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Peritoneal dissemination is a major cause of recurrence in patients with malignant tumors in the peritoneal cavity. Effective anticancer agents and treatment protocols are necessary to improve outcomes in these patients. However, previous studies using mouse models of peritoneal dissemination have not detected any drug effect against peritoneal micrometastasis. Here we used the luciferase assay to evaluate peritoneal micrometastasis in living animals and established an accurate mouse model of early peritoneal microdissemination to evaluate tumorigenesis and drug efficacy. There was a positive correlation between luminescence intensity in in vivo luciferase assay and the extent of tumor dissemination evaluated by ex vivo luciferase assay and mesenteric weight. This model has advantages over previous models because optimal luciferin concentration without cell damage was validated and peritoneal microdissemination could be quantitatively evaluated. Therefore, it is a useful model to validate peritoneal micrometastasis formation and to evaluate drug efficacy without killing mice. [ABSTRACT FROM AUTHOR]

The natural killer group 2 member D (NKG2D) receptor and its ligands are important mediators of immune responses to tumors. NKG2D ligands are overexpressed in several malignant tumor types; however, the prognostic value of these ligands is unclear. Here, we aimed to elucidate the role of NKG2D ligands in extrahepatic cholangiocarcinoma (EHCC). We therefore investigated the expression of the NKG2D receptor and its ligands MHC class I chain-related proteins A and B (MICA/B), unique long 16 binding protein (ULBP) 1, and ULBP2/5/6 in resected specimens from 82 patients with EHCC. All NKG2D ligands were highly expressed in EHCC. High expression of MICA/B or ULBP2/5/6 correlated with overall and disease-free survival. In contrast, high expression of ULBP1 was significantly associated with improved overall survival, but not disease-free survival. Concurrent high expression of multiple NKG2D ligands revealed significantly better overall and disease-free survival than that observed with the overexpression of any one NKG2D ligand. Co-expression of multiple NKG2D ligands was an independent prognostic indicator of improved survival. Furthermore, co-overexpression of multiple NKG2D ligands was significantly correlated with high expression of the NKG2D receptor. Inhibiting interactions between multiple NKG2D ligands and the NKG2D receptor might be a promising approach for controlling cancer progression and improving patient prognosis in EHCC. [ABSTRACT FROM AUTHOR]

Objective To assess and compare abdominal distention and stress in unsedated colonoscopy using carbon dioxide (CO2) and air insufflations. Methods Two hundred and five patients underwent colonoscopic examinations without sedation using either CO2 or air insufflation. Abdominal circumference and salivary amylase (sAMY) activities before and 0 and 15 min after colonoscopy were measured by a nurse who was blinded to the grouping of the patients. Results In all, 102 and 103 patients were randomly recruited in the CO2 and air insufflation groups, respectively. sAMY activities before and 0 and 15 min after colonoscopy were not significantly different between the two groups. Abdominal circumference measured immediately and 15 min after colonoscopy was significantly smaller in CO2 insufflation group than in the air insufflation group (81.2 cm vs 84.0 cm, and 79.7 cm vs 83.6 cm, respectively; P <0.05). The increasing ratio of abdominal circumference immediately after colonoscopy was not significantly different between the two groups; however, the ratio at 15 min after colonoscopy using CO2 insufflation was significantly lower than that in the air insufflation group (1.007 vs 1.028, P <0.001). Conclusion sAMY activities after unsedated colonoscopy using CO2 insufflation were not improved; however, CO2 insufflation decreases abdominal circumference after colonoscopy compared with air insufflation. [ABSTRACT FROM AUTHOR]

