Randomized controlled trial to examine the tolerability of bronchoscopy with and without pharyngeal laryngeal anesthesia (TACOYAKI study).

BACKGROUND: The SARS-CoV-2 pandemic, pharyngeal anesthesia such as nebulizer or lidocaine pump spray is the risk of droplet transmission to health care workers from coughing due to spraying anesthesia. Absence of pharyngeal anesthesia may induce coughing and reduce patient and operator satisfaction, but the efficacy of pharyngeal anesthesia under sedation is still limited. Therefore we evaluated a prospective, randomized, single-blind trial to evaluate efficacy of pharyngeal anesthesia in patients receiving sedation. MATERIALS AND METHODS: We conducted a randomized comparison of pharyngeal anesthesia with or without bronchoalveolar lavage in patients undergoing bronchoscopy at our hospital between March and October 2022. Pharyngeal anesthesia was performed using 8％ lidocaine spray and the operators were blinded to eliminate bias. Two hundred patients were entered into the study and divided into two groups: those who received pharyngeal anesthesia(control group) and did not receive pharyngeal anesthesia(test group). The primary endpoint was the operator's satisfaction with the procedure. The secondary endpoints were the patient's cough during the examination as perceived by the operator, cough and discomfort experienced by the patient and the dose of analgesic/sedative/lidocaine administered. These scales were scored from 0 to 100. RESULT: In primary endpoint, there was no significant difference in the operator-rated procedure satisfaction between the 2 groups. The median for the discomfort score for patients in the control group was tendency higher than in the test group. There were no significant differences in other secondary endpoints. CONCLUSION: Pharyngeal anesthesia may not be recommended for flexible bronchoscopy performed under combined sedation and analgesia. TRIAL REGISTRATION: Registration number: UMIN000046975Date of registration: 2022/03/07.

Effect of Thyrocervical Artery Embolization for Mediastinal Hemangioma with Pleural Effusion.

A 72-year-old man was admitted to our hospital with a complaint of breathlessness. Computed tomography (CT) revealed a tumor with intense early enhancement and pleural effusion. Although the pleural effusion was not bloody, the tumor showed a hypervascular area on angiography. Left thyrocervical artery embolization was performed to prevent bleeding during the operation. After embolization, chest radiography revealed decreased pleural effusion. The tumor was resected and pathologically diagnosed as a mediastinal cavernous hemangioma. To our knowledge, mediastinal hemangiomas with pleural effusion are extremely rare; thus, this is the first report of reduced pleural effusion in mediastinal hemangiomas after artery embolization.

Effect of the third dose of BNT162b2 COVID-19 mRNA vaccine on anti-SARS-CoV-2 antibody levels in healthcare workers.

PURPOSE: Administration of three doses of Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine was completed in Japan in the spring of 2022. This study aimed to evaluate the antibody responses, and kinetics of three doses of vaccine in healthcare workers (HCWs). PATIENTS AND METHODS: We conducted a longitudinal cohort study with HCWs, who had no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, from a single hospital. Immunoglobulin G (IgG) titers of anti-SARS-CoV-2 spike protein (SP) and nucleocapsid protein (NP) titers were measured using an automated chemiluminescent enzyme immunoassay system. RESULTS: A total of 636 HCWs participated in the study. The anti-SP IgG titers decreased slowly after the second dose of the BNT162b2 vaccine in all participants, and robust antibody response was observed after the third dose of the vaccine. The peak anti-SP IgG titer after the third dose was approximately 4.1-fold higher than that after the first and second doses, and the rate of decrease in the anti-SP IgG titer after the third dose was significantly more gradual, than that after the second dose. After the second dose of vaccine, the antibody response was weaker in older participants than in younger participants, and in males than in females respectively, whereas the response to the third dose of vaccine did not differ significantly by sex or age. Adverse events following immunization were generally mild to moderate. CONCLUSION: The third dose of the BNT162b2 vaccine induced a significant and sustained increase in anti-SP IgG titers, and was generally safe and well-tolerated.

