Primary lung cancer with pulmonary alveolar proteinosis treated with immune checkpoint inhibitor: A case report.

Primary lung cancer with pulmonary alveolar proteinosis (PAP) is a rare condition. We present a case of a patient with primary lung cancer with PAP treated with an immune checkpoint inhibitor (ICI). A 62-year-old man was diagnosed with autoimmune PAP 8 years prior to current admission. Lung adenocarcinoma was found in his right lung, and platinum-based chemotherapy was administered, followed by atezolizumab. He experienced disease progression after atezolizumab treatment, whereas ICI-induced pneumonia or exacerbation of PAP did not occur. This indicates that ICI may be safely used in patients with primary lung cancer with PAP.

Whole lung lavage decreases physiological dead space in patients with pulmonary alveolar proteinosis: two case reports.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by progressive accumulation of the alveolar surfactant. Whole lung lavage (WLL) using a high volume of warmed saline remains the standard therapy. However, no established bedside monitoring tool can evaluate the physiological effect of WLL in the perioperative period. Indirect calorimetry, which is generally used to measure resting energy expenditure, can detect carbon dioxide (CO2) production and mixed-expired partial pressure of CO2 breath by breath. In this physiological study, we calculated CO2 elimination per breath (VTCO2,br) and Enghoff's dead space using indirect calorimetry and measured the extravascular lung water index to reveal the effect of WLL. CASE PRESENTATION: We measured VTCO2,br, Enghoff's dead space, and the extravascular lung water and cardiac indices before and after WLL to assess the reduction in shunt by washing out the surfactant. A total of four WLLs were performed in two PAP patients. The first case involved an Asian 62-year-old man who presented with a 3-month history of dyspnea on exertion. The second case involved an Asian 48-year-old woman with no symptoms. VTCO2,br increased, and the Enghoff's dead space decreased at 12 h following WLL. An increase in the extravascular lung water was detected immediately following WLL, leading to a transient increase in Enghoff's dead space. CONCLUSION: WLL can increase efficient alveolar ventilation by washing out the accumulated surfactant. However, the lavage fluid may be absorbed into the lung tissues immediately after WLL and result in an increase in the extravascular lung water.

Comparison of Ultra-Magnifying Endocytoscopic and Hematoxylin-Eosin-Stained Images of Lung Specimens.

Endocytoscopy enables real-time observation of lesions at ultra-magnification. In the gastrointestinal and respiratory fields, endocytoscopic images are similar to hematoxylin-eosin-stained images. This study aimed to compare the nuclear features of pulmonary lesions in endocytoscopic and hematoxylin-eosin-stained images. We performed an endocytoscopy to observe resected specimens of normal lung tissue and lesions. Nuclear features were extracted using ImageJ. We analyzed five nuclear features: nuclear number per area, mean nucleus area, median circularity, coefficient of variation of roundness, and median Voronoi area. We conducted dimensionality reduction analyses for these features, followed by assessments of the inter-observer agreement among two pathologists and two pulmonologists to evaluate endocytoscopic videos. We analyzed the nuclear features of hematoxylin-eosin-stained and endocytoscopic images from 40 and 33 cases, respectively. Endocytoscopic and hematoxylin-eosin-stained images displayed a similar tendency for each feature, despite there being no correlation. Conversely, the dimensionality reduction analyses demonstrated similar distributions of normal lung and malignant clusters in both images, thus differentiating between the clusters. The diagnostic accuracy of the pathologists was 58.3% and 52.8% (κ-value 0.38, fair), and that of the pulmonologists was 50% and 47.2% (κ-value 0.33, fair). The five nuclear features of pulmonary lesions were similar in the endocytoscopic and hematoxylin-eosin-stained images.

Usefulness of endocytoscopy in evaluating transbronchial biopsy specimens.

BACKGROUND: Endocytoscopy (ECS) provides a magnification of approximately 450× for real-time observation of lesion nuclei. Using ECS, we aimed to evaluate whether sufficient samples for diagnosis can be obtained during bronchoscopy. We also investigated whether ECS can enable two-class diagnosis of malignant or non-malignant transbronchial biopsy specimens in real-time during bronchoscopy. METHODS: This was a single-facility, prospective, observational, ex vivo study. Forty cases with localized peripheral pulmonary lesions underwent transbronchial biopsy with endobronchial ultrasonography using a guide sheath. Each biopsy specimen was immediately observed and evaluated endocytoscopically after the collection by the bronchoscopic procedure. RESULTS: Thirty-seven cases were enrolled. The diagnostic accuracy achieved by ECS was 91.9% (34/37). The agreement rate between the endocytoscopic evaluation and pathological diagnosis of each specimen (170 specimens) was 65.3% (111/170). The median time required for endocytoscopic evaluation per specimen was 70 s. When we judged a specimen to be malignant a second time on ECS evaluations of five specimens in one case, pathologically malignant specimens were collected in 26 of 27 cases (96.3%). CONCLUSIONS: ECS with methylene blue staining may aid in the two-class diagnosis of malignant or non-malignant transbronchial biopsy specimens during bronchoscopy. This may reduce the number of tissue biopsies.

