Publications by authors named "Koji Sakamoto"

124 Publications

Bilobed flap for reconstruction of skin defect after excision of parotid carcinoma: a case report.

J Nippon Med Sch 2021 Sep 14. Epub 2021 Sep 14.

Department of Otorhinolaryngology Head and Neck Surgery Keio University.

Objectives: Reconstruction of medium-sized skin defect after excision of parotid carcinoma is performed using local flaps, pedicled flaps, or free flaps. The bilobed flap is one of the local flaps adopted by plastic surgeons primarily for a small nasal skin defect. We report a case of a patient with parotid carcinoma with skin infiltration who successfully underwent skin reconstruction with the bilobed flap.

Methods: An 84-year-old man had visited our hospital with a parotid mass 2 months earlier. He was diagnosed with parotid carcinoma with skin infiltration and underwent radical surgery. The skin defect was round-shaped with a 6 cm diameter. It was resected and reconstructed using a bilobed flap designed caudal to the defect.

Results: Except for the postoperative facial nerve palsy, which improved within 6 months, the postoperative course was uneventful, and the patient was discharged on the seventh postoperative day. Pathological examination revealed a sarcomatoid salivary duct carcinoma.

Conclusions: The bilobed flap is useful for reconstructing skin defects measuring up to 6 cm in diameter.
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http://dx.doi.org/10.1272/jnms.JNMS.2022_89-603DOI Listing
September 2021

Trapezius muscle branch of the spinal accessory nerve without penetrating the sternocleidomastoid muscle as a pitfall in neck dissection: prevalence in a Japanese institution and a protocol for the prevention of iatrogenic injury.

Acta Otolaryngol 2021 Aug 12;141(8):825-829. Epub 2021 Aug 12.

Department of Otorhinolaryngology, Head and Neck Surgery, Keio University, Tokyo, Japan.

Background: The spinal accessory nerve (SAN) has several anatomical variations, which may be a pitfall in neck dissection (ND). These include the trapezius muscle branch (TB), which stems from the common trunk before entering the sternocleidomastoid muscle (SCM).

Aims/objectives: To investigate the prevalence of this variation and suggest a protocol for preventing unexpected injury of the TB in ND.

Materials And Methods: We conducted a retrospective cohort study for 93 patients who had undergone neck dissection (117 sides) without resection of the SCM nor SAN. We recorded the division of the TB after and before penetration of the SCM by the common trunk (penetrating type TB [PTB]) and non-penetrating type TB [NPTB], respectively).

Results: Among NDs, PTB and NPTB were observed in 61 (52%) and 56 (48%) sides, respectively. In the subgroup of 24 cases with bilateral ND, PTB/PTB, NPTB/NPTB, and NPTB/PTB were observed in eight (33%), nine (38%), and seven (29%) cases, respectively. The prevalence of PTB/NPTB did not differ according to age, sex, or laterality.

Conclusions And Significance: NPTB is a common anatomical variation. The presence or absence of a branch from the common trunk must be initially checked to avoid unexpected damage to the TB.
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http://dx.doi.org/10.1080/00016489.2021.1954688DOI Listing
August 2021

Size and surface modification of silica nanoparticles affect the severity of lung toxicity by modulating endosomal ROS generation in macrophages.

Part Fibre Toxicol 2021 06 17;18(1):21. Epub 2021 Jun 17.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

Background: As the application of silica nanomaterials continues to expand, increasing chances of its exposure to the human body and potential harm are anticipated. Although the toxicity of silica nanomaterials is assumed to be affected by their physio-chemical properties, including size and surface functionalization, its molecular mechanisms remain unclear. We hypothesized that analysis of intracellular localization of the particles and subsequent intracellular signaling could reveal a novel determinant of inflammatory response against silica particles with different physico-chemical properties.

Results: We employed a murine intratracheal instillation model of amorphous silica nanoparticles (NPs) exposure to compare their in vivo toxicities in the respiratory system. Pristine silica-NPs of 50 nm diameters (50 nm-plain) induced airway-centered lung injury with marked neutrophilic infiltration. By contrast, instillation of pristine silica particles of a larger diameter (3 μm; 3 μm-plain) significantly reduced the severity of lung injury and neutrophilic infiltration, possibly through attenuated induction of neutrophil chemotactic chemokines including MIP2. Ex vivo analysis of alveolar macrophages as well as in vitro assessment using RAW264.7 cells revealed a remarkably lower cellular uptake of 3 μm-plain particles compared with 50 nm-plain, which is assumed to be the underlying mechanism of attenuated immune response. The severity of lung injury and neutrophilic infiltration was also significantly reduced after intratracheal instillation of silica NPs with an amine surface modification (50 nm-NH) when compared with 50 nm-plain. Despite unchanged efficacy in cellular uptake, treatment with 50 nm-NH induced a significantly attenuated immune response in RAW264.7 cells. Assessment of intracellular redox signaling revealed increased reactive oxygen species (ROS) in endosomal compartments of RAW264.7 cells treated with 50 nm-plain when compared with vehicle-treated control. In contrast, augmentation of endosomal ROS signals in cells treated with 50 nm-NH was significantly lower. Moreover, selective inhibition of NADPH oxidase 2 (NOX2) was sufficient to inhibit endosomal ROS bursts and induction of chemokine expressions in cells treated with silica NPs, suggesting the central role of endosomal ROS generated by NOX2 in the regulation of the inflammatory response in macrophages that endocytosed silica NPs.

Conclusions: Our murine model suggested that the pulmonary toxicity of silica NPs depended on their physico-chemical properties through distinct mechanisms. Cellular uptake of larger particles by macrophages decreased, while surface amine modification modulated endosomal ROS signaling via NOX2, both of which are assumed to be involved in mitigating immune response in macrophages and resulting lung injury.
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http://dx.doi.org/10.1186/s12989-021-00415-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210371PMC
June 2021

Fibroblasts positive for meflin have anti-fibrotic property in pulmonary fibrosis.

