Intratracheal instillation of polyacrylic acid induced pulmonary fibrosis with elevated transforming growth factor-ß1 and connective tissue growth factor.

We investigated the intratracheal instillation of Polyacrylic acid (PAA) in rats to determine if it would cause pulmonary disorders, and to see what factors would be associated with the pathological changes. Male F344 rats were intratracheally instilled with low (0.2 mg/rat) and high (1.0 mg/rat) doses of PAA. They were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months after PAA exposure to examine inflammatory and fibrotic changes in the lungs. There was a persistent increase in the neutrophil count, lactate dehydrogenase (LDH) levels, cytokine-induced neutrophil chemoattractant (CINC) values in bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in lung tissue. Transforming growth factor-beta 1 (TGF-ß1), a fibrotic factor, showed a sustained increase in the BALF until 6 months after intratracheal instillation, and connective tissue growth factor (CTGF) in lung tissue was elevated at 3 days after exposure. Histopathological findings in the lung tissue showed persistent (more than one month) inflammation, fibrotic changes, and epithelial-mesenchymal transition (EMT) changes. There was also a strong correlation between TGF-ß1 in the BALF and, especially, in the fibrosis score of histopathological specimens. Intratracheal instillation of PAA induced persistent neutrophilic inflammation, fibrosis, and EMT in the rats' lungs, and TGF-ß1 and CTGF appeared to be associated with the persistent fibrosis.

The Effects of Endoplasmic Reticulum Stress via Intratracheal Instillation of Water-Soluble Acrylic Acid Polymer on the Lungs of Rats.

Polyacrylic acid (PAA), an organic chemical, has been used as an intermediate in the manufacture of pharmaceuticals and cosmetics. It has been suggested recently that PAA has a high pulmonary inflammatory and fibrotic potential. Although endoplasmic reticulum stress is induced by various external and intracellular stimuli, there have been no reports examining the relationship between PAA-induced lung injury and endoplasmic reticulum stress. F344 rats were intratracheally instilled with dispersed PAA (molecular weight: 269,000) at low (0.5 mg/mL) and high (2.5 mg/mL) doses, and they were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure. PAA caused extensive inflammation and fibrotic changes in the lungs' histopathology over a month following instillation. Compared to the control group, the mRNA levels of endoplasmic reticulum stress markers Bip and Chop in BALF were significantly increased in the exposure group. In fluorescent immunostaining, both Bip and Chop exhibited co-localization with macrophages. Intratracheal instillation of PAA induced neutrophil inflammation and fibrosis in the rat lung, suggesting that PAA with molecular weight 269,000 may lead to pulmonary disorder. Furthermore, the presence of endoplasmic reticulum stress in macrophages was suggested to be involved in PAA-induced lung injury.

A case of idiopathic multicentric Castleman's disease with secondary autoimmune neutropenia.

A 73-year-old Japanese woman with productive cough and dyspnoea on exertion was admitted, and she showed neutropenia and pulmonary reticular opacities and axial and mediastinal lymphadenopathies on chest computed tomography. The clinical findings and surgical lung and lymph node biopsies were diagnostic for idiopathic multicentric Castleman's disease (iMCD) complicated by secondary autoimmune neutropenia (AIN). iMCD is often complicated with hematologic disorders, however, iMCD complicated with AIN has not been reported; therefore, if iMCD is accompanied by neutropenia, the anti-neutrophil antibodies should be measured.

Difficulty differentiating primary mediastinal classical Hodgkin lymphoma from inflammatory myofibroblastic tumor: A case report.

A 20-year-old Japanese man visited our hospital because an enlarged mediastinal shadow had been detected on chest x-ray. Chest computed tomography revealed a large mediastinal mass with multiple lymph node enlargement, pericardial effusion, and bilateral pleural effusion. He was diagnosed with inflammatory myofibroblastic tumor (IMT) based on a thoracoscopic tumor biopsy. Initial corticosteroid and celecoxib treatment was only partially effective; therefore, additional tumor rebiopsy and left axillary lymph node biopsy were performed. Based on the findings, the patient was rediagnosed with classical Hodgkin lymphoma (CHL). To date, there has only been one report of a case initially diagnosed as IMT and rediagnosed as CHL, as in our case, and only three reports of malignant lymphoma mimicking IMT. When IMT is suspected based on pathological findings and subsequently with treatment failure, possible CHL and performing rebiopsy should be considered.

