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Olfactory mucus contributes to the specific functions of the olfactory mucosa, but the composition and source of mucus proteins have not been fully elucidated. In this study, we used comprehensive proteome analysis and identified lipocalin 15 (LCN15), a human-specific lipocalin family protein, as an abundant component of the olfactory mucus. Western blot analysis and enzyme-linked immunosorbent assay (ELISA) using a newly generated anti-LCN15 antibody showed that LCN15 was concentrated in olfactory mucus samples, but not in respiratory mucus samples. Immunohistochemical staining using anti-LCN15 antibody revealed that LCN15 localized to the cytokeratin 18-positive Bowman's glands of the olfactory cleft mucosa. Quantitative image analysis revealed that the area of LCN15 immunoreactivity along the olfactory cleft mucosa significantly correlated with the area of neuron-specific Protein-Gene Product 9.5 (PGP9.5) immunoreactivity, suggesting that LCN15 is produced in non-degenerated areas of the olfactory neuroepithelium. ELISA demonstrated that the concentration of LCN15 in the mucus was lower in participants with normal olfaction (≥ 50 years) and also tended to be lower in patients with idiopathic olfactory loss (≥ 50 years) than in participants with normal olfaction (< 50 years). Thus, LCN15 may serve as a biomarker for the activity of the Bowman's glands. [ABSTRACT FROM AUTHOR]

The oncological and functional outcomes in glioblastoma (GBM) patients following supratotal resection (SupTR), involving complete resection of contrast-enhancing enhanced (CE) tumors and areas of methionine (Met) uptake on 11C-met positron emission tomography (Met-PET), are unknown. We conducted a retrospective review in newly diagnosed, IDH1 wild-type GBM patients, comparing SupTR with gross total resection (GTR), in which only CE tumor tissue was resected. All patients underwent standard radiotherapy and temozolomide treatment, and were followed for tumor recurrence and overall survival (OS). Among the 30 patients included in this study, 7 underwent SupTR and 23 underwent GTR. Awake craniotomy with cortical and subcortical mapping was more frequently performed in the SupTR group than in the GTR group. During the follow-up period, significantly different patterns of disease progression were observed between groups. Although more than 80% of recurrences were local in the GTR group, all recurrences in the SupTR group were distant. Median OS in the GTR and SupTR groups was 18.5 months (95% confidence interval [CI] 14.2–35.1) and not reached (95% CI 30.5-not estimable), respectively; this difference was statistically significant (p = 0.03 by log-rank test). No postoperative neurocognitive decline was evident in patients who underwent SupTR. Compared to GTR alone, aggressive resection of both CE tumors and areas with Met uptake (SupTR) under awake craniotomy with functional mapping results in a survival benefit associated with better local control and neurocognitive preservation. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most common and aggressive type of brain tumor with high recurrence and fatality rates. Although various therapeutic strategies have been explored, there is currently no effective treatment for glioblastoma. Recently, the number of immunotherapeutic strategies has been tested for malignant brain tumors. Invariant natural killer T (iNKT) cells play an important role in anti-tumor immunity. To address if iNKT cells can target glioblastoma to exert anti-tumor activity, we assessed the expression of CD1d, an antigen-presenting molecule for iNKT cells, on glioblastoma cells. Glioblastoma cells from 10 of 15 patients expressed CD1d, and CD1d-positive glioblastoma cells pulsed with glycolipid ligand induced iNKT cell-mediated cytotoxicity in vitro. Although CD1d expression was low on glioblastoma stem-like cells, retinoic acid, which is the most common differentiating agent, upregulated CD1d expression in these cells and induced iNKT cell-mediated cytotoxicity. Moreover, intracranial administration of human iNKT cells induced tumor regression of CD1d-positive glioblastoma in orthotopic xenografts in NOD/Shi-scid IL-2RγKO (NOG) mice. Thus, CD1d expression represents a novel target for NKT cell-based immunotherapy for glioblastoma patients. [ABSTRACT FROM AUTHOR]