Eur Respir J 2021 May 28. Epub 2021 May 28.

National Hospital Organization Nagoya Medical Center, Nagoya, Japan.

The prognosis of elderly individuals with idiopathic pulmonary fibrosis (IPF) remains poor. Fibroblastic foci, in which aggregates of proliferating fibroblasts and myofibroblasts are involved, are the pathological hallmark lesions in IPF to represent focal areas of active fibrogenesis. Fibroblast heterogeneity in fibrotic lesions hampers the discovery of the pathogenesis of pulmonary fibrosis. Therefore, to determine of the pathogenesis of IPF, identification of functional fibroblasts is warranted. This study was aimed to determine the role of fibroblasts positive for meflin, identified as a potential marker for mesenchymal stromal cells, during the development of pulmonary fibrosis. We characterised meflin-positive cells in a single cell atlas established by single-cell RNA sequencing (scRNA-seq)-based profiling of 243 472 cells from 32 IPF lungs and 29 normal lung samples. scRNA-seq combined with RNA hybridisation identified proliferating fibroblasts positive for meflin in fibroblastic foci, not dense fibrosis, of fibrotic lungs in IPF patients. We determined the role of fibroblasts positive for meflin using bleomycin (BLM)-induced pulmonary fibrosis. A BLM-induced lung fibrosis model for meflin-deficient mice showed that fibroblasts positive for meflin had anti-fibrotic property to prevent pulmonary fibrosis. Although transforming growth factor-β-induced fibrogenesis and cell senescence with senescence-associated secretory phenotype were exacerbated in fibroblasts the repression or lack of meflin, these were inhibited in meflin-deficient fibroblasts with meflin reconstitution. These findings provide evidence to show the biological importance of meflin expression on fibroblasts and myofibroblasts in the active fibrotic region of pulmonary fibrosis.
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http://dx.doi.org/10.1183/13993003.03397-2020DOI Listing
May 2021

The Importance of Appropriate Diagnosis in the Practical Management of Chronic Obstructive Pulmonary Disease.

Diagnostics (Basel) 2021 Mar 30;11(4). Epub 2021 Mar 30.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.

Chronic obstructive pulmonary disease (COPD) is projected to continue to contribute to an increase in the overall worldwide burden of disease until 2030. Therefore, an accurate assessment of the risk of airway obstruction in patients with COPD has become vitally important. Although the Global Initiative for Chronic Obstructive Lung Disease (GOLD), the American Thoracic Society (ATS) and European Respiratory Society (ERS), and the Japanese Respiratory Society (JRS) provide the criteria by which to diagnose COPD, many studies suggest that it is in fact underdiagnosed. Its prevalence increases, while the impact of COPD-related systemic comorbidities is also increasingly recognized in clinical aspects of COPD. Although a recent report suggests that spirometry should not be used to screen for airflow limitation in individuals without respiratory symptoms, the early detection of COPD in patients with no, or few, symptoms is an opportunity to provide appropriate management based on COPD guidelines. Clinical advances have been made in pharmacotherapeutic approaches to COPD. This article provides a current understanding of the importance of an appropriate diagnosis in the real-world management of COPD.
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http://dx.doi.org/10.3390/diagnostics11040618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067197PMC
March 2021

Impact of post-capillary pulmonary hypertension on mortality in interstitial lung disease.

Respir Investig 2021 May 10;59(3):342-349. Epub 2021 Feb 10.

National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.

Background: Pulmonary hypertension (PH) influences mortality in patients with interstitial lung disease (ILD). Almost all studies on patients with ILD, have focused on the clinical impact of pre-capillary PH on survival. Therefore, little is known about the influence of post-capillary PH. We aimed to assess the prevalence of post-capillary PH and its clinical impact on survival in patients with ILD, followed by comparison with pre-capillary PH.

Methods: This retrospective study enrolled 1152 patients with ILD who were diagnosed with PH using right heart catheterization between May 2007 and December 2015. We analyzed the demographics and composite outcomes (defined as death from any cause or lung transplantation) of patients with post-capillary PH and compared them with patients with pre-capillary PH.

Results: Thirty-two (20%) of the 157 patients with ILD-PH were diagnosed with post-capillary PH. Patients with post-capillary PH had significantly lower modified Medical Research Council scores, higher diffusion capacity for carbon monoxide, higher resting PaO, lower pulmonary vascular resistance (PVR), and higher lowest oxygen saturation during the 6-min walk test compared to those with pre-capillary PH. Cardiovascular diseases were associated with a higher risk of mortality in patients with post-capillary PH. Multivariate Cox proportional hazards analysis demonstrated no significant difference between the composite outcomes in pre-capillary and post-capillary PH, while PVR and the ILD Gender-Age-Physiology Index were significantly associated with the composite outcome.

Conclusions: We found that approximately one-fifth of patients with ILD-PH were diagnosed with post-capillary PH, and that PVR and not post-capillary PH was associated with mortality.
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http://dx.doi.org/10.1016/j.resinv.2020.12.010DOI Listing
May 2021

Long noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state.

Physiol Rep 2021 02;9(3):e14727

Pulmonary, Critical Care and Sleep Medicine Section, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.

