The First Case Report of Effective Treatment With Sotorasib for Metastatic Atypical Lung Carcinoid Harboring KRAS G12C Mutation and Aggressive Disseminated Lung Metastasis: A Case Report.

Pulmonary neuroendocrine tumors are rare, accounting for approximately 1% to 2% of lung cancers. Atypical carcinoids account for approximately 10% of pulmonary neuroendocrine tumors and are categorized as moderately malignant. Treatment options for advanced-stage atypical carcinoids include everolimus, cytotoxic anticancer agents, and peptide receptor radionuclide therapy. In this report, we present the first case of KRAS G12C mutation-positive atypical carcinoid that was successfully treated with sotorasib. Therapeutically important mutations observed in non-small cell lung cancer are seldom found in atypical carcinoid tumors. Nonetheless, it is worthwhile to search for genetic mutations in atypical carcinoid tumors, considering the potential for molecular targeted therapy to be effective in their treatment as well.

A case of non-neutropenic invasive pulmonary aspergillosis under immune checkpoint inhibitor therapy for malignant melanoma.

The patient was a 70-year-old man with diabetes mellitus, alcoholic liver disease and bronchial asthma treated with corticosteroid and long-acting ß-agonist inhalants. He had also been treated with nivolumab for advanced malignant melanoma for two years with a partial response. He presented to our department with intractable cough, which was attributed to uncontrolled bronchial asthma. Two weeks later, he presented with a high fever and worsened cough. He was diagnosed with bacterial pneumonia based on severe inflammation revealed by laboratory tests and right upper lung consolidation on chest radiography. Antibiotics via either oral or parenteral administration were ineffective and no pathogen was detected in sputum or blood cultures. Based on the air-crescent sign observed on chest computed tomography and a diffuse pseudomembranous lesion on the airway epithelium that was observed via bronchoscopy along with positive serum Aspergillus antigen, a clinical diagnosis of invasive pulmonary aspergillosis (IPA) was made and liposomal amphotericin B was initiated. Three days later, the patient developed massive hemoptysis, and he died of respiratory failure. Later, aspergillus-like mycelia were observed in the pathology of bronchial biopsy, supporting the clinical diagnosis of IPA. Although the use of immune checkpoint inhibitors has been reported to be beneficial for patients with some infectious diseases, it does not seem to be the case for patients with other infectious diseases including our patient.

Dramatic response to alectinib in an ALK-positive LCNEC patient with a poor performance status: A case report.

The echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene, a driver mutation in lung carcinoma, is fairly common in lung adenocarcinoma but rare in large cell neuroendocrine carcinoma (LCNEC). Here we report a case of stage IV LCNEC positive for this fusion gene in a patient with a poor performance status (PS) who was effectively treated with alectinib. The patient was a 72-year-old non-smoking man diagnosed as LCNEC with multiple metastases. Because of his poor PS, cytotoxic chemotherapy was not indicated, but he was later found to be positive for the ALK fusion gene and treated with alectinib as first-line therapy. One month later, the tumour had shrunk remarkably, and the therapeutic effect was rated as a partial response. The PS also improved from 4 to 1. Investigating actionable driver mutations seems worth doing for advanced LCNEC, especially if the patient's PS is poor.

A case of cervical lymph node tuberculosis and metastatic squamous cell carcinoma in the same lymph node.

We report a rare coexistence of tuberculosis and squamous cell carcinoma (SCC) of the same lymph node (LN). A 74-year-old woman with a swollen right cervix underwent computed tomography, which showed a nodule in the right lung and swollen LNs of the mediastinum and right supraclavicular fossa. She was diagnosed with LN tuberculosis; the puncture cytology of the clavicular LN was class IV. Anti-tuberculosis treatment was initiated. Her neck was compressed due to LN enlargement, and dyspnea appeared. A biopsy was performed to diagnose the SCC. We propose that malignancy should be considered if the patient has a narrowed airway due to an enlarged LN or if the response to tuberculosis treatment is poor.

Significant therapeutic effectiveness of durvalumab after chemoradiotherapy for a patient with post-operative recurrent pulmonary pleomorphic carcinoma.

Pulmonary pleomorphic carcinoma (PPC) is a poorly differentiated non-small cell lung cancer. Because of its rarity, no standard therapy has been established for advanced disease. We herein report on a 62-year-old man with recurrent post-operative PPC, for whom durvalumab after chemoradiotherapy was effective. He was referred to our hospital because of an abnormal shadow in the right upper lung on chest X-ray. After surgical resection was performed, the imaging and histopathological findings revealed PPC (T4N0M0, stage IIIA) with elevated expression of programmed cell death-ligand 1 (PD-L1). A metastasis was found in the left hemithorax 22 months later, and chemoradiotherapy consisting of 60 Gy of radiation and cisplatin plus tegafur/gimeracil/oteracil potassium was administered. Durvalumab was then begun as consolidation therapy. The efficacy of the treatments has continued for longer than 10 months. This case suggests that multidisciplinary treatment with chemoradiotherapy and consolidation immunotherapy may improve the prognosis of locally advanced PPC.

