[Surgical Case of Bronchial Mucoepidermoid Carcinoma Safely Diagnosed by Enucleation Under the Bronchoscopy After Bronchial Arterial Embolization].

A 28-year-old male presented to our hospital with hemoptysis and his chest computerized tomography (CT) showed the right middle and lower lobe atelectasis due to the tumor of right intermediate bronchial trunk. To reduce the blood flow to the tumor, bronchial arterial embolization was performed and the tumor was resected using Cryoprobe with a flexible endobronchial scope. Thus, we could observe the tumor localization and diagnose before the surgical procedure. We performed the right sleeve middle lobectomy and the right lower lobe was safely preserved.

Ligamentum Flavum Hematoma Accompanied by Intraspinal and Extraspinal Hematomas: A Case Report.

Studies on ligamentum flavum hematoma (LFH) have been gradually increasing; however, no study has reported an LFH spreading to the intraspinal and extraspinal spaces. The purpose of this report is to discuss this rare condition and report that extraspinal hematoma can be formed by LFH. The authors present the case of a 78-year-old man presented with right L5 radiculopathy caused by a space-occupying lesion with intraspinal and extraspinal expansions at the L4-L5 vertebral levels demonstrated on MRI. We tentatively diagnosed these lesions as intraspinal and extraspinal hematomas originating from the ligamentum flavum based on the chronological changes seen on MRI and computed tomography-based needle biopsy. After the extirpation of these lesions, the symptoms were relieved. Three months later, the patient could walk without a cane. From the intraoperative findings and pathological examination, we concluded that the extraspinal hematoma in paravertebral muscle was caused by an LFH of unknown etiology. This case report describes the difficulty in diagnosing LFH accompanied by an extraspinal hematoma with wide-spreading expansion and highlights the usefulness of repetitive MRI over time in capturing chronological changes of the hematoma. As far as we know, this is the first study on an LFH accompanied by an extraspinal hematoma in the multifidus.

Perpendicular probing and screwing technique: A simple method for accurate pedicle screw placement based on the human internal reference frame for angle estimation.

The pedicle screw (PS) is widely used for spinal fixation surgery. However, PS malpositioning can cause critical complications; thus, the accuracy of ascertaining PS trajectory is paramount. This study aimed to demonstrate the accuracy and safety of a simple and cost-effective PS placement technique using a human internal reference frame for angle estimation. Ex vivo lumbar porcine spine samples were fixed to a wooden board with rostrocaudal and mediolateral rotational angles adjusted by two angle vises. PS entry points (EPs) were identified using clear anatomical vertebral landmarks. PS placement was performed on one side using the perpendicular probing and screwing technique (PPST), wherein the attitude angle of the sample was adjusted such that the longitudinal axis of the target pedicle was perpendicular to the ground. The pedicle probe and PS driver were manually maintained perpendicular to the ground during probing and PS placement. PS placement on the contralateral side was performed freehand as a control. Offsets between the preoperatively planned and implanted PS rotational angles measured using computed tomography for PPST and freehand method were analyzed. Pedicle wall penetration was also evaluated. The mean ± standard error of the medial rotational offsets was 5.83° ± 0.57° in the freehand group versus 2.89° ± 0.31° in the PPST group (p <0.001), and the rostrocaudal rotational offsets were 4.81° ± 0.65° in the freehand group versus 2.92° ± 0.45° in the PPST group (p = 0.01). The mean pedicle wall penetration distance was significantly reduced by PPST (0.28 ± 0.12 mm vs 0.80 ± 0.17 mm in the freehand group, p = 0.0071). Thus, PPST improved PS positioning accuracy, resulting in reduced pedicle wall penetration and increased PS placement safety. This simple technique is also potentially cost-effective for institutions without computer-assisted surgical systems.

Acute Generalized Exanthematous Pustulosis Caused by Erlotinib in a Patient with Lung Cancer.

Acute generalized exanthematous pustulosis (AGEP) is a rare drug-related adverse skin reaction caused mainly by antibiotics. Erlotinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used to treat lung cancer. A 69-year-old woman with primary lung cancer (adenocarcinoma, cT3N1M1b, stage IVB) developed erythema and multiple skin pustules on her abdomen and both thighs after 7 weeks of erlotinib treatment. She also had fever and general fatigue. Histological examination of a skin biopsy specimen showed intraepidermal pustules with neutrophil and eosinophil infiltration. She was diagnosed with erlotinib-induced AGEP. AGEP resolved by erlotinib discontinuation and systemic corticosteroid treatment. The lung cancer progressed when erlotinib was discontinued, so afatinib, a second-generation EGFR-TKI, was administrated without any skin adverse effects. Afatinib successfully decreased the lung cancer, and maintained the disease stable for 1 year. Although acneiform rash was the most common skin adverse event caused by EGFR, AGEP rarely occurred. The present case also demonstrated that it is possible to switch agents, from erlotinib to afatinib, even though they have the same pharmacological effects. Although AGEP is a rare drug-related skin disorder, physicians should be aware that erlotinib may induce AGEP.