Long-noncoding RNAs (lncRNAs) have numerous biological functions controlling cell differentiation and tissue development. The knowledge about the role of lncRNAs in human lungs remains limited. Here we found the regulatory role of the terminal differentiation-induced lncRNA (TINCR) in bronchial cell differentiation. RNA in situ hybridization revealed that TINCR was mainly expressed in bronchial epithelial cells in normal human lung. We performed RNA sequencing analysis of normal human bronchial epithelial cells (NHBECs) with or without TINCR inhibition and found the differential expression of 603 genes, which were enriched for cell adhesion and migration, wound healing, extracellular matrix organization, tissue development and differentiation. To investigate the role of TINCR in the differentiation of NHBECs, we employed air-liquid interface culture and 3D organoid formation assay. TINCR was upregulated during differentiation, loss of TINCR significantly induced an early basal-like cell phenotype (TP63) and a ciliated cell differentiation (FOXJ1) in late phase and TINCR overexpression suppressed basal cell phenotype and the differentiation toward to ciliated cells. Critical regulators of differentiation such as SOX2 and NOTCH genes (NOTCH1, HES1, and JAG1) were significantly upregulated by TINCR inhibition and downregulated by TINCR overexpression. RNA immunoprecipitation assay revealed that TINCR was required for the direct bindings of Staufen1 protein to SOX2, HES1, and JAG1 mRNA. Loss of Staufen1 induced TP63, SOX2, NOTCH1, HES1, and JAG1 mRNA expressions, which TINCR overexpression suppressed partially. In conclusion, TINCR is a novel regular of bronchial cell differentiation, affecting downstream regulators such as SOX2 and NOTCH genes, potentially in coordination with Staufen1.
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http://dx.doi.org/10.14814/phy2.14727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851438PMC
February 2021

Early hearing improvement predicts the prognosis of idiopathic sudden sensorineural hearing loss.

Eur Arch Otorhinolaryngol 2021 Jan 2. Epub 2021 Jan 2.

Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, 160-8582, Japan.

Purpose: To determine pre- and post-treatment factors that are useful for predicting the prognosis of hearing improvement in idiopathic sudden sensorineural hearing loss (ISSHL).

Methods: This retrospective study included 332 patients with ISSHL. Patients received intravenous steroid treatment (prednisolone sodium succinate; 120 mg/day followed by dose tapering). Complete recovery of hearing levels was defined as a final pure-tone audiometry of ≤ 20 dB HL or the same level as the contralateral ear. Patients' age; sex; side of hearing loss; initial hearing level; days from onset to treatment; presence of vertigo, diabetes, and hypertension; and hearing improvement on days 3-4 and 6-7 after treatment initiation were analyzed as potential prognostic factors.

Results: Overall, 109 patients (32%) had complete recovery. Results of the multivariate logistic regression model identified age (odds ratio [OR] = 0.974), initial hearing level (OR = 0.949), vertigo (OR = 0.409), and hearing improvement on days 6-7 after treatment initiation (OR = 1.11) as significant independent predictors of complete recovery. Age ≥ 60 years, initial hearing level ≥ 72.5 dB HL, and vertigo contributed to poor prognosis. Patients without these three factors and a hearing improvement of ≥ 10 dB HL on days 6-7 post-treatment had a complete recovery rate of 80%. Only 1.5% of the patients with 2-3 of these factors and a hearing improvement of < 10 dB HL on days 6-7 after treatment initiation achieved complete recovery.

Conclusion: Age, initial hearing level, vertigo, and hearing improvement on days 6-7 after treatment initiation were independent predictors of hearing recovery in ISSHL.
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http://dx.doi.org/10.1007/s00405-020-06532-4DOI Listing
January 2021

A confocal Raman microscopic visualization of small penetrants in cellulose acetate using a deuterium-labeling technique.

Sci Rep 2020 10 2;10(1):16426. Epub 2020 Oct 2.

Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.

The purpose of the present study was to visualize the sorption dynamics of small compounds, such as propylene glycol (PG) in cellulose acetate (CA) film, by deuterium (d) labeling-aided confocal Raman spectroscopy (CRM). Substitution of hydrogen atoms in the target molecule with deuterium caused a marked shift of C-H bond-related Raman bands to low wavenumbers, while the number of deuterium did not affect the magnitude of the shift. Raman bands derived from the stretching vibration of C-H near 2900 cm for PG and ethanol were shifted to approximately 2100 cm for PG-d6 and ethanol-d5 in the silent region of the CA Raman spectrum. When PG-d6 was dissolved in glycerol triacetate (GTA), the observed Raman intensity ratio at 2123 cm of PG-d6 against 1739 cm of GTA (C=O bond-related) showed a linear relationship between the molar and intensity ratios, indicating that the observed Raman intensity can be used for quantitative assay of the target in polymer film. The depth profiling experiments by CRM revealed that the distribution (or sorption) of PG-d6 in CA film was successfully visualized as a function of Raman band at the characteristic 2123 cm intensity ratio.
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http://dx.doi.org/10.1038/s41598-020-73464-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532217PMC
October 2020

Clinical burden of immune checkpoint inhibitor-induced pneumonitis.

Respir Investig 2020 Sep 23;58(5):305-319. Epub 2020 Jul 23.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550. Japan. Electronic address:

Immune checkpoint inhibitors (ICIs) have been a breakthrough in medical oncology. However, many patients experience a novel type of adverse drug reaction that has a unique clinical presentation, called immune-related adverse events (irAEs). A breakdown of self-tolerance and an exaggerated autoimmune reaction by the host are assumed to be the underlying mechanisms. Therefore, special attention to the optimal diagnosis and management is required. Among the various effects of irAE, pneumonitis has been recognized as an important manifestation because of its high morbidity and mortality. As the application of ICIs is expanding to a wider variety of tumor types, as well as its use with cytotoxic agents and radiation, clinicians are highly likely to encounter this complication. In this review, we will summarize the current understanding of the underlying mechanisms, incidence, risk factors, optimal diagnostic workup, and management of ICI-related pneumonitis (IRP). We will also review fundamental information on drug-induced lung toxicity in the oncology setting. In addition, research perspectives focused on better risk stratification and management to avoid serious complications in the future are presented.
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http://dx.doi.org/10.1016/j.resinv.2020.05.008DOI Listing
September 2020

Acute Exacerbation of Pleuroparenchymal Fibroelastosis Secondary to Allogenic Hematopoietic Stem Cell Transplantation.

Intern Med 2020 Nov 14;59(21):2737-2743. Epub 2020 Jul 14.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Japan.

