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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.

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.

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.

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.

Various oligo- and poly-saccharides differing in sugar compositions and types of linkage were examined for their ability to activate a limulus coagulation factor G, the first protease in an alternative coagulation cascade of the horseshoe crab, Tachypleus tridentatus , whose amebocytes have originally been known to contain a lipopolysacchaide(LPS)-driven pathway leading to the formationof coagulin gel. Linear and branched (1 → 3)-β- d -glucans and mixed linkage (1 → 3),(1 → 4)-β- d -glucans were found to exhibit the ability to activate factor G at concentrations of 10 −8 –10 −10 g/mL as assayed by amidolytic activity of the clotting enzyme. Laminaran oligosaccharides, laminaran dextrins (number-average mol. wt. ≦ 5800), and other polysaccharides including carboxymethylcellulose, amylose, starch, d -fructans, α- l -arabinan, β- d -xylans, (1 → 3)-β- d -galactan, water-soluble chitin derivatives, chondroitin, chondroitin sulfates, hyaluronan, keratan sulfate, heparins, heparan sulfate, and LPS's were virtually inactive as activators even at a concentration of 10 −7 g/mL. The activating ability increased with increasing number-average mol. wt. (6800–216 000) of linear (1 → 3)-β- d -glucans. The apparent activating ability of gyrophoran, nigeran, and yeast α- d -mannan was largely abolished by digestion with a highly purified Arthrobacter luteus endo-(1 → 3)-β- d -glucanase, which provided supportive evidence for the activation to be ascribed to contaminating (1 → 3)-β- d -glucan(s). Possible participation of ordered structures of (1 → 3)-β- d -glucans in the activation of factor G is discussed.

A disintegration test of protective coated preparations in human bodies was carried out by determining the riboflavin amount excreted in urine after administration of the riboflavin tablets coated with the previously reported protective-coating agents. Though the rate of the riboflavin excretion was somewhat slow, there was no indication of unusual disintegration of the coated tablets in human bodies.