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Background: Eribulin is typically used to treat patients with advanced breast cancer, and anti-cancer agents often cause the development of interstitial pneumonia in Japanese patients with advanced cancer. However, few case reports have addressed eribulin-induced interstitial pneumonia. Herein, we report a rare case of interstitial pneumonia- specifically, organized pneumonia-during treatment with eribulin in a patient with advanced breast cancer. Case presentation: A 52-year-old Japanese woman was diagnosed as having advanced breast cancer 3 years before the admission described in the present report. She had received eribulin as third-line chemotherapy. Five days after her second treatment with eribulin, she was admitted to our hospital with dyspnea and dry cough. Upon admission, a chest computed tomography scan showed consolidation, with air bronchograms along the bronchovascular bundle of both lower lobes. The patient's serum levels of sialylated carbohydrate antigen Krebs von den Lungen-6 were high, as were her surfactant protein-D levels. There was no evidence of heart failure, renal failure, or infection. Based on the clinical cause, as well as on the findings of organized pneumonia, the patient was diagnosed as having interstitial pneumonia and treated with corticosteroids. After the initiation of steroid treatment, her respiratory condition and chest radiological findings improved. Conclusions: This case reveals an association between eribulin treatment and interstitial pneumonia. To our knowledge, this is the first case report to describe eribulin-induced organized pneumonia. Clinicians should be aware that interstitial pneumonia can develop during treatment with anti-cancer agents. [ABSTRACT FROM AUTHOR]

Background: Nerve growth factor (NGF) is not only an important factor in nerve growth but also a major contributor to the production of inflammation. It has been reported that inhibiting NGF could reduce several types of pain in several animal models. Here, we aimed to clarify the efficacy of NGF antibody in a knee osteoarthritis (OA) pain model in mice.Method: Six-week-old male C57BR/J mice were used (n = 30). Ten mice comprised the control group, which received saline injection into the right knee joints; the other 20 mice comprised the experimental group, which received monoiodoacetate (MIA) injection into the right knee joints. Three weeks after surgery, the 20 experimental mice were randomly placed into treatment groups which received either sterile saline (non-treat group: 10 mg/kg, i.p.) or an anti-NGF antibody (anti-NGF group: 10 mg/kg, i.p.). Simultaneously, all mice received fluorogold (FG) retrograde neurotracer injection into their right joints. In a behavioral study, we evaluated gait using the CatWalk quantitative gait analysis system before surgery, 3 weeks after surgery (before treatment), 4 weeks after surgery (one week after surgery), and 5 weeks after surgery (2 weeks after surgery). In immunohistochemical analysis, the right dorsal root ganglia (DRGs) from the L4-L6 levels were resected 5 weeks after surgery (2 weeks after surgery). They were immunostained for calcitonin gene-related peptide (CGRP), and the number of FG-labeled or CGRP-immunoreactive (IR) DRG neurons was counted.Results: On gait analysis using the CatWalk system, duty cycle, swing speed, and print area were decreased in non-treat group compared with those in control group and improved in the anti-NGF group compared with those in non-treat group. CGRP expression in DRGs was up-regulated in non-treat group compared with that in control group and suppressed in the anti-NGF group compared with that in non-treat group (both p < 0.05).Conclusions: MIA injection into the knee joint induced gait impairment and the up-regulation of CGRP in DRG neurons in a knee OA pain model in mice. Intraperitoneal injection of anti-NGF antibody suppressed this impairment of gait and up-regulation of CGRP in DRG neurons. These finding suggest that anti-NGF therapy might be valuable in the treatment of OA pain in the knee. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung diseases induced by anticancer agents (ILD-AA) are rare adverse effects of anticancer therapy. However, prognostic biomarkers for ILD-AA have not been identified in patients with advanced lung cancer. Our aim was to analyze the association between serum biomarkers sialylated carbohydrate antigen Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), and clinical characteristics in patients diagnosed with ILD-AA.Methods: Between April 2011 and March 2016, 1224 advanced lung cancer patients received cytotoxic agents and epidermal growth factor receptor tyrosine kinase inhibitors at Juntendo University Hospital and Juntendo University Urayasu Hospital. Of these patients, those diagnosed with ILD-AA were enrolled in this case control study. ΔKL-6 and ΔSP-D were defined as the difference between the levels at the onset of ILD-AA and their respective levels prior to development of ILD-AA. We evaluated KL-6 and SP-D at the onset of ILD-AA, ΔKL-6 and ΔSP-D, the risk factors for death related to ILD-AA, the chest high resolution computed tomography (HRCT) findings, and survival time in patients diagnosed with ILD-AA.Results: Thirty-six patients diagnosed with ILD-AA were enrolled in this study. Among them, 14 patients died of ILD-AA. ΔSP-D in the patients who died was significantly higher than that in the patients who survived. However, ΔKL-6 did not differ significantly between the two groups. Moreover, ΔSP-D in patients who exhibited diffuse alveolar damage was significantly higher than that in the other patterns on HRCT. Receiver operating characteristic curve analysis was used to set the optimal cut off value for ΔSP-D at 398 ng/mL. Survival time for patients with high ΔSP-D (≥ 398 ng/mL) was significantly shorter than that for patients with low ΔSP-D. Multivariate analysis revealed that ΔSP-D was a significant prognostic factor of ILD-AA.Conclusions: This is the first research to evaluate high ΔSP-D (≥ 398 ng/mL) in patients with ILD-AA and to determine the risk factors for ILD-AA in advanced lung cancer patients. ΔSP-D might be a serum prognostic biomarker of ILD-AA. Clinicians should evaluate serum SP-D during chemotherapy and should carefully monitor the clinical course in patients with high ΔSP-D. [ABSTRACT FROM AUTHOR]