In this article, we report a case with pleuroparenchymal fibroelastosis (PPFE) following hematopoietic stem cell transplantation (HSCT) that developed acute respiratory failure with new bilateral ground glass opacity, which could not be explained by either a pulmonary infection, drug toxicity or extraparenchymal causes. Although combination therapy with multiple immunosuppressants was transiently effective, the patient died from a recurrent exacerbation. Autopsied lungs demonstrated diffuse alveolar damage superimposed on PPFE. There was no evidence of any coexisting interstitial pneumonia with the usual interstitial pneumonia (UIP) pattern. Our case suggests that acute exacerbation can occur in patients with post-HSCT PPFE, even when a coexisting UIP pattern is absent.
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http://dx.doi.org/10.2169/internalmedicine.4995-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691016PMC
November 2020

High-flow nasal cannula therapy for acute respiratory failure in patients with interstitial pneumonia: a retrospective observational study.

Nagoya J Med Sci 2020 May;82(2):301-313

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

High-flow nasal cannula (HFNC) oxygen is a therapy that has demonstrated survival benefits in acute respiratory failure (ARF). However, the role of HFNC in ARF due to interstitial pneumonia (IP) is unknown. The aim of this study was to compare the effects of HFNC therapy and non-invasive positive pressure ventilation (NPPV) in ARF due to IP. This retrospective observational study included 32 patients with ARF due to IP who were treated with HFNC (n = 13) or NPPV (n = 19). The clinical characteristics, intubation rate and 30-day mortality were analyzed and compared between the HFNC group and the NPPV group. Predictors of 30-day mortality were evaluated using a logistic regression model. HFNC group showed higher mean arterial blood pressure (median 92 mmHg; HFNC group vs 74 mmHg; NPPV group) and lower APACHEII score (median 22; HFNC group vs 27; NPPV group) than NPPV group. There was no significant difference in the intubation rate at day 30 between the HFNC group and the NPPV group (8% vs 37%: p = 0.069); the mortality rate at 30 days was 23% and 63%, respectively. HFNC therapy was a significant determinant of 30-day mortality in univariate analysis, and was confirmed to be an independent significant determinant of 30-day mortality in multivariate analysis (odds ratio, 0.148; 95% confidence interval, 0.025-0.880; p = 0.036). Our findings suggest that HFNC therapy can be a possible option for respiratory management in ARF due to IP. The results observed here warrant further investigation of HFNC therapy in randomized control trials.
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http://dx.doi.org/10.18999/nagjms.82.2.301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276417PMC
May 2020

Supplemental oxygen improves exercise capacity in IPF patients with exertional desaturation.

Respirology 2020 11 5;25(11):1152-1159. Epub 2020 May 5.

Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan.

Background And Objective: The efficacy of supplemental oxygen during exercise remains unclear for patients with IPF, as there have been conflicting results from recent prospective studies with small sample sizes.

Methods: This prospective, single-blind, randomized, crossover trial evaluated the efficacy of supplemental oxygen compared with placebo air during exercise in consecutive patients with IPF without resting hypoxaemia at initial evaluation. Patients with <90% SpO in a 6MWT using room air were randomly assigned to a CWRET at 80% of peak work rate with oxygen or placebo air gas via nasal cannula at 4 L/min. The primary endpoint was the effect of supplemental oxygen on endurance time.

Results: We recruited 72 consecutive patients (median age: 66.5 years, % FVC: 84.6%, % DL : 61.4%). Supplemental oxygen significantly increased the endurance time (340-424 s; P < 0.001) and minimum SpO (88.0-94.0%; P < 0.001) compared with placebo air. Furthermore, supplemental oxygen significantly improved dyspnoea and leg fatigue. In a multivariate linear regression analysis, the endurance time on air was an independent explanatory variable of the improvement rate of endurance time (P = 0.02).

Conclusion: In mild-moderate IPF with exercise-induced hypoxaemia even without resting hypoxaemia, supplemental oxygen during exercise improved the endurance time, desaturation and subjective symptoms. Patients with shorter endurance times with placebo air showed better improvement with supplemental oxygen.
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http://dx.doi.org/10.1111/resp.13829DOI Listing
November 2020

Selective EP2 and Cox-2 inhibition suppresses cell migration by reversing epithelial-to-mesenchymal transition and Cox-2 overexpression and E-cadherin downregulation are implicated in neck metastasis of hypopharyngeal cancer.

Am J Transl Res 2020 15;12(3):1096-1113. Epub 2020 Mar 15.

Department of Otorhinolaryngology-Head and Neck Surgery, Keio University School of Medicine Tokyo, Japan.

Cyclooxygenase-2 (Cox-2) has been shown to promote cancer initiation and progression through pleiotropic functions including induction of epithelial-to-mesenchymal transition (EMT) via its predominant product prostaglandin E that binds to the cognate receptor EP2. Hence, pharmacological inhibition at the level of EP2 is assumed to be a more selective alternative with less risk to Cox-2 inhibition. However, little is known regarding the anti-cancer effect of an EP2 antagonist on the malignant properties of cancers including hypopharyngeal squamous cell carcinoma (HPSCC). The present study found that both the Cox-2 inhibitor celecoxib and the EP2 antagonist PF-04418948 upregulated CDH-1 expression, restored membranous localization of E-cadherin, and reduced vimentin expression, by downregulating the transcriptional repressors of E-cadherin in BICR6 and FaDu cells. Such Cox-2 or EP2 inhibition-induced EMT reversal led to repressed migration ability in both cells. Immunohistochemical analysis of surgical HPSCC specimens demonstrated an inverse relationship in expression between Cox-2 and E-cadherin both in the context of statistics (P = 0.028) and of reciprocal immunolocalization . Multivariate logistic regression revealed that overexpression of Cox-2 (P < 0.001) and downregulation of E-cadherin (P = 0.016) were both independently predictive of neck metastasis. These results suggest that suppression of cell migration ability via reversing EMT by inhibiting the Cox-2/EP2 signaling may contribute to preventing the development and progression of lymphatic metastasis. Collectively, targeting Cox-2/EP2, especially using EP2 antagonist, can be a promising therapeutic strategy by exerting an anti-metastatic effect via EMT reversal for improving the treatment outcomes of patients with various cancers including HPSCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137058PMC
March 2020

<Editors' Choice> Renewed Japanese spirometric reference variables and risk stratification for postoperative outcomes in COPD patients with resected lung cancer.

