Conventionally, when diagnosing cases of malignant pleural effusion, examinations have been performed by thoracentesis and a blind pleural biopsy, but the diagnosis rate has never been satisfactory. In particular, malignant pleural mesothelioma has a low positive rate using the above-mentioned method, which may lead to a misdiagnosis, so careful judgment is required. In Japan, medical thoracoscopy has been introduced since 1990, and it has become possible to directly observe and biopsy pleural lesions, which has dramatically improved the diagnosis rate. In lung cancer treatment, this approach is useful not only for making a pathological diagnosis but also for performing biomarker tests. However, pleural lesions often become thickened, fibrous and hard, regardless of the cause, so improvement of the biopsy technique is required. This review outlines the advances in medical thoracoscopy and ingenuity concerning pleural biopsy techniques.

Molecular subtypes of small-cell lung cancer have been recently reported to be determined by lineage transcription factors, such as ASCL1, NEUROD1, POU2F3 and YAP1. In parallel with investigations of these neuroendocrine lineage factors, the roles of MYC family transcription factors MYC, MYCL and MYCN in small-cell lung cancer have been explored, and it is suggested that these factors are not just general oncogenes but actually control transcriptional programs determining neuroendocrine differentiation subtypes. In large-cell neuroendocrine carcinoma of the lung, which is classified as a neuroendocrine carcinoma, similar to small-cell lung cancer, these neuroendocrine lineage factors are expected to play major roles, as in small-cell lung cancer. However, since this histological type is more heterogeneous genetically and molecular-pathologically, further studies concerning the significance of these factors in this context are warranted. The translational implications of molecular subtype classifications, such as differences in drug sensitivities, including to immunotherapy, and heterogeneity/plasticity of the tumor differentiation status related to the subtypes have also been investigated and reported. This review summarizes the recent molecular subtype classifications of lung neuroendocrine carcinomas, spanning from how research has progressed over the years to future perspectives.

Background/Objective. While osimertinib is recommended as the first-line treatment of EGFR mutation-positive non-small cell lung cancer, it is known that drug-induced lung injury occurs frequently in patients receiving osimertinib. In addition, the presence of interstitial lung abnormalities (ILAs) is also known to be a risk factor for drug-induced lung injury. Therefore, we investigated whether or not ILAs were a risk factor for drug-induced lung injury caused by osimertinib based on the clinical experience at our hospital. Study Design. We retrospectively reviewed 106 patients with advanced-stage non-small cell lung cancer treated with osimertinib at our hospital from September 2018 to September 2020. Results. A multivariate logistic regression analysis showed that the presence of ILAs prior to treatment with osimertinib was a significant risk factor for drug-induced lung injury (odds ratio: 4.93, p<0.05). In addition, patients with a subpleural fibrotic pattern tended to have more severe drug-induced lung injury than others. Conclusion. ILAs may be a risk factor for drug-induced lung injury with osimertinib. In particular, patients with subpleural fibrotic pattern are at an increased risk of severe lung injury and thus should be carefully observed.

Objectives. This study verified whether or not high-resolution computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT are useful for predicting the tumor malignancy grade in lung adenocarcinoma. Materials and Methods. We identified 78 patients with cTis/T1 adenocarcinoma of the lung who underwent FDG-PET/CT at the same hospital and received surgery between April 2016 and February 2021. We classified them into three groups based on the 5^th WHO grade classification. The relationships between the groups and clinicopathological factors, including the consolidation tumor ratio (CTR) and maximum standardized uptake value (SUVmax), were investigated. The cut-off values of the CTR and SUVmax, which predict high-grade malignant tumors, were obtained by a receiver operating characteristic (ROC) analysis, and we combined both values for the evaluation. Results. There were significant differences in the CTR and SUVmax values among the three groups. The rates of lymphovascular invasion and lymph node metastasis were higher in the high-grade group than in the low-grade group. The cut-off values for predicting high-grade malignancy were 97.6% and 3.35 for the CTR and SUVmax, respectively. When the CTR of the tumor was ≥98% and the SUVmax was >3.35, the sensitivity and specificity for the detection of high-grade lesions were 87.5% and 85.5%, respectively. Conclusion. High-grade malignant cTis/T1 lung adenocarcinoma can be detected by high-resolution CT and FGD-PET/CT.