A case of exogenous lipoid pneumonia diagnosed by transbronchial lung cryobiopsy.

A 57-year-old man visited a referral physician due to abnormal chest shadows. Transbronchial lung biopsy (TBLB) failed to diagnose his condition. As antibiotics and systemic steroids did not improve the condition, he was referred to our hospital. A second TBLB in our hospital also failed to diagnose the disease. Transbronchial lung cryobiopsy (TBLC) was performed using radial endobronchial ultrasound with guide sheath (EBUS-GS), and the patient was diagnosed with lipoid pneumonia. Right upper lobe resection was performed, and lipoid pneumonia was confirmed from the surgical specimen. We report a case of lipoid pneumonia diagnosed by EBUS-GS TBLC.

Tolerability and safety of nintedanib in elderly patients with idiopathic pulmonary fibrosis.

BACKGROUND: In the phase III trial of nintedanib, only 10.8% of participants were aged ≥75 years. Here, we aimed to evaluate the tolerability and safety of nintedanib in elderly patients with idiopathic pulmonary fibrosis (IPF). METHODS: In total, 71 consecutive patients with (1) IPF, (2) age ≥75 years, and (3) newly prescribed nintedanib from September 2015 to April 2018 (elderly group) were retrospectively reviewed. Patient characteristics, treatment status, and adverse events (AEs) were compared between the elderly group and 126 patients with IPF, aged <75 years, with newly prescribed nintedanib during the same period (non-elderly group). RESULTS: In the elderly group, 32 patients (46.4%) discontinued nintedanib within 6 months. Body size was significantly smaller, the incidence rates of anorexia and nausea were significantly higher, and early termination within 6 months were more common in the elderly than in the non-elderly group. In elderly patients, a univariate logistic regression analysis showed that body mass index (BMI) and percentage forced vital capacity (FVC) were risk factors for early termination (p = 0.02 and 0.03, respectively). A low initial nintedanib dose did not reduce the incidence of AEs and early termination rate in the elderly group. CONCLUSIONS: In elderly patients with IPF, the incidence of early nintedanib termination was higher, and anorexia and nausea were common AEs compared with those in non-elderly IPF patients. Treatment was frequently discontinued in elderly patients with low BMI and FVC, and chest physicians should be aware that nintedanib therapy may result in early termination in these patients.

MK615 Suppresses Hypoxia Tolerance by Up-regulation of E-cadherin in Colorectal Cancer Cells With Mutant KRAS.

BACKGROUND/AIM: The Japanese apricot "Prunus mume" is a traditional Japanese medicine. MK615, a compound extract from Prunus mume has been reported to have anti-tumor effects. Herein, we used 3D floating (3DF) culture to evaluate the anticancer effects of MK615 against human colorectal cancer (CRC) cells that contain mutant (mt) KRAS. MATERIALS AND METHODS: HKe3 cells exogenously expressing mtKRAS (HKe3-mtKRAS) were treated with MK615 in 3DF cultures. The protein levels of hypoxia-inducible factor 1 (HIF-1) and E-cadherin were quantified by western blotting. RESULTS: MtKRAS enhanced hypoxia tolerance via up-regulation of HIF-1. The expression of HIF-1 protein was suppressed by constitutive overexpression of E-cadherin in CRC HCT116 spheroids. MK615 increased the expression of E-cadherin and decreased the expression of HIF-1 in HKe3-mtKRAS. These results suggest that MK615 suppresses hypoxia tolerance by up-regulation of E-cadherin in CRC cells with mtKRAS. CONCLUSION: MK615 exhibits properties useful for the potential treatment of CRC patients with mtKRAS.

Correction to: Ultra-high-resolution computed tomography can demonstrate alveolar collapse in novel coronavirus (COVID-19) pneumonia.

The correct caption is given below.

Ultra-high-resolution computed tomography can demonstrate alveolar collapse in novel coronavirus (COVID-19) pneumonia.