The pathogenesis of sarcomatous component in spindle cell carcinoma ( SpCC) of the esophagus is unclear. To investigate the involvement of epithelial-mesenchymal transition ( EMT) in sarcomatous differentiation, we performed immunohistochemistry for Slug, Twist, ZEB1, and ZEB2, transcription factors associated with EMT and E-cadherin, in 14 cases of SpCC of the esophagus. In order to verify the neoplastic nature of sarcomatous components, TP53 mutation status and protein expression were examined in each case. Nuclear ZEB1 expression was extensive in the sarcomatous component, greater than invasive front of carcinoma components ( P < 0.0001). Membranous E-cadherin expression was mostly lost in sarcomatous cells in all cases ( P < 0.0001). The p53 expression pattern was almost concordant between the two areas in all cases. TP53 mutation analysis revealed that seven cases harbored identical mutations in both components. One case had mutations only in the sarcomatous component. It is noteworthy that none of them harbored mutation in exon 5, unlike conventional esophageal squamous cell carcinoma. These findings show that ZEB1 are widely expressed in the sarcomatous area of SpCC of the esophagus, suggesting the involvement of EMT. The avoidance of exon 5 in terms of TP53 mutation may also be a feature of the tumor. [ABSTRACT FROM AUTHOR]

Background Although lobe-specific nodal spread of primary lung cancer has been recently described, segment-specific nodal spread remains unclear. We investigated the frequency of hailer and mediastinal lymph node involvement and survival in patients with tumors located in the superior segment ( SS) and basal segment ( BS) in the right lower lobe. Methods Two hundred and sixty-three patients with primary lung cancer originating in the right lower lobe underwent lobectomy with systematic mediastinal lymph node dissection. Patients were categorized into two groups: SS (n = 114) or BS (n = 149). Results Frequencies of metastasis to station 11s and 11i were significantly higher in the SS ( P < 0.0001) and BS groups ( P = 0.022), respectively. Both the SS and BS groups showed a high frequency of subcarinal mediastinal zone (station 7) metastasis (96.9% and 90.6%, respectively; P = 0.271). The frequencies of superior mediastinal zone (station 2 R and 4 R) metastasis were 37.5% in the SS and 35.8% in the BS group ( P = 0.878). In patients with pN2 disease, three-year disease-free survival was significantly shorter in the SS (22.6%) than the BS group (42.1%; P = 0.020). In the BS group, the independent predictive factors of a poor or good prognosis were metastasis to station 11i or skip metastasis, respectively; however, we did not detect an independent prognostic factor in the SS group. In the right lower lung lobe, there was no segment-specific nodal spread. Conclusion When segmentectomy is undertaken, mediastinal lymph node dissection should be performed in proportion to lobectomy. [ABSTRACT FROM AUTHOR]

Background and objective It is difficult to verify the bacteriological diagnosis of M ycobacterium avium complex ( MAC) infection. The anti-glycopeptidolipid ( GPL)-core IgA antibody test was recently developed as a diagnostic method for MAC pulmonary disease. Only a few studies evaluate its clinical efficacy. We conducted retrospective evaluations of clinical characteristics of patients suspected of MAC infection to explore the usefulness of the anti- GPL-core IgA antibody test. Methods We retrospectively evaluated 296 patients who were suspected to have MAC infection and underwent anti- GPL-core IgA antibody test between March 2013 and July 2014 in Jikei University hospital. Results A total of 29 patients were diagnosed with 'definite MAC' based on the American Thoracic Society ( ATS) criteria with multiple identifications of MAC. On the other hand, 106 patients were diagnosed with other pulmonary diseases than MAC. The sensitivity and specificity of anti- GPL-core IgA antibody test for MAC diagnosis were 58.6% and 98.1%, respectively. The definite MAC group showed no significant differences in strains, treatment history or number of segments involved. The duration of MAC disease in the positive-antibody group was significantly longer than in the negative-antibody group ( P = 0.046). A significant increase in the false-negative rate was observed in patients with malignant disease ( P = 0.029). Conclusions The anti- GPL-core IgA antibody test demonstrated high sensitivity and specificity for the diagnosis of MAC infection especially in patients without malignant diseases. [ABSTRACT FROM AUTHOR]