Nagoya J Med Sci 2019 Aug;81(3):427-438

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Although the lower limit of normal (LLN) of FEV1/FVC detects at-risk patients for postoperative outcomes among Japanese chronic obstructive pulmonary disease (COPD) patients with resected lung cancer, there was a lack of a Japanese reference equation to calculate the LLN of FEV1/FVC. Renewed Japanese spirometric reference variables might enable us to verify clinical impact of the LLN of FEV1/FVC among the Japanese population. To evaluate the clinical impact of the LLN of FEV1/FVC by using this renewed reference, data were retrospectively analyzed from 609 newly diagnosed lung cancer patients who had undergone thoracic surgery between 2006 and 2011. The combined assessment of the 0.70 fixed ratio and the LLN of the FEV1/FVC ratio classified the 609 subjects into the COPD (214 subjects), non-COPD (337 subjects), and in-between (58 subjects) groups, respectively. All of the relative odds ratios (ORs) of postoperative outcomes for the comparison between the in-between and non-COPD groups did not show significant confidence intervals (CIs). On the other hand, the adjusted ORs of postoperative outcomes for the COPD group versus the non-COPD group were 2.840 (95% CI: 1.824-4.421) for prolonged oxygen therapy (POT), 1.836 (95% CI: 1.166-2.890) for prolonged postoperative stays, and 1.637 (95% CI: 1.007-2.663) for combined complications. Adjusted comparisons of POT between the in-between and COPD groups also showed a significant relative OR of 2.984 (95% CI: 1.447-6.153). A standardized assessment of the LLN of FEV1/FVC by a renewed Japanese spirometric reference provides risk stratification for postoperative outcomes in the population.
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http://dx.doi.org/10.18999/nagjms.81.3.427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728190PMC
August 2019

Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With Non-Small-Cell Lung Cancer Who Received Programmed Death 1 Inhibitors.

Clin Lung Cancer 2019 11 1;20(6):442-450.e4. Epub 2019 Aug 1.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Introduction: Pneumonitis is one of the immune-related adverse events of programmed death 1 (PD-1) inhibitors that sometimes cause lethal outcomes. Although some recent reports have described PD-1 inhibitors as more effective in non-small-cell lung cancer (NSCLC) patients with immune-related adverse events than in those without, few data are available on the prognosis of those treated with PD-1 inhibitors who developed immune-related pneumonitis (IRP). Additionally, the robust risk factors of IRP have not been well elucidated.

Patients And Methods: A retrospective review of patients with recurrent or advanced NSCLC who took a PD-1 inhibitor (nivolumab or pembrolizumab monotherapy) between January 2016 and March 2018 was undertaken. Radiologic findings such as unilateral infiltration were also defined as IRP as long as they were deemed relevant to PD-1 inhibitors.

Results: Twenty-seven (16%) of 170 patients developed IRP. Although 22 (81%) of 27 patients with IRP recovered with drug cessation with or without corticosteroid therapy, 8-week landmark analysis showed the overall survival after administration of the PD-1 inhibitor was significantly shorter in patients with IRP than in those without (8.7 vs. 23.0 months, P = .015). Patients with IRP tended to not receive next-line treatment and choose best supportive care after cessation of PD-1 inhibitor therapy. In the multivariate analysis, pembrolizumab (vs. nivolumab) and low serum albumin were independent risk factors for IRP.

Conclusion: Development of IRP was correlated with poor prognosis in patients with NSCLC. Further study is necessary for establishing the best prediction and management strategies for IRP.
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http://dx.doi.org/10.1016/j.cllc.2019.07.006DOI Listing
November 2019

Acute exacerbations of fibrotic interstitial lung diseases.

Respirology 2020 05 19;25(5):525-534. Epub 2019 Aug 19.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background And Objective: Acute exacerbation (AE) is a severe complication of idiopathic pulmonary fibrosis (AE-IPF). In 2016, an international working group revised its definition and diagnostic criteria; however, few studies have assessed the frequency and prognosis of AE in patients with other fibrotic interstitial lung diseases (FILD).

Methods: We used data from 1019 consecutive interstitial lung disease (ILD) patients initially evaluated between January 2008 and July 2015. All subject diagnoses were made by multidisciplinary discussion in December 2018. ILD was categorized as IPF (n = 462) and other FILD which included non-specific interstitial pneumonia (n = 22), chronic hypersensitivity pneumonitis (n = 29), connective tissue disease-associated ILD (n = 205) and unclassifiable ILD (n = 209). Using the 2016 definition of AE-IPF, we identified all subjects with an AE.

Results: During the observational period, 193 patients experienced a first AE (AE-FILD n = 69, AE-IPF n = 124). The time to first AE was significantly longer in FILD than IPF (log-rank test, P < 0.001). After adjusting for potentially influential confounders, FILD remained a significant predictor of longer time to first AE compared with IPF (hazard ratio: 0.453; 95% CI: 0.317-0.647, P = 0.006). In a multivariate Cox proportional analysis, baseline disease severity was closely associated with the incidence of AE-ILD. Even after adjustment for other clinical variables, AE had a negative impact on overall survival. AE-FILD and AE-IPF showed similar poor short-term outcomes.

Conclusion: All forms of ILD are at risk of AE and have a similar outcome to AE-IPF.
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http://dx.doi.org/10.1111/resp.13682DOI Listing
May 2020

Repressive role of stabilized hypoxia inducible factor 1α expression on transforming growth factor β-induced extracellular matrix production in lung cancer cells.

