Diagnosis and Treatment of Pulmonary Nontuberculous Mycobacterial Disease : Focusing on Differences from Pulmonary Tuberculosis and Atypical Cases

In public hospital peer groups such as the National Hospital Organization (NHO) and JA Welfare Federation, hospitals are set up in various places around Japan and play an important role in clinical researches including clinical trials on a nationwide scale. In particular, NHO has contributed to policies such as vaccination against new viruses by conducting clinical studies that are directly linked to medical administration. NHO is also conducting clinical researches to promote EBM in Japan and organ-specific network researches. Many multi-institutional joint studies on pulmonary mycobacterial disease are also underway, and in recent years the weight of research on pulmonary nontuberculous mycobacterial disease (PNTMD) has increased rather than pulmonary tuberculosis (PTB). Epidemiological studies of PNTMD in Japan have been conducted mainly by joint research groups of the former National Sanatorium (now NHO), but with the increase in prevalence, they are now a national survey with the additional participation of community hospitals. The incidence rate of PNTMD in Japan is exceeding that of culture-positive PTB and the highest among major industrialized nations. Although the typical clinical course and radiological manifestations of PNTMD differ from those of PTB, physicians with little experience in treating tuberculosis patients sometimes confuse these mycobacterial diseases. This review describes the diagnosis and treatment of PNTMD, with an emphasis on differences from pulmonary tuberculosis. In addition, I present our own cases of PNTMD at NHO Kochi Hospital and explain the atypical cases and pitfalls that may be encountered in daily practice

Varying clinical presentations of NTM disease

The incidence rate of pulmonary nontuberculous mycobacterial disease (PNTMD) in Japan is the highest among major industrialized nations. Although the typical clinical course and radiological manifestations of PNTMD are different from those of pulmonary tuberculosis (TB), confusion about these mycobacterial diseases leads to a diagnostic pitfall. Diagnostic challenges include the coexistence of Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM), false positives for NTM in MTB nucleic acid amplification tests, microbial substitution, and abnormal radiological manifestations caused by NTM. Features of extrapulmonary NTM diseases, such as pleurisy, vertebral osteomyelitis, and disseminated disease, are different from the corresponding tuberculous diseases. Moreover, the immunological background of the patient (status of human immunodeficiency virus infection with or without antiviral therapy, continuation or discontinuation of immunosuppressive therapy, use of immune checkpoint inhibitor, pregnancy and delivery, etc.) influences the pathophysiology of mycobacterial diseases. This review describes the varying clinical presentations of NTM disease with emphasis on the differences from TB

Type A thymoma : a rare cause of neoplastic cardiac tamponade with long-term survival

Background: The prognosis of thymoma with cardiac tamponade is generally poor. Most of the reported thymomas with cardiac tamponade were type B or type AB (mixed thymoma), and cardiac tamponade due to type A thymoma, which has a better prognosis compared to type B thymoma, is extremely rare. Case presentation: We encountered a case of cardiac tamponade in a 71-year-old male. He visited our emergency department due to exacerbation of fatigue and dyspnea on exertion that lasted for two weeks. Chest imaging revealed a large amount of pericardial fluid and a contrast-enhanced tumor with calcification in the anterior mediastinum. The patient underwent thoracoscopic tumor biopsy and pathological examinations revealed type A thymoma. In this case, long-term disease-free survival (7.5 years) was achieved by multidisciplinary treatment (preoperative chemotherapy, surgical excision, and postoperative radiation therapy), in accordance with the histological type. Conclusions: This case indicates that neoplastic cardiac tamponade, even in elderly patients, should not necessarily be regarded as a terminal cancer and requires a systematic investigation for underlying causes

Eosinophilic pleural effusion due to lung cancer has a better prognosis than non-eosinophilic malignant pleural effusion

Objective Tumor-related eosinophilia may have extended survival benefits for some cancer patients. However, there has been no report on the prognosis difference between eosinophilic pleural effusion (EPE) and non-EPE in lung cancer patients. Our study aimed to investigate the prognosis difference between EPE and non-EPE due to lung cancer. Patients and methods We retrospectively reviewed patients diagnosed with lung cancer who presented with malignant pleural effusion (MPE) between May 2007 and September 2020 at the National Hospital Organization Kochi Hospital. EPE is defined as pleural fluid with a nucleated cell count containing 10% or more eosinophils. Results A total of 152 patients were included: 89 were male (59%). The median age was 74.4 years (range 37–101), and all patients were pathologically shown to have MPE. Most patients (140; 92%) had an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0/1. Twenty patients had EPE. The median overall survival (OS) of all 152 lung cancer patients with MPE was 298 days. The median OS of the patients with EPE was 766 days, and the median OS of the patients with non-EPE was 252 days. Kaplan–Meier univariate analysis showed that lung cancer patients with EPE had a significantly better prognosis than patients with non-EPE (P < 0.05). Cox proportional regression analysis showed that EPE, ECOG PS, sex, and the neutrophil-to-lymphocyte ratio in the serum (sNLR) may be independent prognostic factors affecting survival in patients with MPE. Conclusion Lung cancer patients with EPE have a better prognosis than those with non-EPE

La5Ti2Cu1-xAgxS5O7 photocathodes operating at positive potentials during photoelectrochemical hydrogen evolution under irradiation of up to 710 nm