Plastic bronchitis caused by Haemophilus influenzae.

Plastic bronchitis is characterized by sputum obstructing the bronchus and causing atelectasis. Bronchoscopic removal of the clogged bronchial cast is typically performed, but small-diameter bronchoscopes with narrow suction ports cannot achieve adequate suction. Suction using a bronchoscope as a guide sheath may be effective for treating plastic bronchitis in children.

A rare case of double primary lung adenocarcinomas with uncommon complex EGFR G719X and S768I mutations and pleomorphic carcinoma.

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-targeted therapy has emerged as a viable treatment for patients with advanced non-small cell lung cancer with common EGFR mutations. The uncommon G719X and S768I mutations can co-occur as complex mutations in the same tumor. Here we report a case of a 72-year-old male patient with double lung carcinoma, with G719X and S768I complex mutations detected in the right upper lung lobe along with brain metastases. Osimertinib (80 mg/day) was administered as the first-line treatment, and a reduction in the right lobe tumor and brain lesions was achieved. However, the left upper lung lobe mass remained unchanged; histopathological examination via a lobectomy revealed pleomorphic carcinoma. Thus, the patient was diagnosed with multiple primary lung cancers. In conclusion, osimertinib is a viable treatment option for lung cancer with rare EGFR G719X and S768I complex mutations.

Fatal limbic encephalitis as paraneoplastic neurological syndrome in a patient with lung adenocarcinoma positive for antiamphiphysin antibody after durvalumab treatment.

A 69-year-old Japanese male with advanced lung adenocarcinoma developed neurological symptoms after chemoradiotherapy and durvalumab maintenance therapy. He was positive for serum antiamphiphysin antibody, which is rarely seen in patients with lung adenocarcinoma. Additionally, his brain magnetic resonance images showed limbic encephalitis which led to the diagnosis of classic paraneoplastic neurological syndrome (PNS). Immune checkpoint inhibitors (ICIs) activate T cells and may also activate antineuronal antibodies that cause PNS. Durvalumab, which is an ICI, may have led to antiamphiphysin antibody-positive PNS in our patient. Treatment with systemic high-dose methylprednisolone was unsuccessful and he died 2 months later. PNS should be considered as one of the differential diagnoses in patients with lung cancer and neurological symptoms during, or after, ICI treatment.

Crosslinked Structure of Polyacrylic Acid Affects Pulmonary Fibrogenicity in Rats.

We conducted intratracheal instillations of polyacrylic acid (PAA) with crosslinking and non-crosslinking into rats in order to examine what kinds of physicochemical characteristics of acrylic-acid-based polymers affect responses in the lung. F344 rats were intratracheally exposed to similar molecular weights of crosslinked PAA (CL-PAA) (degree of crosslinking: ~0.1%) and non-crosslinked PAA (Non-CL-PAA) at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months post-exposure. Both PAAs caused increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 6 months following instillation. The release of lactate dehydrogenase (LDH) activity in the BALF was higher in the CL-PAA-exposed groups. Histopathological findings of the lungs demonstrated that the extensive fibrotic changes caused by CL-PAA were also greater than those in exposure to the Non-CL- PAA during the observation period. CL-PAA has more fibrogenicity of the lung, suggesting that crosslinking may be one of the physicochemical characteristic factors of PAA-induced lung disorder.

Autopsy case of a patient with rapidly progressive combined small-cell lung carcinoma with spindle-shaped cell tumor.