Cancer Sci 2019 Jun 13;110(6):1959-1973. Epub 2019 May 13.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Activation of transforming growth factor β (TGF-β) combined with persistent hypoxia often affects the tumor microenvironment. Disruption of cadherin/catenin complexes induced by these stimulations yields aberrant extracellular matrix (ECM) production, characteristics of epithelial-mesenchymal transition (EMT). Hypoxia-inducible factors (HIF), the hallmark of the response to hypoxia, play differential roles during development of diseases. Recent studies show that localization of cadherin/catenin complexes at the cell membrane might be tightly regulated by protein phosphatase activity. We aimed to investigate the role of stabilized HIF-1α expression by protein phosphatase activity on dissociation of the E-cadherin/β-catenin complex and aberrant ECM expression in lung cancer cells under stimulation by TGF-β. By using lung cancer cells treated with HIF-1α stabilizers or carrying doxycycline-dependent HIF-1α deletion or point mutants, we investigated the role of stabilized HIF-1α expression on TGF-β-induced EMT in lung cancer cells. Furthermore, the underlying mechanisms were determined by inhibition of protein phosphatase activity. Persistent stimulation by TGF-β and hypoxia induced EMT phenotypes in H358 cells in which stabilized HIF-1α expression was inhibited. Stabilized HIF-1α protein expression inhibited the TGF-β-stimulated appearance of EMT phenotypes across cell types and species, independent of de novo vascular endothelial growth factor A (VEGFA) expression. Inhibition of protein phosphatase 2A activity abrogated the HIF-1α-induced repression of the TGF-β-stimulated appearance of EMT phenotypes. This is the first study to show a direct role of stabilized HIF-1α expression on inhibition of TGF-β-induced EMT phenotypes in lung cancer cells, in part, through protein phosphatase activity.
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http://dx.doi.org/10.1111/cas.14027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549927PMC
June 2019

Performance of the COPD Assessment Test in patients with connective tissue disease-associated interstitial lung disease.

Respir Med 2019 04 1;150:15-20. Epub 2019 Feb 1.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. Electronic address:

Background: Patients with connective tissue disease-associated interstitial lung disease (CTD-ILD) often experience impaired health status. In daily clinical practice, a short and easy instrument for assessing health status would be useful to help better understand the patient's condition. The COPD Assessment Test (CAT) is a simple questionnaire about respiratory symptoms and their impact. We aimed to examine the CAT's performance characteristics and to generate data to support its reliability and validity in patients with CTD-ILD.

Methods: We used data from 132 CTD-ILD patients evaluated at Tosei General Hospital from July 2011 to July 2016 to assess the cross-sectional and longitudinal validity of the CAT.

Results: The mean age of the patients was 64.5 years and 87 (66%) were women. There were no significant differences in CAT score between any of the CTD subgroups. Internal consistency (Cronbach's α = 0.881) and repeatability (intraclass correlation coefficient [ICC] = 0.803) for the CAT score were acceptable. At baseline, CAT score was significantly associated with clinically meaningful measures of physiologic function, exercise capacity, and dyspnea. Change in CAT score over 6-12 months was also associated with change in other measures. In the distribution- and anchor-based analyses, the estimated minimal clinically important difference of CAT score was 1-4 points.

Conclusion: These data support the validity and reliability of CAT as a sensitive measure for assessing health status in patients with CTD-ILD.
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http://dx.doi.org/10.1016/j.rmed.2019.01.017DOI Listing
April 2019

VEGF-C/Flt-4 axis in tumor cells contributes to the progression of oral squamous cell carcinoma via upregulating VEGF-C itself and contactin-1 in an autocrine manner.

Am J Cancer Res 2018 1;8(10):2046-2063. Epub 2018 Oct 1.

Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Keio University Tokyo, Japan.

Tumor cell-derived vascular endothelial growth factor (VEGF)-C has been primarily implicated in promoting lymphangiogenesis by activating Flt-4 (VEGFR-3) expressed on lymphatic endothelial cells via a paracrine mechanism. Flt4 has also been shown to be expressed selectively in subsets of cancer cells. However, little is known about the functional role of VEGF-C/Flt4 signaling via an autocrine mechanism, as well as the clinicopathological implication of the VEGF-C/Flt4 axis and its downstream effector molecules, in head and neck squamous cell carcinoma (HNSCC), including oral squamous cell carcinoma (OSCC). In the present study, we detected Flt-4 expression selectively in several HNSCC cell lines by quantitative PCR, and its internalization reflecting receptor activation was confirmed by immunocytochemistry in SAS and HO1U1 cells. Flt-4 stimulation upregulated the expression of contactin-1 (CNTN-1, a neural cell adhesion molecule) and VEGF-C itself in SAS cells, while Flt-4 inhibition downregulated the expression of CNTN-1 in both SAS and HO1U1 cells and that of VEGF-C itself in SAS cells. cell proliferation and migration assays using SAS cells demonstrated that both cell proliferation and migration were promoted by Flt-4 stimulation, while those were suppressed by Flt-4 inhibition. Clinicopathological factors and immunohistochemical expression of Flt-4, VEGF-C, and CNTN-1 in tumor cells were evaluated using surgical specimens from patients with tongue squamous cell carcinoma. We found a significant correlation of CNTN-1 expression with both VEGF-C and Flt-4 expression, but not between VEGF-C and Flt-4. Multivariate logistic regression analysis revealed that T classification (P = 0.003), lymphatic invasion (P = 0.024), and Flt-4 expression in tumor cells (P = 0.046) were independently predictive of neck lymph node metastasis. These results suggest that the VEGF-C/Flt-4 axis in tumor cells enhances tumor cell proliferation and migration via upregulating the expression of VEGF-C itself and CNTN-1 in an autocrine manner, thereby contributing to cancer progression of OSCC, including neck metastasis. Hence, targeting the VEGF-C/Flt-4 axis in tumor cells can be an attractive therapeutic strategy for the treatment of cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220132PMC
October 2018

Outcomes with newly proposed classification of acute respiratory deterioration in idiopathic pulmonary fibrosis.

Respir Med 2018 10 13;143:147-152. Epub 2018 Sep 13.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Background: Respiratory-related hospitalization, in particular acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), is common and associated with increasing mortality in patients with IPF. We aimed to evaluate the implications of a newly proposed framework of acute respiratory deterioration (ARD) and AE-IPF in hospitalized patients.