A previous study showed that people living in urban areas are generally exposed to low-frequency noise (LFN) with frequencies below 100 Hz and sound levels of 60–110 dB in daily and occupational environments. Exposure to LFN has been shown to affect balance in humans and mice. However, there is no information about prevention of LFN-mediated imbalance because of a lack of information about the target region based on health risk assessment of LFN exposure. Here, we show that acute exposure to LFN at 100 Hz, 95 dB, but not at 85 dB or 90 dB, for only 1 h caused imbalance in mice. The exposed mice also had decreased cervical vestibular-evoked myogenic potential (cVEMP) with impaired activity of vestibular hair cells. Since imbalance in the exposed mice was irreversible, morphological damage in the vestibules of the exposed mice was further examined. The exposed mice had breakage of the otoconial membrane in the vestibule. LFN-mediated imbalance and breakage of the otoconial membrane in mice were rescued by overexpression of a stress-reactive molecular chaperone, heat shock protein 70 (Hsp70), which has been shown to be induced by exposure of mice to 12 h per day of LFN at 95 dB for 5 days. Taken together, the results of this study demonstrate that acute exposure to LFN at 100 Hz, 95 dB for only 1 h caused irreversible imbalance in mice with structural damage of the otoconial membrane as the target region for LFN-mediated imbalance, which can be rescued by Hsp70. [ABSTRACT FROM AUTHOR]

Introduction: Chromosomes 1p/19q co-deletion is a robust molecular marker for the diagnosis of oligodendroglial tumors, and has been included in the 2016 WHO modified classification. Although treatment for oligodendroglioma is controversial, upfront chemotherapy is regarded as one of the treatment option for low-grade tumor. We have treated all the 1p/19q co-deleted oligodendrogliomas, both grades II and III, with upfront chemotherapy without conventional radiotherapy for 20 years. The clinical experience from this trial may be suggestive for understanding of the biological features of oligodendroglioma with 1p/19q co-deletion toward precision medicine.Methods: This is a long-term retrospective data of the non-selected patients with 1p/19q co-deleted oligodendrogliomas uniformly treated with up-front chemotherapy. Seventy consecutive patients (48 with grade II and 22 with grade III tumors) were included.Results: The median follow-up period was 13 years. The 5-, 10-, and 15-year progression-free survival (PFS) rates were 85.7%, 54.8%, and 31.5%, respectively, and the median PFS was 146 months. In most cases, tumor recurrence was remained local and could be controlled by salvage surgery and/or chemotherapy. The 5-, 10-, and 15-year overall survival (OS) rates were 96.8%, 88.7%, and 80.0%, respectively, and the median OS was not reached. These survival data compared favorably with previous large clinical studies employing radiotherapy. Tumor grades based on World Health Organization classification, extent of surgery, and age affected neither PFS nor OS. Most patients were able to return to their premorbid social life.Conclusions: The long-term results drawn from 20-years of single institution experience show that the patients with 1p/19q co-deleted oligodendrogliomas can be successfully treated with up-front chemotherapy alone without compromising OS. [ABSTRACT FROM AUTHOR]