Background. Immunotherapy is now widely used in the treatment of non-small cell lung cancer (NSCLC). In the cancer immune response, priming of T lymphocytes in the draining lymph nodes is considered necessary. In this context, the effect of programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors may be weakened after lymph node dissection. We therefore evaluated the differences in the clinical response to PD-1/PD-L1 inhibitors in NSCLC patients with and without lymph node dissection. Methods. We conducted a retrospective study of NSCLC patients treated with PD-1/PD-L1 inhibitors at Otsu Red Cross Hospital by November 2020. Results. There were 25 cases of lymph node dissection and 63 unresectable cases. The disease control rates in the groups with and without resection were 10 (40%) and 16 (25%), the overall response rate was 6 (24%) and 6 (9%), the median overall survival was 19.5 and 10.5 months (P=0.47), and the median progression-free survival was 8.3 and 5.6 months (P=0.86), respectively. There were 4 (16%) and 7 (11%) (P=0.5) grade ≥3 immune-related adverse events in the groups with and without resection, respectively. Conclusion. In patients with recurrent disease after curative resection who underwent lymph node dissection for NSCLC, the therapeutic effect of PD-1/PD-L1 inhibitors was not inferior to that of unresectable cases, both in terms of the therapeutic effect and the risk of adverse events.

Objective. In our country, nowadays, there are few confirm for the labor insurance system primary lung cancer from asbestos that is suspected about twice times of mesothelioma. We hypothesize that one of the reasons is that there is no established medical order for interview surveys in relation to asbestos exposure. Thus, in the present study, we consider the current status of the established medical order as well as forthcoming issues. Study Design. We conducted a web questionnaire survey of lung cancer patients and their family to investigate their knowledge of asbestos, damage to health, the labor insurance system, and the presence of subjective symptoms of asbestos exposure. Results. Regarding the status knowledge, most lung cancer patients knew basic details about asbestos and health damage from asbestos. However, few knew about mesothelioma, causes of cancer, and systems. Fewer respondents knew how to suspect their own health damage caused by indirect exposure or understand the clinical findings of asbestos exposure. Conclusion. As a remedial measure, a system for learning about asbestos exposure must be established through awareness-raising activities for patient groups and the use of hospital departments that provide counseling and support.

Background. Chordoma, a rare malignant tumor that originates from primitive notochord remnants, commonly affects the sacrum, skull base, and mobile spine. However, chordomas may rarely present as paravertebral mediastinal tumors. Case. A 54-year-old man at his annual checkup underwent chest radiography, which revealed an extra-pleural nodule in the right upper lung field. Chest computed tomography (CT) revealed a right paravertebral tumor at the upper mediastinum. We clinically diagnosed the mass as a benign neurogenic tumor, and it was removed surgically. A histopathological examination showed large vacuolated cells arranged in sheets and myxoma-like tissues characteristic of chordoma. We pathologically diagnosed the tumor as chordoma based on the brachyury-positive status. No subsequent therapies were administered, and no recurrence was observed at the six-month follow-up. Conclusion. We herein report a case of mediastinal chordoma treated with surgical resection.

Background. Fulminant type 1 diabetes mellitus caused by immune checkpoint inhibitors is a rare adverse event. In lung cancer, several cases have been reported in non-small-cell lung cancer. We herein report a patient with small-cell lung cancer who developed fulminant type 1 diabetes mellitus after administration of durvalumab. Case. A 71-year-old man with extensive-stage small-cell lung cancer (cT4N3M1b, stage IVA) with no history of diabetes mellitus received combination therapy of carboplatin, etoposide, and durvalumab on May 20XX. He became aware of anorexia and fatigue on day 27. He was diagnosed with fulminant type 1 diabetes mellitus caused by durvalumab with hyperglycemia of 761 mg/dl, positive urine ketones, and urinary C-peptide of 3.9 μg/day on the second course of treatment (day 30). After his blood glucose level had been stabilized with insulin therapy, an additional three cycles of chemotherapy with carboplatin and etoposide were administered. A significant response was achieved, and the patient survived without disease progression. Conclusion. Fulminant type 1 diabetes mellitus caused by durvalumab for small-cell lung cancer is a rare but urgent immune-related adverse event that requires attention.