Background: Age-related sarcopenia can cause various forms of physical disabilities. We investigated how sarcopenia affects degenerative lumbar scoliosis (DLS) and lumbar spinal canal stenosis (LSCS). Methods: Subjects comprised 40 elderly women (mean age 74 years) with spinal disease whose chief complaints were low back pain and lower limb pain. They included 15 cases of DLS (mean 74.8 years) and 25 cases of LSCS (mean age 72.9 years). We performed whole-body dual-energy X-ray absorptiometry (DXA) to analyze body composition, including appendicular and trunk skeletal muscle mass index (SMI; lean mass (kg)/height (m)²) and bone mineral density (BMD). A diagnostic criterion for sarcopenia was an appendicular SMI <5.46. To check spinal alignment, lumbar scoliosis (LS), sagittal vertical axis (SVA), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), sacral slope (SS), and vertebral rotational angle (VRA) were measured. Clinical symptoms were determined from the Japanese Orthopedic Association scores, low back pain visual analog scale, and Roland-Morris Disability Questionnaire (RDQ). Criteria for DLS were lumbar scoliosis >10° and a sagittal vertical axis (SVA) >50 mm. Sarcopenia prevalence, correlations between spinal alignment, BMD, and clinical symptoms with appendicular and trunk SMIs, and correlation between spinal alignment and clinical symptoms were investigated. Results: DLS cases had significantly lower body weight, BMI, lean mass arm, and total lean mass than LSCS cases. Sarcopenia prevalence rates were 4/25 cases (16%) in LSCS and 7/15 cases (46.6%) in DLS, revealing a high prevalence in DLS. Appendicular SMIs were DLS 5.61 and LSCS 6.13 (p < 0.05), and trunk SMIs were DLS 6.91 and LSCS 7.61 (p < 0.01) showing DLS to have significantly lower values than LSCS. Spinal alignment correlations revealed the appendicular SMI was negatively correlated with PT (p < 0.05) and the trunk SMI was found to have a significant negative correlation with SVA, PT, LS, and VRA (p < 0.05). The trunk SMI was found to have a significant positive correlation with BMD (p < 0.05). As for clinical symptoms, RDQ was negatively correlated with appendicular SMI and positively correlated with PT (P < 0.05). Conclusions: Sarcopenia complications were noted in 16% of LSCS patients and a much higher percentage, or 46. 6%, of DLS patients. Appendicular and trunk SMIs were both lower in DLS, suggesting that sarcopenia may be involved in scoliosis. The appendicular skeletal muscle was related to posterior pelvic tilt, while the trunk muscle affected stooped posture, posterior pelvic tilt, lumbar scoliosis, and vertebral rotation. Decreases in trunk muscle mass were also associated with osteoporosis. Moreover, RDQ had a negative correlation with appendicular skeletal muscle mass and a positive correlation with PT, suggesting that sarcopenia may be associated with low back pain as a result of posterior pelvic tilt. Our research reveals for the first time how sarcopenia is involved in spinal deformations, suggesting decreases in pelvic/lumbar support structures such as trunk and appendicular muscle mass may be involved in the progression of spinal deformities and increased low back pain. [ABSTRACT FROM AUTHOR]

Background: Airway fibrosis is one of the pathological features of chronic obstructive pulmonary disease (COPD), and recent studies revealed that acetylcholine plays an important role in the development of airway remodeling by stimulating proliferation and collagen synthesis of lung fibroblasts. This study was designed to examine the effects of a long-acting muscarinic receptor antagonist (LAMA) glycopyrronium and a long-acting β2 adrenergic receptor agonist (LABA) indacaterol on acetylcholine-mediated fibrotic responses in lung fibroblasts.Methods: After carbachol (CCh) or transforming growth factor-β1 (TGF-β1) exposure, the response to glycopyrronium and indacaterol was determined in vitro in fibroblasts isolated from mild-to-moderate COPD lung tissue. The ability of fibroblasts to mediate the contraction of collagen gels was assessed. The expression of α-smooth muscle actin (α-SMA) and the phosphorylation of extracellular-signal-regulated kinase 5 (ERK5) were determined by immunoblot. TGF-β1 was quantified by ELISA and acetylcholine was quantified by liquid chromatography tandem-mass spectrometry.Results: CCh stimulated fibroblast-mediated collagen gel contraction and α-SMA expression and TGF-β1 release by fibroblasts. Blockade of autocrine TGF-β1 attenuated CCh-mediated fibrotic responses, while TGF-β1 did not stimulate acetylcholine release. Glycopyrronium plus indacaterol significantly attenuated CCh- and TGF-β1-mediated fibrotic responses through inhibition of ERK5 phosphorylation. Notably, the magnitudes of CCh- and TGF-β1-stimulated gel contraction, CCh-induced TGF-β1 release, and ERK5 phosphorylation were greater in fibroblasts isolated from COPD subjects than in those from non-smokers.Conclusions: CCh induced TGF-β1 self-sustaining signaling loops by potentiating ERK5 signaling and promoted myofibroblast activity. This autocrine signaling mechanism may be an attractive therapeutic target to block the fibrotic response, which was modulated by the combination of glycopyrronium and indacaterol. [ABSTRACT FROM AUTHOR]

