Impact of the micropapillary component on the timing of recurrence in patients with resected lung adenocarcinoma.

OBJECTIVES: A micropapillary (MIP) component is reported to be associated with a poor prognosis in patients with completely resected lung adenocarcinoma. The purpose of this study was to investigate the impact of an MIP component on the timing of postoperative recurrence using hazard curves. METHODS: A total of 1289 patients with lung adenocarcinoma who underwent complete pulmonary resection from 2008 to 2015 were studied. Hazard curves representing the changes in hazard over time were evaluated. RESULTS: The hazard curve displayed an initial wide, high peak within 1 year after surgery in patients with an MIP component, whereas some gentle peaks around the second year were noted in patients without an MIP component. The presence of an MIP component was associated with a worse recurrence-free survival and an early recurrence in stage I patients but not in advanced-stage patients. In multivariable Cox regression, the presence of an MIP component and lymph node metastasis, pleural invasion and gender were associated with a poor prognosis. CONCLUSIONS: Patients with an MIP component retained a high risk of early recurrence after surgery, and the risk for recurrence persisted over the long term. Even after complete resection in stage I lung adenocarcinoma patients, an MIP component remains correlated with a poor prognosis.

Pulmonary adenocarcinoma with high-grade fetal adenocarcinoma component has a poor prognosis, comparable to that of micropapillary adenocarcinoma.

Fetal adenocarcinoma is a rare variant of lung adenocarcinoma, which is subcategorized into low-grade and high-grade forms. High-grade fetal adenocarcinoma confers worse prognosis than low-grade fetal adenocarcinoma, but the prognostic differences between high-grade fetal adenocarcinoma and conventional lung adenocarcinoma are unknown. We reviewed tissue sections of 3719 cases of surgically resected primary lung cancers and found 53 lung cancers with a high-grade fetal adenocarcinoma component. We analyzed their clinicopathological and immunohistochemical features, and performed a prognostic analysis of adenocarcinomas with the fetal-type component. We further analyzed the prognostic differences between adenocarcinomas with the fetal-type component and conventional adenocarcinomas without the fetal-type component. Lung cancers with the fetal-type component predominantly occurred in elderly men with a smoking history. Twenty-nine patients had stage I disease, 13 patients had stage II, and 11 patients had stage III. The fetal-type histology was combined with conventional-type adenocarcinoma (41 cases), squamous cell carcinoma (5 cases), large cell neuroendocrine carcinoma (5 cases), enteric adenocarcinoma (2 cases), and small cell carcinoma (1 case). The fetal-type component showed immunopositivity for α-fetoprotein (39%), glypican-3 (37%), and SALL4 (17%). The 5-year overall survivals of fetal-type-predominant and fetal-type-nonpredominant patients were 44 and 56%, respectively (P = 0.962). The 5-year overall survivals of lepidic-, acinar-, papillary-, solid-, and micropapillary-predominant adenocarcinomas, invasive mucinous adenocarcinomas, and adenocarcinomas with the fetal-type component were 94, 82, 77, 69, 57, 83, and 41%, respectively (P < 0.001). Univariate and multivariate analyses showed that adenocarcinomas with the fetal-type component had a significantly lower overall survival rate than the other histological subtypes, except for the micropapillary-predominant subtype. Our study demonstrated that adenocarcinomas with the fetal-type component had a poor prognosis that was comparable to that of micropapillary adenocarcinoma. The presence of the high-grade fetal adenocarcinoma component in lung adenocarcinomas is an important prognostic marker.

Rhodoligotrophos appendicifer gen. nov., sp. nov., an appendaged bacterium isolated from a freshwater Antarctic lake.

A Gram-stain-negative, non-spore-forming, non-motile, irregularly circular, aerobic/microaerobic appendaged bacterium (strain 120-1(T)) was isolated from Naga-ike, one of the freshwater lakes in the Skarvsnes ice-free area of Antarctica. Strain 120-1(T) grew between 5 and 35 °C, with optimum growth at 30 °C. The pH range for growth was between 6.0 and 9.0 (optimum of approximately pH 7.0). The range of NaCl concentration allowing growth of strain 120-1(T) was between 0 and 5.0%, with an optimum of 0.5-1.0%. Strain 120-1(T) was able to utilize organic compounds such as glucose, arabinose, gluconate, adipate and malate. Red colonies were formed on plate medium and the carotenoids were present in the cells. Ubiquinones Q-9 and Q-10 were the major respiratory quinones. The major cellular fatty acids were C(16:0), C(18:1)ω9c and C(18:1)ω7c. The G+C content of the genomic DNA was 61.1 mol%. Comparative analyses of 16S rRNA gene sequences and physiological characteristics of strain 120-1(T) indicate that strain 120-1(T) is a phylogenetically novel bacterium, and that it represents a novel species in a new genus, Rhodoligotrophos gen. nov., in the order Rhizobiales, family Rhodobiaceae. The name Rhodoligotrophos appendicifer gen. nov. sp. nov. is proposed as the type species of this new genus, with 120-1(T) ( = JCM 16873(T) = ATCC BAA-2115(T)) as the type strain.