Malignant lymphoma mimics miliary tuberculosis by diffuse micronodular radiographic findings.

This case reports rare findings on computed tomography of a manifestation of malignant lymphoma, in which diffuse lung shadows appeared as miliary nodules distributed throughout the lungs bilaterally. The patient had a history of surgical treatment of rectal cancer and had received chemotherapy for suspicious liver metastasis. At her current presentation for evaluation suspected miliary tuberculosis on chest radiography, subsequent liver biopsy revealed a mass infiltration of atypical lymphocytes, which was diagnosed as follicular lymphoma. The miliary tuberculosis was suspected more than neoplastic lesions, such as metastatic rectal cancer or malignant lymphoma. Despite repeated bacteriologic tests of various samples, including sputum, urine, bronchial secretion, peripheral blood, bone marrow aspiration, and gastric lavage, all results were negative for mycobacterium tuberculosis. Finally, multiple, small, mass lesions of lymphocytes were demonstrated in the lung obtained from video-assisted thoracic surgery, and a diagnosis of follicular lymphoma was given. The final interpretations of liver mass and military lung lesions were tumor involvement by the follicular lymphoma. This radiologic findings of multiple miliary opacities throughout the whole lungs confused definite diagnosis because these images were remarkably similar with miliary tuberculous. This case reminds us to consider a wide variety of differential diagnoses even we assumed to be familiar with radiographic imaging at first glance.

Elevated serum ß-d-glucan levels in cavitary pulmonary nocardiosis.

An 86-year-old woman with Borrmann type III colorectal cancer (Union for International Cancer Control pT4aN2bM1c, pStage IVc) had received dexamethasone for the last 6 months as palliative care. She presented with a low-grade fever, chest pain and cough. Chest radiography on admission showed cavities and consolidations bilaterally in the upper lobes. A blood examination on admission revealed highly elevated serum ß-d-glucan levels. The diagnosis by bronchoscopy was pulmonary nocardiosis. With trimethoprim/sulfamethoxazole and imipenem/cilastatin, the ß-d-glucan levels were decreased, and chest X-ray showed improvement after 1 month. ß-d-glucan is known to be a biomarker of fungal infection. It is possible that ß-d-glucan levels also indicate a pulmonary infection by Nocardia.

Cancer-associated Retinopathy with Neuroendocrine Combined Large-cell Lung Carcinoma and Adenocarcinoma.

We herein report the case of a 74-year-old woman with a lung tumor. She presented with complaints of blurred and rapid, progressively impaired vision. A visual field examination revealed bilateral concentric contraction of the visual field and a ring scotoma in the right eye. She was diagnosed with cancer-associated retinopathy (CAR) combined with large-cell neuroendocrine carcinoma (LCNEC) of the lung via a visual field examination and underwent thoracoscopic surgery. CAR has been mostly associated with small-cell lung cancer (SCLC). Combined LCNEC is relatively rare and accounts for 10.6% of all LCNECs. This is the first case report of CAR-combined LCNEC.

A case of lung tumorlets secondary to pulmonary hypoplasia with recurrent haemoptysis.

Most patients with lung tumorlets are usually asymptomatic, and most diagnoses are incidental findings during microscopic lung examinations at autopsy or after excision of a tissue lesion. A 73-year-old woman was admitted to our hospital due to recurrent haemoptysis. Chest computed tomography demonstrated right inferior lobe collapse with bronchiectasis. Bronchoscopic examination revealed the right inferior lobar bronchus to be filled with blood clots. Haemoptysis persisted even after two arterial embolization trials and occlusion with endobronchial Watanabe spigot. Therefore, right lower lobectomy was performed, and multiple tumorlets on lobar hypoplasia were observed on histopathological examination of the excised specimen. We believe that the haemoptysis in our patient was possibly caused by the lung tumorlets secondary to lobar hypoplasia.