A 69-year-old Japanese man visited our hospital because of worsening shortness of breath. His chest computed tomography (CT) showed a giant left lung mass with a massive left pleural effusion. He could not be treated with chemotherapy and eventually died from a rapidly progressive tumor. He was diagnosed with combined small cell lung carcinoma (C-SCLC) with spindle-shaped cell tumor at autopsy. C-SCLC is characterized by pathologically concurrent SCLC and adenocarcinoma or squamous cell carcinoma, or rarely, spindle-shaped cell tumor. The clinical course of C-SCLC with spindle-shaped cell tumor has not previously been determined. Our patient's tumor increased by 2.59-fold in 20 days. The combination of C-SCLC with spindle-shaped cell tumor suggested rapid progression and a poor prognosis.

Paraneoplastic neuromyelitis optica spectrum disorder associated with malignant melanoma: A case report.

Neuromyelitis optica spectrum disorders (NMOSDs) are autoimmune demyelinating diseases involving the central nervous system, affecting the spinal cord and optic nerves. There are few reports of paraneoplastic NMOSD associated with malignant melanoma. Here, we report a rare case of anti-aquaporin 4 (AQP4) antibody-positive NMOSD associated with malignant melanoma. A 61-year-old Japanese woman was diagnosed with malignant melanoma and lung metastasis four years after a diagnosis of anti-AQP4 antibody-positive NMOSD. When diagnosing and treating patients with NMOSD, physicians should be aware of the development of malignancy for at least several years.

Paraneoplastic Sensory Polyneuropathy Related to Anti-PD-L1-including Anticancer Treatment in a Patient with Lung Cancer.

Paraneoplastic neurological syndromes (PNS), such as sensory polyneuropathy, are rare, and serum neuronal antibodies that are used for diagnosing this syndrome are occasionally positive. Similarly, neurological immune-related adverse events due to immune checkpoint inhibitors (ICIs) are also rare. However, their etiologies and the relationship between them remain unclear. We herein report a patient with suspected small cell lung cancer who showed sensory polyneuropathy after treatment with atezolizumab in combination with cytotoxic agents (carboplatin and etoposide) and was doubly positive for serum anti-Hu and anti-SOX-1 antibodies. Treatment with ICI and cytotoxic agents may sometimes lead to the development of PNS.

[A Case of a Bronchial Foreign Body (Artificial Tooth) in the Right Middle Bronchus Without Respiratory Symptoms].

Patients with bronchial foreign bodies often present with subjective symptoms, mainly cough, and removing the foreign bodies is difficult. Bronchial foreign bodies are mostly located in the right lower bronchus, and rarely in the right middle bronchus. An 85-year-old man had no subjective symptoms. He aspirated an artificial tooth during dental treatment the day before visiting our clinic, and consulted his home doctor. He was admitted to our hospital because a chest radiograph indicated the presence of a foreign body in the right middle and lower lung field. Chest computed tomography showed that the bronchial foreign body was located in the right middle bronchus, and it was accompanied by an artifact in the circumference of the lesion, and it seemed to be the metal piece of an artificial tooth. Three-dimensional CT showed the root of the artificial tooth located in center side of the right middle bronchus, and, considering the invasiveness, we decided to remove the tooth by flexible bronchoscopy. The bronchoscopy revealed a metal piece occluding the right middle bronchus without granulation, and we could remove the tooth immediately by grasping the root of the tooth with alligator forceps. We experienced a case of a foreign body located in the right middle bronchus without respiratory symptoms. It is important to carry out image examinations, because elderly patients may not exhibit respiratory symptoms.

[A Case of Papillary Thyroid Cancer Diagnosed as Recurrent Pulmonary Metastases Diagnosed by Transbronchial Biopsies 18 Years After Surgery].