Prognosis of frail older patients treated with intubation and artificial ventilation for respiratory failure.

BACKGROUND: Older patients with severe respiratory failure have higher mortality rates and are more likely to experience impairments in activities of daily living (ADL). METHODS: We retrospectively reviewed patients (??75 years) who received intubation and artificial ventilation for respiratory failure at Shimane University Hospital between November 2014 and December 2020. We compared the outcomes of frail patients with those of self-sufficient patients. RESULTS: Thirty-two patients were included. ADL ability before respiratory failure was rated self-sufficient in 18 patients (self-sufficient group) and not self-sufficient in 14 patients (frail group). None of the patients in either group underwent advanced care planning prior to the onset of respiratory failure. In the self-sufficient and frail groups, the in-hospital mortality rates were 33% and 50%, and the incidence of bedridden patients at discharge was 6% and 43%, respectively. Most patients in the frail group (93%) died or were bedridden. The median hospitalization cost was JPY 2,984,000 for the self-sufficient group and JPY 3,008,000 for the frail group. CONCLUSION: The overall prognosis of frail older patients who underwent intubation and artificial ventilation was poor. When providing intensive care to such patients, it is important to carefully consider their suitability for the treatment. J. Med. Invest. 70 : 494-498, August, 2023.

Multiple Mass Lesions in Pneumocystis Pneumonia.

We encountered a case of pneumocystis pneumonia (PCP) presenting with multiple mass lesions in a human immunodeficiency virus (HIV)-negative patient. Diagnosis of PCP before bronchoscopy was difficult because chest computed tomography (CT) findings were atypical of PCP and a serum (1,3)-ß-D-glucan concentration was within normal limits. Bronchoscopic biopsy and Grocott's staining enabled the diagnosis of PCP. PCP can show various patterns on chest CT images, depending on the immune status of the host. In high-risk patients, such as those who are immunocompromised, bronchoscopy should be performed with suspected cases of PCP, even if CT imaging does not show typical ground-glass opacity.

Deep learning-based diagnosis from endobronchial ultrasonography images of pulmonary lesions.

Endobronchial ultrasonography with a guide sheath (EBUS-GS) improves the accuracy of bronchoscopy. The possibility of differentiating benign from malignant lesions based on EBUS findings may be useful in making the correct diagnosis. The convolutional neural network (CNN) model investigated whether benign or malignant (lung cancer) lesions could be predicted based on EBUS findings. This was an observational, single-center cohort study. Using medical records, patients were divided into benign and malignant groups. We acquired EBUS data for 213 participants. A total of 2,421,360 images were extracted from the learning dataset. We trained and externally validated a CNN algorithm to predict benign or malignant lung lesions. Test was performed using 26,674 images. The dataset was interpreted by four bronchoscopists. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the CNN model for distinguishing benign and malignant lesions were 83.4%, 95.3%, 53.6%, 83.8%, and 82.0%, respectively. For the four bronchoscopists, the accuracy rate was 68.4%, sensitivity was 80%, specificity was 39.6%, PPV was 76.8%, and NPV was 44.2%. The developed EBUS-computer-aided diagnosis system is expected to read EBUS findings that are difficult for clinicians to judge with precision and help differentiate between benign lesions and lung cancers.

Nontuberculous Mycobacterium-associated immune reconstitution inflammatory syndrome in a non-HIV immunosuppressed patient.

A 69-year-old woman with rheumatoid arthritis, using immunosuppressants, including etanercept-a tumour necrosis factor (TNF)-α antagonist-was referred to our hospital with fever and fatigue. Chest computed tomography revealed cavities in the left upper lobe. As Mycobacterium intracellulare infection was diagnosed, all immunosuppressants were discontinued, and treatment with anti-nontuberculous Mycobacterium drugs was initiated. However, her condition worsened paradoxically. We diagnosed immune reconstitution inflammatory syndrome (IRIS) resulting from the discontinuation of the TNF-α antagonist. Her condition improved with prednisolone treatment. IRIS is generally observed during HIV treatment, but a good understanding of immunosuppressant-related non-HIV IRIS is needed.

Ultra-magnifying Imaging of Thoracoscopic Biopsy Specimens Using Ex vivo Endocytoscopy in Three Patients with Mesothelioma.