PURPOSE: To review the chest computed tomography (CT) findings on the ultra-high-resolution CT (U-HRCT) in patients with the Novel coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: In February 2020, six consecutive patients with COVID-19 pneumonia (median age, 69 years) underwent U-HR CT imaging. U-HR-CT has a larger matrix size of 1024 × 1024 thinner slice thickness of 0.25 mm and can demonstrate terminal bronchioles in the normal lungs; as a result, Reid's secondary lobules and their abnormalities can be identified. The distribution and hallmarks (ground-glass opacity, consolidation with or without architectural distortion, linear opacity, crazy paving) of the lung opacities on U-HRCT were visually evaluated on a 1 K monitor by two experienced reviewers. The CT lung volume was measured, and the ratio of the measured lung volume to the predicted total lung capacity (predTLC) based on sex, age and height was calculated. RESULTS: All cases showed crazy paving pattern in U-HRCT. In these lesions, the secondary lobules were smaller than those in the un-affected lungs. CT lung volume decreased in two cases comparing predTLC. CONCLUSION: U-HRCT can evaluate not only the distribution and hallmarks of COVID-19 pneumonia but also visualize local lung volume loss.

Coexistence of dementia with smear-positive pulmonary tuberculosis is associated with patient in-hospital mortality.

BACKGROUND: The impact of dementia on the survival of patients with pulmonary tuberculosis (TB) remains unclear. This study sought to describe the risk factors influencing in-hospital mortality in patients with pulmonary TB and comorbid dementia. METHODS: A 9-y, medical record-based retrospective study of hospitalized adult patients with newly diagnosed, smear-positive, non-multidrug-resistant pulmonary TB without human immunodeficiency virus infection was performed. Clinical presentations, biochemical tests, radiographic findings, and clinical outcomes were collected. Variables were compared between groups. Statistically significant (p-value < 0.05) variables were entered into a multivariate stepwise logistic regression model. Survival analysis was performed using the Kaplan-Meier method, and groups were compared by log-rank test. RESULTS: Of the 279 enrolled patients (178 men; median age, 76 y), the mortality rate was 12.2% (34/279). Univariate analysis showed a higher frequency of dementia in patients who died in hospital than that in surviving patients. Multivariate stepwise logistic analysis showed that dementia was significantly associated with higher rates of in-hospital mortality (odds ratio, 3.20; 95% confidence interval, 1.15-8.88, p = 0.026). In addition, subgroup survival curves showed that dementia was associated with reduced survival rates, even after adjusting for age (log-rank test, p = 0.0007). CONCLUSIONS: The comorbidity of dementia with pulmonary TB was associated with patient in-hospital mortality. Medical practitioners should be aware of dementia in patients with smear-positive pulmonary TB to identify high-mortality groups.

Successful management of recurrent adenoid cystic carcinoma in the deep infratemporal fossa by maxillo-orbito-zygomatic approach.

OBJECTIVE: In the case of deep invasion of an infratemporal fossa (ITF) tumor, surgeons find it difficult to gain sufficient visualization and working space by conventional surgical approaches. To overcome these limitations, we have developed a novel surgical technique, maxillo-orbito-zygomatic (MOZ) approach, by combining partial lateral maxillectomy with the conventional orbito-zygomatic approach. METHODS: A 63-year-old male presented with the fifth recurrent adenoid-cystic carcinoma in the right deep ITF. Using a Weber-Ferguson-type incision and partial dismasking, we elevated the skin and scalp flap, while preserving the facial nerve and orbicularis oculi muscle intact in the flap. Then, we performed MOZ osteotomy using three cut lines, the zygomatic arch, the frontozygomatic suture, and from the inferior orbital fissure to the anterolateral wall of the maxilla. Following this, we temporarily elevated the bone flap by partially opening the lateral maxillary sinus. We obtained an excellent surgical view of the ITF, middle skull base, and pterygopalatine fossa with this technique, which facilitated the safe removal of the tumor. RESULTS: The postoperative course remained almost uneventful, and we obtained favorable cosmetic results. CONCLUSIONS: Our novel MOZ approach could be a robust approach to remove deep ITF tumors.

A case report of granulomatous polyangiitis complicated by tuberculous lymphadenitis.

RATIONAL: Granulomatous polyangiitis (GPA) is a type of vasculitis involving medium and small arteries, typically affecting the upper and lower respiratory tract with coexisting glomerulonephritis. GPA is also characterized by necrotizing granulomatous inflammation and the presence of antineutrophil cytoplasm antibodies (ANCA). So far, various infections have lead to elevation of titers of serum ANCA, making it difficult to diagnose. PATIENT CONCERNS: We report a 50-year-old woman who was diagnosed as tuberculous lymphadenitis. During the treatment by anti-tuberculosis (TB) drugs, rapidly progressive renal failure and pleurisy had appeared with elevated titer of PR3-ANCA. Renal biopsy revealed crescentic glomerulonephritis. DIAGNOSIS: Renal biopsy revealed crescentic glomerulonephritis and diagnosis of GPA was made. INTERVENTIONS: Steroid therapy had been started with continuation of anti-TB drugs. OUTCOMES: Renal dysfunction had gradually recovered and pleurisy had disappeared with decreasing titer of PR3-ANCA. LESSONS: This is the first report of GPA complicated by TB infection. When we encounter a case with rapidly progressive renal failure during the TB infection, complication of GPA should be suspected as 1 of the different diagnosis.