We report a 79-year-old woman, who had undergone surgery for papillary thyroid carcinoma 18 years previously and lung adenocarcinoma 15 years previously. She didn't receive any follow-up because she had no recurrence for 5 years in both diseases. She visited a local doctor with precordial pain and thorax discomfort as her chief complaints, where chest computed tomography indicated a 14 mm-sized nodule in the right lower lobe and 5-7 mm-sized small nodules in both lungs. Using endobronchial ultrasonography with a guide sheath (EBUS-GS) for the diagnosis in our department, the lesions were confirmed by ultrasonography, and a transbronchial biopsy was carried out under fluoroscopy. Pathologically, a sufficient amount of tumor cells were collected, and the findings of adenocarcinoma were obtained. Her condition was diagnosed as recurrent pulmonary metastases of thyroid papillary carcinoma because of the atypical columnar epithelial cells with nuclear variants and the papillary proliferation of intranuclear inclusion, and because of the positive findings in immunohistochemical staining for thyroglobulin. Since papillary thyroid carcinoma is positive for thyroid transcription factor-1 (TTF-1), which is widely used as a marker of lung adenocarcinoma, it cannot be used to differentiate between the two. It is often difficult to diagnose papillary thyroid carcinoma by bronchoscopy, because its progress is slow and the origin of the metastatic lung tumor is not in the bronchus, unlike primary lung cancer. However, a devised transbronchial biopsy procedure for slowly progressive metastatic lung tumors such as papillary thyroid carcinoma is considered to be a useful technique for diagnosis.

A Case of Pulmonary Infectious Bulla Caused by Mycobacterium Avium.

A 37-year-old Japanese man presented with a bulla with niveau-like opacity in the right upper lung on chest radiography. Air-fluid level gradually increased despite broad-spectrum antibiotic therapy. Right upper lobectomy was performed, and epithelioid granuloma with mycobacteria was histopathologically observed. Bacterial culture of the fluid was negative, but mycobacterial culture was positive for Mycobacterium avium; therefore, the patient was diagnosed with pulmonary infected bulla caused by Mycobacterium avium. He was further treated with antimycobacterial agents after resection of the infected bulla. To our knowledge, this is the first report of pulmonary infected bulla caused by only Mycobacterium avium in the English literature.

[A Retrospective Study of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) Performed on Tuberculous Lymphadenitis Cases].

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been reported to be useful not only for the diagnosis of lymph node metastasis of lung cancer but also for benign diseases. We retrospectively analyzed the results of patients with tuberculous lymphadenitis (TL) who had undergone EBUS-TBNA between November 2010 and January 2016. EBUS-TBNA was performed in 427 cases during that period. Six cases were finally diagnosed as TL. The punctured lymph node was 8 lesions. Pathological findings consistent with TL were obtained in all 6 cases (100%), and the tissue specimens were positive in Ziehl-Neelsen staining in 3 of the 6 cases (50%). In all 6 cases, the acid-fast bacteria (AFB) smear test of the needle rinse fluid was negative, 2 cases were positive for AFB culture (33.3%), and 2 cases were positive for Mycobacterium tuberculosis (MTB)-PCR test (33.3%). In this study, the positive rate of mycobacterial culture and the MTB-PCR test of the needle rinse fluid was low, though the concordance rate of pathological findings with TL was high (100%). The results suggest that EBUS-TBNA should be carefully evaluated in patients with TL, considering the low positive rate of mycobacterial culture and MTB-PCR test in the needle rinse fluid.

Good appearance of food gives an appetizing impression and increases cerebral blood flow of frontal pole in healthy subjects.

We investigated the effect of food appearance on appetite and on left-frontal pole blood flow in healthy young subjects. The iEat, a new form of foods with good appearance and greater softness was hypothesized to have the better effects to the subjects than blender-processed foods. The effect on appetite and left-frontal pole blood flow using hemoencephalography was assessed while participants were viewing the slideshows of two kinds of foods respectively. The slideshows were used to control the showing time and other variables. The pictures of iEat foods stimulated both of them more than the blender-processed ones. The measurement of cerebral blood flow could be a useful method to monitor the cognitive and emotional aspects of feeding behavior that are important for humans. Like iEat, the foods that look as good as ordinary food yet are softer can be used for people with poor appetite and eating difficulties to ordinary food.