We present the first reported case of lung large cell neuroendocrine carcinoma ( LCNEC) with spontaneous regression followed by progression. An 85-year-old woman presented with a 2.8-cm nodule in the right upper lung lobe on chest computed tomography. After four months, the tumor decreased to 1.8 cm and remained unchanged in size for the next three months, but it grew to 8.6 cm and invaded the mediastinal fat tissue after approximately one year. Ultrasound echo-guided percutaneous biopsy revealed the tumor to be LCNEC. The patient underwent a right upper lobectomy with lymph node dissection. She had a good postoperative course with no complications. Physicians and surgeons should be aware that radiographic regression of a pulmonary nodule does not necessarily exclude the possibility of lung cancer. [ABSTRACT FROM AUTHOR]

Key Clinical Message PTTM (Pulmonary tumor thrombotic microangiopathy) is very difficult to diagnose before death. We report a case of urothelial carcinoma of the urinary bladder associated with PTTM in which an antemortem diagnosis by PMC (pulmonary microvascular cytology). PMC may represent the only chance for diagnosis and achievement of remission in PTTM. [ABSTRACT FROM AUTHOR]

The band gap of and disordered structure in Li8SiN4 (lattice constant: a = 10.148 Å, c = 9.567 Å) are studied by optical absorption, photoacoustic spectroscopy, X-ray diffraction, and Raman scattering spectroscopy. Li8SiN4 is a semiconductor with a band gap of 2.4 eV, suggesting the transition from the N-2p valence band to the conduction band mainly consisting of Si-3s and/or -3p orbitals. A broad Raman peak is observed at 586 cm-1, indicating the homogenously random distribution of Li and Si atoms. Li8SiN4 crystallizes in a superstructure of eight face-centered N sublattices. In each sublattice, one Li and one Si atom are randomly and diagonally occupied at two tetrahedral sites next to N, while six Li atoms reside at the other sites next to N. The possible locations of one remaining Li atom are also discussed. Li8SiN4 is a direct transition, which is slightly larger than the d-d electron transitions in the typical cathode materials LiMn2O4 and LiCoO2. For a 5 × 5 mm2 sized lithium secondary battery with the Li8SiN4 + acetylene black cathode/propylene carbonate + LiClO4 electrolyte/Li anode structure, the capacity for the discharge current of 10 µA is between 2.44 µAh/cm2 and 3.56 µAh/cm2 for a potential range between 2.8 V and 3.8 V. (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

The safety of weekly regional hyperthermia performed with 8 MHz radiofrequency (RF) capacitive heating equipment has been established in rectal cancer. We aimed to standardize hyperthermia treatment for scientific evaluation and for assessing local tumor response to RF hyperthermia in rectal cancer. Fortynine patients diagnosed with rectal adenocarcinoma were included in the study. All patients received chemoradiation with intensity-modulated radiation therapy 5 days/week (dose, 50 Gy/25 times) concomitant with 5 days/week for five times of capecitabine (1700 mg/m2 per day) and once a week for five times of 50 min irradiations by an 8 MHz RF capacitive heating device. Thirty-three patients underwent surgery 8 weeks after treatment. Three patients did not undergo surgery because of progressive disease (PD) and 13 refused. Eight (16.3%) patients had a pathological complete response (ypCR) after surgery. Among patients without surgery, 3 (6.1%) had clinical complete response (CR) and 3 (6.1%) had local CR but distant PD (CRPD). Ninety percent of ypCR + CR patients were shown in 6.21 W min-1 m-2/treatment or higher group of average total accumulated irradiation output with 429°C min-1 m-2 or higher group of total accumulated thermal output. However, a patient with CRPD was in the higher total accumulated thermal output group. We propose a new quantitative parameter for the hyperthermia and demonstrated that patients can benefit from mild irradiation with mild temperature. Using these parameters, the exact output, optimal thermal treatment, and contraindications or indications of this modality could be determined in a multi-institutional, future study. [ABSTRACT FROM AUTHOR]