Eosinophilic granulomatous polyangiitis with IgG4 hypergammaglobulinaemia and salivary gland swelling.

A 51-year-old woman was admitted to our hospital for cough, fever, purpura in the legs, and salivary gland swelling. Six years ago, she had been diagnosed with bronchial asthma and was treated with a combination of inhaled corticosteroid and long-acting beta2-agonist. Blood examination showed increased eosinophils at 3027 cells/µL and elevated levels of immunoglobulin (Ig) G4 at 261 mg/dL and C-reactive protein at 2.76 mg/dL. Chest radiograph and computed tomography (CT) showed infiltrates in the bilateral lower lobes. Neck CT showed bilateral salivary gland swelling. Pathological examinations of the lungs and skin purpura showed granuloma with eosinophilic infiltration and perivascular dermatitis, respectively. She was diagnosed with eosinophilic granulomatous polyangiitis (EGPA) and treated with corticosteroids, which resolved the eosinophilia, salivary gland swelling, elevated IgG4 titre, and lung infiltration. As our patient did not meet the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2019 criteria of IgG4-related disease, the diagnostic was EGPA with IgG4 hypergammaglobulinaemia and salivary gland swelling.

Effect of cartilaginous endplates on extruded disc resorption in lumbar disc herniation.

OBJECTIVE: The aim of this study was to investigate the clinicopathologic features of lumbar disc herniation (LDH) with endplate degeneration and the association between cartilaginous fragments and inflammatory response to the herniated disc. SUMMARY OF BACKGROUND DATA: LDH often involves hyaline cartilage fragments pulled from the vertebral endplates. Modic changes are closely associated with LDH that contains hyaline cartilage, and cartilaginous endplates seem to affect resorption of the herniated disc. METHODS: A total of 78 patients who underwent microscopic discectomy between 9 and 16 weeks after an occurrence of LDH were reviewed. Modic changes, disc degeneration, high-intensity zone, and vertebral corner defect were evaluated using magnetic resonance imaging (MRI). Histopathological observations of cartilaginous endplates and inflamed granulation tissue in the herniated disc were made. In cases with inflamed granulation tissue, neovascularization and macrophage infiltration were also evaluated using immunohistochemical analysis. RESULTS: Modic changes were observed in approximately one-third of the patients (26 cases: type 1, 7; type 2, 17; and type 3, 2). Cartilaginous endplates were observed in 32 cases (41%) and in the majority of cases with Modic changes compared with cases without Modic changes (65%, p = 0.001). Although inflamed granulation tissue was observed in 60 cases (77%), no significant differences were detected in patient age and the composition of the herniated material. Immunohistochemical analysis showed that fewer CD34-positive capillaries and CD68-positive cells were found in cases with cartilaginous fragments compared with those without cartilaginous fragments (p < 0.001). In addition, a higher immunoreactivity to CD34 and CD68 was found in herniated discs <25% of whose area was occupied by cartilaginous endplates compared with discs whose area was occupied at 25% or more (p < 0.001). CONCLUSION: There is an association between LDH with endplate degeneration and cartilaginous herniation, with Modic type 2 predominating. Furthermore, neovascularization and macrophage infiltration, especially if the amount of cartilage is high, are likely to be less frequent in cartilaginous herniation, leading to failure in the spontaneous remission of clinical symptoms.

Double non-contiguous fractures in a patient with spondylo-epiphyseal dysplasia with spinal ankylosis treated with open and percutaneous spinal fixation technique: a case report.

