrap around glomerular capillaries and function as a part of the glomerular filtration barrier in the kidney. Therefore, podocyte injury with morphological alteration and detachment from glomerular capillaries leads to severe proteinuria and subsequent renal failure through glomerulosclerosis. Previous RNA sequencing analysis of primary rat podocytes exposed to puromycin aminonucleoside (PAN), a well-known experimental model of injured podocytes, identified several transcripts as being aberrantly expressed. However, how the expression of these transcripts is regulated remains unclear. MicroRNAs (miRNAs) are small noncoding RNAs that posttranscriptionally inhibit the expression of their target transcripts. In this study, using small RNA sequencing analysis, miR-217-5p was identified as the most upregulated transcript in PAN-treated rat podocytes. MiR-217-5p overexpression in E11 podocyte cells led to shrunken cells with abnormal actin cytoskeletons. Consistent with these changes in cell morphology, gene ontology (GO) enrichment analysis showed that interactive GO terms related to cell morphogenesis were enriched with the predicted targets of miR-217-5p. Of the predicted targets highly downregulated by PAN, Myosin 1d (Myo1d) is a nonmuscle myosin predicted to be involved in actin filament organization and thought to play a role in podocyte morphogenesis and injury. We demonstrated that miR-217-5p targets Myo1d by luciferase assays, qRT-PCR, and Western blotting. Furthermore, we showed that miR-217-5p was present in urine from PAN- but not saline-administrated rats. Taken together, our data suggest that miR-217-5p may serve as a therapeutic target and a biomarker for podocyte injury.

VsN, a Reliability-index of Shear-wave Measurement in Sonoelastography, Is Useful for the Diagnosis of Thyroid Tumor Malignancy.

BACKGROUND/AIM: Shear wave measurement (SWM) is a new elastography modality that quantifies the shear wave velocity (Vs) and the percentage of the net effective shear wave velocity (VsN). This study examined whether these parameters could be used to differentiate between malignant and benign thyroid tumors. PATIENTS AND METHODS: The study of SWM enrolled 111 patients (133 nodules) who underwent thyroid surgery. Overall, 61 nodules were diagnosed as benign and 72 as malignant, of which 68 nodules were diagnosed as papillary thyroid carcinoma (PTC) and 4 as follicular thyroid carcinoma (FTC). RESULTS: A preoperative SWM revealed that Vs was significantly higher and VsN significantly lower in the PTC compared to the benign nodules. The VsN of FTC was significantly lower than that of follicular adenoma. Multivariate analysis revealed that VsN significantly correlated with nodule malignancy. CONCLUSION: SWM parameters, especially VsN, can potentially differentiate between benign and malignant thyroid nodules non-invasively.

RNA recovery from specimens of duct-washing cytology performed contemporaneously with mammary ductoscopy.

OBJECTIVE: Conventional cytological diagnosis including duct-washing cytology (DWC) is sometimes performed using ductal epithelial cells collected during mammary ductoscopy; it is useful for detection of early-stage breast cancer such as ductal carcinoma in situ (DCIS). However, conventional cytological diagnosis focuses exclusively on cellular morphology; false negatives and false positives may be caused by inadequate specimen preparation (triggering cell degeneration) or poor examiner diagnostic skills. Molecular diagnosis using RNA biomarkers is expected to compensate for the weaknesses of cytological diagnosis. We previously employed microarray analysis to identify highly expressed genes in DCIS, suggesting that they may be useful for DCIS diagnosis. Here, we explored whether DWC samples yielded RNA of sufficient quantity and quality for RNA biomarker-based diagnosis. RESULTS: We extracted RNAs from 37 DWC samples. RNA from 12 samples exhibited RNA integrities of ≥ 6, indicative of moderate-to-high quality. We then showed that cocaine and amphetamine regulated transcript prepropeptide (CARTPT) and breast cancer-associated transcript 54 (BRCAT54) mRNA-previously shown by microarray analysis to be highly expressed in DCIS-were detectable in these samples. Therefore, DWC samples may be useful for molecular diagnosis involving RNA biomarkers.

Usefulness of ultrasonographic detective flow imaging to diagnose parathyroid tumors: two case reports.

Parathyroid tumors (PTs) are sometimes difficult to diagnose because they are small and have a low-velocity blood flow, which can be missed by current imaging modalities. PTs consist of parathyroid adenoma (PA), parathyroid cyst, and parathyroid carcinoma (PC). Detective flow imaging (DFI) is a new imaging technology that displays a low-velocity blood flow. Herein, we report two cases in which DFI was useful for the diagnosis of PTs. One case consisted of a PA and a parathyroid cyst in close proximity, and the other was a PC. To the best of our knowledge, this is the first report to demonstrate the usefulness of DFI in the diagnosis of PTs.

Clinical Utility of Fine-Needle Aspiration Cytology for Adenoid Cystic Carcinoma of the Trachea with Thyroid Invasion: A Case Report.