Background: Age-related sarcopenia may cause physical dysfunction. We investigated the involvement of sarcopenia in dropped head syndrome (DHS). Methods: Our study subjects were ten elderly women with idiopathic DHS (mean age 75.1 years, range 55-89). Twenty age- and sex-matched volunteers (mean age 73.0, range 58-83) served as controls. We used a bioelectrical impedance analyzer (BIA) to analyze body composition, including appendicular skeletal muscle mass index (SMI; appendicular lean mass (kg)/(height (m))²). SMI <5.75 was considered diagnostic for sarcopenia. Cervical sagittal plane alignment: C2-7 sagittal vertical axis (SVA), C2-7 angle (C2-C7 A), and C2 slope (C2S) were also measured. We investigated sarcopenia prevalence in both groups, height, weight, BMI, lean mass arm, lean mass leg, lean mass trunk, appendicular lean mass, total lean mass, and SMI. In addition, we also examined the correlation between cervical spine alignment and SMI in DHS. Results: Sarcopenia was observed at a high rate in DHS subjects: 70% compared to 25% of healthy controls. Height, weight, BMI, lean mass arm, lean mass leg, axial lean mass, appendicular lean mass, total lean mass, and SMI all had significantly lower values in the DHS group. In particular, total lean mass, lean mass arm, and lean mass trunk were considerably lower in the DHS group. There was no correlation noted between cervical spine alignment and SMI. Conclusions: Sarcopenia prevalence was high in the DHS group--70 versus 25% in the control group, suggesting the involvement of sarcopenia in DHS. In particular, axial lean mass and lean mass arm were markedly reduced in the DHS group. DHS is due to significant weakness of the neck extensor group, and chin-on-chest deformity occurs. Until the present, evaluation of DHS has been done using only MRI; no studies have systematically examined skeletal muscle mass. In the present study, muscle mass decrease was noted not only in the neck muscles but also throughout the entire body. Involvement of trunk and upper limb muscles in particular suggests a disuse atrophy of the upper body and spinal muscles. BIA can easily and systemically evaluate skeletal muscle mass. We expect it to contribute to further elucidating the pathogenesis of DHS. [ABSTRACT FROM AUTHOR]

Background: The purpose of this prospective cohort study was to clarify the safety and efficacy of total hip arthroplasty via the direct anterior approach in the supine position with a novel mobile traction table.Methods: The first experience of consecutive surgeries by a single surgeon using the direct anterior approach with a traction table is described with a two-year follow-up period. Of 121 patients, 100 patients without previous hip surgeries, severe deformity, or cemented implants were divided into two groups comprising the first 50 patients and the second 50 patients.Results: The implant survival rate was 99% at the two-year follow-up. Revision surgery was required for periprosthetic femoral fracture in one patient. The complication rate possibly related to the traction table was 5% (5 patients): three anterior dislocations, one periprosthetic femoral fracture, and one intraoperative perforation caused by femoral rasping. The complication rate tended to decrease in the second group compared to the first group (4% versus 6%). Mean surgical time (72.0 minutes versus 82.5 min, p = 0.027), rate of allogeneic blood transfusion (2% versus 24%, p = 0.001), and cup alignment in the safe zone (100% versus 88%, p = 0.027) were significantly improved in the second group compared to the first group.Conclusion: The direct anterior approach with a novel mobile traction table showed a positive learning curve for surgical time, rate of allogeneic blood transfusion, and cup alignment in the safe zone. [ABSTRACT FROM AUTHOR]

Background: Receptor for advanced glycation end-products (RAGE), a receptor for amyloids, is constitutively expressed in lungs and generally observed to be downregulated in lung cancer tissues. However, increasing levels of RAGE or serum amyloids is associated with poor outcome in lung cancer patients. We report a rare case of primary systemic amyloid light-chain (AL) amyloidosis in biopsy-proven multiple organs with early-stage non-small cell lung cancer (NSCLC) that displayed strong staining for RAGE in the tumour tissue. Interestingly, compared with randomly selected lung cancer biopsy samples, including all representative histological subtypes of NSCLC and small-cell lung cancer, only the NSCLC in the present case showed strong expression for RAGE that can bind amyloids.Case Presentation: A 71-year-old woman was admitted to our hospital for comprehensive investigation of nephrotic syndrome. Computed tomography showed a small nodule in the right upper lung lobe with hilar mediastinal lymph node enlargement. Pathological examination of transbronchial biopsy samples of the nodule yielded a diagnosis of lung adenocarcinoma. Furthermore, the pathological detection of amyloid deposition in biopsy samples of a subcarinal lymph node, gastric and duodenal mucosa, cardiac muscle, and bone marrow led to a diagnosis of primary systemic AL amyloidosis with nephrotic syndrome and cardiomyopathy. In addition, RAGE was detected in lung tumour tissues surrounded by normal lung tissues with amyloid deposition.Conclusion: The RAGE positivity of the lung cancer cells in this case suggests an interaction between amyloid-containing tissues and RAGE-expressing cancer cells. Lung adenocarcinoma with RAGE expression may be a complication of underlying amyloidosis. [ABSTRACT FROM AUTHOR]