BACKGROUND: Patients with ankylosing spines are susceptible to developing spinal fractures even with minor trauma and can develop early or late neurological injuries. These fractures require early and aggressive surgical management to enable spinal stability and/or neural decompression. Being highly unstable by nature, they require relatively long segment instrumentation and fusion, which can increase paravertebral soft tissue damage and perioperative bleeding. The purpose of this report is to describe a rare case of traumatic double fractures at the cervico-thoracic and thoraco-lumbar transition zones in ankylosing spine with spondylo-epiphyseal dysplasia (SED) of unknown cause, which were successfully treated with a combined open and percutaneous spinal fusion procedure. CASE PRESENTATION: A 46-year-old woman who was diagnosed with non-contiguous fractures in cervico-thoracic and thoraco-lumbar junction zones among multiple injuries sustained in a traffic accident was treated with hybrid techniques for posterior instrumentation with an open approach using a computed tomography (CT)-based navigation system and percutaneous pedicle-screwing method. She regained mobility to pre-admission levels and started walking on crutches 3 months postoperatively. Genetic testing for the cause of SED revealed no mutation in the COL2A1 or TRPVR4 genes. The union of fractured spine was confirmed on CT scan 1 year postoperatively. CONCLUSION: This is the first report of double spinal fractures in an ankylosing spine with genetically undetermined spondyloepiphyseal dysplasia. A long-segment posterior instrumentation procedure incorporating the invasive treatment of spinal fractures in ankylosing spondylitis or diffuse idiopathic hyperostosis was effective.

Saturated Fatty Acid Increases Lung Macrophages and Augments House Dust Mite-Induced Airway Inflammation in Mice Fed with High-Fat Diet.

Obesity is one of the phenotypes of severe asthma, which is considered to be a heterogeneous syndrome; however, its interaction with airway inflammation is not fully understood. The aim of this study was to clarify the role of saturated fatty acids in augmenting airway inflammation induced by house dust mite (HDM) in obesity. Subjects were Balb/c mice fed a high-fat diet (HFD) for 10 weeks, followed by sensitization and exposure to HDM. Subjects were also administered palmitic acid (PA) for 4 weeks with concurrent sensitization and exposure to HDM. Airway inflammation was assessed by quantifying the amount of inflammatory cells in bronchoalveolar lavage (BAL) and airway resistance was measured. In vitro, lipopolysaccharide (LPS)-primed macrophages were stimulated by PA. The amount of monocyte chemoattractant protein-1 (MCP-1), interleukin-1ß (IL-1ß), and tumor necrosis factor α (TNF-α) was examined in the supernatant. Compared to normal chow mice, HFD mice underwent significant increases in body weight; increases in number of lung macrophages, including circulating monocytes and alveolar macrophages; and increases in bronchoalveolar lavage fluid (BALF) total cell count, including neutrophils but not eosinophils, after HDM sensitization and exposure. In vitro, PA induced MCP-1 and augmented LPS-primed production of IL-1ß and TNF-α in macrophages. Among HDM mice that were administered PA, there was an increase BALF total cell count, including neutrophils but not eosinophils, compared to vehicle mice. In conclusion, saturated fatty acid increased the number of lung macrophages and augmented HDM-induced neutrophilic airway inflammation in a HFD mouse model.

Microglial Contact Prevents Excess Depolarization and Rescues Neurons from Excitotoxicity.

Microglia survey and directly contact neurons in both healthy and damaged brain, but the mechanisms and functional consequences of these contacts are not yet fully elucidated. Combining two-photon imaging and patch clamping, we have developed an acute experimental model for studying the role of microglia in CNS excitotoxicity induced by neuronal hyperactivity. Our model allows us to simultaneously examine the effects of repetitive supramaximal stimulation on axonal morphology, neuronal membrane potential, and microglial migration, using cortical brain slices from Iba-1 eGFP mice. We demonstrate that microglia exert an acute and highly localized neuroprotective action under conditions of neuronal hyperactivity. Evoking repetitive action potentials in individual layer 2/3 pyramidal neurons elicited swelling of axons, but not dendrites, which was accompanied by a large, sustained depolarization of soma membrane potential. Microglial processes migrated to these swollen axons in a mechanism involving both ATP and glutamate release via volume-activated anion channels. This migration was followed by intensive microglial wrapping of affected axons and, in some cases, the removal of axonal debris that induced a rapid soma membrane repolarization back to resting potentials. When the microglial migration was pharmacologically blocked, the activity-induced depolarization continued until cell death ensued, demonstrating that the microglia-axon contact served to prevent pathological depolarization of the soma and maintain neuronal viability. This is a novel aspect of microglia surveillance: detecting, wrapping, and rescuing neuronal soma from damage due to excessive activity.