Invasive pulmonary aspergillosis mimicking organizing pneumonia after mTOR inhibitor therapy: A case report.

A 67-year-old man presented to the hospital with complaints of fever and cough. He had a past medical history of renal cell carcinoma and had just started treatment with temsirolimus, a mammalian target of rapamycin (mTOR) inhibitor. A 1-week course of antibiotics did not have any effect on his symptoms. A chest computed tomography (CT) scan showed the reversed halo sign (RHS). Organizing pneumonia induced by mTOR inhibitor treatment was initially considered. However, transbronchial biopsy revealed clusters of fungal organisms, suggesting infection with Aspergillus spp. Within just 2 weeks, a CT scan showed drastic enlargement of the cavitary lesion, with multiple newly formed consolidations. The patient was diagnosed with invasive pulmonary aspergillosis. Concomitant treatment with voriconazole and micafungin was started. Two weeks after the initiation of treatment, he became afebrile with gradual regression of the cavitary lesion and consolidations.

Utility of chemoradioselection for the optimization of treatment intensity in advanced hypopharyngeal and laryngeal carcinoma.

Definitive concomitant chemoradiotherapy (CRT) with high-dose cis-platinum (CDDP) is a current standard protocol for advanced laryngeal and hypopharyngeal cancer sparing surgery for salvage. However, this modality is associated with limited feasibility and frequent sever toxicities. In the present study, a 'chemoradioselection' protocol with minimal toxicity was developed using initial response to CRT as a biomarker for patient selection. Between 2000, March and 2012, September 123 patients with stage III (44), IV (79) laryngeal (64) and hypopharyngeal carcinoma (59) excluding T4 cases were enrolled to this protocol. Two cycles of split (15 mg/m2 ×5 days, 2000-2008) or bolus (80 mg/m2, 2009-present) CDDP was concurrently administered. Tumor responses were evaluated after 40 Gy of CRT and 64 responders (chemoradioselected, CRS) received further CRT up to 70 Gy, while radical surgery was recommended for the 59 non-responders (N-CRS), and 34 underwent surgery (N-CRS-ope). The remaining 25 patients who refused surgery (N-CRS-refu) were treated with continuous CRT. The 5-year overall survival (OS) and disease-specific survival (DSS) were 67, and 77%, respectively. The CRS demonstrated favorable 5-year OS (73%) and laryngo-esophageal dysfunction-free survival (LEDFS, 69%) rates. In contrast, the N-CRS-refu showed significantly lower 5-year OS (47%) compared with CRS (73%) and N-CRS-ope (70%) (P=0.0193), and significantly lower 5-year LEDFS (20%) compared with the CRS (69%) (P<0.0001). On multivariate analyses, including T, N, primary site and planned treatment (CRS + N-CRS-ope) or not (N-CRS-refu), unplanned treatment alone showed a significant correlation with poor OS [hazard ratio (HR), 2.584; 95% confidence interval (CI), 1.313-4.354; P=0.007). Chemoradioselection reflects the biological aggressiveness of each tumor, and is able to segregate patients for functional laryngeal preservation with moderate intensity CRT (150-160 mg/m2 of CDDP) from those who would be better treated with surgery. This strategy may be useful for the optimization of the therapeutic intensity.

Very early response of circulating tumour-derived DNA in plasma predicts efficacy of nivolumab treatment in patients with non-small cell lung cancer.

INTRODUCTION: Immunotherapy has become a treatment option for lung cancer. The utility of nivolumab as second-line treatment for non-small cell lung cancer has been proven, but predictive biomarkers influencing its efficacy remain unknown. METHODS: This study involved 14 patients who were treated with nivolumab from February 1 to September 30, 2016. The early response of the level of circulating tumour DNA (ctDNA) after starting nivolumab was evaluated to ascertain whether it could predict treatment outcome. RESULTS: Of the 14 patients, six were responders and eight were non-responders. DNA was analysed in both tumour tissue and plasma samples. Only somatic mutations confirmed by analysis of tumour tissue were defined as ctDNA. ctDNA was detected more often in the serial plasma samples of patients with high tumour volume (TV) (p = 0.02). ctDNA was detected in seven cases; basal and serial ctDNA analysis revealed that a decrease in allelic frequency (AF) of ctDNA showed high-level correspondence with a good durable response. When "2 weeks" was set as a clinically significant time point, changes in representative mutations of each case, defined as one of the highest baseline AF, showed 100% concordance with the response. CONCLUSIONS: In patients with high TV, plasma analysis of ctDNA, as validated by tumour tissue, suggested that a durable good response to nivolumab could be predicted within 2 weeks.