Background: Birt-Hogg-Dubé (BHD) syndrome is a rare inherited autosomal genodermatosis and caused by germline mutation of the folliculin (FLCN) gene, a tumor suppressor gene of which protein product is involved in mechanistic target of rapamycin (mTOR) signaling pathway regulating cell growth and metabolism. Clinical manifestations in BHD syndrome is characterized by fibrofolliculomas of the skin, pulmonary cysts with or without spontaneous pneumothorax, and renal neoplasms. There has been no pulmonary neoplasm reported in BHD syndrome, although the condition is due to deleterious sequence variants in a tumor suppressor gene. Here we report, for the first time to our knowledge, a patient with BHD syndrome who was complicated with a clear cell "sugar" tumor (CCST) of the lung, a benign tumor belonging to perivascular epithelioid cell tumors (PEComas) with frequent causative relation to tuberous sclerosis complex 1 (TSC1) or 2 (TSC2) gene. Case presentation: In a 38-year-old Asian woman, two well-circumscribed nodules in the left lung and multiple thin-walled, irregularly shaped cysts on the basal and medial area of the lungs were disclosed by chest roentgenogram and computer-assisted tomography (CT) during a preoperative survey for a bilateral faucial tonsillectomy. Analysis of the resected tumor showed large polygonal cells with clear cytoplasm proliferating in a solid pattern. Immunohistochemistry revealed that these tumor cells were positive for microphthalmia-transcription factor, S100, and CD1a but negative for HMB45, indicating that the tumor was a CCST. Genetic testing indicated that the patient had a germline mutation on exon 12 of the FLCN gene, i.e., insertion of 7 nucleotides (CCACCCT) (c.1347_1353dupCCACCCT). Direct sequencing of the FLCN exon 12 using genomic DNA obtained from her microdissected CCST cells clearly revealed loss of the wild-type FLCN sequence, which confirmed complete functional loss of the FLCN gene. On the other hand, no loss of heterozygosity around TCS1- or TSC2-associated genetic region was demonstrated. Conclusion: To our knowledge, this is the first report of CCST of the lung in a patient with BHDS, indicating that CCST should be added to the spectrum of pulmonary manifestations of BHDS. [ABSTRACT FROM AUTHOR]

Background: The majority of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR tyrosine kinase inhibitors (TKIs). Minimal information exists regarding genetic alterations in rebiopsy samples from Asian NSCLC patients who develop acquired resistance to EGFR-TKIs. Methods: We retrospectively reviewed the medical records of patients with NSCLC harboring EGFR mutations who had undergone rebiopsies after developing acquired resistance to EGFR-TKIs. We analyzed 27 practicable samples using a tumor genotyping panel to assess 23 hot-spot sites of genetic alterations in nine genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2), gene copy number of EGFR, MET, PIK3CA, FGFR1, and FGFR2, and ALK, ROS1, and RET fusions. Additionally, 34 samples were analyzed by commercially available EGFR mutation tests. Results: Sixty-one patients underwent rebiopsy. Twenty-seven samples were analyzed using our tumor genotyping panel, and 34 samples were analyzed for EGFR mutations only by commercial clinical laboratories. Twenty-one patients (34%) had EGFR T790M mutation. Using our tumor genotyping panel, MET gene copy number gain was observed in two of 27 (7%) samples. Twenty patients received continuous treatment with EGFR-TKIs even after disease progression, and 11 of these patients had T790M mutation in rebiopsy samples. In contrast, only 10 of 41 patients who finished EGFR-TKI treatment at disease progression had T790M mutation. The frequency of T790M mutation in patients who received continuous treatment with EGFR-TKIs after disease progression was significantly higher than that in patients who finished EGFR-TKI treatment at disease progression (55% versus 24%, p = 0.018). Conclusions: The frequency of T790M mutation in this study was lower than that in previous reports examining western patients. These results suggest that continuous treatment with EGFR-TKI after disease progression may enhance the frequency of EGFR T790M mutation in rebiopsy samples. [ABSTRACT FROM AUTHOR]

Background: Far-out syndrome was reported by Wiltse et al. in 1984, which is a condition characterized by L5 spinal nerve radiculopathy due to nerve compression between the L5 transverse process and sacral alar. Although many cases of far-out syndrome have been reported, to our knowledge, the present case firstly showed far-out syndrome due to assimilated L4 hemivertebra and L5 vertebra through which abnormal nerve root passed. Case presentation: A 71-year-old man presented with left lower back pain and intermittent claudication accompanied by severe left buttock pain. Radiological examination showed assimilation between the L4 hemivertebra and L5 vertebra, which had two pedicles on the right side, with no canal stenosis. However, computed tomography and magnetic resonance imaging of coronal sections showed extraforaminal stenosis between the L5 transverse process and sacral alar, whereby the L5 spinal nerve was pinched ("far-out lesion"), and an abnormal nerve root passage in the assimilated vertebral corpus. We performed transforaminal lumbar interbody fusion, then resected the L5 transverse process to decompress the extraforaminal stenosis, and finally installed pedicle screws, but not at the one of pedicles of the assimilated vertebra in order to prevent nerve injury. Postoperatively, the patient had no symptoms up to 1.5 years after the surgery. Conclusion: The current case suggests the importance of detailed preoperative examination of patients with anatomical abnormalities such as assimilated vertebrae, which may result in incorrect diagnosis and failed surgery. [ABSTRACT FROM AUTHOR]