In Vivo Two-Photon Imaging of Dendritic Spines in Marmoset Neocortex

Two-photon microscopy in combination with a technique involving the artificial expression of fluorescent protein has enabled the direct observation of dendritic spines in living brains. However, the application of this method to primate brains has been hindered by the lack of appropriate labeling techniques for visualizing dendritic spines. Here, we developed an adeno-associated virus vector-based fluorescent protein expression system for visualizing dendritic spines in vivo in the marmoset neocortex. For the clear visualization of each spine, the expression of reporter fluorescent protein should be both sparse and strong. To fulfill these requirements, we amplified fluorescent signals using the tetracycline transactivator (tTA)-tetracycline-responsive element system and by titrating down the amount of Thy1S promoter-driven tTA for sparse expression. By this method, we were able to visualize dendritic spines in the marmoset cortex by two-photon microscopy in vivo and analyze the turnover of spines in the prefrontal cortex. Our results demonstrated that short spines in the marmoset cortex tend to change more frequently than long spines. The comparison of in vivo samples with fixed samples showed that we did not detect all existing spines by our method. Although we found glial cell proliferation, the damage of tissues caused by window construction was relatively small, judging from the comparison of spine length between samples with or without window construction. Our new labeling technique for two-photon imaging to visualize in vivo dendritic spines of the marmoset neocortex can be applicable to examining circuit reorganization and synaptic plasticity in primates.

Recurrent dislocations of the atlantooccipital and atlantoaxial joints in a halo vest fixator are resolved by backrest elevation in an elevation angle-dependent manner.

BACKGROUND CONTEXT: Halo fixation is now universally performed in the initial reduction and fixation of unstable upper cervical spine injuries; however, persistent high instability and recurrent dislocations of the atlantooccipital and atlantoaxial joints after fixation are not well recognized. PURPOSE: The aim was to describe persistent instability of traumatic dislocations of the atlantooccipital and atlantoaxial joints after halo fixation and a useful method for preventing instability. STUDY DESIGN: This was a case report of a patient who survived traumatic dislocations of the atlantooccipital and atlantoaxial joints. PATIENT SAMPLE: A 73-year-old woman diagnosed with dislocations of the atlantooccipital and atlantoaxial joints along with multiple other injuries sustained in a traffic accident was included. METHODS: After initial closed reduction and halo fixation, congruity of the atlantooccipital and atlantoaxial joints was evaluated using, condylar gap, atlantodental interval, and flexion angulation of C1-C2 after the initial examination and before surgery. RESULTS: Changes in parameters 12 hours after halo fixation revealed re-dislocations and instability of the joints. Backrest elevation with halo fixation tended to reduce re-dislocations. Therefore, we carefully increased the backrest angle and measured the parameters at several angles of elevation within a range that did not affect vital signs to observe the effectiveness of elevation against re-dislocations. Elevation changed the parameters in an elevation angle-dependent manner, and these changes suggested that elevation was effective for reducing re-dislocation of both the atlantooccipital and atlantoaxial joints during halo fixation. With no major complications, this method enabled us to maintain good congruity of the joints for approximately 2 weeks until posterior spinal fusion with internal fixation. CONCLUSIONS: Backrest elevation with halo fixation appears safe to be performed without any other devices and is beneficial for blocking re-dislocation of both the atlantooccipital and atlantoaxial joints as well as possible secondary damage to the upper cervical spinal cord during the external fixation period.

ß2 adrenergic agonist attenuates house dust mite-induced allergic airway inflammation through dendritic cells.

BACKGROUND: Long-acting ß2 adrenergic agonists (LABAs) are commonly used combined with inhaled corticosteroids (ICS) to treat asthmatic patients. Previous reports suggest that LABAs have an anti-inflammatory effect in bronchial asthma, and this should be further investigated. The aim of this study was to investigate whether LABAs inhibit allergic airway inflammation and how this occurs. RESULTS: We assessed the effect of the LABA formoterol (FORM) on inflammatory cell responses in airway, lung and regional lymph nodes, using an HDM-induced murine allergic asthma model in vivo. The effect of FORM on cytokine production from bone marrow derived dendritic cells (BMDCs) stimulated with HDM was evaluated in vitro. Adoptive transfer of BMDCs pulsed with HDM in the presence or absence of FORM to naïve mice was performed and the inflammatory response to subsequent HDM challenge was analyzed. FORM treatment suppressed HDM-induced changes and caused an increase in the number of eosinophils and neutrophils in bronchoalveolar lavage. The concentration of IL-4 and IL-17 in lung tissue homogenate was elevated and led to an accumulation of IL-4, IL-13, IL-5 and IL-17 producing cells in regional lymph nodes. FORM inhibited the production of IL-6 and IL-23 from BMDCs stimulated with HDM in vitro, and enhanced IL-10 production. The BMDCs adoptive transfer experiment indicated that dendritic cells mediate the effect of FORM, since FORM treatment of BMDCs in vitro attenuated airway inflammation. CONCLUSION: These results suggested that FORM modulates dendritic cell function and attenuates Th2 and Th17 responses induced by HDM. Thus, we propose that the clinical significance of LABAs should be re-investigated taking into account these immune-modulating effects.