Methods: Using the data of an IPF cohort consisting of 225 consecutive patients, we retrospectively studied first hospitalizations from January 2008 to December 2017. We analysed the demographics and 90-day mortality of patients with AE-IPF and those with parenchymal cause of ARD other than AE.

Results: Among 122 patients with first hospitalization for ARD, 35 patients were diagnosed with AE-IPF, including 11 patients with triggered AE. Parenchymal cause of ARD other than AE was diagnosed in 71 patients, and extra-parenchymal cause in 16 patients. Almost all hospitalized patients (93%) underwent chest CT, and 83% of patients with AE-IPF underwent bronchoalveolar lavage. There was a significant difference in the anti-inflammatory therapy between the AE-IPF group and parenchymal cause of ARD other than AE group (p < 0.001). AE-IPF was independently associated with poor survival in multivariate Cox proportional regression analysis.

Conclusions: AE-IPF accounted for about 30% of first hospitalizations for ARD, and differentiation between AE-IPF and the other categories in ARD is important from a therapeutic and a prognostic point of view.
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http://dx.doi.org/10.1016/j.rmed.2018.09.011DOI Listing
October 2018

Multidimensional improvement in connective tissue disease-associated interstitial lung disease: Two courses of pulse dose methylprednisolone followed by low-dose prednisone and tacrolimus.

Respirology 2018 11 16;23(11):1041-1048. Epub 2018 Jul 16.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background And Objective: Corticosteroids and immunosuppressive agents are considered mainstays of therapy for connective tissue disease-related interstitial lung disease (CTD-ILD); however, tacrolimus with corticosteroid therapy has not been fully investigated. Our objectives were to examine the multidimensional therapeutic benefit and tolerability of the combined therapy for the initial treatment of patients with CTD-ILD.

Methods: In this retrospective case series, we identified consecutive CTD-ILD patients treated with tacrolimus plus intravenous (i.v.) methylprednisolone (1000 mg i.v. 3 days a week for 2 weeks) followed by low-dose prednisolone (10 mg/day). We assessed the multidimensional therapeutic benefit and tolerability including lung physiology, exercise capacity, exercise oxygen desaturation, modified Medical Research Council (MMRC) and St George's Respiratory Questionnaire (SGRQ).

Results: A total of 26 ILD patients with the underlying CTD diagnoses included 11 with rheumatoid arthritis, 9 with dermatomyositis, 4 with Sjögren's syndrome and 2 others. From baseline to 12 months, the combined therapy significantly improved forced vital capacity (FVC; 77.8% to 94.6%, P < 0.001), diffusing capacity of the lung for carbon monoxide (DL ; 66.1% to 75.1%, P < 0.001), 6-min walk distance (6MWD; 530 to 568 m, P = 0.02), lowest oxygen saturation on pulse oximetry (SpO ; 85% to 89%, P = 0.01), MMRC (1.3 to 0.8, P = 0.01) and SGRQ (38 to 21, P < 0.001). During the study period, only one patient's therapy was discontinued due to an adverse event and none had a life-threatening adverse event attributed to the combined therapy.

Conclusion: In our cohort of CTD-ILD, two courses of pulse dose methylprednisolone therapy followed by prednisone and oral tacrolimus appeared to be well tolerated, and to have multidimensional efficacy.
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http://dx.doi.org/10.1111/resp.13365DOI Listing
November 2018

Performance of the St George's Respiratory Questionnaire in patients with connective tissue disease-associated interstitial lung disease.

Respirology 2018 Mar 25. Epub 2018 Mar 25.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background And Objective: The St George's Respiratory Questionnaire (SGRQ) is a self-administered questionnaire used to assess health-related quality of life (HRQoL) in various chronic respiratory diseases. Few studies have assessed the performance of the SGRQ in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). We aimed to examine the SGRQ's performance characteristics and generate data to support its reliability and validity in patients with CTD-ILD.

Methods: We used data from 193 CTD-ILD patients evaluated at Tosei General Hospital from May 2007 to July 2016 to assess the cross-sectional and longitudinal validity of the SGRQ.

Results: The mean age of the patients was 64.2 years and 122 (63.2%) were women. There were no significant differences in SGRQ scores between any of the CTD groups. Internal consistency (Cronbach's α = 0.905) and repeatability (intraclass correlation coefficient (ICC) = 0.873) for the SGRQ total score were excellent. At baseline, SGRQ total score was significantly associated with clinically meaningful measures of physiological function, exercise capacity and dyspnoea. Change in SGRQ total score over 6 months was also associated with change in other measures. Cox proportional hazards models showed that higher baseline SGRQ total score was a significant predictor of mortality. The estimated minimal clinically important difference of SGRQ total score was 4-13 points.

Conclusion: These data support the validity and reliability of SGRQ as a sensitive measure for capturing HRQoL in patients with CTD-ILD.
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http://dx.doi.org/10.1111/resp.13293DOI Listing
March 2018

A scoring system to predict the elevation of mean pulmonary arterial pressure in idiopathic pulmonary fibrosis.

Eur Respir J 2018 01 18;51(1). Epub 2018 Jan 18.

Dept of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Elevated mean pulmonary arterial pressure (MPAP; ≥21 mmHg) is sometimes seen in patients with idiopathic pulmonary fibrosis (IPF) and has an adverse impact upon survival. Although early diagnosis is crucial, there is no established screening tool that uses a combination of noninvasive examinations.We retrospectively analysed IPF patients at initial evaluation from April 2007 to July 2015 and, using logistic regression analysis, created a screening tool to identify elevated MPAP. Internal validation was also assessed for external validity using a bootstrap method.Using right-heart catheterisation (RHC), elevation of MPAP was determined to be present in 55 out of 273 patients. Multivariate models demonstrated that % predicted diffusing capacity of the lung for carbon monoxide () <50%, ratio of pulmonary artery diameter to aorta diameter (PA/Ao) on computed tomography (CT) ≥0.9 and arterial oxygen tension ( ) <80 Torr were independent predictors. When we assigned a single point to each variable, the prevalence of elevation of MPAP with a score of zero, one, two or three points was 6.7%, 16.0%, 29.1% and 65.4%, respectively. The area under curve (AUC) for the receiver operating characteristic (ROC) curve was good at 0.757 (95% CI 0.682-0.833).A simple clinical scoring system consisting of % predicted , PA/Ao ratio on CT and can easily predict elevation of MPAP in patients with IPF.
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http://dx.doi.org/10.1183/13993003.01311-2017DOI Listing
January 2018

Thin-section computed tomography-determined usual interstitial pneumonia pattern affects the decision-making process for resection in newly diagnosed lung cancer patients: a retrospective study.