Visible light-induced crosslinkable gelatin.

A novel visible light-crosslinkable porcine gelatin was prepared for gelation and micropatterning. The preparation employed a photo-oxidation-induced crosslinking mechanism. First, furfuryl groups were incorporated into the gelatin. Second, the modified gelatin was mixed in water with Rose Bengal, which is a visible light sensitizer. Irradiation by visible light solidified the aqueous solution. In addition, when the solution was cast on a plate, dried and photo-irradiated in the presence of a photomask a micropattern was formed that matched the micropattern on the photomask. The gelatin-immobilized regions enhanced cell adhesion. It was also confirmed that the gelatin incorporating furfuryl and Rose Bengal have no significant toxicity. The photo-crosslinkable gelatin was employed as a direct pulp capping material in the dental field. Considering these results, this system could be useful as a new type of visible light-induced crosslinkable biosealant.

[A case of drug-induced pneumonia caused by clopidogrel].

A 65-year-old man, who had been given a diagnosis of angina pectoris, developed pneumonia 6 months after the initiation of clopidogrel to inhibit platelet aggregation. Chest radiography showed bilateral invasive shadows, and he was admitted to our hospital. He was asymptomatic, but his C-reactive protein and erythrocyte sedimentation rate were elevated. A lymphocyte stimulation test (DLST) with clopidogrel was positive, and bronchoalveolar lavage fluid showed an increase in lymphocytes and a decrease in the CD4+/CD8+ ratio. We noticed no radiologic improvement a week after prednisolone therapy (30 mg/day) with clopidogrel as stated. However, the airspace consolidation had slightly reduced after clopidogrel was halted. We found a few cases of ticlopidine-induced pneumonia, in the literature, but we found no cases of pulmonary adverse events caused by clopidogrel. To the best of our knowledge this is the first case of clopidogrel-induced pneumonia.

[A case of primary Sjögren's syndrome presenting with middle lobe syndrome complicated by nontuberculous mycobacteriosis].

A 52-year-old woman was found to have abnormal shadows in her chest radiograph in a health examination. At the age of 47 middle lobe syndrome had been pointed out and Mycobacterium intracellulare had been cultured from her sputum. Chest computed tomography scans showed a coin lesion and bronchiectasis in the middle lobe. On the other hand she suffered xerostomia and had a high level of serum anti-SS-A antibody. Further examination of her eyes and mouth gave her a diagnosis of primary Sjögren's syndrome (pSS). By video-assisted thoracoscopic surgery we resected the coin lesion which contained an abscess with acid-fast bacilli, identical to Mycobacterium intracellulare. The histopathology showed lymphocytic infiltration, caseous necrosis with Langhans' giant cells, and epithelioid granulomas. We finally made a diagnosis of pSS presenting with middle lobe syndrome (MLS) complicated by nontuberculous mycobacterial disease (NTM). We discuss the mechanism by which pSS could be complicated by NTM and MLS. Clinicians should pay attention to this possible relationship, especially among middle-aged and elderly women.

[A case of interstitial pneumonia preceding microscopic polyangiitis].

We encountered a case of interstitial pneumonia preceding microscopic polyangiitis (MPA). A 64-year-old asymptomatic woman was found to have interstitial pneumonia on a chest radiograph taken during a work-up before an operation for cataract. Six months later she presented with non-productive cough, low grade fever and renal dysfunction. Interstitial pneumonia worsened with new lesions. The test for MPO-ANCA was positive, though it had been negative six months previously. The histopathology of the lung by video-assisted lung biopsy showed the usual interstitial pneumonitis pattern and small vessel pulmonary vasculitis. Renal biopsy showed necrotizing glomerulonephritis. She was given a diagnosis of MPA and was immediately treated with methylprednisolone pulse therapy and a combination of prednisolone and cyclophosphamide. She has remained stable for two years. This positive inversion of MPO-ANCA, while interstitial pneumonia advanced, was of interest concerning the etiology of MPA. We discuss the important topic of the mechanism of the development of MPA.