[Analgesia with paravertebral block for postoperative pain after thoracic or thoracoabdominal aortic aneurysm repair].

Paraplegia is a serious complication after thoracoabdominal aortic aneurysm repair. Therefore, maintenance of spinal cord perfusion pressure, drainage of cerebrospinal fluid, and avoidance of opioids are important for prevention of paraplegia Management of acute post-thoracotomy pain is necessary not only to keep the patient comfortable but also to minimize postoperative complications. However, epidural analgesia, a common method of pain control, is hard to use because of existing postoperative coagulopathy and avoidance of spinal cord ischemia Although both paravertebral block and epidural analgesia provide comparable pain relief after thoracic surgery, paravertebral block has lesser detrimental effects on spinal cord perfusion and better preserves the possibility to monitor neurologic function than epidural analgesia. We report 7 cases in which paravertebral blockade was used for analgesia in patients who underwent thoracoabdominal aneurysm repair.

[Effective glucocorticoid treatment in a case of idiopathic fibrosing mediastinitis].

A 54-year-old man was admitted to Saga University hospital with dyspnea on effort and a sensation of pressure in the chest. Chest CT images showed a low-density mass in the mediastinum surrounding the carina and left hilus, causing narrowing of both the left pulmonary artery and left main bronchus. The pathological findings from a surgical biopsy showed markedly fibrotic tissue with lymphocytes and plasmacytes, and we diagnosed idiopathic fibrosing mediastinitis, stage II. Oral glucocorticoid treatment of 30 mg/day prednisolone reduced the mass and improved the narrowing of the left pulmonary artery and left main bronchus. The patient was given low-dosage glucocorticoids as maintenance treatment. Previous reports indicated that idiopathic fibrosing mediastinitis with severe tissue fibrosis is difficult to control with glucocorticoid monotherapy. Here, we report a case of idiopathic fibrosing mediastinitis that was effectively treated with glucocorticoids.

[A case of hard metal lung disease in a man who worked as an iron grinder].

The patient was a man who had suffered from repeated pneumothoraces since August 2003, when he was 16 years old. A right pneumothorax was observed at age 21 years, in April 2008. At the same time, a dry cough began to appear and diffuse small nodular shadows in both lung fields were found on a chest X-ray film. Due to worsening symptoms and the chest X-ray findings, a transbronchial lung biopsy was performed in September 2008. Pathological examination showed mural type organization, and large numbers of multinucleated giant cells that were engulfing nucleated cells and had black pigment in their cytoplasm. Giant cell interstitial pneumonia and hard metal lung disease (HMLD) were suspected because of the patient's occupational history as a metal grinder, which included the use of a hard metal tool for three years since August 2005. In an elementary analysis using an electron probe microanalyzer, tungsten was detected in resected lung tissue obtained in April 2008 which confirmed the diagnosis. His symptoms improved after the initiation of corticosteroid therapy, which continued but with a gradual decrease in the dose. In this case, HMLD developed over a relatively short period despite the low level of dust dispersal of a hard-metal tool, perhaps because of a hypersensitivity of the patient to hard metal.

Compound heterozygosity for the Xeroderma pigmentosum complementation group A gene associated with a mild phenotype.

We describe a case of a 7-year-old boy diagnosed as xeroderma pigmentosum complementation group A (XPA). Severe photosensitivity developed at 5 months after birth, and at a visit to our hospital at the age of five years, multiple brownish freckles were present on the face. XPA complementing (XPAC) gene compensated the ability of DNA repair after UV-irradiation of the fibroblasts. PCR-RFLP and DNA sequencing analyses revealed compound heterozygosity for a splicing mutation (IV3 -1G => C) at the splicing acceptor site of intron 3 and a nonsense mutation (Arg228 => stop) in exon 6. The former mutation can be detected by a restriction enzyme Alw NI and the latter detected by Hph I. Neither obvious neurological symptoms nor malignant skin tumors were noted. This genotype is associated with milder clinical symptoms than homozygosity for the IV3 -1G => C mutation.