Background: Loxoprofen is a nonsteroidal anti-inflammatory drug used in the treatment of many diseases. However, there are no case reports about loxoprofen-induced pneumonia. We have encountered a rare case of loxoprofen-induced pneumonia. Case Presentation: We report the case of a 71-year-old Japanese woman who was initially treated with loxoprofen for fever. She was admitted to our hospital because of worsening of her symptoms, including fever and dyspnea. Her symptoms improved after treatment with ceftriaxone. Seven days after admission, she again developed high fever. She was again treated with loxoprofen and levofloxacin. However, acute respiratory failure developed after initiation of loxoprofen treatment. Chest computed tomography showed peribronchovascular consolidation. She was diagnosed with loxoprofen-induced pneumonia for which she was administered steroids. After treatment, her dyspnea and radiological findings improved. Conclusions: The findings in this case report reveal an association between treatment with a nonsteroidal anti-inflammatory drug and pneumonia. This rare case was diagnosed after accidental retreatment with loxoprofen. This is the first report of loxoprofen-induced pneumonia. [ABSTRACT FROM AUTHOR]

Background: The mechanism for hip pain has been unclear because of a lack of experimental animal models. We aimed to establish an intra-articular injection technique to the rat hip and to document the effect of intra-articular mono-iodoacetate (MIA) injection to the rat hip with radiography and histology.Methods: Using 60 6-week-old male Sprague Dawley rats, 25 μl of sterile saline (control group; n = 30) and 25 μl of sterile saline with 2 mg of MIA (MIA group; n = 30) was injected into the right hip joints via posterior approach using a 27G needle. The animals were examined with X-ray and histology 7, 14, 28, 42, and 56 days later (MIA group [n = 6] and control group [n = 6], respectively).Results: The MIA group showed progressive radiographic changes to the hip joint during the experimental period, whereas the control group maintained a normal appearance. The microanatomic appearance was consistent with X-ray images of progressive destruction in the MIA group and normal tissue in the control group. Osteoarthritic (OA) changes became apparent at 42 and 56 days in the MIA group.Conclusions: We established an intra-articular injection technique to the rat hip, creating a hip OA model in the rat by intra-articular injection of MIA. [ABSTRACT FROM AUTHOR]

Background: Advanced non-small cell lung cancer (NSCLC) patients often develop thromboembolic events, including cerebral infarction (CI). However, the relationship between advanced NSCLC and CI has not been thoroughly investigated. We examined the association between advanced NSCLC and CI and risk factors for CI in advanced or post-operative recurrent NSCLC patients.Methods: We retrospectively investigated 515 patients diagnosed with advanced or post-operative recurrent NSCLC at Juntendo University Hospital between April 2009 and March 2014.Results: Among the 515 patients evaluated, 15 patients (2.9%) developed CI after diagnosis of advanced or post-operative recurrent NSCLC. Univariate and multivariate analyses were conducted, and brain metastasis was the only significant independent risk factor for CI (odds ratio 5.24, 95% confidence interval 1.72-16.10, p = 0.004). The incidence was 6.3% in these patients. The median survival time was 36 days, and 1-year survival rate was 6.7% after development of CI. Overall survival from diagnosis of advanced NSCLC or post-operative recurrence was significantly shorter in patients with CI than in patients without CI (223 days versus 895 days; HR, 3.46; 95% confidence interval, 2.04-6.02; p = 0.001).Conclusions: The incidence of CI is high in advanced or post-operative recurrent NSCLC, and is especially higher in patients with brain metastasis than in those without brain metastasis. Moreover, CI may affect patient's prognosis. Careful monitoring for the development of CI in patients with advanced or post-operative recurrent NSCLC is needed, especially for patients with brain metastasis. [ABSTRACT FROM AUTHOR]

Background: Lumbar floating fusion occasionally causes postoperative adjacent segment disorder (ASD) at lumbosacral level, causing L5 spinal nerve disorder by L5-S1 foraminal stenosis. The disorder is considered to be one of the major outcomes of L5-S1 ASD, which has not been evaluated yet. The present study aimed to evaluate the incidence and risk factors of postoperative L5 spinal nerve disorder after lumbar interbody fusion extending to the L5 vertebra. Methods: We evaluated 125 patients with a diagnosis of spondylolisthesis who underwent floating fusion surgery with transforaminal lumbar interbody fusion with average postoperative period of 25.2 months. The patients were regarded as symptomatic with postoperative L5 spinal nerve disorder such as radicular pain/numbness in the lower limbs and/or motor dysfunction. We estimated and compared the wedging angle (frontal view) and height (lateral view) of the lumbosacral junction in pre- and postoperative plain X-ray images and the foraminal ratio (ratio of the narrower foraminal diameter to the wider diameter in the craniocaudal direction) in the preoperative magnetic resonance image. Risk factors for the incidence of L5 spinal nerve disorder were explored using multivariate logistic regression. Results: Eight of the 125 patients (6.4 %) were categorized as symptomatic, an average of 13.3 months after surgery. The wedging angle was significantly higher, and the foraminal ratio was significantly decreased in the symptomatic group (both P< 0.05) compared to the asymptomatic group. Multivariate logistic regression analysis of possible risk factors revealed that the wedging angle, foraminal ratio, and multileveled fusion were statistically significant. Conclusions: Higher wedging angle and lower foraminal ratio in the lumbosacral junction were significantly predictive for the incidence of L5 nerve root disorder as well as multiple-leveled fusion. These findings indicate that lumbosacral fixation should be considered for patients with these risk factors even if they have few symptoms from the L5-S1 junction. [ABSTRACT FROM AUTHOR]