Critical behavior of megabase-size DNA toward the transition into a compact state.

We studied the changes in the higher-order structure of a megabase-size DNA (S120-1 DNA) under different spermidine (SPD) concentrations through single-molecule observations using fluorescence microscopy (FM) and atomic force microscopy (AFM). We examined the difference between the folding transitions in S120-1 DNA and sub-megabase-size DNA, T4 DNA (166 kbp). From FM observations, it is found that S120-1 DNA exhibits intra-chain segregation as the intermediate state of transition, in contrast to the all-or-none nature of the transition on T4 DNA. Large S120-1 DNA exhibits a folding transition at lower concentrations of SPD than T4 DNA. AFM observations showed that DNA segments become aligned in parallel on a two-dimensional surface as the SPD concentration increases and that highly intense parallel alignment is achieved just before the compaction. S120-1 DNA requires one-tenth the SPD concentration as that required by T4 DNA to achieve the same degree of parallel ordering. We theoretically discuss the cause of the parallel ordering near the transition into a fully compact state on a two-dimensional surface, and argue that such parallel ordering disappears in bulk solution.

Papillary adenoma of the lung with a peculiar raw macroscopic feature.

We report a case of papillary adenoma of the lung with a peculiar raw macroscopic feature at intraoperative consultation. A 52-year-old man was admitted to our hospital for the evaluation of a solitary peripheral nodule in the left lower lobe which was detected with chest CT. When we took staples off from the stump of the partially resected lung in order to make a frozen section diagnosis, granular fragments leaked out from the stump. On the cut surface, the dark reddish and granular tumor grew expansively; however, hemorrhage and necrosis were absent. Histologically, granular fragments were mainly composed of papillary structures, which consisted of a single layer of cuboidal to low columnar cells with round to oval nuclei lining the surface of the fibrovascular cores. Characteristically, papillary structures lacked elastic fibers in the stroma and were packed within an elastic fiber framework derived from pre-existing alveolar structures. We considered that high intratumoral pressure might have made the granular fragments leak out of the stump as soon as we removed staples and that peculiar macroscopic findings before fixation may be a diagnostic clue for papillary adenoma.

Simple and precise detection of UGT1A1 polymorphisms with a modified loop-hybrid mobility shift assay using Cy5-labeled loop probes.

BACKGROUND: Irinotecan, an inhibitor of topoisomerase I, has been widely used as an important anti-cancer therapeutic drug. Deleterious effects of the drug in hypersensitive patients are known to be associated with genetic polymorphisms of the UGT1A1 gene, namely the polymorphic variants, *28 and *6. METHODS: A modified form of loop-hybrid mobility shift assay using a Cy5-tagged loop-hybrid probe was proposed as a precise and easy method of determining TA repeat polymorphisms at the *28 locus. RESULTS: In this modified method, only loop-hybrid bands were detected by a Cy5-fluorescent signal, despite several irregular electrophoretic bands due to TA repeats in the PCR product. CONCLUSIONS: When a loop-hybrid using a Cy5-tagged probe for the *28 locus and *6 locus were combined and used for mobility shift assay, simultaneous typing of the *28 and *6 variants was achieved in a single lane.

Alveolar space filling ratio as a favorable prognostic factor in small peripheral squamous cell carcinoma of the lung.

INTRODUCTION: Squamous cell carcinomas (SqCCs) of the lung can be divided into two types according to the location of primary site; one is central type and another is peripheral type. Many reports on the central type revealed the clinicopathological characteristics relating carcinogenesis, therapeutics and prognosis. On the other hand, those on the peripheral type are very a few and prognostic indicators of peripheral type have not been enough elucidated. The aim of this study was to clarify clinicopathological prognostic factors of small peripheral SqCCs of the lung 30 mm or less. MATERIALS AND METHODS: We evaluated various 15 clinicopathological parameters in 81 patients with peripheral type SqCCs, which are defined as tumors located in or more peripheral from the third branching bronchus, measuring 30 mm or less in diameter. RESULTS: Univariate analyses were performed using the log lank test and multivariate analyses using logistic regression model. As a result, two factors had a statistically significant influence on outcome of the patients in the univariate analysis; no relapse was observed in the patients with the ratio of alveolar space filling (ASF) area to tumor area of 70% or more and the maximum diameter of invasive area measuring 10 mm or less in size (P=0.0214, P=0.0373, respectively). Meanwhile, multivariate analysis showed that the ASF ratio of 70% or more significantly affected the outcome of the patients (P=0.0337), however the maximum diameter of invasive area did not (P=0.2136). We could not show the unfavorable prognostic factor contributory to tumor relapse. CONCLUSIONS: We have shown that the ASF ratio is a significantly favorable prognostic factor for small peripheral type. Especially the focally invasive tumors with ASF ratio of 70% or more might be classified as "a microinvasive carcinoma" of the peripheral SqCCs of the lung and tumors with ASF ratio 100% as noninvasive carcinoma.