To determine the efficacy of endoscopic electrocauterization for pyriform sinus fistula (PSF) using a flexible Bugbee cautery electrode. From 2009 to 2016, a total of eight patients with acute suppurative thyroiditis or cervical abscess secondary to PSF were retrospectively registered in our study (three males, five females; median age 6.5 years). All patients underwent endoscopic electrocauterization as treatment for PSF. Six of eight patients had no recurrence after the initial endoscopic electrocauterization of PSF. One patient with recurrence developed symptoms 9 days after cauterization and another experienced recurrence after 2 years. Mean follow-up for the eight patients was 50 months (range 5-96 months). No post-operative complication was reported. Endoscopic electrocauterization appears to be a less-invasive, safe, and effective method for the treatment of PSF. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed the incidence of malnutrition caused by preoperative chemoradiotherapy (CRT) in rectal cancer patients, which is seemingly underestimated; however, malnutrition affects treatment tolerability, postoperative complications, including anastomotic leakage (AL), and oncological outcomes. Methods: Between January 2008 and December 2014, 54 consecutive patients with T3-4, N0-2, M0-1 resectable rectal cancer received CRT comprising 45 Gy radiotherapy and S-1 alone or with irinotecan for 5 weeks and then underwent curative surgery with diverting or permanent stomas 6-8 weeks after CRT. We assessed malnutrition after completion of CRT (5-6 weeks after CRT start date) and at surgery (11-14 weeks after CRT start date), defining weight loss as ≥5 % of pre-CRT weight; this definition differs from commonly used criteria for adverse events. We evaluated the incidence of malnutrition associated with CRT and influence of malnutrition on treatment tolerability, AL, and disease-free survival (DFS). We also assessed the influence of CRT on the rate of postoperative complications by comparing the study group with 61 patients who had undergone excision with diverting or permanent stomas alone. Results: Malnutrition was observed in 51 % of patients after CRT and in 29 % at surgery. Malnutrition after CRT was associated with treatment tolerability, and malnutrition at surgery was significantly associated with AL, which significantly influenced DFS in stage 1-3 patients. Conclusion: Malnutrition caused by CRT is common and is associated with treatment tolerability and AL. Nutritional assessment and support seem indispensable for the rectal cancer patients receiving CRT. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare the pathological response of mesorectal positive nodes between short-course chemoradiotherapy with delayed surgery (SCRT-delay) and long-course chemoradiotherapy (LC-CRT) in patients with rectal cancer. Method: The resected primary tumor specimens following the two different approaches were assessed utilizing the tumor regression grade (TRG 0-4), and each positive lymph node was assessed according to the lymph node regression grade (LRG 1-3), with TRG 4 and LRG 3 indicating total regression. The lymph node sizes were measured to elucidate any correlation with LRG scores. Results: Seventy-four patients with ypN-positive rectal cancer had 220 positive lymph nodes following the SCRT-delay, and 48 patients had 141 positive lymph nodes following the LC-CRT. The distribution of LRG 1/2/3 in the two groups was 123/72/25 and 60/31/50 ( p < 0.001), respectively, and the distribution of TRG 0/1/2/3/4 in the two groups was 36/19/19/0 and 12/15/20/1 ( p = 0.005), respectively. The requirements of total regression of positive lymph nodes were a primary tumor degenerated to TRG 3 with a size less than 6 mm in SCRT-delay (sensitivity, 60.9 %) or a primary tumor degenerated to TRG 2-4 with a size less than 5 mm at TRG 2 (sensitivity, 57.6 %) or 6 mm at TRG 3 and 4 (sensitivity, 84.2 %) in LC-CRT as indicated by the receiver operating characteristic curve analysis. Conclusion: The tumor regression effect of LC-CRT on the primary tumor and positive nodes was more favorable than SCRT-delay, and LC-CRT is able to predict the LRG 3 response with a high sensitivity. [ABSTRACT FROM AUTHOR]

Blake's pouch cyst (BPC), a rare cystic malformation in the posterior fossa, is believed to be caused by the congenital expansion of the posterior membranous area that normally regresses during embryogenesis. However, due to the wide spectrum of the onset pattern and age of patients, the natural history and the pathogenesis are poorly understood. The authors describe the case of a girl who admitted with headache and right abducens nerve paresis at the age of 3 years and 10 months. Magnetic resonance (MR) imaging demonstrated a tetraventricular hydrocephalus, an open aqueduct, and a posterior fossa cyst compatible with BPC. Multiple tumors were also noticed in the ventricular wall. Tumor biopsy and an endoscopic third ventriculostomy were performed. Intraoperative observation confirmed the BPC, and pathological diagnosis was pilomyxoid astrocytoma. In retrospect, MR imaging was performed twice in the past, at the age of 8 months and again at 22 months, and no anomaly was detected, suggesting that Blake's pouch was once regressed. Therefore, a BPC in this patient was certainly developed after her second or third year of life. The ventricular tumors may influence the cerebrospinal fluid (CSF) absorption, which triggered the re-expansion of BPC from the possible remnant of Blake's pouch. This is a rare but important report providing evidence that in addition to the classic congenital BPC in which the remnant of Blake's pouch remains persistent, there could be postnatal or secondary BPC, which develops after birth. Possible mechanisms include that the remnant of Blake's pouch, which originally disappears, may re-expand postnatally in association with unknown trigger or a change in CSF dynamics or absorption. [ABSTRACT FROM AUTHOR]