Background: The importance of pelvic incidence-lumbar lordosis (PI-LL: PI minus LL) mismatch is emphasized in long-segment fusion for adult spinal deformity; however, there are few studies evaluating the influence of PI-LL on surgical outcomes after short-segment fusion. In this study, we have examined the effects of PI-LL mismatch on surgical outcomes of short-segment lumbar intervertebral fusion for lumbar degenerative diseases. Methods: Patients with lumbar degenerative disease treated by short-segment (1 or 2 levels) transforaminal lumbar interbody fusion were divided into Group A (PI-LL ≤ 10°: n = 22) and Group B (PI-LL ≥ 11°: n = 30). Pre-and post-operative patient symptoms were assessed by the visual analogue scale (VAS: scores 0-100 mm; for LBP, lower-extremity pain, and lower-extremity numbness), a detailed VAS for LBP while in motion, standing, and sitting, and the Oswestry disability index (ODI). Surgical outcomes were evaluated by the Nakai score (3 = excellent to 0 = poor. Post-operative data were acquired for at least one year following surgery and were compared between the two groups. Multiple regression analyses were used to evaluate the relative influence of PI-LL on each pre-and post-operative parameter (VAS, detailed VAS and ODI) adjusted for age, sex, fusion levels, body mass index, presence of scoliosis, diabetes mellitus and depression. Results: The surgical outcomes in Group A were significantly better than those of Group B. Group A showed better post-operative VAS scores for LBP, particularly LBP while standing (11.9 vs. 25.8). The results of the multivariate analyses showed no significant correlation between PI-LL and pre-operative symptoms, but did show a significant correlation between PI-LL and the post-operative VAS score for LBP, lower extremity pain, and numbness. Conclusions: This study is the first to find that PI-LL mismatch influences post-operative residual symptoms, such as LBP, lower extremity pain and numbness. Among the three types of LBP examined in the detailed VAS, LBP while standing was most strongly related to PI-LL mismatch. The importance of maintaining spinopelvic alignment is emphasized, particularly when treating patients with adult spinal deformity using long-segment fusion surgery. However, our results indicate that surgeons should pay attention to sagittal spinopelvic alignment and avoid post-operative PI-LL mismatch even when treating patients with short-segment lumbar interbody fusion. [ABSTRACT FROM AUTHOR]

Background: Muscle injury is common and is thought to account for 10%-50% of all sports-related injuries. The use of rest, ice, compression, and elevation is common in clinical practice, but many treatments over a long period are required to produce a therapeutic effect. We evaluated the utility of photodynamic therapy as a new treatment option for the acute stage of muscle injury. Methods: Twenty 8-week-old Sprague-Dawley male rats underwent experimental injury of the right gastrocnemius muscle with a drop-mass method. After muscle injury was induced, a liposomally formulated indocyanine green derivative (7 mg/kg) near-infrared laser irradiation was performed at 18 h after injury. Local time-dependent changes in the treatment (n = 14) and no treatment (n = 14) groups were evaluated with in vivo imaging, histologic examination, and enzyme-linked immunosorbent assay methods. Results: In vivo imaging fluorescence values were significantly higher in the no treatment group, whereas interleukin-6 and tumor necrosis factor-α levels were significantly higher in the treatment group at 18 h after injury. Histologic examination results revealed that the treatment group had less bleeding and more degeneration repair processes than the no treatment group at 24 h and 1 week after muscle injury. Conclusions: These findings suggest that photodynamic therapy promotes a tissue-repairing effect during the early stage of muscle injury. [ABSTRACT FROM AUTHOR]