Patients with systemic sclerosis ( SSc) have an increased risk of malignancy compared with the general population. Recently, SSc patients with anti- RNA polymerase III antibody have been reported to have an increased risk of malignancy as compared with those with other disease-specific autoantibodies in US, European and Australian populations. Therefore, we studied the relationship between disease-specific autoantibodies and malignancy in 261 Japanese SSc patients. The prevalence of malignancy was significantly higher in patients with anti- RNA polymerase III antibody (7/22, 31.8%) than in those with anti-topoisomerase I antibody (2/82, 2.4%) and in those with anticentromere antibody (8/137, 5.8%). Importantly, among seven patients with anti- RNA polymerase III antibody and malignancy, three patients (42.9%) developed malignancy from 6 months before to 12 months after SSc onset. Thus, malignancy complication in Japanese SSc patients with anti- RNA polymerase III antibody is as high as that in other races, suggesting that SSc patients with anti- RNA polymerase III antibody share the same pathological process among different ethnic groups. [ABSTRACT FROM AUTHOR]

The asymmetric hydrogenation of pyrimidines proceeded with high enantioselectivity (up to 99 % ee) using an iridium catalyst composed of [IrCl(cod)]2, a ferrocene-containing chiral diphosphine ligand (Josiphos), iodine, and Yb(OTf)3 (cod=1,5-cyclooctadiene). The chiral catalyst converted various 4-substituted pyrimidines into chiral 1,4,5,6-tetrahydropyrimidines in high yield. The lanthanide triflate is crucial for achieving the high enantioselectivity as well as for activating the heteroarene substrate. [ABSTRACT FROM AUTHOR]

A divergent synthesis of cyclitol derivatives has been developed utilizing an N-heterocyclic carbene-catalyzed benzoin-type cyclization of C2-symmetrical dialdoses. The resulting inososes are versatile intermediates, which are readily converted into not only inositols but also amino-, deoxy-, O-methyl- and C-methyl-inositols. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs), such as exosomes and microvesicles, encapsulate proteins and microRNAs (miRNAs) as new modulators of both intercellular crosstalk and disease pathogenesis. The composition of EVs is modified by various triggers to maintain physiological homeostasis. In response to cigarette smoke exposure, the lungs develop emphysema, myofibroblast accumulation and airway remodelling, which contribute to chronic obstructive pulmonary disease (COPD). However, the lung disease pathogenesis through modified EVs in stress physiology is not understood. Here, we investigated an EV-mediated intercellular communication mechanism between primary human bronchial epithelial cells (HBECs) and lung fibroblasts (LFs) and discovered that cigarette smoke extract (CSE)-induced HBEC-derived EVs promote myofibroblast differentiation in LFs. Thorough evaluations of the modified EVs and COPD lung samples showed that cigarette smoke induced relative upregulation of cellular and EV miR-210 expression of bronchial epithelial cells. Using co-culture assays, we showed that HBEC-derived EV miR-210 promotes myofibroblast differentiation in LFs. Surprisingly, we found that miR-210 directly regulates autophagy processes via targeting ATG7, and expression levels of miR-210 are inversely correlated with ATG7 expression in LFs. Importantly, autophagy induction was significantly decreased in LFs from COPD patients, and silencing ATG7 in LFs led to myofibroblast differentiation. These findings demonstrate that CSE triggers the modification of EV components and identify bronchial epithelial cell-derived miR-210 as a paracrine autophagy mediator of myofibroblast differentiation that has potential as a therapeutic target for COPD. Our findings show that stressor exposure changes EV compositions as emerging factors, potentially controlling pathological disorders such as airway remodelling in COPD. [ABSTRACT FROM AUTHOR]