Pancreatic involvement is an extremely rare manifestation of lymphoblastic lymphoma (LBL), and only a few cases have been reported. We report a case of LBL arising from the pancreas that was diagnosed using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The patient was a 57-year-old female who had suffered from abdominal pain for 2 weeks. A physical examination revealed an upper abdominal mass, but did not detect peripheral lymphadenopathy. Imaging studies including computed tomography (CT) and F-fluorodeoxy glucose (FDG)-positron emission tomography-CT revealed an enlarged pancreatic body, which was positive for FDG uptake. EUS-FNA detected medium-sized proliferating atypical lymphocytes, and immunohistochemical staining demonstrated that these cells were positive for CD20, CD10, PAX5, and terminal deoxynucleotidyl transferase. A bone marrow examination was negative for lymphoma infiltration, and a diagnosis of LBL arising from the pancreas was made. The patient was successfully treated with a combination of chemotherapy and pancreatic irradiation. [ABSTRACT FROM AUTHOR]

Purpose: Under pathological conditions, the Notch signal pathway is involved in the inflammatory process in arteriosclerosis, atherosclerosis and angiogenesis under ischemic conditions. The purpose of this study was to observe whether or not Buerger's disease is associated with Notch signal activation. Methods: All the patients were diagnosed between 1980 and 2009 at Nagoya University Hospital. Twenty-two specimens from 12 patients with Buerger's disease (TAO) and 13 specimens from nine patients with arteriosclerosis obliterans (ASO) were analyzed by immunohistochemistry for Notch1, Jagged-1 (a Notch ligand) and Hes-1 (a Notch 1 target transcription factor). Results: Notch1 and Jagged-1 were highly expressed in the endothelium in the new vasa vasorum and in the smooth muscle cells in the media of specimens from both groups. These Notch-related proteins were also remarkably expressed in inflammatory cells in the intima of specimens from TAO patients. Fewer inflammatory cells expressed Notch-related proteins in atheromatous plaques (Notch1 (%): 8.4 ± 0.76 versus 1.3 ± 0.43, P < 0.001; Jagged-1(%): 9.3 ± 1.1 versus 5.2 ± 1.1, P = 0.03). Indeed, Hes-1, which is a transcription factor downstream of Notch1, was remarkably expressed in the endothelium of new capillary vessels and inflammatory cells in TAO patients. Notch1-positive mononuclear cells were also seen in the thrombus in samples from the TAO group. Conclusions: Our findings are the first demonstration that Notch signal activation in inflammatory cells may be involved in the pathophysiological mechanism underlying Buerger's disease. [ABSTRACT FROM AUTHOR]

The present case involved a 76-year-old man with a cystic mass in the head of his pancreas. The cystic lesion, which measured 17.7 × 9.8 mm, was first detected by ultrasonography (US) at the age of 72 years. Follow-up endoscopic ultrasonography (EUS) performed at 4 years after the lesion had first been detected revealed a mural nodule measuring 14.0 × 8.4 mm in the cyst. Endoscopic retrograde pancreatography (ERP) imaging revealed that the main pancreatic duct was in communication with the cyst and that there was no irregular narrowing of the main pancreatic duct. On the basis of these results, the patient was diagnosed with an intraductal papillary mucinous neoplasm (IPMN), and stomach-preserving pancreaticoduodenectomy was performed. A histopathological examination revealed that the interior of the cystic part of the lesion was lined by a pancreatic ductal epithelium. A pathological examination of the nodular lesion detected storiform fibrosis, severe lymphoplasmacytic infiltration, and hyperplasia in the pancreatic duct epithelium together with a small amount of mucus. On immunohistological staining, the infiltrating lymphoplasmacytes were found to be positive for IgG4. Accordingly, the patient was diagnosed with focal autoimmune pancreatitis (AIP). In conclusion, we reported a case of focal AIP mimicking IPMN. This case showed neither enlargement of the pancreas nor irregular narrowing of the main pancreatic duct. [ABSTRACT FROM AUTHOR]