Background: We see patients who present with spirometry airflow limitation despite their forced expiratory volume in one second (FEV1) as well as forced vital capacity (FVC) to be supernormal (FEV1/FVC < 70%, both the %FEV1 and the % FVC ♧ 100%) in asymptomatic healthy non-smokers. Based on previous studies, we hypothesized these spirometry conditions (results measured with spirometry) could be suitably used as a practical surrogate marker of pulmonary dysanapsis: the condition of disproportionate but physiologically normal growth between airways and lung parenchyma. Methods: We compared the conventional surrogate marker of dysanapsis, maximum mid-expiratory flow to FVC (MMF/FVC), in SUBJECTS (FEV1/FVC < 70%, both the %FEV1 and the %FVC ♧ 100% in healthy non-smokers) (n = 25), in EMPHYSEMA (CT confirmed pulmonary emphysema, same spirometry results with SUBJECTS) (n = 55), and in CONTROLS (age- and height- matched, normal spirometry results) (n = 25). Next we added imaging analysis to evaluate the relationship between the cross sectional airway luminal area (X-Ai) and the lung volume results among the three groups. Results: The MMF/FVC was significantly lower in SUBJECTS and in EMPHYSEMA compared to CONTROLS. However, percent predicted peak expiratory flow (%PEFR) was significantly lower only in SUBJECTS and not in EMPHYSEMA compared to CONTROLS. The ratio of the X-Ai of the trachea and right apical bronchus to lung volume was significantly lower in SUBJECTS compared to CONTROLS. Conclusion: The simple spirometry conditions in SUBJECTS are highly suggestive of practical surrogate marker of pulmonary dysanapsis. Awareness of this concept would help to attenuate the risk of overdiagnosis of obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Background: Corrective surgery for kyphoscoliosis patients tend to be highly invasive due to osteotomy. The present case introduce less invasive corrective surgery using anterior oblique lateral interbody fusion (OLIF) technique. Case presentation: An 80-year-old Japanese man with a history of Parkinson's disease presented to our hospital because of severe kyphoscoliosis and gait disturbance. Considering the postsurgical complications due to osteotomy, we performed an anterior-posterior combined corrective fusion surgery: OLIF of Lumbar (L) 2-3, L3-4, and L4-5 (Medtronic Sofamor Danek, Memphis, TN, USA) followed by L5-Sacral (S) 1 anterior lumbar fusion via the OLIF approach using an anterior intervertebral cage, and posterior L3-4 and L4-5 facetectomy and posterior fusion using percutaneous pedicle screws from Thoracic (T) 10 to S1 with a T-9 hook system. The surgery was performed in a less invasive manner with no osteotomy, and it improved the sagittal alignments with moderate restoration, which improved the patient's posture and gait disturbance. The patient showed transient muscle weakness of proximal lower extremity contralateral side to the surgical site, which fully recovered by physical rehabilitation 3 months after the surgery. Conclusion: The surgical corrective procedure using the minimally invasive OLIF method including L5-S1 fusion showed a great advantage in treating degenerative kyphoscoliosis in a Parkinson's disease patient in its less-invasive approac. [ABSTRACT FROM AUTHOR]

Background: Chronic airway inflammatory disorders, such as asthma, are characterized by airway inflammation and remodeling. Chronic inflammation and damage to the airway epithelium cause airway remodeling, which is associated with improper epithelial repair, and is characterized by elevated expression of transforming growth factor-β (TGF-β). Epithelial-mesenchymal transition (EMT) is an important mechanism during embryonic development and tissue remodeling whereby epithelial cells gain the capacity to increase motility by down-regulation of epithelial markers and up-regulation of mesenchymal markers. TGF-β is a central inducer of EMT, and TGF-β-induced EMT is enhanced by pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β. We investigated whether the pro-inflammatory cytokine TWEAK (TNF-like weak inducer of apoptosis) enhanced TGF-β1-induced EMT in the human bronchial epithelial cell line BEAS-2B. Methods: Quantitative RT-PCR and western blotting were used to define alterations in epithelial and mesenchymal marker expression in BEAS-2B cells. The cells were assessed for 48 h after stimulation with TGF-β1 alone or in combination with TWEAK. Results: TGF-β1 induced spindle-like morphology and loss of cell contact, and reduced the expression of epithelial marker E-cadherin and increased the expression of mesenchymal markers N-cadherin and vimentin. Our data, for the first time, show that TWEAK reduced the expression of E-cadherin, and that co-treatment with TGF-β1 and TWEAK enhanced the TGF-β1-induced features of EMT. Moreover, hyaluronan synthase 2 expression was up-regulated by a combination with TGF-β1 and TWEAK, but not TNF-α. We also demonstrated that the Smad, p38 MAPK, and NF-κB signaling pathways, and the transcriptional repressor ZEB2 might mediate N-cadherin up-regulation by TGF-β1 in combination with TWEAK. Conclusions: These findings suggest that the pro-inflammatory cytokine TWEAK and TGF-β1 have synergistic effects in EMT and may contribute to chronic airway changes and remodeling. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) need to be approached carefully given the high incidence of pulmonary toxicity. Pemetrexed (PEM) is the key drug for the treatment of NSCLC. However, its safety, especially with respect to the exacerbation of ILD, and efficacy in NSCLC patients with ILD have yet to be established. Method: We investigated the safety and efficacy of PEM monotherapy in NSCLC patients with or without idiopathic interstitial pneumonia (IIPs). The medical charts of these patients were retrospectively reviewed. Results: Twenty-five patients diagnosed as having IIPs (IIPs group) and 88 patients without ILD (non-ILD group) were treated with PEM monotherapy at Juntendo University Hospital between 2009 and 2013. In the IIPs group, 12 patients were found to have usual interstitial pneumonitis (UIP) on chest computed tomography (CT) (UIP group) and the other 13 patients showed a non-UIP pattern on chest CT (non-UIP IIPs group). Three patients in the IIPs group (2 in the UIP group and 1 in the non-UIP IIPs group) and 1 in the non-ILD group developed pulmonary toxicity during treatment (3.5% overall, 12.0% in the IIPs group versus 1.1% in the non-ILD group). Moreover, all 3 patients in the IIPs group died of pulmonary toxicity. Overall survival tended to be longer in the non-ILD group than in the IIPs group (p = 0.08). Multivariate analyses demonstrated that IIPs was the only significant independent risk factor for PEM-related pulmonary toxicity. Conclusion: We found that the incidence of PEM-related pulmonary toxicity was significantly higher amongst NSCLC patients with IIPs than among those without IIPs. Particular care must be taken when administering PEM to treat NSCLC patients with IIPs. [ABSTRACT FROM AUTHOR]