Background Early lesions of localized scleroderma are histologically characterized by perivascular lymphocytic infiltrate in the reticular dermis and swollen endothelial cells. However, there have been few information regarding histological features other than these findings in localized scleroderma. Objective Since en coup de sabre ( ECDS) is a certain subset of localized scleroderma with a relatively uniform clinical manifestation, we focused on this disease subset and evaluated its histopathological features. Methods A total of 16 patients with ECDS were retrospectively evaluated on the basis of clinical and histological findings. Results Regardless of clinical manifestations, vacuolar degeneration was found in all of the ECDS patients. Importantly, keratinocyte necroses were restricted to early and active ECDS lesions. In early ECDS patients (disease duration of <3 years), moderate to severe perivascular and/or periappendageal lymphocytic infiltrate and vacuolar changes in follicular epithelium were more prominent, whereas epidermal atrophy was less frequently observed, than in late ECDS patients (disease duration of ≥6 years). Conclusion Vacuolar degeneration at the dermoepidermal junction is a common histological feature in ECDS and perivascular and/or periappendageal lymphocytic infiltrate and vacuolar degeneration of follicular epithelium are characteristic especially in early ECDS, further supporting a canonical idea that the elimination of mutated epidermal cells by immune surveillance contributes to tissue damage and resultant fibrosis in localized scleroderma. [ABSTRACT FROM AUTHOR]

Interstitial lung disease ( ILD) occurrence and risk factors were investigated in the Japanese non-small-cell lung cancer, post-marketing, large-scale surveillance study, POLARSTAR. All patients with unresectable, recurrent/advanced non-small-cell lung cancer who were treated with erlotinib in Japan between December 2007 and October 2009 were enrolled. Primary endpoints were patterns of ILD and risk factors for onset of ILD and ILD-related death. Overall survival, progression-free survival, and occurrence of adverse drug reactions were secondary endpoints. Interstitial lung disease was confirmed in 429 (4.3%) patients. Concurrent/previous ILD (hazard ratio, 3.19), emphysema or chronic obstructive pulmonary disease (hazard ratio, 1.86), lung infection (hazard ratio, 1.55), smoking history (hazard ratio, 2.23), and period from initial cancer diagnosis to the start of treatment (<360 days; hazard ratio, 0.58) were identified as significant risk factors for developing ILD by Cox multivariate analysis. Logistic regression analysis identified Eastern Cooperative Oncology Group performance status 2-4 (odds ratio, 2.45 [95% confidence interval, 1.41-4.27]; P = 0.0016), ≤50% remaining normal lung area (odds ratio, 3.12 [1.48-6.58]; P = 0.0029), and concomitant honeycombing with interstitial pneumonia (odds ratio, 6.67 [1.35-32.94]; P = 0.02) as poor prognostic factors for ILD death. Median overall survival was 277 days; median progression-free survival was 67 days. These data confirm the well-characterized safety profile of erlotinib. Interstitial lung disease is still an adverse drug reaction of interest in this population, and these results, including ILD risk factors, give helpful information for treatment selection and monitoring. Erlotinib efficacy was additionally confirmed in this population. ( POLARSTAR trial ML21590.) [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to clarify the anatomy between the left triangular ligament (LTL) and the appendix fibrosa hepatis (AFH) in order not to sever the AFH when dissecting the LTL. Methods: Totals of 43 and 27 cadaveric livers were examined macroscopically and histologically, respectively. Results: The LTL attached itself to the diaphragmatic surface of the AFH through almost all lengths of the AFH. This might be the reason why AFH is so often dissected together with the LTL. There were two types of relation between the LTL and the AFH; in one type, the starting point of the LTL existed on the left liver and in the other type, it was on the AFH. Twenty‐five of 27 AFH included remnants of the bile duct and 12 of 25 AFH had comparatively large bile ducts, which was unexceptionally accompanied by the well‐developed peribiliary vascular plexus. AFH showed a variety of shapes, such as rectangular (6/43), long triangular (4/43), short triangular (7/43), triangular plus cordlike (11/43), cordlike (12/43) and bifurcated (3/43) types. Conclusions: As AFH sometimes includes relatively large bile ducts, it is recommended for surgeons to sever the AFH not just simply by electrocautery but by ligating its stump securely. [ABSTRACT FROM AUTHOR]