This study aims to identify predisposing characteristics of descending necrotizing mediastinitis (DNM) arising from deep neck infection (DNI) and to determine appropriate therapeutic intervention strategies. We retrospectively reviewed 54 patients (male, n = 34; female, n = 20; mean age, 64.5 years) who had been treated at Mie University Hospital for DNI between April 2001 and October 2011. Eight of nine patients who developed DNM confirmed by computed tomography of the neck and chest, underwent mediastinal drainage (video-assisted thoracic surgical drainage, n = 6; mediastinoscopy-assisted drainage, n = 2). A patient developed uncontrolled acute respiratory distress syndrome after aggressive surgery, resulting in a mortality rate of 12 %. High blood CRP values, and the pharynx and tonsils as origins of infection were factors involved in the development of DNM arising from DNI. In conclusion, DNM remains a destructive and fatal disease that requires aggressive treatment including mediastinal exploration. [ABSTRACT FROM AUTHOR]

We report a case of late type III B endoleak from a fabric tear in the main body of a Zenith bifurcated stent-graft approximately 19 months after implantation. A follow-up computed tomography (CT) scan showed gradual growth in the size of the aneurysm, but no apparent endoleak was recognized. However, the CT scan had demonstrated a mosaic pattern in the aneurysm sac, which could indicate an endoleak from a fabric tear. The defect was repaired by implantation of body extensions, but the patient died 5 h after the procedure. [ABSTRACT FROM AUTHOR]

Purpose: We conducted this study to compare the cost of open surgical repair (OR) with that of endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm (AAA). Methods: Between January 2007 and November 2008, 70 patients underwent open repair and 57 patients underwent EVAR. We evaluated the total cost, including that of the Diagnosis Procedure Combination (DPC), that of the surgical procedure, that of materials such as grafts and guide wires, and that of the anesthesia. Results: The mean costs for OR versus EVAR were as follows: DPC, ¥632370 versus ¥490050, respectively, which was significant; anesthesia, ¥123540 versus ¥86220, respectively (P < 0.05); and materials, ¥257770 versus ¥2113280, respectively (P < 0.05). Thus, the mean total cost was ¥1825830 versus ¥3159270 for open repair and EVAR, respectively (P < 0.05). Conclusions: New technologies should not only be clinically effective, but also cost effective. EVAR is less invasive clinically, but the cost of endovascular prostheses and other materials remains high. [ABSTRACT FROM AUTHOR]

Purpose: In Japan, the incidence of venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), has been relatively low; however, the incidence has recently been increasing. Since April 2004, we have developed an original computer-linked VTE prophylaxis in order to decrease the incidence of in-hospital VTE. Our objective has been to evaluate the efficacy of the VTE prophylaxis guideline. Methods: A retrospective pre- and postintervention study was conducted (preintervention phase, n = 17 854; postintervention phase, n = 26 831). Data were obtained from the clinical records of patients who underwent vascular surgery and were screened for DVT at our institution. Results: The frequency of patients screened for DVT increased significantly from 70 (0.4%) to 209 (0.8%) after the establishment of a guideline ( P < 0.001). Asymptomatic DVT patients increased from 5 (12.5%) in the control group to 33 (50.0%) in the intervention group ( P < 0.0001), while symptomatic DVT events with leg swelling decreased from 29 (72.5%) to 16 (24.2%) ( P < 0.0001). Furthermore, shock and massive PE events were significantly lower (from 31.3% to 0%; P < 0.05). Conclusion: Our VTE prophylaxis guidelines are considered to be useful for the detection of asymptomatic DVT patients during hospitalization, thus leading to a significantly lower incidence of postoperative VTE. [ABSTRACT FROM AUTHOR]