Abstract In the present case of postoperative lumbar spinal stenosis after non-instrumented intertransverse fusion with granules of hydroxyapatite (HA), bone union was not completed and the patient felt the recurrence of his symptoms within two years. We performed re-decompression with fusion, and in hematoxylin and eosin staining of HA granulation harvested during revision surgery, fibrous tissue with hyaline degeneration surrounded the cavity where the HA had existed. Multinuclear giant cells and lymphocytes infiltrated some parts of the marginal layer of the cavity, and no obvious bony bridge had regenerated from autologous bone. No tartrate-resistant acid phosphate (TRAP) -positive osteoclasts could be seen in the new bone, suggesting that the activity of osteoclasts in the new bone decreased during the seven years after the primary surgery. [ABSTRACT FROM AUTHOR]

Background: Dropped head syndrome (DHS) is defined as weakness of the neck extensor muscles causing a correctable chin-on-the-chest deformity. Here we report the case of a patient with severe pain from lower leg ischemia showing DHS whose symptoms were attenuated by pain relief after amputation of the severely ischemic lower leg. To our knowledge this is the first report indicating that severe pain can cause DHS. Case presentation: A 64-year-old Asian woman was referred to our department with a 1-month history of DHS. She also suffered from severe right foot pain because of limb ischemia. She began to complain of DHS as her gangrenous foot pain worsened. She had neck pain and difficulty with forward gaze. We found no clinical or laboratory findings of neuromuscular disorder or isolated neck extensor myopathy. We amputated her leg below the knee because of progressive foot gangrene. Her severe foot pain resolved after the surgery and her DHS was attenuated. Conclusion: Severe pain can cause DHS. If a patient with DHS has severe pain in another part of the body, we recommend considering aggressive pain relief as a treatment option [ABSTRACT FROM AUTHOR]

Background: Cervical deformity can influence global sagittal balance. We report two cases of severe low back pain and lower extremity radicular pain associated with dropped-head syndrome. Symptoms were relieved by cervical corrective surgery. Case presentation: Two Japanese women with dropped head syndrome complained of severe low back pain and lower extremity radicular pain on walking. Radiographs showed marked cervical spine kyphosis and lumbar spine hyperlordosis. After cervicothoracic posterior corrective fusion was performed, cervical kyphosis was corrected and lumbar lordosis decreased, and low back pain and leg pain were relieved in both patients. Conclusions: Cervical deformity can influence global sagittal balance. Marked cervical kyphosis in patients with dropped-head syndrome can induce compensatory thoracolumbar hyperlordosis. Low back symptoms in patients with dropped-head syndrome are attributable to this compensatory lumbar hyperlordosis. Symptoms of lumbar canal stenosis may result from cervical deformity and can be improved with cervical corrective surgery. [ABSTRACT FROM AUTHOR]

Introduction: Epidermoid cysts are known as embryonic or acquired ectopic aberrations of the ectoderm. To the best of our knowledge, there are only a few reports of elderly onset intramedullary epidermoid cysts. We report a case of elderly onset intramedullary epidermoid cyst at the conus medullaris. Case presentation: A 63-year-old Japanese woman working as a farmer presented with slowly progressive gait disturbance and voiding dysfunction. A magnetic resonance imaging scan revealed an intramedullary mass lesion at L1 to L3. We diagnosed the lesion as an intramedullary spinal cord tumor. A laminectomy was performed at the level of Th12 to L3. Upon spinal cord dissection, a yellowish milky exudation erupted from the cystic lesion. We resected white cartilage-like pieces from the cystic cavity. Because the wall of the cystic lesion tightly adhered to the spinal cord parenchyma, we abandoned complete resection of the cyst wall. The pathological diagnosis was an epidermoid cyst. Conclusions: We propose that evacuation of the cyst contents is preferable, especially in cases with elderly onset and congenital origin. [ABSTRACT FROM AUTHOR]

Background: We report on Japanese patients who showed neurological deterioration induced by sitting after cervicothoracic posterior decompression with instrumented fusion, but showed immediate neurological recovery after bed rest. Case Presentation: Patients showed incomplete paraparesis caused by the ossification of the posterior longitudinal ligament at uppermost thoracic spine. Cervicothoracic posterior decompression with instrumented fusion was performed. Postoperatively, the patients showed partial paraparesis when they were sitting. They showed rapid recovery from lower extremity paralysis upon lying down. After strict bed rest for one month, those patients showed no apparent development of paralysis during sitting. Conclusion: In patients with postoperative residual anterior spinal cord compression, micromotion might exacerbate neurological symptoms. [ABSTRACT FROM AUTHOR]