BACKGROUND: Adenoid cystic carcinoma of the trachea (ACCT) is a rare cancer; ACCT with thyroid invasion is particularly rare. We first suspected anaplastic thyroid carcinoma (ATC) but diagnosed ACC after performing fine-needle aspiration cytology (FNAC). Tracheal origin was confirmed postoperatively. CASE DESCRIPTION: A 77-year-old woman presented to our hospital with acute inspiratory dyspnea requiring emergency tracheotomy. Physical examination revealed swelling of the right anterior neck and a hard, immobile mass. Computed tomography (CT) and ultrasonography (US) showed tumor extension to the right thyroid lobe and between the first and third tracheal rings, which caused severe stenosis of the lumen. We performed FNAC. Clinical findings were highly suggestive of ACCT with thyroid invasion. She underwent total laryngectomy, cervical esophagectomy, and thyroidectomy with bilateral selective neck dissection at another hospital. The tumor was located in the right posterior wall of the trachea and extended into the right thyroid gland. Pathological examination showed infiltrative carcinomatous proliferation with tubular and cribriform patterns. The tumor was classified as pT4N1. A definite diagnosis was made after histopathological analysis of the surgical specimen confirmed ACCT. The tumor was positive for FABP7, a putative prognostic marker of ACC, and metastasized to the lungs 3 years after surgery. CONCLUSIONS: ACCT with thyroid invasion is an extremely rare malignant neoplasm. FNAC was useful for differentiating ACCT from other diagnoses and enabled appropriate surgical treatment.

Structure-based prediction of the IgE epitopes of the major dog allergen Can f 1.

Allergy to dogs has become increasingly prominent worldwide. Seven dog allergens have been identified, including Canis familiaris allergen 1-7 (Can f 1-7). Although Can f 1 is a major dog allergen sensitized to 50-75% of dog-allergic subjects, its IgE epitopes have not been identified. The structural analysis of an allergen is important to identify conformational epitopes. In this study, we generated a recombinant Can f 1 protein and determined its crystal structure using X-ray crystallography. Can f 1 had a typical lipocalin fold, which is composed of an eight-stranded ß-barrel and α-helix, and has high similarity to Can f 2, Can f 4, and Can f 6 in overall structure. However, the localizations of surface charges on these proteins were quite different. Based on sequence alignment and tertiary structure, we predicted five critical residues (His86, Glu98, Arg111, Glu138, and Arg152) for the IgE epitopes. The relevance of these residues to IgE reactivity was assessed by generating Can f 1 mutants with these residues substituted for alanine. Although the effects of the mutation on IgE binding depended on the sera of dog-allergic patients, H86A and R152A mutants showed reduced IgE reactivity compared with wild-type Can f 1. These results suggest that Can f 1 residues His86 and Arg152 are candidates for the IgE conformational epitope.

Imaging characteristics of nontuberculous mycobacterial pulmonary nodules.

Introduction. Nontuberculous mycobacteriosis (NTM) of the lungs can develop nodules. In order to clarify some of the characteristics of lung NTM nodules, we examined volume doubling time (VDT) and maximum standardized uptake value (SUVmax) in positron emission tomography (PET) of pathologically diagnosed NTM nodules. Methods. From November 2012 to August 2018, clinical and radiological information were retrospectively investigated in eight patients who were surgically resected and diagnosed as NTM. These eight patients were followed up until November 2020 and were confirmed to have no appearance of lung cancer or reappearance of lung NTM nodules. The VDT was calculated using the Schwartz formula. Results. The median maximum diameter of the nodule at the time of the first CT scan was 16.0 (range: 9.9-20.0) mm. The median maximum diameter of the nodule on CT performed before the surgical biopsy was 18.8 (range: 10.4-32.8) mm. The median doubling time calculated from these results was 203 (range: 20-568) days. Caseous granulomas and acid-fast bacilli were histologically confirmed in all eight patients. Culture of excised nodules revealed Mycobacterium intracellulare in five patients and Mycobacterium avium in three patients. Six patients received PET, and median SUVmax was: 7.0 (range: 3.3-21.0). Median VDT was around 200 days. Some patients had irregular-shaped nodules. Conclusions. CT/PET-CT characteristics of lung nodules are not reliable in differentiating lung NTM nodules from malignant ones. To avoid unnecessary resection, it may be better to collect various information on imaging findings in the nodule itself and in opacities other than the nodule.

Microarray analysis of ductal carcinoma in situ samples obtained by puncture from surgical resection specimens.

OBJECTIVE: The incidence of ductal carcinoma in situ (DCIS) is increasing due to more widespread mammographic screening. DCIS, the earliest form of breast cancer, is non-invasive at the time of detection. If DCIS tissues are left undetected or untreated, it can spread to the surrounding breast tissue. Thus, surgical resection is the standard treatment. Understanding the mechanism underlying the non-invasive property of DCIS could lead to more appropriate medical treatments, including nonsurgical options. DATA DESCRIPTION: We conducted a microarray-based genome-wide transcriptome analysis using DCIS specimens obtained by puncture from surgical specimens immediately after surgery.

A population-based study of outcomes in patients with surgically resected non-small cell lung cancer with anaplastic lymphoma kinase-rearranged mutations: A matched-pair study.

The present study aimed to evaluate clinical outcomes in patients with surgically resected non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK)-rearranged mutations. A matched-pair analysis in completely resected ALK-rearranged NSLC patients and those with neither ALK nor epidermal growth factor receptor (EGFR) mutations diagnosed at 11 institutes was performed between April 2008 and March 2019. A total of 51 patients with surgically resected ALK-rearranged NSCLC were included. Women constituted 68.6%, and smokers 29.4%. The median age was 65 years. In matched-pair analysis, disease-free survival and overall survival did not differ between patients with ALK-rearranged mutations and those without mutations. Post-recurrence survival in patients with ALK mutations was longer than that of patients with neither ALK nor epidermal growth factor receptor mutations. ALK genetic testing should be performed, even in elderly patients with NSCLC. Favorable prognosis might be expected after appropriate treatment for patients with recurrent ALK-mutated disease.