Tumors originating from the nasolacrimal duct are exceedingly rare. Only a few cases have been reported previously. In advanced cases with extended tumor, differential diagnosis from lacrimal sac tumor is difficult. A 68-year-old Japanese man with intractable dacryocystitis was examined with intranasal endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI). Squamous cell carcinoma extended from a medial site in the left orbit to the lacrimal orifice. En bloc resection was performed and histopathological examination of the surgical specimen using serial section suggested that the origin of the tumor was located in the nasolacrimal duct. This is the first case in nasolacrimal duct carcinoma whose differential diagnosis of origin has been studied in detail. We showed that pathological study using serial section along the duct provides useful information for diagnosing the tumor origin in addition to that obtained from imaging studies. [ABSTRACT FROM AUTHOR]

The smaller pore size of a ceramic membrane contributed to an increase in the selectivity of C2 hydrocarbons in the oxidative coupling of methane, with keeping high CH conversions about 50 %. [ABSTRACT FROM AUTHOR]

Two functional lattice oxygens on the surface of a Mn-mixed Mg oxide were distinguished in the oxidative coupling of methane: the oxygen of MgO, which was active for methyl radical formation, and that of a Mn-Mg oxide solid solution, which was active for the dehydrogenation of ethane. [ABSTRACT FROM AUTHOR]

Lithium made a Mn-Mg-O solid solution stable upon exposure of methane, decreased the ethane and ethylene formation rates, and increased the COx formation rate during the oxidative coupling of methane. On the other hand, on MgO, lithium inhibited COx formation markedly and enhanced the selectivity of ethane 47% to 76%. [ABSTRACT FROM AUTHOR]

Ca2+-deficient hydroxyapatite (r-HAp) originated from cattle bones and stoichiometric hydroxyapatite (s-HAp) derived from reagents were prepared by wet syntheses. The adsorption characteristics of albumin (BSA) and lysozyme (LSZ) on the two HAp surfaces were compared by changing the heating temperature of the powders at 273–1073 K in a stream of water vapour. The saturated amount of adsorption (ASA(B) for BSA and ASA(L) for LSZ) on these HAp powders changed little at 273–673 K (Region I), but at 673–1073 K (Region II), clearly increased with crystallite size growth and transformation of crystal morphology. As far as the surface proportions of HAp for P- and C-adsorption sites (the ratios ASA(L)/ASA(B)) are concerned, r-HAp gave no change in Region I and decreased in Region II, whereas those for s-HAp were kept constant through all regions. The heats of LSZ adsorption, QL, for r-HAp and s-HAp, respectively, increased and decreased in Region II. These differences could be a result of the Ca2+-deficient structure of r-HAp with the OH−-vacancy and loosening surface structure due to segregation of impurities in Region II. r-HAp exhibited a 157% higher heat of BSA adsorption, QB, and a 60% lower QL in Region I than s-HAp. Conclusively, r-HAp can be used as an excellent adsorbent, rather than s-HAp, because of its chromatographic characteristics for the separation of acidic and basic proteins. © 1998 Chapman & Hall [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) in vitro microvasculature in a polydimethylsiloxane-based microdevice was developed as a physiologically relevant model of angiogenesis. The angiogenic process is monitored using stage-top optical coherence tomography (OCT). OCT allows non-invasive monitoring of the 3D structures of the prepared host microvasculature and sprouted neovasculature without fluorescence staining. OCT monitoring takes only a few minutes to scan through the several-millimetre scale range, which provides the advantage of rapid observation of living samples. The obtained OCT cross-sectional images capture 3D features of the angiogenic sprouting process and provide information on the dynamics of luminal formation. The stage-top system used in this study enables the observer to visualize the in vitro dynamics of 3D cultured cells simply and conveniently, offering an alternative monitoring method for studies on angiogenesis and providing quantitative information about vascular morphological changes. [ABSTRACT FROM AUTHOR]