[A case of primary Sjögren's syndrome complicated with lung adenocarcinoma].

A 69-year-old woman presented with headache. Her chest radiograph and computed tomographic scans showed a mass shadow causing superior vena cava syndrome. Bronchofiberscopic examination was nonproductive. The serum value of carcinoembryonic antigen was highly elevated, so we made a presumed diagnosis of primary non-small lung cancer. She also complained of dry eyes and mouth. The elevated values of serum antibodies against SS-A and SS-B and further examinations resulted in a definitive diagnosis of primary Sjögren's syndrome. Chemotherapy was not effective and she died 14 months later. Autopsy revealed that the mass shadow was a primary lung adenocarcinoma. At the age of 66 she suffered a refractory pneumothorax and her pulmonary cysts or bullae were surgically resected. Those lesions had bullae, emphysema, and alveolar septae thickened by infiltration of lymphoplasmacytic cells. Because she had complained of xerostomia for the last few decades, we associated the cysts with Sjögren's syndrome. Thoracic CT scans at that time showed a nodule next to a cystic lesion. We raise a possibility that lung cancer might derive from cystic lesions associated with Sjögren's syndrome.

[A human T-cell lymphotropic virus type 1 carrier presenting with Sjögren's syndrome and bronchopneumopathy].

A 77-year-old asymptomatic woman was found to have a coin lesion on a chest radiograph. Chest computed tomography scans showed the coin lesion, bronchiectasis, tree-in-bud appearance, and ground glass opacity. The histopathology of the lung by video-assisted thoracic surgery showed organizing pneumonia, follicular bronchiolitis, and non-specific interstitial pneumonitis patterns, all of which consisted of mainly mature lymphocytes and plasma cells. She suffered from dry eyes and had a high level of serum anti-SS-A antibody. Examination of her eyes and mouth revealed Sjögren's syndrome. The patient herself and her parents were born in Nagasaki prefecture, an area where human T-cell lymphotropic virus type 1 (HTLV-1) is endemic, and her sister suffered from a hematological malignancy. She was found to be an HTLV-1 carrier. We finally made a diagnosis of an HTLV-1 carrier presenting with Sjögren's syndrome and bronchopneumopathy. This combination (HTLV-1, Sjögren's syndrome, and bronchopneumopathy) is rarely reported.

Microscopic polyangiitis after influenza vaccination.

After influenza vaccination an 83-year-old woman was referred to us because of fever and sore throat with no response to antibiotics. Chest computed tomography showed thickened bronchovascular bundles, multiple nodules with feeding vessels, and consolidation. Laboratory tests showed a high level of serum myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) and soluble interleukin-2 receptor (sIL-2R), as well as abnormal renal function and urinary sediment. Transbronchial lung biopsy revealed organizing pneumonia. We made a diagnosis of microscopic polyangiitis after influenza vaccination. Corticosteroids and cyclophosphamide were effective. Careful attention should be paid to severe adverse effects such as systemic vasculitides after influenza vaccination.

[A case of effective readministration of itraconazole for recurrent allergic bronchopulmonary aspergillosis].

A 67-year-old woman suffered from productive cough but not from bronchial asthma. Her peripheral blood showed eosinophilia, a high serum level of total immunoglobulin E (IgE), and elevated specific IgE and positive precipitating antibody against Aspergillus fumigatus. Her chest radiograph and computed tomography revealed infiltrative shadows but not central bronchiectasis. Fibreoptic bronchoscopy detected some mucous plugs which grew Aspergillus fumigatus on culture. We therefore made a diagnosis of allergic bronchopulmonary aspergillosis (ABPA). We treated her using only itraconazole. Her respiratory symptoms, eosinophilia, serum IgE level, and pulmonary infiltration gradually improved, but withdrawal of itraconazole exacerbated her respiratory symptom and laboratory data. Administration of itraconazole again resulted in improvement of her symptoms and laboratory data. We report a case of ABPA without bronchial asthma or central bronchiectasis and refer to our diagnostic rationale. Furthermore, we discuss the decrease of allergens by the eradication of Aspergillus fumigatus in the airway with itraconazole to reduce the allergic reaction and improve the clinical symptoms.