We performed endocytoscopy (ECS) for the ex vivo evaluation of mesothelioma in specimens biopsied during medical thoracoscopy in three patients. We evaluated 19 biopsy specimens based on the density of nuclei and irregularity in the nuclei shape using ECS and compared them with the histopathological findings. All 10 specimens considered malignant based on ECS were diagnosed as malignant based on histopathology. The nine specimens evaluated as non-malignant based on ECS consisted of six specimens diagnosed as malignant based on histopathology and three diagnosed as non-malignant based on histopathology. ECS was feasible and had some utility for ex vivo ultra-magnifying imaging of thoracoscopic biopsy specimens from patients with mesothelioma.

Results of 10-year mobile low-dose computed tomography screenings for lung cancer in Shimane, Japan.

BACKGROUND: Some randomized controlled trials have evaluated the effects of low-dose computed tomography (CT) screening on lung cancer mortality in heavy smokers. Based on the results of those trials, our CT screening program recommended screening for people aged ≥40 years with a history of smoking. This retrospective study aimed to verify the validity of our CT screening program and elucidate the current state of CT screening program. METHODS: We retrospectively examined lung cancer detection in 25,189 participants who underwent chest CT screening by a mobile low-dose CT screening unit in the 10-year period from April 2009 to March 2019. Participants were recruited at Japan Agricultural Cooperatives (JA) Shimane Kouseiren. Participants requested CT screening for lung cancer. CT images were read by two pulmonologists. RESULTS: Lung cancer was identified in 82 of the 25,189 participants over 10 years, an overall lung cancer detection rate (percentage of lung cancers detected among all participants) of 0.33%. Lung cancer among never smokers accounted for 54.9% of the detected cases. The lung cancer detection rate was similar for smokers versus never smokers. The stage IA detection rate (percentage of stage IA lung cancers among all lung cancers detected) was 62%, while the stage Ⅳ detection rate was 10%. CONCLUSIONS: Chest CT detected lung cancer in never smokers as well as current or former smokers. Our CT screening program was not effective for never smokers; thus, further study of the effectiveness of CT screening in never smokers is needed.

Prospective clinical trial evaluating vulnerability and chemotherapy risk using geriatric assessment tools in older patients with lung cancer.

AIM: In Japan, the number of older patients with cancer has been increasing. Assessment of performance status, cognitive function and social background is necessary for the treatment of older patients. The aims of the present study were: (i) to establish an evaluation system using electronic medical records; and (ii) to distinguish older patients as fit versus vulnerable or frail according to a geriatric assessment (GA) system score. METHODS: We incorporated GA tools in our electronic medical records system and carried out comprehensive assessments for patients with newly diagnosed lung cancer aged ≥65 years. The decision about primary treatment followed consultation with the clinical team and was not guided by GA scores. Subsequent treatment and outcomes were recorded. RESULTS: A total of 100 patients had completed GA. The average age was 75 years (range 65-94 years). Regarding GA results, 63% were positive on the Comprehensive Geriatric Assessment 7, 39% on the Vulnerable Elderly Survey-13 and 84% on the Geriatric 8. The percentage of vulnerable patients (positive on all three GA) was significantly higher in the non-standard therapy group (n = 19) than in the standard therapy group (n = 81; 78.9% vs 21.0%, P < 0.001). Among vulnerable patients who received standard therapy, 47% discontinued chemotherapy as a result of toxicity. Even if a patient was considered vulnerable based on GA scores, chemotherapy is possibly safe for those with EGFR mutations. CONCLUSIONS: We confirmed the feasibility of this system. During decision-making for older patients with cancer, a combination of GA helps prevent undertreatment or overtreatment. Geriatr Gerontol Int 2019; 19: 1108-1111.

Successful rechallenge with ceritinib after leukocytoclastic vasculitis during ceritinib treatment for non-small cell lung cancer harboring the EML4-ALK fusion protein.

Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (TKIs) dramatically improve progression-free survival compared to cytotoxic agents. It is therefore important to manage patients with ALK-TKIs until drug resistance occurs. Leukocytoclastic vasculitis (LCV) is a rare complication during cancer treatment and is associated with a variety of factors. Currently, it is unclear whether we should withdraw a treatment when drug-induced LCV develops. We report a 40-year-old man with advanced pulmonary adenocarcinoma harboring the EML4-ALK fusion protein who developed LCV during ceritinib treatment. Four weeks after withdrawing ceritinib, we could successfully perform rechallenge with ceritinib at the normal dose. Rapid and massive tumor apoptosis due to ceritinib treatment may lead to neoantigen release and immune complexes deposition. To the best of our knowledge, we report the first case of LCV in a patient during ALK-TKI treatment. Following this occurrence, we were able to successfully perform rechallenge with ceritinib. Therefore, key drugs used in a patient's treatment regimen should not be discontinued without careful evaluation, and we should also consider the possibility of rechallenge.