Constrictibacter antarcticus gen. nov., sp. nov., a cryptoendolithic micro-organism from Antarctic white rock.

A Gram-negative, non-spore-forming, ovoid to rod-shaped aerobic or microaerobic bacterium, strain 262-8(T), was isolated from a cavity within white rock collected in Antarctica. Strain 262-8(T) grew at 5-30 °C (optimum 25 °C), at pH 6-8 (optimum approximately pH 7) and with 0.1-2.0 % (w/v) NaCl (optimum 0.5 % NaCl). The addition of tryptone or yeast extract was essential for growth. Strain 262-8(T) was able to utilize organic compounds such as ribose, pyruvate and succinate in the presence of a low concentration of tryptone. Ubiquinone 10 was the major respiratory quinone. The major fatty acids were C(18 : 1), C(16 : 0) and C(18 : 0). The G+C content of the genomic DNA was 69.8 mol%. Comparative analyses of 16S rRNA gene sequences and physiological characteristics indicated that strain 262-8(T) was a phylogenetically novel bacterium that should be classified in a new genus of the family Rhodospirillaceae, for which the name Constrictibacter antarcticus gen. nov., sp. nov. is proposed. The type strain of the type species is 262-8(T) ( = JCM 16422(T) = ATCC BAA-1906(T)).

Progression of a sessile serrated adenoma to an early invasive cancer within 8 months.

Recent studies suggest that serrated polyps, including hyperplastic polyps, traditional serrated adenomas, and sessile serrated adenomas, may be morphologically and genetically distinct and linked to microsatellite unstable colorectal cancers, and thus the concept of a hyperplastic polyp-serrate adenoma-carcinoma pathway has been suggested. Furthermore, it has been suggested that transformation from serrated polyps to invasive cancers can be rapid and occurs when the lesions are small; however, direct evidence for this issue is scant. We herein describe a case of a sessile serrated adenoma showing rapid transformation into a submucosal invasive carcinoma with remarkable morphological change in a short period of 8 months. This case is unique and suggestive, as it provided information about the natural history of a sessile serrated adenoma.

CT-guided needle biopsy of lung lesions: a survey of severe complication based on 9783 biopsies in Japan.

PURPOSE: The aim of our study was to update the rate of severe complications following CT-guided needle biopsy in Japan via a mailed survey. MATERIALS AND METHODS: Postal questionnaires regarding CT-guided needle biopsy were sent out to multiple hospitals in Japan. The questions regarded: the total number and duration of CT-guided lung biopsies performed at each hospital, and the complication rates and numbers of pneumothorax, hemothorax, air embolism, tumor seeding, tension pneumothorax and other rare complications. Each severe complication was followed with additional questions. RESULTS: Data from 9783 biopsies was collected from 124 centers. Pneumothorax was the most common complication, and occurred in 2412 (35%) of 6881 cases. A total of 39 (35%) hospitals reported 74 (0.75%) cases with severe complications. There were six cases (0.061%) with air embolism, six cases (0.061%) with tumor seeding at the site of the biopsy route, 10 cases (0.10%) with tension pneumothorax, six cases (0.061%) with severe pulmonary hemorrhage or hemoptysis, nine cases (0.092%) with hemothorax, and 27 cases (0.26%) with others, including heart arrest, shock, and respiratory arrest. From a total of 62 patients with severe complications, 54 patients (0.55%) recovered without sequela, however one patient (0.01%) recovered with hemiplegia due to cerebral infarction, and the remaining seven patients (0.07%) died. CONCLUSIONS: This is the first national study documenting severe complications with respect to CT-guided needle biopsy in Japan. The complication rate in Japan is comparable to internationally published figures. We believe this data will improve both clinicians as well as patients understanding of the risk versus benefit of CT-guided needle biopsy, resulting better decisions.