[Sucessful treatment by micafungin of pulmonary aspergillosis occurring in an old lung abscess].

A 55-year-old man, who had diabetes from age 46 years old had been treated for a lung abscess in the right upper lobe at age 51. He underwent an operation for stomach cancer at age 52. When he was 55 years old, a cavity lesion appeared in his right upper lobe at the site of the treated lung abscess. Pulmonary aspergillosis was diagnosed by bronchial biopsy. In this case, we controlled his diabetes and used micafungin which has a mechanism unlike other conventional antifungal agents. The shadow decreased and examination of the resected specimen showed that the fungus had disappeard. Pulmonary aspergillosis is an important mycosis profunda and micafungin seems to be an effective antifungal agent against it.

[Carbamazepine-induced pneumonitis definitively diagnosed by accidental readministration].

An 82-year-old man had been treated by carbamazepine for convulsions. A month later he felt febrile and malaise. Laboratory data revealed liver dysfunction, hypoxemia, and chest radiograph and computed tomography (CT) of the thorax showed ground glass opacity in both lungs and mediastinal lymphadenopathy. Analysis of bronchoalveolar lavage fluid revealed pulmonary lymphocytosis. Drug-induced lymphocyte stimulation test (DLST) for carbamazepine using peripheral blood lymphocytes was negative. We gave him a possible diagnosis of carbamazepine-induced liver damage and pneumonitis. After stopping carbamazepine, we initiated corticosteroid therapy and he recovered well. One year later he again suffered from convulsions and was treated with carbamazepine in another hospital. A week later he became febrile and suffered appetite loss, and came to our hospital. His chest radiograph and CT again showed ground glass opacity and pleural effusion in both lungs. Along with the laboratory data we established a definitive diagnosis of carbamazepine-induced pneumonitis. We discuss the mechanism of carbamazepine-induced pneumonitis in which the DLST results were negative and the challenge test was positive.

[Case report of limited form of Wegener's granulomatosis detected by a health examination with no subjective symptoms].

A 60-year-old woman with no subjective symptoms was admitted to our hospital because of chest radiograph abnormality detected by a health examination. A computed tomographic scan of the thorax showed multiple nodules in both lungs without cavitation. Other organ lesions were not detected. Specimens from transbronchial lung biopsy revealed non-specific granuloma with necrosis. Antituberculous therapy was not effective, and serum PR 3-ANCA revealed to be positive. So we performed an excisional biopsy of the lung by video-assisted thoracoscopic surgery. The specimens showed necrotizing vasculitides, and granulomata which consisted of mainly lymphocytes, epithelioid cells and Langhans' giant cells. We here report a rare case of a patient with a limited form of Wegener's granulomatosis suffering from no subjective symptoms detected by a health examination.

[Two cases of prostate cancer found primarily from lung metastatic lesions].

We report two cases of prostate cancer found primarily from a metastatic lesion appearing in a chest radiograph. Patient 1 was admitted to our hospital because his chest radiograph and chest CT showed pleural effusion on the left. Thoracocentesis and pleural biopsy were unremarkable, so he was observed as both an outpatient and an inpatient. His general condition worsened, and after the third admission, he died. His autopsy revealed prostate cancer and positive immunohistochemical reactions for PSA and PSAP in both lungs, and prostate specimens demonstrated that prostate cancer had metastasized to the lung. Patient 2 was referred for evaluation of a bilateral multiple nodular shadow in a chest radiograph, and prostate cancer was discovered. Immunohistochemical reactions for PSA and PSAP were positive in both specimens of TBLB and prostate biopsy, confirming that the multiple lung tumors were metastases from prostate cancer.