Background. Tracheal adenoid cystic carcinoma (TACC) is the most common type of cancer among tracheal tumors. However, the findings of molecular analyses for TACC have rarely been reported. Case. Case 1: A woman in her 80s complaining of dyspnea on effort was found to have a 1.3-cm tracheal tumor just below the vocal folds and a solitary pulmonary metastasis on computed tomography (CT). After tracheal tumor resection with rigid bronchoscopy, radiation therapy was performed. Subsequently, lobectomy was performed. Case 2: A woman in her 40s complaining of wheezing was found to have 6-cm upper tracheal stenosis due to a tumor on CT. After tumor resection and Dumon^® stent insertion with rigid bronchoscopy, radiation therapy was performed. Case 3: A woman in her 40s complaining of dyspnea was found to have 6.6-cm upper tracheal stenosis due to a circumferential tumor and invasion into the surrounding tissue on CT. She underwent the same treatments as Case 2. Case 4: A man in his 40s complaining of wheezing was found to have 5.5-cm lower and carinal tracheal stenosis induced by a tumor on CT. The same treatments as in Cases 2 and 3 were performed. All four cases were diagnosed with TACC by a histopathological study. Conclusion. We report our clinical experiences with four cases of TACC and a molecular analysis.

Background. Thymic carcinoma is a rare cancer that occurs in 0.02 per 100,000 persons per year. At the diagnosis, 30% of patients are at the advanced stage of the disease. Furthermore, there are some cases in which aggressive treatment cannot be performed due to the poor general condition of the patients at the time of the diagnosis. Case. A 44-year-old woman visited our medical institution due to upper abdominal distension. Positron emission tomography-computed tomography (PET-CT) showed an abnormal fluorodeoxyglucose accumulation in the thymus, liver, and bone. A CT-guided biopsy was performed on the thymus, and the patient was diagnosed with thymic carcinoma. Rapid deterioration of the liver function, jaundice, and hyperammonemia also appeared and worsened. She was treated with a combination of carboplatin (area under the curve=6) and paclitaxel (100 mg/m²). At the end of the first course, her liver function improved, and the primary tumor, as well as the diffuse liver tumors, was markedly reduced. Conclusion. Thymic carcinoma is a rare disease with a poor prognosis. There is a lack of published studies on advanced stages, and there are few reports on chemotherapy for patients with severe liver dysfunction. Our case showed that the combination of carboplatin and paclitaxel resulted in a favorable response to advanced thymic carcinoma with liver failure.

Background. Tyrosine kinase inhibitors targeting the ALK domain (ALK-TKIs) play an important role in the treatment of ALK-positive lung cancer. However, it is difficult for patients who have dysphagia to benefit from ALK-TKIs, as ALK-TKIs are oral medications. Few data are available on the efficiency of a simple suspension method for and tube administration of ALK-TKIs. Case. A 71-year-old man was diagnosed with ALK-positive lung adenocarcinoma with multiple brain and lung metastases and left-sided malignant pleural effusion at our department in 2015. He was treated with crizotinib as the first-line treatment, but the tumors grew after 10 months. Thereafter he received alectinib as the second-line treatment, and the tumors remained controlled for four years and nine months. However, in February 2021, he experienced difficulty swallowing. His dysphagia gradually worsened, and in March 2021, he became unable to take anything but water orally. Upper gastrointestinal endoscopy and CT revealed that the paraesophageal lymph node metastasis had caused a stenosis to develop in the esophagus. He underwent gastric fistula placement and received brigatinib via gastrostomy. Thereafter, the esophageal stenosis was improved, and he was able to take food orally. Conclusion. We successfully administered brigatinib via gastrostomy using a simple suspension method in a case of ALK-positive lung cancer with esophageal stenosis.

Background. Pleural biopsy during semiflexible thoracoscopy is useful for the diagnosis of pleural effusion. However, we sometimes experience cases in which the tumor is difficult to grasp with a flexible forceps because of the properties of the pleura. Case. The patient was a 51-year-old man with idiopathic interstitial pneumonia, who was found to have left pleural effusion. We attempted to perform pleural biopsy using a flexible forceps during semiflexible thoracoscopy; however, it was impossible because it was fibrous and hard lesion. Therefore, we performed thoracoscopic pleural biopsy with a cryoprobe. Cryobiopsy enabled us to obtain a specimen. A thoracic SMARCA4-deficient undifferentiated tumor was diagnosed based on the pathological findings. Conclusion. Pleural cryobiopsy during semiflexible thoracoscopy may be useful for the diagnosis of patients with an extensive fibrous pleura, in which the tumor is difficult to grasp with a flexible forceps.