A photoelectrochemical (PEC) cell based on a series-connected photocathode and photoanode made of particulate semiconductors is a potentially scalable and inexpensive device for renewable solar hydrogen production via PEC water splitting without any external power supply. The realisation of such PEC devices hinges on the development of photoelectrodes that operate at a small applied voltage. In this study, solid solutions of La5Ti2CuS5O7 (LTC) and La5Ti2AgS5O7 (LTA) were synthesised, and their physical, optical, and PEC properties in the water splitting reaction were discussed. LTC and LTA formed a La5Ti2Cu1-xAgxS5O7 solid solution (LTC(1-x)A(x)) over the whole compositional range. The indirect bandgap energy of LTC(1-x)A(x) changed nonlinearly with respect to composition, attaining its minimum value (ca. 1.8 eV) at a composition of x approximate to 0.16. Photoelectrodes of Al-doped LTC(1-x)A(x) solid solution powder fabricated using the particle transfer method exhibited a photocathodic response regardless of the Ag content. 1% Al-LTC(0.9)A(0.1) photocathodes exhibited the best PEC properties in the hydrogen evolution reaction and yielded a hypothetical half-cell solar-to-hydrogen energy conversion efficiency of 0.25% at +0.6 V vs. RHE, three times higher than the previously reported 1% Sc-LTC. In addition, 1% Al-LTC(0.9)A(0.1) photocathodes were fairly stable at + 0.7 V vs. RHE without any protective modifications. Owing to the positive operational electrode potential of 1% Al-LTC(0.9)A(0.1), unassisted PEC water splitting was accomplished using series-connected photoelectrodes made of 1% Al-LTC(0.9)A(0.1) and BaTaO2N, particulate semiconductors with absorption edge wavelengths of 710 and 660 nm, respectively, at a Faradaic efficiency of unity and a solar-to-hydrogen energy conversion efficiency of approximately 0.1%.ArticleEnergy & Environmental Science.8(11):3354-3362(2015)journal articl

Late-onset acute type 1 diabetes mellitus 7 months after discontinuation of pembrolizumab against lung cancer

Immune-related adverse events (irAEs) occur in rare cases, even after the completion of immune checkpoint inhibitor (ICI) therapy. We encountered a lung cancer patient diagnosed with acute-onset type 1 diabetes mellitus (DM) 7 months after the cessation of ICI. A 68-year old woman was referred to our hospital for chest abnormalities. She was diagnosed with lung adenocarcinoma cT4N2M1c, stage IVB. Immunostaining showed that the expression of programmed death ligand 1 in tumor cells was negative. A genetic analysis using the Oncomine Dx Target Test Multi-CDx System revealed that the primary tumor was positive for ERBB2. Combined immunotherapy with carboplatin, pemetrexed, and pembrolizumab was performed as first-line therapy, followed by maintenance therapy with pemetrexed plus pembrolizumab, which was successful. After the seventh course, maintenance therapy was stopped because only the primary tumor showed local enlargement. Local chest radiotherapy (66 Gy/33 Fr) was performed, and the patient was followed up. HbA1c was 4.9% 3 months after the completion of pembrolizumab, and dry mouth and polyuria occurred after 5 months. Seven months later, the patient developed diabetic ketoacidosis with a blood glucose of 348 mg/dL and an HbA1c of 11.3%. Antiglutamic acid decarboxylase antibodies were negative and urinary C-peptide was 9.3 μg/day. The patient was diagnosed with acute-onset type 1 diabetes and received insulin therapy. There has been no case report of type 1 diabetes diagnosed 7 months after the last administration of an ICI. These results indicate that irAE needs to be considered even after the cessation of ICI

Non-small cell lung cancer with EGFR (L858R and E709X) and CNNB1 mutations responded to afatinib

Lung cancer with complex epidermal growth factor receptor (EGFR) and CTNNB1 comutations is rare, and the efficacy of tyrosine kinase inhibitors (TKIs) is generally poor. Here, we encountered a lung cancer patient with complex EGFR (L858R and E709X) and CTNNB1 comutations who successfully responded to afatinib. A 78-year-old woman visited our hospital with a cough and bloody sputum that had worsened over the past year. She had multiple mass shadows in both lungs and nodular shadows in the bronchi. The patient was diagnosed with lung adenocarcinoma cT4N3M1c stage IVB. A genetic analysis of the primary tumor using the Oncomine Dx target test multi-CDx system revealed positivity for EGFR (L858R and E709X) and CTNNB1 mutations. The expression of programmed death ligand 1 (22C3 clones) in tumor cells was negative by immunostaining. The patient was treated with afatinib as first-line therapy and achieved clinical improvement and a partial response and is continuing treatment 1 year later. Case reports of lung cancer patients with EGFR/CTNNB1 comutations are rare, and TKIs are not considered to be effective. We herein present the first case report of lung cancer with the co-occurrence of uncommon and complex EGFR (L858R and E709X) and CTNNB1 mutations that was successfully treated with afatinib

A single dose of pembrolizumab treatment causing a profound and durable response in lung cancer

Profound and durable responses to a single dose of pembrolizumab in lung cancer are rare. We encountered a non-small cell lung cancer patient showing a deep and durable response with a single dose of pembrolizumab. A 79-year-old man reported bloody sputum for several weeks and visited a general physician. A chest x-ray revealed a tumor shadow in the right middle lung field at that time, and the patient was referred to our hospital. He was diagnosed with adenocarcinoma of the lung by transbronchial biopsy. The expression of programmed death ligand 1 in tumor cells was 100% by immunostaining. Based on the above, immunotherapy with pembrolizumab was performed as first-line therapy. Cancer cells had significantly shrunk at the end of the first cycle. The patient had grade-3 immune-related hepatitis at the end of the first cycle. Pembrolizumab treatment was stopped and prednisolone (80 mg/body) was initiated. Subsequently, liver function normalized, and prednisolone was tapered and discontinued. Since then, no tumor recurrence has been detected for 1.5 years without treatment. There have been few reports of profound and durable responses to a single dose of pembrolizumab in lung cancer. The results indicate that a single dose of pembrolizumab alone may be sufficient to cause durable response and serious immune-related adverse events in some cases