BMC Pulm Med 2018 Jan 5;18(1). Epub 2018 Jan 5.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

Background: There is only limited information on the impact of thin-section computed tomography (TSCT)-determined usual interstitial pneumonia (UIP) pattern in the decision-making for resection in newly diagnosed lung cancer patients.

Methods: In this retrospective analysis, data were reviewed from 499 newly diagnosed lung cancer patients who received bronchoscopy between 2010 and 2014. The clinical impact of TSCT-determined UIP pattern on the decision-making process for resection in this cohort was evaluated.

Results: The prevalence rate of TSCT-determined fibrosis was 14.8% (74/499 cases), 86.5% (64/74 cases) of which also had TSCT-determined emphysema. The fibrosis group comprised 40 patients with possible UIP and 34 patients with the UIP pattern. Among surgical candidates, the number of surgeries performed was lower in the fibrosis group (60.8%) than in the normal and emphysema groups (84.7 and 77.3%, respectively). Although the proportion of possible UIP did not differ between surgical candidates and patients with resected lung cancer, the proportion of UIP pattern in patients with resected lung cancer was decreased by 8.5%, compared to the surgical candidates. Although measurement of diffusing capacity of the lung for carbon monoxide (DLCO) was performed in more than 97% of patients with thoracic surgery, only 58% of patients without thoracic surgery had DLCO measurement. Multivariate analysis showed that the finding of UIP pattern independently affects the decision-making process for thoracic surgery. The adjusted odds ratios for the comparison between the patients without fibrosis and the patients with UIP pattern was 0.266 (95% confidence intervals: 0.087-0.812).

Conclusions: The presence of TSCT-determined UIP pattern might independently affect the decision-making process for proposing thoracic surgery with curative intent.
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http://dx.doi.org/10.1186/s12890-017-0565-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756392PMC
January 2018

Impact of mild to moderate COPD on feasibility and prognosis in non-small cell lung cancer patients who received chemotherapy.

Int J Chron Obstruct Pulmon Dis 2017 11;12:3541-3547. Epub 2017 Dec 11.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: Non-small cell lung cancer (NSCLC) is the predominant cause of death in patients with COPD, and the severity of COPD in NSCLC patients is classified mainly as mild to moderate. Most advanced NSCLC patients with mild to moderate COPD are treated with chemotherapy; however, the feasibility for and prognosis after chemotherapy of these patients are not well understood. The aim of this study was to elucidate the impact of mild to moderate COPD on the feasibility for and prognosis after chemotherapy in NSCLC patients.

Patients And Methods: A retrospective review was performed on 268 NSCLC patients who received first-line chemotherapy from 2009 to 2014 in our institution. Finally, 85 evaluable patients were included in this study. The clinical characteristics, toxicity profile, objective response rate, and prognosis were analyzed and compared between patients with mild to moderate COPD and those without COPD (non-COPD).

Results: Forty-three patients were classified as COPD (27 cases mild and 16 cases moderate) and 42 patients as non-COPD. The COPD group were older and had fewer never-smokers than the non-COPD group. The objective response rate did not differ between groups (=0.14). There was no significant difference in overall survival between COPD and non-COPD groups (15.0 and 17.0 months, log-rank test =0.57). In the multivariate Cox's proportional hazard model, the adjusted hazard ratio (HRadj) was statistically significant for male sex (HRadj =5.382, 95% CI: 1.496-19.359; =0.010), pathological diagnosis of adenocarcinoma (HRadj =0.460, 95% CI: 0.223-0.948; =0.035), and epithelial growth factor receptor negative mutation (HRadj =6.040, 95% CI: 1.158-31.497; =0.033), but not for the presence of COPD (HRadj =0.661, 95% CI: 0.330-1.325; =0.24). Toxicity profile in COPD group was favorable, as in the non-COPD group.

Conclusion: Mild to moderate COPD did not have a significant deleterious impact on toxicity and prognosis in NSCLC patients.
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http://dx.doi.org/10.2147/COPD.S149456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729822PMC
September 2018

Clinical diagnosis and treatment outcomes for parapharyngeal space schwannomas: A single-institution review of 21 cases.

Head Neck 2018 03 21;40(3):569-576. Epub 2017 Nov 21.

Department of Otorhinolaryngology - Head and Neck Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan.

Background: Because the incidence of schwannoma arising from the parapharyngeal space (PPS) is very low, no studies have analyzed extirpation methods and postoperative neurological complications exclusively in PPS schwannomas.

Methods: The preoperative diagnosis and clinical outcomes of surgical treatment in 21 patients with PPS schwannoma who underwent surgery were investigated.

Results: Neurological deficit of the involved nerve developed in all patients regardless of the extirpation method used. However, the incidence of first bite syndrome in sympathetic chain schwannoma was significantly lower after intracapsular enucleation (40%) than after total resection (100%; P = .045). Furthermore, the incidence of postoperative complications unrelated to the involved nerve was lower after intracapsular enucleation (0%) than after total resection (42.9%; P = .055).

Conclusion: Although postoperative neurological deficit of the involved nerve was unavoidable in PPS schwannoma, intracapsular enucleation could be beneficial by reducing its severity and the incidence of complications unrelated to the involved nerve.
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http://dx.doi.org/10.1002/hed.25021DOI Listing
March 2018
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